Chapter 29: Colon, Rectum, and Anus

1. Resection principles: The mesenteric clearance technique dictates the extent of resection and is determined by the nature of the primary pathology, the intent of resection, the location of the lesion, and the condition of the mesentery.

2. Function after resection: Bowel function is often compromised after colorectal resection, especially after low anterior resection. For this reason, it is important to obtain a history of prior anorectal trauma and/or incontinence before considering a low anastomosis.

3. Ostomies: Preoperative marking for a planned stoma is critical for a patient’s quality of life. Ideally, a stoma should be located within the rectus muscle, in a location where the patient can easily see and manipulate the appliance, and away from previous scars, bony prominences, or abdominal creases.

4. Inflammatory bowel disease: Both Crohn’s disease and ulcerative colitis are associated with an increased risk of colorectal carcinoma. Risk depends on the amount of colon involved and the duration of disease.

5. Pathogenesis of colorectal cancer: A variety of mutations have been identified in colorectal cancer. Mutations may cause activation of oncogenes (K-ras) and/or inactivation of tumor suppressor genes (adenomatous polyposis coli [APC], deleted in colorectal carcinoma [DCC], p53).

6. Minimally invasive resection: Laparoscopy and HAL have been shown to be both safe and efficacious for colorectal resection.

7. Anal epidermoid carcinoma: Unlike rectal adenocarcinoma, anal epidermoid carcinoma is treated primarily with chemoradiation. Surgery is reserved for patients with persistent or recurrent disease.

8. Rectal prolapse: Rectal prolapse occurs most commonly in elderly women. Transabdominal repair (rectopexy with or without resection) offers more durability than perineal proctosigmoidectomy, but carries greater operative risk.

9. Hemorrhoids: Hemorrhoids are cushions of submucosal tissue containing venules, arterioles, and smooth muscle fiber. They are thought to play a role in maintaining continence. Resection is only indicated for refractory symptoms.

10. Fistula in ano: Treatment of fistula in ano depends on the location of the fistula, amount of anal sphincter involved in the fistula, and the underlying disease process.

Embryology

The embryonic gastrointestinal tract begins developing during the fourth week of gestation. The primitive gut is derived from the endoderm and divided into three segments: foregut, midgut, and hindgut. Both midgut and hindgut contribute to the colon, rectum, and anus.

The midgut develops into the small intestine, ascending colon, and proximal transverse colon, and receives blood supply from the superior mesenteric artery. During the sixth week of gestation, the midgut herniates out of the abdominal cavity, and then rotates 270° counterclockwise around the superior mesenteric artery to return to its final position inside the abdominal cavity during the tenth week of gestation. The hindgut develops into the distal transverse colon, descending colon, rectum, and proximal anus, all of which receive their blood supply from the inferior mesenteric artery. During the sixth week of gestation, the distal-most end of the hindgut, the cloaca, is divided by the urorectal septum into the urogenital sinus and the rectum.

The distal anal canal is derived from ectoderm and receives its blood supply from the internal pudendal artery. The dentate line divides the endodermal hindgut from the ectodermal distal anal canal.

Anatomy

The large intestine extends from the ileocecal valve to the anus. It is divided anatomically and functionally into the colon, rectum, and anal canal. The wall of the colon and rectum comprise five distinct layers: mucosa, submucosa, inner circular muscle, outer longitudinal muscle, and serosa. In the colon, the outer longitudinal muscle is separated into three teniae coli, which converge proximally at the appendix and distally at the rectum, where the outer longitudinal muscle layer is circumferential. In the distal rectum, the inner smooth muscle layer coalesces to form the internal anal sphincter. The intraperitoneal colon and proximal one-third of the rectum are covered by serosa; the mid and lower rectum lack serosa.

Colon Landmarks

The colon begins at the junction of the terminal ileum and cecum and extends 3 to 5 feet to the rectum. The rectosigmoid junction is found at approximately the level of the sacral promontory and is arbitrarily described as the point at which the three teniae coli coalesce to form the outer longitudinal smooth muscle layer of the rectum. The cecum is the widest diameter portion of the colon (normally 7.5–8.5 cm) and has the thinnest muscular wall. As a result, the cecum is most vulnerable to perforation and least vulnerable to obstruction. The ascending colon is usually fixed to the retroperitoneum. The hepatic flexure marks the transition to the transverse colon. The intraperitoneal transverse colon is relatively mobile, but is tethered by the gastrocolic ligament and colonic mesentery. The greater omentum is attached to the anterior/superior edge of the transverse colon. These attachments explain the characteristic triangular appearance of the transverse colon observed during colonoscopy. The splenic flexure marks the transition from the transverse colon to the descending colon. The attachments between the splenic flexure and the spleen (the lienocolic ligament) can be short and dense, making mobilization of this flexure during colectomy challenging. The descending colon is relatively fixed to the retroperitoneum. The sigmoid colon is the narrowest part of the large intestine and is extremely mobile. Although the sigmoid colon is usually located in the left lower quadrant, redundancy and mobility can result in a portion of the sigmoid colon residing in the right lower quadrant. This mobility explains why volvulus is most common in the sigmoid colon and why diseases affecting the sigmoid colon, such as diverticulitis, may occasionally present as right-sided abdominal pain. The narrow caliber of the sigmoid colon makes this segment of the large intestine the most vulnerable to obstruction.

Colon Vascular Supply

The arterial supply to the colon is highly variable (Fig. 29-1). In general, the superior mesenteric artery branches into the ileocolic artery (absent in up to 20% of people), which supplies blood flow to the terminal ileum and proximal ascending colon; the right colic artery, which supplies the ascending colon; and the middle colic artery, which supplies the transverse colon. The inferior mesenteric artery branches into the left colic artery, which supplies the descending colon; several sigmoidal branches, which supply the sigmoid colon; and the superior rectal artery, which supplies the proximal rectum. The terminal branches of each artery form anastomoses with the terminal branches of the adjacent artery and communicate via the marginal artery of Drummond. This arcade is complete in only 15% to 20% of people.

Except for the inferior mesenteric vein, the veins of the colon parallel their corresponding arteries and bear the same terminology (Fig. 29-2). The inferior mesenteric vein ascends in the retroperitoneal plane over the psoas muscle and continues posterior to the pancreas to join the splenic vein. During a colectomy, this vein is often mobilized independently and ligated at the inferior edge of the pancreas.

Colon Lymphatic Drainage

The lymphatic drainage of the colon originates in a network of lymphatics in the muscularis mucosa. Lymphatic vessels and lymph nodes follow the regional arteries. Lymph nodes are found on the bowel wall (epicolic), along the inner margin of the bowel adjacent to the arterial arcades (paracolic), around the named mesenteric vessels (intermediate), and at the origin of the superior and inferior mesenteric arteries (main). The sentinel lymph nodes are the first one to four lymph nodes to drain a specific segment of the colon and are thought to be the first site of metastasis in colon cancer. The utility of sentinel lymph node dissection and analysis in colon cancer remains controversial.

Colon Nerve Supply

The colon is innervated by both sympathetic (inhibitory) and parasympathetic (stimulatory) nerves, which parallel the course of the arteries. Sympathetic nerves arise from T6-T12 and L1-L3. The parasympathetic innervation to the right and transverse colon is from the vagus nerve; the parasympathetic nerves to the left colon arise from sacral nerves S2-S4 to form the nervi erigentes.

Anorectal Landmarks

The rectum is approximately 12 to 15 cm in length. Three distinct submucosal folds, the valves of Houston, extend into the rectal lumen. Posteriorly, the presecral fascia separates the rectum from the presacral venous plexus and the pelvic nerves. At S4, the rectosacral fascia (Waldeyer’s fascia) extends forward and downward and attaches to the fascia propria at the anorectal junction. Anteriorly, Denonvilliers’ fascia separates the rectum from the prostate and seminal vesicles in men and from the vagina in women. The lateral ligaments support the lower rectum.

The anatomic anal canal extends from the dentate or pectinate line to the anal verge. The dentate or pectinate line marks the transition point between columnar rectal mucosa and squamous anoderm. The anal transition zone includes mucosa proximal to the dentate line that shares histologic characteristics of columnar, cuboidal, and squamous epithelium. Although the anal transition zone was long thought to extend only 1 to 2 cm proximal to the dentate line, it is known that the proximal extent of this zone is highly variable and can be as far as 15 cm proximal to the dentate line. The dentate line is surrounded by longitudinal mucosal folds, known as the columns of Morgagni, into which the anal crypts empty. These crypts are the source of cryptoglandular abscesses (Fig. 29-3). In contrast to the anatomic anal canal, the surgical anal canal begins at the anorectal junction and terminates at the anal verge. The surgical anal canal measures 2 to 4 cm in length and is generally longer in men than in women. It begins at the anorectal junction and terminates at the anal verge.

In the distal rectum, the inner smooth muscle is thickened and comprises the internal anal sphincter that is surrounded by the subcutaneous, superficial, and deep external sphincter. The deep external anal sphincter is an extension of the puborectalis muscle. The puborectalis, iliococcygeus, and pubococcygeus muscles form the levator ani muscle of the pelvic floor (Fig. 29-4).

Anorectal Vascular Supply

The superior rectal artery arises from the terminal branch of the inferior mesenteric artery and supplies the upper rectum. The middle rectal artery arises from the internal iliac; the presence and size of these arteries are highly variable. The inferior rectal artery arises from the internal pudendal artery, which is a branch of the internal iliac artery. A rich network of collaterals connects the terminal arterioles of each of these arteries, thus making the rectum relatively resistant to ischemia (Fig. 29-5).

The venous drainage of the rectum parallels the arterial supply. The superior rectal vein drains into the portal system via the inferior mesenteric vein. The middle rectal vein drains into the internal iliac vein. The inferior rectal vein drains into the internal pudendal vein, and subsequently into the internal iliac vein. A submucosal plexus deep to the columns of Morgagni forms the hemorrhoidal plexus and drains into all three veins.

Anorectal Lymphatic Drainage

Lymphatic drainage of the rectum parallels the vascular supply. Lymphatic channels in the upper and middle rectum drain superiorly into the inferior mesenteric lymph nodes. Lymphatic channels in the lower rectum drain both superiorly into the inferior mesenteric lymph nodes and laterally into the internal iliac lymph nodes. The anal canal has a more complex pattern of lymphatic drainage. Proximal to the dentate line, lymph drains into both the inferior mesenteric lymph nodes and the internal iliac lymph nodes. Distal to the dentate line, lymph primarily drains into the inguinal lymph nodes, but can also drain into the inferior mesenteric lymph nodes and internal iliac lymph nodes.

Anorectal Nerve Supply

Both sympathetic and parasympathetic nerves innervate the anorectum. Sympathetic nerve fibers are derived from L1-L3 and join the preaortic plexus. The preaortic nerve fibers then extend below the aorta to form the hypogastric plexus, which subsequently joins the parasympathetic fibers to form the pelvic plexus. Parasympathetic nerve fibers are known as the nervi erigentes and originate from S2-S4. These fibers join the sympathetic fibers to form the pelvic plexus. Sympathetic and parasympathetic fibers then supply the anorectum and adjacent urogenital organs.

The internal anal sphincter is innervated by sympathetic and parasympathetic nerve fibers; both types of fibers inhibit sphincter contraction. The external anal sphincter and puborectalis muscles are innervated by the inferior rectal branch of the internal pudendal nerve. The levator ani receives innervation from both the internal pudendal nerve and direct branches of S3 to S5. Sensory innervation to the anal canal is provided by the inferior rectal branch of the pudendal nerve. While the rectum is relatively insensate, the anal canal below the dentate line is sensate.

Congenital Anomalies

Perturbation of the embryologic development of the midgut and hindgut may result in anatomic abnormalities of the colon, rectum, and anus. Failure of the midgut to rotate and return to the abdominal cavity during the tenth week of gestation results in varying degrees of intestinal malrotation and colonic nonfixation. Failure of canalization of the primitive gut can result in colonic duplication. Incomplete descent of the urogenital septum may result in imperforate anus and associated fistulas to the genitourinary tract. Many infants with congenital anomalies of the hindgut have associated abnormalities in the genitourinary tract.

Fluid and Electrolyte Exchanges

Water, Sodium, Potassium, Chloride, Bicarbonate, and Ammonia

The colon is a major site for water absorption and electrolyte exchange. Under normal circumstances, approximately 90% of the water contained in ileal fluid is absorbed in the colon (1000–2000 mL/d), but up to 5000 mL of fluid can be absorbed daily. Sodium is absorbed actively via sodium-potassium (Na⁺/K⁺) ATPase. The colon can absorb up to 400 mEq of sodium per day. Water accompanies the transported sodium and is absorbed passively along an osmotic gradient. Potassium is actively secreted into the colonic lumen and absorbed by passive diffusion. Chloride is absorbed actively via a chloride-bicarbonate exchange.

Bacterial degradation of protein and urea produces ammonia. Ammonia is subsequently absorbed and transported to the liver. Absorption of ammonia depends in part on intraluminal pH. A decrease in colonic bacteria (e.g., due to broad-spectrum antibiotic use) and/or a decrease in intraluminal pH (e.g., due to lactulose administration) will decrease ammonia absorption.

Short-Chain Fatty Acids

Short-chain fatty acids (acetate, butyrate, and propionate) are produced by bacterial fermentation of dietary carbohydrates. Short-chain fatty acids are an important source of energy for the colonic mucosa, and metabolism by colonocytes provides energy for processes such as active transport of sodium. Lack of a dietary source for production of short-chain fatty acids, or diversion of the fecal stream by an ileostomy or colostomy, may result in mucosal atrophy and inflammation, the latter termed “diversion colitis.”

Colonic Microflora and Intestinal Gas

Approximately 30% of fecal dry weight is composed of bacteria (10¹¹–10¹² bacteria/g of feces). Anaerobes are the predominant class of microorganism, and Bacteroides species are the most common (10¹¹–10¹² organisms/mL). Escherichia coli are the most numerous aerobes (10⁸–10¹⁰ organisms/mL). Endogenous microflora are crucial for the breakdown of carbohydrates and proteins in the colon and participate in the metabolism of bilirubin, bile acids, estrogen, and cholesterol. Colonic bacteria also are necessary for production of vitamin K. Endogenous bacteria also are thought to suppress the emergence of pathogenic microorganisms, such as Clostridium difficile, a phenomenon termed “colonization resistance.” However, the high bacterial load of the large intestine may contribute to sepsis in critically ill patients and may contribute to intra-abdominal sepsis, abscess, and wound infection following colectomy.

Intestinal gas arises from swallowed air, diffusion from the blood, and intraluminal production. Nitrogen, oxygen, carbon dioxide, hydrogen, and methane are the major components of intestinal gas. Nitrogen and oxygen are largely derived from swallowed air. Carbon dioxide is produced by the reaction of bicarbonate and hydrogen ions and by the digestion of triglycerides to fatty acids. Hydrogen and methane are produced by colonic bacteria. The production of methane is highly variable. The gastrointestinal tract usually contains between 100 and 200 mL of gas, and 400 to 1200 mL/d are released as flatus, depending on the type of food ingested.

Motility, Defecation, and Continence

Motility

Unlike the small intestine, the large intestine does not demonstrate cyclic motor activity characteristic of the migratory motor complex. Instead, the colon displays intermittent contractions of either low or high amplitude. Low-amplitude, short-duration contractions occur in bursts and appear to move the colonic contents both antegrade and retrograde. It is thought that these bursts of motor activity delay colonic transit and thus increase the time available for absorption of water and exchange of electrolytes. High-amplitude contractions occur in a more coordinated fashion and create “mass movements.” Bursts of “rectal motor complexes” also have been described. In general, cholinergic activation increases colonic motility.

Defecation

Defecation is a complex, coordinated mechanism involving colonic mass movement, increased intra-abdominal and rectal pressure, and relaxation of the pelvic floor. Distention of the rectum causes a reflex relaxation of the internal anal sphincter (the rectoanal inhibitory reflex) that allows the contents to make contact with the anal canal. This “sampling reflex” allows the sensory epithelium to distinguish solid stool from liquid stool and gas. If defecation does not occur, the rectum relaxes and the urge to defecate passes (accommodation response). Defecation proceeds by coordination of increasing intra-abdominal pressure via the Valsalva maneuver, increased rectal contraction, relaxation of the puborectalis muscle, and opening of the anal canal.

Continence

The maintenance of fecal continence is at least as complex as the mechanism of defecation. Continence requires adequate rectal wall compliance to accommodate the fecal bolus, appropriate neurogenic control of the pelvic floor and sphincter mechanism, and functional internal and external sphincter muscles. At rest, the puborectalis muscle creates a “sling” around the distal rectum, forming a relatively acute angle that distributes intra-abdominal forces onto the pelvic floor. With defecation, this angle straightens, allowing downward force to be applied along the axis of the rectum and anal canal. The internal and external sphincters are tonically active at rest. The internal sphincter is responsible for most of the resting, involuntary sphincter tone (resting pressure). The external sphincter is responsible for most of the voluntary sphincter tone (squeeze pressure). Branches of the pudendal nerve innervate both the internal and external sphincter. Finally, the hemorrhoidal cushions may contribute to continence by mechanically blocking the anal canal. Thus, impaired continence may result from poor rectal compliance, injury to the internal and/or external sphincter or puborectalis, or nerve damage or neuropathy.

Clinical Assessment

Obtaining a complete history and performing a physical examination are the starting points for evaluating any patient with suspected disease of the colon, rectum, or anus. Special attention should be paid to the patient’s past medical and surgical history to detect underlying conditions that might contribute to a gastrointestinal problem. If patients have had prior intestinal surgery, it is essential that one understand the resultant gastrointestinal anatomy. A history of anorectal surgery may be critical for patients with either abdominal or anorectal complaints. The obstetrical history in women is essential to detect occult pelvic floor and/or anal sphincter damage. Identifying a family history of colorectal disease, especially inflammatory bowel disease, polyps, and colorectal cancer, is crucial. In addition to a family history of colorectal disease, a history of other malignancies may suggest the presence of a genetic syndrome. Medication use must be detailed as many drugs cause gastrointestinal symptoms. Before recommending operative intervention, the adequacy of medical treatment must be ascertained. In addition to examining the abdomen, visual inspection of the anus and perineum and careful digital rectal exam are essential.

Endoscopy

Anoscopy

The anoscope is a useful instrument for examination of the anal canal. Anoscopes are made in a variety of sizes and measure approximately 8 cm in length. A larger anoscope provides better exposure for anal procedures such as rubber band ligation or sclerotherapy of hemorrhoids. The anoscope, with obturator in place, should be adequately lubricated and gently inserted into the anal canal. The obturator is withdrawn, inspection of the visualized anal canal is done, and the anoscope should then be withdrawn. It is rotated 90° and reinserted to allow visualization of all four quadrants of the canal. If the patient complains of severe perianal pain and cannot tolerate a digital rectal examination, anoscopy should not be attempted without anesthesia.

Proctoscopy

The rigid proctoscope is useful for examination of the rectum and distal sigmoid colon and is occasionally used therapeutically. The standard proctoscope is 25 cm in length and available in various diameters. Most often, a 15- or 19-mm diameter proctoscope is used for diagnostic examinations. The large (25-mm diameter) proctoscope is useful for procedures such as polypectomy, electrocoagulation, or detorsion of a sigmoid volvulus. A smaller “pediatric” proctoscope (11-mm diameter) is better tolerated by patients with anal stricture. Suction is necessary for an adequate proctoscopic examination.

Flexible Sigmoidoscopy and Colonoscopy

Video or fiberoptic flexible sigmoidoscopy and colonoscopy provide excellent visualization of the colon and rectum. Sigmoidoscopes measure 60 cm in length. Full depth of insertion may allow visualization as high as the splenic flexure, although the mobility and redundancy of the sigmoid colon often limit the extent of the examination. Partial preparation with enemas is usually adequate for sigmoidoscopy, and most patients can tolerate this procedure without sedation. Colonoscopes measure 100 to 160 cm in length and are capable of examining the entire colon and terminal ileum. A complete oral bowel preparation is usually necessary for colonoscopy, and the duration and discomfort of the procedure usually require conscious sedation. Both sigmoidoscopy and colonoscopy can be used diagnostically and therapeutically. Electrocautery should generally not be used in the absence of a complete bowel preparation because of the risk of explosion of intestinal methane or hydrogen gases. Diagnostic colonoscopes possess a single channel through which instruments such as snares, biopsy forceps, or electrocautery can be passed; this channel also provides suction and irrigation capability. Therapeutic colonoscopes possess two channels to allow simultaneous suction/irrigation and the use of snares, biopsy forceps, or electrocautery.

Capsule Endoscopy

Capsule endoscopy is an emerging technology that uses a small ingestible camera. After swallowing the camera, images of the mucosa of the gastrointestinal tract are captured, transmitted by radiofrequency to a belt-held receiver, and then downloaded to a computer for viewing and analysis. Capsule endoscopy largely has been used to detect small bowel lesions. However, it has been suggested that this technique might also be useful for diagnosing colorectal disease, although utility in the evaluation of colorectal disease remains unproven.^1,2,3,4,5 Finally, recent advances in the development of maneuverable capsules may improve the sensitivity of this procedure.⁵

Imaging

Plain X-Rays and Contrast Studies

Despite advanced radiologic techniques, plain X-rays and contrast studies continue to play an important role in the evaluation of patients with suspected colon and rectal diseases. Plain X-rays of the abdomen (supine, upright, and diaphragmatic views) are useful for detecting free intra-abdominal air, bowel gas patterns suggestive of small or large bowel obstruction, and volvulus. Contrast studies are useful for evaluating obstructive symptoms, delineating fistulous tracts, and diagnosing small perforations or anastomotic leaks. Although Gastrografin cannot provide the mucosal detail provided by barium, this water-soluble contrast agent is recommended if perforation or leak is suspected. Double-contrast barium enema (use of barium followed by the insufflation of air into the colon) has been reported to be 70% to 90% sensitive for the detection of mass lesions greater than 1 cm in diameter.⁶ Detection of small lesions can be extremely difficult, especially in a patient with extensive diverticulosis. For this reason, a colonoscopy is preferred for evaluating nonobstructing mass lesions in the colon. Double-contrast barium enema has been used as a back-up examination if colonoscopy is incomplete.

Computed Tomography

Computed tomography (CT) commonly is employed in the evaluation of patients with abdominal complaints. Its utility is primarily in the detection of extraluminal disease, such as intra-abdominal abscesses and pericolic inflammation, and in staging colorectal carcinoma, because of its sensitivity in detection of hepatic metastases.⁷

Extravasation of oral or rectal contrast may also confirm the diagnosis of perforation or anastomotic leak. Nonspecific findings such as bowel wall thickening or mesenteric stranding may suggest inflammatory bowel disease, enteritis/colitis, or ischemia. A standard CT scan is relatively insensitive for the detection of intraluminal lesions; however, improved CT technology is increasing the ability to assess bulky rectal tumors and perirectal adenopathy.

Computed Tomography Colonography

CT colonography (virtual colonoscopy) is a radiologic technique that is designed to overcome some of the limitations of traditional CT scanning. This technology uses helical CT and three-dimensional reconstruction to detect intraluminal colonic lesions. Oral bowel preparation, oral and rectal contrast, and colon insufflation have been used to maximize sensitivity. Experience with this technology has shown a sensitivity and specificity for detecting 1 cm or larger polyps of 85% to 90% in most studies, making it comparable to traditional colonoscopy. The addition of “fecal tagging” agents that create a distinct difference in appearance between stool and mucosa during imaging studies holds promise for increasing accuracy and possibly decreasing the need for mechanical bowel preparation.⁸

Magnetic Resonance Imaging

The main use of magnetic resonance imaging (MRI) in colorectal disorders is in evaluation of pelvic lesions. MRI is more sensitive than CT for detecting bony involvement or pelvic sidewall extension of rectal tumors. MRI accurately determines the extent of spread of rectal cancer into the adjacent mesorectum and can reliably predict difficulty achieving radial margin clearance of a rectal cancer by surgery alone. When the radial margin is threatened, neoadjuvant chemoradiation is generally indicated. MRI also can be helpful in the detection and delineation of complex fistulas in ano. The use of an endorectal coil may increase sensitivity.

Positron Emission Tomography

Positron emission tomography (PET) is used for imaging tissues with high levels of anaerobic glycolysis, such as malignant tumors.^{6 18}F-fluorodeoxyglucose (FDG) is injected as a tracer; metabolism of this molecule then results in positron emission. PET has been used as an adjunct to CT in the staging of colorectal cancer and may prove useful in discriminating recurrent cancer from fibrosis. By combining PET and CT technology (PET/CT), anatomic correlation between regions of high isotope accumulation (“hot spots”) on PET and abnormalities on CT can be determined. PET/CT increasingly is used to diagnose recurrent and/or metastatic colorectal cancer. However, the efficacy and utility of this technology remains unproven.

Angiography

Angiography is occasionally used for the detection of bleeding within the colon or small bowel. To visualize hemorrhage angiographically, bleeding must be relatively brisk (approximately 0.5 to 1.0 mL per minute). If extravasation of contrast is identified, infusion of vasopressin or angiographic embolization can be therapeutic. If surgical resection is required, the angiographic catheter can be left in place to assist with identification of the bleeding site intraoperatively.

CT and magnetic resonance angiography are also useful for assessing patency of visceral vessels. This technique uses three-dimensional reconstruction to detect vascular lesions. If an abnormality is found, more traditional techniques (angiography, surgery) may then be used to further define and/or correct the problem.

Endorectal and Endoanal Ultrasound

Endorectal ultrasound is primarily used to evaluate the depth of invasion of neoplastic lesions in the rectum. The normal rectal wall appears as a five-layer structure (Fig. 29-6). Ultrasound can reliably differentiate most benign polyps from invasive tumors based on the integrity of the submucosal layer. Ultrasound can also differentiate superficial T1-T2 from deeper T3-T4 tumors. Overall, the accuracy of ultrasound in detecting depth of mural invasion ranges between 81% and 94%.⁹ This modality also can detect enlarged perirectal lymph nodes, which may suggest nodal metastases; accuracy of detection of pathologically positive lymph nodes is 58% to 83%. Ultrasound may also prove useful for early detection of local recurrence after surgery.

Endoanal ultrasound is used to evaluate the layers of the anal canal. Internal anal sphincter, external anal sphincter, and puborectalis muscle can be differentiated. Endoanal ultrasound is particularly useful for detecting sphincter defects and for outlining complex anal fistulas.

Physiologic and Pelvic Floor Investigations

Anorectal physiologic testing uses a variety of techniques to investigate the function of the pelvic floor. These techniques are useful in the evaluation of patients with incontinence, constipation, rectal prolapse, obstructed defecation, and other disorders of the pelvic floor.

Manometry

Anorectal manometry is performed by placing a pressure-sensitive catheter in the lower rectum. The catheter is then withdrawn through the anal canal and pressures recorded. A balloon attached to the tip of the catheter also can be used to test anorectal sensation. The resting pressure in the anal canal reflects the function of the internal anal sphincter (normal, 40–80 mmHg), whereas the squeeze pressure, defined as the maximum voluntary contraction pressure minus the resting pressure, reflects function of the external anal sphincter (normal, 40–80 mmHg above resting pressure). The high-pressure zone estimates the length of the anal canal (normal, 2.0–4.0 cm). The rectoanal inhibitory reflex can be detected by inflating a balloon in the distal rectum; absence of this reflex is characteristic of Hirschsprung’s disease.

Neurophysiology

Neurophysiologic testing assesses function of the pudendal nerves and recruitment of puborectalis muscle fibers. Pudendal nerve terminal motor latency measures the speed of transmission of a nerve impulse through the distal pudendal nerve fibers (normal, 1.8–2.2 ms); prolonged latency suggests the presence of neuropathy. Electromyographic (EMG) recruitment assesses the contraction and relaxation of the puborectalis muscle during attempted defecation. Normally, recruitment increases when a patient is instructed to “squeeze” and decreases when a patient is instructed to “push.” Inappropriate recruitment is an indication of paradoxical contraction (nonrelaxation of the puborectalis). Needle EMG has been used to map both the pudendal nerves and the anatomy of the internal and external sphincters. However, this examination is painful and poorly tolerated by most patients. Needle EMG has largely been replaced by pudendal nerve motor latency testing to assess pudendal nerve function and endoanal ultrasound to map the sphincters.

Rectal Evacuation Studies

Rectal evacuation studies include the balloon expulsion test and video defecography. Balloon expulsion assesses a patient’s ability to expel an intrarectal balloon. Video defecography provides a more detailed assessment of defecation. In this test, barium paste is placed in the rectum, and defecation is then recorded fluoroscopically. Defecography is used to differentiate nonrelaxation of the puborectalis, obstructed defecation, increased perineal descent, rectal prolapse and intussusception, rectocele, and enterocele. The addition of vaginal contrast and intraperitoneal contrast is useful in delineating complex disorders of the pelvic floor.

Laboratory Studies

Fecal Occult Blood Testing

Fecal occult blood testing (FOBT) has been used as a screening test for colonic neoplasms in asymptomatic, average-risk individuals. The efficacy of this test is based on serial testing because the majority of colorectal malignancies will bleed intermittently. FOBT has been a nonspecific test for peroxidase contained in hemoglobin; consequently, occult bleeding from any gastrointestinal source will produce a positive result. Similarly, many foods (red meat, some fruits and vegetables, and vitamin C) will produce a false-positive result. Increased specificity is now possible by using immunochemical FOBT. These tests rely on monoclonal or polyclonal antibodies to react with the intact globin portion of human hemoglobin and are more specific for identifying occult bleeding from the colon or rectum. Any positive FOBT mandates further investigation, usually by colonoscopy.

Stool Studies

Stool studies are often helpful in evaluating the etiology of diarrhea. Wet-mount examination reveals the presence of fecal leukocytes, which may suggest colonic inflammation or the presence of an invasive organism such as invasive E. coli or Shigella species. Stool cultures can detect pathogenic bacteria, ova, and/or parasites. C. difficile colitis is diagnosed by detecting bacterial toxin in the stool.¹⁰ Steatorrhea may be diagnosed by adding Sudan red stain to a stool sample.

Serum Tests

Specific laboratory tests that should be performed will be dictated by the clinical scenario. Preoperative studies generally include a complete blood count and electrolyte panel. The addition of coagulation studies, liver function tests, and blood typing/cross-matching depends on the patient’s medical condition and the proposed surgical procedure.

Tumor Markers

Carcinoembryonic antigen (CEA) may be elevated in 60% to 90% of patients with colorectal cancer. Despite this, CEA is not an effective screening tool for this malignancy. Many practitioners follow serial CEA levels after curative-intent surgery in order to detect early recurrence of colorectal cancer. However, this tumor marker is nonspecific, and no survival benefit has yet been proven. It is also important to note that CEA may be mildly elevated in patients who smoke tobacco. Other biochemical markers (ornithine decarboxylase, urokinase) have been proposed, but none has yet proven sensitive or specific for detection, staging, or predicting prognosis of colorectal carcinoma.¹¹

Genetic Testing

Although familial colorectal cancer syndromes, such as familial adenomatous polyposis (FAP) and hereditary nonpolyposis colon cancer (HNPCC) are rare, information about the specific genetic abnormalities underlying these disorders has led to significant interest in the role of genetic testing for colorectal cancer.¹²

Tests for mutations in the adenomatous polyposis coli (APC) gene responsible for FAP and in mismatch repair genes responsible for HNPCC are commercially available and extremely accurate in families with known mutations. However, in the absence of an identified mutation, a negative result is uninformative. For individuals from high-risk families without an identified mutation, increased surveillance is recommended.¹³ Although many of these mutations are also present in sporadic colorectal cancer, the accuracy of genetic testing in average-risk individuals is considerably lower, and these tests are not recommended for screening. Because of the potential psychosocial implications of genetic testing, it is strongly recommended that professional genetic counselors be involved in the care of any patient considering these tests.

Evaluation of Common Symptoms

Pain

Abdominal Pain

Abdominal pain is a nonspecific symptom with myriad causes. Abdominal pain related to the colon and rectum can result from obstruction (either inflammatory or neoplastic), inflammation, perforation, or ischemia. Plain X-rays and judicious use of contrast studies and/or a CT scan can often confirm the diagnosis. Gentle retrograde contrast studies (Gastrografin enema) may be useful in delineating the degree of colonic obstruction. Sigmoidoscopy and/or colonoscopy performed by an experienced endoscopist can assist in the diagnosis of ischemic colitis, infectious colitis, and inflammatory bowel disease. However, if perforation or near complete obstruction is suspected, colonoscopy and/or sigmoidoscopy are generally contraindicated. Evaluation and treatment of abdominal pain from a colorectal source should follow the usual surgical principles of a thorough history and physical examination, appropriate diagnostic tests, resuscitation, and appropriately timed surgical intervention.

Pelvic Pain

Pelvic pain can originate from the distal colon and rectum or from adjacent urogenital structures. Tenesmus may result from proctitis or from a rectal or retrorectal mass. Cyclical pain associated with menses, especially when accompanied by rectal bleeding, suggests a diagnosis of endometriosis. Pelvic inflammatory disease also can produce significant abdominal and pelvic pain. The extension of a peridiverticular abscess or periappendiceal abscess into the pelvis may also cause pain. CT scan and/or MRI may be useful in differentiating these diseases. Proctoscopy (if tolerated) also can be helpful. Occasionally, laparoscopy will yield a diagnosis.

Anorectal Pain

Anorectal pain is most often secondary to an anal fissure, perirectal abscess and/or fistula, or a thrombosed hemorrhoid. Physical examination can usually differentiate these conditions. Other, less common causes of anorectal pain include anal canal neoplasms, perianal skin infection, and dermatologic conditions. Proctalgia fugax results from levator spasm and may present without any other anorectal findings. Physical exam is critical in evaluating patients with anorectal pain. If a patient is too tender to examine in the office, an examination under anesthesia is necessary. MRI or other imaging studies may be helpful in select cases where the etiology of pain is elusive.

Lower Gastrointestinal Bleeding

The first goal in evaluating and treating a patient with gastrointestinal hemorrhage is adequate resuscitation. The principles of ensuring a patent airway, supporting ventilation, and optimizing hemodynamic parameters apply, and coagulopathy and/or thrombocytopenia should be corrected. The second goal is to identify the source of hemorrhage. Because the most common source of gastrointestinal hemorrhage is esophageal, gastric, or duodenal, nasogastric aspiration should always be performed; return of bile suggests that the source of bleeding is distal to the ligament of Treitz. If aspiration reveals blood or nonbile secretions, or if symptoms suggest an upper intestinal source, esophagogastroduodenoscopy is performed. Anoscopy and/or limited proctoscopy can identify hemorrhoidal bleeding. A technetium-99 (^99mTc)-tagged red blood cell (RBC) scan is extremely sensitive and is able to detect as little as 0.1 mL/h of bleeding; however, localization is imprecise. If the ^99mTc-tagged RBC scan is positive, angiography can then be both diagnostic and potentially therapeutic. If the patient is hemodynamically stable, a rapid bowel preparation (over 4–6 hours) can be performed to allow colonoscopy. Colonoscopy may identify the cause of the bleeding, and cautery or injection of epinephrine into the bleeding site may be used to control hemorrhage. Colectomy may be required if bleeding persists despite these interventions. Intraoperative colonoscopy and/or enteroscopy may assist in localizing bleeding. If colectomy is required, a segmental resection is preferred if the bleeding source can be localized. “Blind” subtotal colectomy may very rarely be required in a patient who is hemodynamically unstable with ongoing colonic hemorrhage of an unknown source. In this setting, just prior to proceeding with a “blind” subtotal colectomy, it is crucial to irrigate the rectosigmoid and re-examine the mucosa of the anal canal and rectum by anoscopy and proctoscopy to ensure the source of ongoing bleeding is not distal to the planned resection margin (Fig. 29-7).

Occult blood loss from the gastrointestinal tract may manifest as iron-deficiency anemia or may be detected with FOBT. Because colon neoplasms bleed intermittently and rarely present with rapid hemorrhage, the presence of occult fecal blood should always prompt a colonoscopy. Unexplained iron-deficiency anemia is also an indication for colonoscopy.

Hematochezia is commonly caused by hemorrhoids or a fissure. Sharp, knife-like pain and bright red rectal bleeding with bowel movements suggest the diagnosis of fissure. Painless, bright red rectal bleeding with bowel movements is often secondary to a friable internal hemorrhoid that is easily detected by anoscopy. In the absence of a painful, obvious fissure, any patient with rectal bleeding should undergo a careful digital rectal examination, anoscopy, and proctosigmoidoscopy. Failure to diagnose a source in the distal anorectum should prompt colonoscopy.

Constipation and Obstructed Defecation

Constipation is an extremely common complaint, affecting more than 4 million people in the United States. Despite the prevalence of this problem, there is lack of agreement about an appropriate definition of constipation. Patients may describe infrequent bowel movements, hard stools, or excessive straining. A careful history of these symptoms often clarifies the nature of the problem.

Constipation has many causes. Underlying metabolic, pharmacologic, endocrine, psychological, and neurologic causes often contribute to the problem. A stricture or mass lesion should be excluded by colonoscopy, barium enema, or CT colonography. After these causes have been excluded, evaluation focuses on differentiating slow-transit constipation from outlet obstruction. Transit studies, in which radiopaque markers are swallowed and then followed radiographically, are useful for diagnosing slow-transit constipation. Anorectal manometry and EMG can detect nonrelaxation of the puborectalis, which contributes to outlet obstruction. The absence of an anorectal inhibitory reflex suggests Hirschsprung’s disease and may prompt a rectal mucosal biopsy. Defecography can identify rectal prolapse, intussusception, rectocele, or enterocele.

Medical management is the mainstay of therapy for constipation and includes fiber, increased fluid intake, and laxatives. Outlet obstruction from nonrelaxation of the puborectalis often responds to biofeedback.¹⁴ Surgery to correct rectocele and rectal prolapse has a variable effect on symptoms of constipation but can be successful in selected patients. Subtotal colectomy is considered only for patients with severe slow-transit constipation (colonic inertia) refractory to maximal medical interventions. While this operation almost always increases bowel movement frequency, complaints of diarrhea, incontinence, and abdominal pain are not infrequent, and patients should be carefully selected and counseled.¹⁵

Diarrhea and Irritable Bowel Syndrome

Diarrhea is also a common complaint and is usually a self-limited symptom of infectious gastroenteritis. If diarrhea is chronic or is accompanied by bleeding or abdominal pain, further investigation is warranted. Bloody diarrhea and pain are characteristic of colitis; etiology can be an infection (invasive E. coli, Shigella, Salmonella, Campylobacter, Entamoeba histolytica, or C. difficile), inflammatory bowel disease (ulcerative colitis or Crohn’s colitis), or ischemia. Stool wet-mount and culture can often diagnose infection. Sigmoidoscopy or colonoscopy can be helpful in diagnosing inflammatory bowel disease or ischemia. However, if the patient has abdominal tenderness, particularly with peritoneal signs, or any other evidence of perforation, endoscopy is contraindicated.

Chronic diarrhea may present a more difficult diagnostic dilemma. Chronic ulcerative colitis, Crohn’s colitis, infection, malabsorption, and short gut syndrome can cause chronic diarrhea. Rarely, carcinoid syndrome and islet cell tumors (vasoactive intestinal peptide–secreting tumor [VIPoma], somatostatinoma, gastrinoma) present with this symptom. Large villous lesions may cause secretory diarrhea. Collagenous colitis can cause diarrhea without any obvious mucosal abnormality. Along with stool cultures, tests for malabsorption, and metabolic investigations, colonoscopy can be invaluable in differentiating these causes. Biopsies should be taken even if the colonic mucosa appears grossly normal.

Irritable bowel syndrome is a particularly troubling constellation of symptoms consisting of crampy abdominal pain, bloating, constipation, and urgent diarrhea. Workup reveals no underlying anatomic or physiologic abnormality. Once other disorders have been excluded, dietary restrictions and avoidance of caffeine, alcohol, and tobacco may help to alleviate symptoms. Antispasmodics and bulking agents may be helpful.

Incontinence

The incidence of fecal incontinence has been estimated to occur in 10 to 13 individuals per 1000 people older than age 65 years. Incontinence ranges in severity from occasional leakage of gas and liquid stool to daily loss of solid stool. The underlying cause of incontinence is often multifactorial, and diarrhea is often contributory. In general, causes of incontinence can be classified as neurogenic or anatomic. Neurogenic causes include diseases of the central nervous system and spinal cord along with pudendal nerve injury. Anatomic causes include congenital abnormalities, procidentia (rectal prolapse), overflow incontinence secondary to impaction or an obstructing neoplasm, and trauma. The most common traumatic cause of incontinence is injury to the anal sphincter during vaginal delivery. Other causes include anorectal surgery, impalement, and pelvic fracture.

After a thorough medical evaluation to detect underlying conditions that might contribute to incontinence, evaluation focuses on assessment of the anal sphincter and pudendal nerves. Pudendal nerve terminal motor latency testing may detect neuropathy. Anal manometry can detect low resting and squeeze pressures. Physical examination and defecography can detect rectal prolapse. Endoanal ultrasound is invaluable in diagnosing sphincter defects (Fig. 29-8).

Therapy depends on the underlying abnormality. Diarrhea should be treated medically (fiber, antidiarrheal agents). Even in the absence of frank diarrhea, the addition of dietary fiber may improve continence. Some patients may respond to biofeedback. Many patients with a sphincter defect are candidates for an overlapping sphincteroplasty. Innovative technologies such as sacral nerve stimulation and the artificial bowel sphincter are proving useful in patients who fail other interventions.¹⁶ The delivery of radiofrequency energy to the anal canal (the Secca procedure) appears to be safe and effective in early studies.¹⁷ Injectable bulking agents are also gaining popularity, but long-term efficacy has not yet been proven.¹⁸ Finally, a stoma can provide relief for severely incontinent patients who have failed or are not candidates for other interventions.¹⁹

Colorectal resections are performed for a wide variety of conditions, including neoplasms (benign and malignant), inflammatory bowel diseases, and other benign conditions. Although the indication and urgency for surgery will alter some of the technical details, the operative principles of colorectal resections, anastomoses, and use of ostomies are well established.

Resections

The mesenteric clearance technique dictates the extent of colonic resection and is determined by the nature of the primary pathology (malignant or benign), the intent of the resection (curative or palliative), the precise location(s) of the primary pathology, and the condition of the mesentery (thin and soft or thick and indurated). In general, a proximal mesenteric ligation will eliminate the blood supply to a greater length of colon and require a more extensive “colectomy.” Curative resection of a colorectal cancer is usually best accomplished by performing a proximal mesenteric vessel ligation and radical mesenteric clearance of the lymphatic drainage basin of the tumor site (Fig. 29-9). Resection of a benign process does not require wide mesenteric clearance.

Emergency Resection

Emergency resection may be required because of obstruction, perforation, or hemorrhage. In this setting, the bowel is almost always unprepared and the patient may be unstable. The surgical principles described earlier apply, and an attempt should be made to resect the involved segment along with its lymphovascular supply. If the resection involves the right colon or proximal transverse colon (right or extended right colectomy), a primary ileocolonic anastomosis can usually be performed safely as long as the remaining bowel appears healthy and the patient is stable. For left-sided tumors, the traditional approach has involved resection of the involved bowel and end colostomy, with or without a mucus fistula. However, there is an increasing body of data to suggest that a primary anastomosis without a bowel preparation or with an on-table lavage, with or without a diverting ileostomy, may be equally safe in this setting. If the proximal colon appears unhealthy (vascular compromise, serosal tears, perforation), a subtotal colectomy can be performed with a small bowel to rectosigmoid anastomosis. Resection and diversion (ileostomy or colostomy) remain safe and appropriate if the bowel appears compromised or if the patient is unstable, malnourished, or immunosuppressed.

Minimally Invasive Techniques of Resection

With advances in minimally invasive technology, many procedures that previously have required laparotomy can now be performed laparoscopically,^20,21 with hand-assisted laparoscopy (HAL), or robotically. Potential advantages of minimally invasive surgery include improved cosmetic result, decreased postoperative pain, and earlier return of bowel function. Moreover, some experimental data suggest that minimally invasive operations have less immunosuppressive impact on the patient and thus might improve postoperative outcome and even long-term survival. To date, most studies have demonstrated equivalence between laparoscopic, HAL, and open resection in terms of extent of resection. Return of bowel function and length of hospital stay are highly variable. Long-term outcome has yet to be determined; however, short-term quality of life appears to be improved by laparoscopy.^22,23 The most recent advances in minimally invasive surgery involve use of robotics and telemanipulation in which the surgeon operates from a console remote from the patient. These procedures have been rapidly gaining in popularity, especially for pelvic and rectal resections. Early studies suggest equivalence between robotic resections and laparoscopic/HAL resections.²⁴

In addition, some proponents have suggested that robotic procedures may be easier to learn (a shorter “learning curve”) and that robotic surgery may be ergonomically better for the operating surgeon. Nevertheless, long-term superiority, or even equivalence, has yet to be demonstrated, and these advanced technologies are likely to be associated with significant cost.

Colectomy

A variety of terms are used to describe different types of colectomy (Fig. 29-10).

Ileocolic Resection

An ileocolic resection describes a limited resection of the terminal ileum, cecum, and appendix. It is used to remove disease involving these segments of the intestine (e.g., ileocecal Crohn’s disease) and benign lesions or incurable cancers arising in the terminal ileum, cecum, and, occasionally, the appendix. If curable malignancy is suspected, more radical resections, such as a right hemicolectomy, are generally indicated. The ileocolic vessels are ligated and divided. A variable length of small intestine may be resected depending on the disease process. A primary anastomosis is created between the distal small bowel and the ascending colon. It is technically difficult to perform an anastomosis at or just proximal to the ileocecal valve; therefore, if the most distal ileum needs to be resected, the cecum is generally also removed.

Right Colectomy

A right colectomy is used to remove lesions or disease in the right colon and is oncologically the most appropriate operation for curative intent resection of proximal colon carcinoma. The ileocolic vessels, right colic vessels, and right branches of the middle colic vessels are ligated and divided. Approximately 10 cm of terminal ileum are usually included in the resection. A primary ileal-transverse colon anastomosis is almost always possible.

Extended Right Colectomy

An extended right colectomy may be used for curative intent resection of lesions located at the hepatic flexure or proximal transverse colon. A standard right colectomy is extended to include ligation of the middle colic vessels at their base. The right colon and proximal transverse colon are resected, and a primary anastomosis is created between the distal ileum and distal transverse colon. Such an anastomosis relies on the marginal artery of Drummond. If the blood supply to the distal transverse colon is questionable, the resection is extended distally beyond the splenic flexure to well-perfused descending colon where the ileocolic anastomosis can be performed safely.

Transverse Colectomy

Lesions in the mid and distal transverse colon may be resected by ligating the middle colic vessels and resecting the transverse colon, followed by a colocolonic anastomosis. However, an extended right colectomy with an anastomosis between the terminal ileum and descending colon may be a safer anastomosis with an equivalent functional result.

Left Colectomy

For lesions or disease states confined to the distal transverse colon, splenic flexure, or descending colon, a left colectomy is performed. The left branches of the middle colic vessels, the left colic vessels, and the first branches of the sigmoid vessels are ligated. A colocolonic anastomosis can usually be performed.

Extended Left Colectomy

An extended left colectomy is an option for removing lesions in the distal transverse colon. In this operation, the left colectomy is extended proximally to include the right branches of the middle colic vessels.

Sigmoid Colectomy

Lesions in the sigmoid colon require ligation and division of the sigmoid branches of the inferior mesenteric artery. In general, the entire sigmoid colon should be resected to the level of the peritoneal reflection and an anastomosis created between the descending colon and upper rectum. Full mobilization of the splenic flexure is often required to create a tension-free anastomosis.

Total and Subtotal Colectomy

Total or subtotal colectomy is occasionally required for patients with fulminant colitis, attenuated FAP, or synchronous colon carcinomas. In this procedure, the ileocolic vessels, right colic vessels, middle colic vessels, and left colic vessels are ligated and divided. The superior rectal vessels are preserved. If it is desired to preserve the sigmoid, the distal sigmoid vessels are left intact, and an anastomosis is created between the ileum and distal sigmoid colon (subtotal colectomy with ileosigmoid anastomosis). If the sigmoid is to be resected, the sigmoidal vessels are ligated and divided, and the ileum is anastomosed to the upper rectum (total abdominal colectomy with ileorectal anastomosis). If an anastomosis is contraindicated, an end ileostomy is created, and the remaining sigmoid or rectum is managed either as a mucus fistula or a Hartmann’s pouch.

Proctocolectomy

Total Proctocolectomy

In this procedure, the entire colon, rectum, and anus are removed and the ileum is brought to the skin as a Brooke ileostomy.

Restorative Proctocolectomy (Ileal Pouch–Anal Anastomosis)

The entire colon and rectum are resected, but the anal sphincter muscles and a variable portion of the distal anal canal are preserved. Bowel continuity is restored by anastomosis of an ileal reservoir to the anal canal. The original technique included a transanal mucosectomy and hand-sewn ileoanal anastomosis. Proponents of this technique argue that mucosectomy guarantees removal of all of the diseased mucosa, including the anal transition zone, and therefore decreases the risk of ongoing disease, dysplasia, and carcinoma.²⁵ Opponents cite the increased risk of incontinence after mucosectomy and argue that even meticulous technique invariably leaves behind mucosal “islands” that are subsequently hidden under the anastomosis. Moreover, the “double-staple” technique using the circular stapling devices is considerably simpler than mucosectomy and a hand-sewn anastomosis and may be associated with a better functional outcome (Fig. 29-11).^26,27,28,29 Regardless of the anastomotic technique, many surgeons recommend that patients undergo annual surveillance of the anastomosis and/or anal transition zone by digital rectal exam and anoscopy or proctoscopy.

The neorectum is made by anastomosis of the terminal ileum aligned in a “J,” “S,” or “W” configuration. Because functional outcomes are similar and because the J-pouch is the simplest to construct, it has become the most used configuration. With increasing experience in laparoscopic and robotic colectomy, some centers have begun performing total proctocolectomy with ileal pouch–anal reconstruction using minimally invasive surgical techniques.²⁰ Most surgeons perform a proximal ileostomy to divert succus from the newly created pouch in an attempt to minimize the consequences of leak and sepsis, especially in patients who are malnourished or immunosuppressed (Fig. 29-12). The ileostomy is then closed 6 to 12 weeks later, after a contrast study confirms the integrity of the pouch. In low-risk patients, however, there are reports of successful creation of an ileoanal pouch without a diverting stoma.

Anterior Resection

Anterior resection is the general term used to describe resection of the rectum from an abdominal approach to the pelvis with no need for a perineal, sacral, or other incision. Three types of anterior resection have been described.

High Anterior Resection

A high anterior resection is the term used to describe resection of the distal sigmoid colon and upper rectum and is the appropriate operation for benign lesions and disease at the rectosigmoid junction such as diverticulitis. The upper rectum is mobilized, but the pelvic peritoneum is not divided and the rectum is not mobilized fully from the concavity of the sacrum. The inferior mesenteric artery is ligated at its base, and the inferior mesenteric vein, which follows a different course than the artery, is ligated separately. A primary anastomosis (usually end-to-end) between the colon and rectal stump with a short cuff of peritoneum surrounding its anterior two thirds generally can be performed.

Low Anterior Resection

A low anterior resection is used to remove lesions in the upper and mid rectum. The rectosigmoid is mobilized, the pelvic peritoneum is opened, and the inferior mesenteric artery is ligated and divided either at its origin from the aorta or just distal to the takeoff of the left colic artery. The rectum is mobilized from the sacrum by sharp dissection under direct view within the endopelvic fascial plane. The dissection may be performed distally to the anorectal ring, extending posteriorly through the rectosacral fascia to the coccyx and anteriorly through Denonvilliers’ fascia to the vagina in women or the seminal vesicles and prostate in men. The rectum and accompanying mesorectum are divided at the appropriate level, depending on the nature of the lesion. A low rectal anastomosis usually requires mobilization of the splenic flexure and ligation and division of the inferior mesenteric vein just inferior to the pancreas. Circular stapling devices have greatly facilitated the conduct and improved the safety of the colon to extraperitoneal rectal anastomosis.

Extended Low Anterior Resection

An extended low anterior resection is necessary to remove lesions located in the distal rectum, but several centimeters above the sphincter. The rectum is fully mobilized to the level of the levator ani muscle just as for a low anterior resection, but the anterior dissection is extended along the rectovaginal septum in women and distal to the seminal vesicles and prostate in men. After resection at this level, a coloanal anastomosis can be created using one of a variety of techniques. An end-to-end stapled or hand-sewn anastomosis has traditionally been the procedure of choice. However, the functional consequences of a “straight” anastomosis have led to consideration for creation of a colon J-pouch or transverse coloplasty to increase the capacity of the neorectal reservoir.³⁰ Because the risk of an anastomotic leak and subsequent sepsis is higher when an anastomosis is created in the distal rectum or anal canal, creation of a temporary ileostomy should be considered in this setting.

Although an anastomosis may be technically feasible very low in the rectum or anal canal, it is important to note that postoperative function may be poor. Because the descending colon lacks the distensibility of the rectum, the reservoir function may be compromised. Pelvic radiation, prior anorectal surgery, and obstetrical trauma may cause unsuspected sphincter damage. Finally, a very low anastomosis may involve and compromise the upper sphincter. Creation of a colon J-pouch or transverse coloplasty may improve function, but few long-term studies have addressed this issue.^30,31

A history of sphincter damage or any degree of incontinence is a relative contraindication for a coloanal anastomosis. In such patients, an end colostomy may be a more satisfactory option.

Hartmann’s Procedure and Mucus Fistula

Hartmann’s procedure refers to a colon or rectal resection without an anastomosis in which a colostomy or ileostomy is created and the distal colon or rectum is left as a blind pouch. The term is typically used when the left or sigmoid colon is resected and the closed off rectum is left in the pelvis. If the distal colon is long enough to reach the abdominal wall, a mucus fistula can be created by opening the defunctioned bowel and suturing the open lumen to the skin.

Abdominoperineal Resection

An abdominoperineal resection (APR) involves removal of the entire rectum, anal canal, and anus with construction of a permanent colostomy from the descending or sigmoid colon. The abdominal-pelvic portion of this operation proceeds in the same fashion as described for an extended low anterior resection. The perineal dissection can be performed with the patient in lithotomy position (often by a second surgeon) or in the prone position after closure of the abdomen and creation of the colostomy. For cancer, the perineal dissection is designed to excise the anal canal with a wide circumferential margin including a cylindrical cuff of the levator muscle. Primary wound closure is usually successful, but a large perineal defect, especially if preoperative radiation has been used, may require a vascularized flap closure in some patients. For benign disease, proctectomy may be performed using an intersphincteric dissection between the internal and external sphincters. This approach minimizes the perineal wound, making it easier to close because the levator muscle remains intact.

Anastomoses

Anastomoses may be created between two segments of bowel in a multitude of ways. The geometry of the anastomosis may be end-to-end, end-to-side, side-to-end, or side-to-side. The anastomotic technique may be hand-sewn or stapled (Fig. 29-13). The submucosal layer of the intestine provides the strength of the bowel wall and must be incorporated in the anastomosis to assure healing. The choice of anastomosis depends on the operative anatomy and surgeon preference. Although many surgeons advocate one method over another, none has been proven to be superior. Accurate approximation of two well-vascularized, healthy limbs of bowel without tension in a normotensive, well-nourished patient almost always results in a good outcome. Anastomoses at highest risk of leak or stricture are those that are in the distal rectal or anal canal, involve irradiated or diseased intestine including perforation with peritoneal soilage, or are performed in malnourished, immunosuppressed, or ill patients.

Anastomotic Configuration

End-to-End

An end-to-end anastomosis can be performed when two segments of bowel are roughly the same caliber. This technique is most often employed in rectal resections, but may be used for colocolostomy or small bowel anastomoses.

End-to-Side

An end-to-side configuration is useful when one limb of bowel is larger than the other. This most commonly occurs in the setting of chronic obstruction.

Side-to-End

A side-to-end anastomosis is used when the proximal bowel is of smaller caliber than the distal bowel. Ileorectal anastomoses commonly make use of this configuration. A side-to-end anastomosis may have a less tenuous blood supply than an end-to-end anastomosis.

Side-to-Side

A side-to-side anastomosis allows a large, well-vascularized connection to be created on the antimesenteric side of two segments of intestine. This technique is commonly used in ileocolic and small bowel anastomoses.

Anastomotic Technique

Hand-Sutured Technique

Any of the configurations described earlier may be created using a hand-sutured or stapled technique. Hand-sutured anastomoses may be single layer, using either running or interrupted stitches, or double layer. A double-layer anastomosis usually consists of a continuous inner layer and an interrupted outer layer. Suture material may be either permanent or absorbable. After distal rectal or anal canal resection, a transanal, hand-sewn coloanal anastomosis may be necessary to restore bowel continuity. This can be done in conjunction with an anal canal mucosectomy to allow the anastomosis to be created at the dentate line.

Stapled Techniques

Linear cutting/stapling devices are used to divide the bowel and to create side-to-side anastomoses. The anastomosis may be reinforced with interrupted sutures if desired. Circular cutting/stapling devices can create end-to-end, end-to-side, or side-to-end anastomoses. These instruments are particularly useful for creating low rectal or anal canal anastomoses where the anatomy of the pelvis makes a hand-sewn anastomosis technically difficult or impossible.

Following resection of the colorectum, a stapled end-to-end colorectal, coloanal canal, or ileal pouch–anal canal anastomosis may be created by one of two techniques. With the open purse-string technique, the distal rectal stump purse-string is placed by hand, and the assembled circular stapler is inserted into the anus and guided up to the rectal purse-string. The stapler is opened, and the distal purse-string is tied. A purse-string is placed in the distal end of the proximal colon; the proximal colon is placed over the anvil and the purse-string tightened. The stapler is closed and fired (Fig. 29-14). With the alternative double-staple technique, the distal rectum or anal canal is closed with a transverse staple line. The circular stapler is inserted through the anus without its anvil until the cartridge effaces the transverse staple line. The stapler is opened, causing the trocar to perforate through the rectal stump adjacent to the transverse staple line. The anastomosis in then completed as described earlier (see Fig. 29-11). After firing and removing the stapler, the resulting anastomotic rings should be inspected to ensure that they are intact. A gap in an anastomotic ring suggests that the circular staple line is incomplete and the anastomosis should be reinforced with suture circumferentially, if technically feasible. A temporary proximal ileostomy may be indicated as well. Most surgeons will also leak test an anastomosis by instilling water or saline into the pelvis and insufflating the rectum with air via a proctoscope or alternatively instilling methylene blue or betadine into the rectum to look for extravasation.

Ostomies and Preoperative Stoma Planning

Depending on the clinical situation, a stoma may be temporary or permanent. It may be end-on or a loop. However, regardless of the indication for a stoma, placement and construction are crucial for function.

The preoperative preparation of a patient who is expected to require a stoma should include a consultation with an enterostomal therapy (ET) nurse. ET nurses are specially trained and credentialed by the Wound, Ostomy and Continence Nurses Society. Preoperative planning includes counseling, education, and stoma siting. Postoperatively, the ET nurse assists with local skin care and pouching. Other considerations in stoma planning include evaluation of other medical conditions that may impact on a patient’s ability to manage a stoma (e.g., eyesight, manual dexterity).

Preoperative stoma siting is crucial for a patient’s postoperative function and quality of life. A poorly placed stoma can result in leakage and skin breakdown. Ideally, a stoma should be placed in a location that the patient can easily see and manipulate, within the rectus muscle, and below the belt line (see Fig. 29-15). Because the abdominal landmarks in a supine, anesthetized patient may be dramatically different from those in an awake, standing, or sitting patient, the stoma site should always be marked with a tattoo, skin scratch, or permanent marker preoperatively, if possible. In an emergency operation where the stoma site has not been marked, an attempt should be made to place a stoma within the rectus muscle and away from both the costal margin and iliac crest. In emergencies, placement high on the abdominal wall is preferred to a low-lying site.

For all stomas, a circular skin incision is created and the subcutaneous tissue dissected to the level of the anterior rectus sheath. The anterior rectus sheath is incised in a cruciate fashion, the muscle fibers separated bluntly, and the posterior sheath identified and incised. Care should be taken to avoid injuring and causing bleeding from the inferior epigastric artery and vein. The size of the defect depends on the size of the bowel used to create the stoma, but should be as small as possible without compromising the intestinal blood supply (usually the width of two to three fingers). The bowel is then brought through the defect and secured with sutures. The abdominal incision is usually closed and dressed prior to maturing the stoma to avoid contaminating the wound. In order to make appliance use easier, a protruding nipple is fashioned by everting the bowel. Three or four interrupted absorbable sutures are placed through the edge of the bowel, then through the serosa, approximately 2 cm proximal to the edge, and then through the dermis (Brooke technique). After the stoma is everted, the mucocutaneous junction is sutured circumferentially with interrupted absorbable suture (Fig. 29-16).

Ileostomy

Temporary Ileostomy

A temporary ileostomy is often used to “protect” an anastomosis that is at risk for leakage (low in the rectum, in an irradiated field, in an immunocompromised or malnourished patient, and during some emergency operations). In this setting, the stoma is often constructed as a loop ileostomy (see Fig. 29-12). A segment of distal ileum is brought through the defect in the abdominal wall as a loop. An enterotomy is created and the stoma matured as described earlier. The loop may be secured with or without an underlying rod. A divided loop may also be created by firing a linear cutting/stapler across the distal limb of the loop flush with the skin followed by maturation of the proximal limb of the loop. This technique prevents incomplete diversion that occasionally occurs with a loop ileostomy.

The advantage of a loop or divided loop ileostomy is that subsequent closure can often be accomplished without a formal laparotomy. An elliptical incision is created around the stoma and the bowel gently dissected free of the subcutaneous tissues and fascia. A hand-sewn or stapled anastomosis can then be created and the intestine returned to the peritoneal cavity. This avoids a long laparotomy incision and generally is well tolerated. The timing of ileostomy closure should take into account anastomotic healing as well as the patient’s overall condition. A flexible endoscopy exam and a contrast enema (Gastrografin) are recommended prior to closure to ensure that the anastomosis has not leaked and is patent. A patient’s nutritional status should be optimized. In cancer patients receiving adjuvant chemotherapy, ileostomy closure should be delayed until the chemotherapy is completed.

Permanent Ileostomy

A permanent ileostomy is sometimes required after total proctocolectomy or in patients with obstruction. An end ileostomy is the preferred configuration for a permanent ileostomy because a symmetric protruding nipple can be fashioned more easily than with a loop ileostomy (see Fig. 29-16). The end of the small intestine is brought through the abdominal wall defect and matured. Stitches are often used to secure the bowel to the posterior fascia.

Complications of Ileostomy

Stoma necrosis may occur in the early postoperative period and is usually caused by skeletonizing the distal small bowel and/or creating an overly tight fascial defect. Limited mucosal necrosis above the fascia may be treated expectantly, but necrosis below the level of the fascia requires surgical revision. Stoma retraction may occur early or late and may be exacerbated by obesity. Local revision may be necessary. The creation of an ileostomy bypasses the fluid-absorbing capability of the colon, and dehydration with fluid and electrolyte abnormalities is not uncommon. Ideally, ileostomy output should be maintained at less than 1500 mL/d to avoid this problem. Bulk agents and opioids (Lomotil, Imodium, tincture of opium) are useful. The somatostatin analogue, octreotide, has been used with varying success in this setting. Skin irritation can also occur, especially if the stoma appliance fits poorly. Skin-protecting agents and custom pouches can help to solve this problem. Obstruction may occur intra-abdominally or at the site where the stoma exits the fascia. Parastomal hernia is less common after an ileostomy than after a colostomy but can cause poor appliance fitting, pain, obstruction, or strangulation. In general, symptomatic parastomal hernias should be repaired. A variety of techniques to repair these hernias have been described, including local repair (either with or without mesh), laparoscopic repair, and stoma resiting. Prolapse is a rare, late complication and is often associated with a parastomal hernia.

Colostomy

Most colostomies are created as end colostomies rather than loop colostomies (Fig. 29-17). The bulkiness of the colon makes a loop colostomy awkward for use of an appliance, and prolapse is more likely with this configuration. Most colostomies are created on the left side of the colon. An abdominal wall defect is created and the end of the colon mobilized through it. Because a protruding stoma is considerably easier to pouch, colostomies should also be matured in a Brooke fashion. The distal bowel may be brought through the abdominal wall as a mucus fistula or left intra-abdominally as a Hartmann’s pouch. Tacking the distal end of the colon to the abdominal wall or tagging it with permanent suture can make identification of the stump easier if the colostomy is closed at a later date. Closure of an end colostomy has traditionally required a laparotomy, but increasingly minimally invasive techniques have been adopted. The stoma is dissected free of the abdominal wall and the distal bowel identified. An end-to-end anastomosis is then created.

Complications of Colostomy

Colostomy necrosis may occur in the early postoperative period and results from an impaired vascular supply (skeletonization of the distal colon or a tight fascial defect). Like ileostomy necrosis, limited suprafascial necrosis may be followed expectantly, but necrosis below the fascia requires surgery. Retraction may also occur but is less problematic with a colostomy than with an ileostomy because the stool is less irritating to the skin than succus entericus. Obstruction is unusual, but may also occur. Parastomal hernia is the most common late complication of a colostomy and requires repair if it is symptomatic. Prolapse occurs rarely, but is more common with a loop colostomy. Interestingly, it is almost always the efferent limb of the loop that prolapses. Dehydration is rare after colostomy, and skin irritation is less common than with ileostomy.

Functional Results

Function following segmental colonic resection and primary anastomosis is generally excellent. A small percentage of patients following subtotal or total colectomy and ileosigmoid or ileorectal anastomosis may experience diarrhea and bowel frequency. This is especially true if the patient is elderly, if significant length of small bowel has been resected, and if residual proctocolitis is poorly controlled. In general, the more distal the anastomosis, the greater is the risk of troublesome diarrhea and frequency. However, some patients develop significant diarrhea after right colectomy due to malabsorption of bile acids; in these cases, bile acid binding resins (e.g., cholestyramine) sometimes can be helpful.

Function following anterior resection is highly dependent on the level of anastomosis, the use of pre- or postoperative pelvic radiation, and underlying sphincter function. Following low anterior or extended low anterior resection, some surgeons prefer to construct a short (5-cm) colon J-pouch to anastomose to the distal rectum or anal canal or, alternatively, a transverse coloplasty to increase the capacity of the neorectum. The reservoirs are thought to lessen urgency, frequency, and incontinence, but some patients have difficulty initiating defecation, and long-term superiority over a “straight” anastomosis has yet to be proven. In addition, these reservoirs can be technically difficult, especially in an obese male with a narrow pelvis.

The physical and psychological problems associated with a permanent Brooke ileostomy led to development of the continent Kock pouch ileostomy. Unfortunately, complications, especially complications related to valve slippage, are common. Despite variations of technique designed to improve the function of the continent ileostomy, most surgeons have abandoned this operation and instead perform restorative proctocolectomy with ileal pouch–anal anastomosis.

Although ileal pouch–anal reconstruction is anatomically appealing, functional outcome is far from perfect.^6,25 Patients should be counseled to expect 8 to 10 bowel movements per day. Up to 50% have some degree of nocturnal incontinence. Pouchitis occurs in nearly 50% of patients who undergo the operation for chronic ulcerative colitis, and small bowel obstruction is not uncommon. Other less common complications include difficulties with pouch evacuation, pouch-anal and/or pouch-vaginal fistula, and anal stricture. Pouch failure rate averages 5% to 10%. Patients who are subsequently diagnosed with Crohn’s disease have a considerably higher pouch failure rate (approximately 50%), whereas patients with indeterminate colitis have a lower pouch failure rate (15%–20%). Despite these drawbacks, the vast majority of patients are satisfied and prefer ileal pouch–anal reconstruction to permanent ileostomy.

Pouchitis is an inflammatory condition that affects both ileoanal pouches and continent ileostomy reservoirs. The incidence of pouchitis ranges from 30% to 55%. Symptoms include increased diarrhea, hematochezia, abdominal pain, fever, and malaise. Diagnosis is made endoscopically with biopsies. Differential diagnosis includes infection and undiagnosed Crohn’s disease. The etiology of pouchitis is unknown. Some believe pouchitis results from fecal stasis within the pouch, but emptying studies are not confirmatory. Antibiotics (metronidazole ± ciprofloxacin) are the mainstays of therapy, and most patients will respond rapidly to either oral preparations or enemas.^32,33 Some patients develop chronic pouchitis that necessitates ongoing suppressive antibiotic therapy. Salicylate and corticosteroid enemas have also been used with some success. Reintroduction of normal flora by ingestion of probiotics and/or an elemental diet have been suggested as a possible treatment in refractory cases. Occasionally, pouch excision is necessary to control the symptoms of chronic pouchitis.

Anesthesia Considerations

Local Anesthesia

Many anorectal procedures can be performed with local anesthetic alone. Intravenous sedation is often provided to calm the patient. Injection of 0.5% lidocaine (short acting) and 0.25% bupivacaine (long acting) into the perianal skin, sphincter, and area around the pudendal nerves usually provides an adequate block. The addition of dilute epinephrine decreases bleeding and prolongs the anesthetic effect.

Regional Anesthesia

Epidural, spinal, and caudal anesthetics can be used for anorectal procedures and transanal resections. In patients with severe medical comorbidity, regional anesthesia may occasionally be used for laparotomy and colectomy. Postoperative epidural anesthesia provides excellent pain relief and improves pulmonary function.

General Anesthesia

General anesthesia is required for the vast majority of intra-abdominal procedures. Patients should undergo a thorough preoperative cardiovascular evaluation. In patients with significant comorbid disease, an anesthesia consultation may be appropriate.

Positioning

Most abdominal colectomies can be performed in the supine position. Anterior resection and APR require lithotomy positioning to facilitate the pelvic dissection and mobilization of the splenic flexure. Adequate padding should be provided for the patient’s sacrum, and care should be taken to avoid stirrup pressure on the peroneal nerves.

Anorectal procedures may be performed in lithotomy or in the prone jackknife position. Some surgeons prefer the prone jackknife position because exposure may be better, especially for anterior lesions. Distal posterior lesions can usually be accessed from either position, but more proximal posterior lesions are better accessed in the prone position.

Operative Preliminaries

Bowel Preparation

The rationale for bowel preparation is that decreasing the bacterial load in the colon and rectum will decrease the incidence of postoperative infection. Mechanical bowel preparation uses cathartics to rid the colon of solid stool the night before surgery.^28,29 The most commonly used regimens include polyethylene glycol (PEG) solutions or magnesium citrate. PEG solutions require patients to drink a large volume of fluid and may cause bloating and nausea. Magnesium citrate solutions are generally better tolerated but are more likely to cause fluid and electrolyte abnormalities. Both are equally efficacious in bowel cleansing. Preparatory formulations have been recently introduced in tablet form in an attempt to improve tolerance. However, these methods of bowel cleansing require ingestion of 40 or more tablets with water over several hours. To date, these formulations have not been proven to be superior to the more traditional products.³⁴ Antibiotic prophylaxis also is recommended. The addition of oral antibiotics to the preoperative mechanical bowel preparation has been thought to decrease postoperative infection by further decreasing the bacterial load of the colon. However, the regimens used (neomycin, erythromycin, or metronidazole) frequently caused gastrointestinal upset that interfered with the mechanical preparation, and many surgeons have abandoned oral antibiotic prophylaxis. Nevertheless, a recent analysis of the Surgical Care Improvement Project-1 (SCIP-1) suggests that oral antibiotics do reduce postoperative wound infection, especially if a mechanical bowel preparation is not used.³⁵

Prospective randomized trials are needed to better understand the role of oral antibiotic prophylaxis in colorectal surgery. In contrast, longstanding, convincing data support the efficacy of parenteral antibiotic prophylaxis at the time of surgery. Broad-spectrum parenteral antibiotic(s) with activity against aerobic and anaerobic enteric pathogens should be administered just prior to the skin incision and redosed as needed depending on the length of the operation. There is no proven benefit to using antibiotics postoperatively after an uncomplicated colectomy.

Despite widespread use of mechanical bowel preparation, the necessity of bowel cleansing prior to colectomy has been questioned. European surgeons in particular have advocated abandoning this practice. Arguments against mechanical bowel preparation include dehydration and electrolyte abnormalities that often result from bowel cleansing, as well as the risk of spillage of liquid stool left over from the “prep.” Arguments in favor of mechanical bowel preparation included easier manipulation of an “empty” colon (especially in minimally invasive procedures) and avoidance of a “stool column” above an anastomosis, especially in the pelvis. Interestingly, a recent meta-analysis of 14 randomized controlled trials suggested that mechanical bowel preparation does not prevent surgical site infection and should be abandoned in clinical practice.³⁶

Ureteral Stents

Ureteral stents may be useful for identifying the ureters intraoperatively and are placed via cystoscopy after the induction of general anesthesia and removed at the end of the operation. Stents can be invaluable during reoperative pelvic surgery or when there is significant retroperitoneal inflammation (such as complicated diverticulitis), as well as in obese patients. Lighted stents may be helpful in laparoscopic and robotic resections. Patients often have transient hematuria postoperatively, but major complications are rare.

Multidisciplinary Teams

Patients with complex colorectal disease often benefit from a multidisciplinary approach to their care. Patients with pelvic floor disorders (especially incontinence) often require evaluation by both a colorectal surgeon and a urologist or urogynecologist. Preoperative evaluation of cancer patients by a medical oncologist and/or radiation oncologist is crucial for planning either neoadjuvant or adjuvant therapy. Intraoperatively, complex pelvic resections often require the involvement of not only a colorectal surgeon but also a urologist, gynecologic oncologist, neurosurgeon, and/or plastic surgeon. Radiation oncologists should be involved in the operation if brachytherapy catheters are to be placed for intracavitary radiation or if intraoperative radiation therapy is planned. Rarely, psychiatric disorders may manifest as colorectal problems (especially functional disorders and chronic pain), and involvement of a psychiatrist or psychologist may be beneficial.

General Considerations

Epidemiology

Inflammatory bowel disease includes ulcerative colitis, Crohn’s disease, and indeterminate colitis. Ulcerative colitis occurs in 8 to 15 people per 100,000 in the United States and Northern Europe. The incidence is considerably lower in Asia, Africa, and South America, and among the nonwhite population in the United States. Ulcerative colitis incidence peaks during the third decade of life and again in the seventh decade of life. The incidence of Crohn’s disease is slightly lower, 1 to 5 people per 100,000. Crohn’s disease also affects Northern European and white populations disproportionately. Crohn’s disease has a similar bimodal incidence, with most cases occurring between ages 15 to 30 years and ages 55 to 60 years. In 15% of patients with inflammatory bowel disease, differentiation between ulcerative colitis and Crohn’s colitis is impossible; these patients are classified as having indeterminate colitis.

Etiology

Many different etiologies for inflammatory bowel disease have been proposed, but none are proven. The consistent geographic differences in incidence suggest an environmental factor such as diet or infection. Alcohol and oral contraceptive use have also been implicated. Smoking has been implicated in the etiology and exacerbation of Crohn’s disease in particular. Family history may play a role because 10% to 30% of patients with inflammatory bowel disease report a family member with the same disease.^37,38 Other theories focus on an autoimmune mechanism and/or a defect in the intestinal immune system. While there is general agreement that interaction among the immune system, the mucosal barrier of the gut, and a variety of infectious agents is involved in the pathogenesis of inflammatory bowel disease, the mechanism(s) by which these interactions produce disease is poorly understood. Bacteria, such as Mycobacterium paratuberculosis and Listeria monocytogenes, and viruses, such as paramyxovirus and measles virus, have been suggested as etiologic agents in Crohn’s disease. A defect in the gut mucosal barrier, which increases exposure to intraluminal bacteria, toxins, or proinflammatory substances, also has been suggested. Finally, as noted earlier, an autoimmune mechanism has been postulated. Although there is no clear evidence linking an immunologic disorder to inflammatory bowel disease, the similarity of many of the extraintestinal manifestations to rheumatologic disorders has made this theory attractive. Regardless of the underlying cause of either ulcerative colitis or Crohn’s disease, both disorders are characterized by intestinal inflammation, and medical therapy is largely based on reducing inflammation.

Pathology and Differential Diagnosis

Although ulcerative colitis and Crohn’s colitis share many pathologic and clinical similarities, these conditions may be differentiated in 85% of patients. Ulcerative colitis is a mucosal process in which the colonic mucosa and submucosa are infiltrated with inflammatory cells. The mucosa may be atrophic, and crypt abscesses are common. Endoscopically, the mucosa is frequently friable and may possess multiple inflammatory pseudopolyps. In long-standing ulcerative colitis, the colon may be foreshortened and the mucosa replaced by scar. In quiescent ulcerative colitis, the colonic mucosa may appear normal both endoscopically and microscopically. Ulcerative colitis may affect the rectum (proctitis), rectum and sigmoid colon (proctosigmoiditis), rectum and left colon (left-sided colitis), or the rectum and entire colon (pancolitis). Ulcerative colitis does not involve the small intestine, but the terminal ileum may demonstrate inflammatory changes (“backwash ileitis”). A key feature of ulcerative colitis is the continuous involvement of the rectum and colon; rectal sparing or skip lesions suggest a diagnosis of Crohn’s disease. Symptoms are related to the degree of mucosal inflammation and the extent of colitis. Patients typically complain of bloody diarrhea and crampy abdominal pain. Proctitis may produce tenesmus. Severe abdominal pain and fever raise the concern of fulminant colitis or toxic megacolon. Physical findings are nonspecific and range from minimal abdominal tenderness and distention to frank peritonitis. In the nonemergent setting, the diagnosis is typically made by colonoscopy and mucosal biopsy.

In contrast to ulcerative colitis, Crohn’s disease is a transmural inflammatory process that can affect any part of the gastrointestinal tract from mouth to anus. Mucosal ulcerations, an inflammatory cell infiltrate, and noncaseating granulomas are characteristic pathologic findings. Chronic inflammation may ultimately result in fibrosis, strictures, and fistulas in either the colon or small intestine. The endoscopic appearance of Crohn’s colitis is characterized by deep serpiginous ulcers and a “cobblestone” appearance. Skip lesions and rectal sparing are common. Symptoms of Crohn’s disease depend on the severity of inflammation and/or fibrosis and the location of inflammation in the gastrointestinal tract. Acute inflammation may produce diarrhea, crampy abdominal pain, and fever. Strictures may produce symptoms of obstruction. Weight loss is common, both because of obstruction and from protein loss. Perianal Crohn’s disease may present with pain, swelling, and drainage from fistulas or abscesses. Physical findings are also related to the site and severity of disease.

In 15% of patients with colitis from inflammatory bowel disease, differentiation of ulcerative colitis from Crohn’s colitis is impossible either grossly or microscopically (indeterminate colitis). These patients typically present with symptoms similar to ulcerative colitis. Endoscopic and pathologic findings usually include features common to both diseases. Increasingly, serologic markers have been employed to differentiate ulcerative colitis from Crohn’s disease. The anti-Saccharomyces cerevisiae antibody (ASCA) and perinuclear anticytoplasmic antibody (pANCA) may be useful in differentiating these two processes but require prospective study.³⁹

Further differential diagnoses include infectious colitides, especially Campylobacter jejuni, Entamoeba histolytica, C. difficile, Neisseria gonorrhoeae, Salmonella, and Shigella species.

Extraintestinal Manifestations

The liver is a common site of extracolonic disease in inflammatory bowel disease. Fatty infiltration of the liver is present in 40% to 50% of patients, and cirrhosis is found in 2% to 5%. Fatty infiltration may be reversed by medical or surgical treatment of colonic disease, but cirrhosis is irreversible. Primary sclerosing cholangitis is a progressive disease characterized by intra- and extrahepatic bile duct strictures. Forty percent to 60% of patients with primary sclerosing cholangitis have ulcerative colitis. Colectomy will not reverse this disease, and the only effective therapy is liver transplantation.⁴⁰ Pericholangitis is also associated with inflammatory bowel disease and may be diagnosed with a liver biopsy. Bile duct carcinoma is a rare complication of long-standing inflammatory bowel disease. Patients who develop bile duct carcinoma in the presence of inflammatory bowel disease are, on average, 20 years younger than other patients with bile duct carcinoma.

Arthritis also is a common extracolonic manifestation of inflammatory bowel disease, and the incidence is 20 times greater than in the general population. Arthritis usually improves with treatment of the colonic disease. Sacroiliitis and ankylosing spondylitis are associated with inflammatory bowel disease, although the relationship is poorly understood. Medical and surgical treatment of the colonic disease does not impact symptoms.

Erythema nodosum is seen in 5% to 15% of patients with inflammatory bowel disease and usually coincides with clinical disease activity. Women are affected three to four times more frequently than men. The characteristic lesions are raised, red, and predominantly on the lower legs. Pyoderma gangrenosum is an uncommon but serious condition that occurs almost exclusively in patients with inflammatory bowel disease. The lesion begins as an erythematous plaque, papule, or bleb, usually located on the pretibial region of the leg and occasionally near a stoma. The lesions progress and ulcerate, leading to a painful, necrotic wound. Pyoderma gangrenosum may respond to resection of the affected bowel in some patients. In others, this disorder is unaffected by treatment of the underlying bowel disease.

Up to 10% of patients with inflammatory bowel disease will develop ocular lesions. These include uveitis, iritis, episcleritis, and conjunctivitis. They usually develop during an acute exacerbation of the inflammatory bowel disease. The etiology is unknown.

Principles of Nonoperative Management

Medical therapy for inflammatory bowel disease focuses on decreasing inflammation and alleviating symptoms, and many of the agents used are the same for both ulcerative colitis and Crohn’s disease. In general, mild to moderate flares may be treated in the outpatient setting. More severe signs and symptoms mandate hospitalization. Pancolitis generally requires more aggressive therapy than limited disease. Because ulcerative proctitis and proctosigmoiditis are limited to the distal large intestine, topical therapy with salicylate and/or corticosteroid suppositories and enemas can be extremely effective. Systemic therapy is rarely required in these patients.

Salicylates

Sulfasalazine (Azulfidine), 5-acetyl salicylic acid (5-ASA), and related compounds are first-line agents in the medical treatment of mild to moderate inflammatory bowel disease. These compounds decrease inflammation by inhibition of cyclooxygenase and 5-lipoxygenase in the gut mucosa. They require direct contact with affected mucosa for efficacy. Multiple preparations are available for administration to different sites in the small intestine and colon (sulfasalazine, mesalamine [Pentasa, Asacol, Rowasa]).

Antibiotics

Antibiotics are often used to decrease the intraluminal bacterial load in Crohn’s disease. Metronidazole has been reported to improve Crohn’s colitis and perianal disease, but the evidence is weak. Fluoroquinolones may also be effective in some cases. In the absence of fulminant colitis or toxic megacolon, antibiotics are not used to treat ulcerative colitis.

Corticosteroids

Corticosteroids (either oral or parenteral) are a key component of treatment for an acute exacerbation of either ulcerative colitis or Crohn’s disease. Corticosteroids are nonspecific inhibitors of the immune system, and 75% to 90% of patients will improve with the administration of these drugs. However, corticosteroids have a number of serious side effects, and use of these agents should be limited to the shortest course possible. In addition, corticosteroids should be used judiciously in children because of the potential adverse effect on growth. Failure to wean corticosteroids is a relative indication for surgery.

Because of the systemic effects of corticosteroids, an effort has been made to develop drugs that act locally and have limited systemic absorption. Agents such as budesonide, beclomethasone dipropionate, and tixocortol pivalate undergo rapid hepatic degradation that significantly decreases systemic toxicity. Budesonide is available as an oral preparation. Corticosteroid enemas provide effective local therapy for proctitis and proctosigmoiditis and have fewer side effects than systemic corticosteroids.

Immunomodulating Agents

Azathioprine and 6-mercatopurine (6-MP) are antimetabolite drugs that interfere with nucleic acid synthesis and thus decrease proliferation of inflammatory cells. These agents are useful for treating ulcerative colitis and Crohn’s disease in patients who have failed salicylate therapy or who are dependent on, or refractory to, corticosteroids. It is important to note, however, that the onset of action of these drugs takes 6 to 12 weeks, and concomitant use of corticosteroids almost always is required.³⁷

Cyclosporine is an immunosuppressive agent that interferes with T-lymphocyte function. While cyclosporine is not routinely used to treat inflammatory bowel disease, up to 80% of patients with an acute flare of ulcerative colitis will improve with its use. However, the majority of these patients will ultimately require colectomy. Cyclosporine is also occasionally used to treat exacerbations of Crohn’s disease, and approximately two-thirds of patients will note some improvement. Improvement is generally apparent within 2 weeks of beginning cyclosporine therapy. Long-term use of cyclosporine is limited by its significant toxicities (e.g., nephrotoxicity, hirsutism, gum hypertrophy).

Methotrexate is a folate antagonist that also has been used to treat inflammatory bowel disease. Although the efficacy of this agent is unproven, there are reports that more than 50% of patients will improve with administration of this drug.⁴¹

Biologic Agents

In an effort to improve treatment for steroid-refractory inflammatory bowel disease, a new class of agents has been developed based on inhibition of tumor necrosis factor alpha (TNF-α). Intravenous infusion of these agents decreases inflammation systemically. Infliximab is a monoclonal antibody directed against TNF-α and was the first biologic agent used to treat Crohn’s disease. More than 50% of patients with moderate to severe Crohn’s disease will improve with infliximab therapy.⁴² This agent also has been useful in treating patients with perianal Crohn’s disease. Recurrence is common, however; and many patients require infusions on a bimonthly basis. Newer anti-TNF-α agents, such as adalimumab and certolizumab pegol, also show promise in treating Crohn’s disease.⁴³

The use of anti-TNF-α agents for the treatment of ulcerative colitis has been less well studied, but there are reports of efficacy in this setting, and adalimumab has been approved for treatment of steroid-refractory ulcerative colitis in Europe.^44,45 Interestingly, anti-TNF-α therapy may also be beneficial in treating the extraintestinal manifestations of inflammatory bowel disease in some patients.⁴⁰

Nutrition

Patients with inflammatory bowel disease are often malnourished. Abdominal pain and obstructive symptoms may decrease oral intake. Diarrhea can cause significant protein loss. Ongoing inflammation produces a catabolic physiologic state. Parenteral nutrition should be strongly considered early in the course of therapy for either Crohn’s disease or ulcerative colitis. The nutritional status of the patient also should be considered when planning operative intervention, and nutritional parameters such as serum albumin, prealbumin, and transferrin should be assessed. In extremely malnourished patients, especially those who are also being treated with corticosteroids, creation of a stoma is often safer than a primary anastomosis.

Ulcerative Colitis

Ulcerative colitis is a dynamic disease characterized by remissions and exacerbations. The clinical spectrum ranges from an inactive or quiescent phase to low-grade active disease to fulminant disease. The onset of ulcerative colitis may be insidious, with minimal bloody stools, or the onset can be abrupt, with severe diarrhea and bleeding, tenesmus, abdominal pain, and fever. The severity of symptoms depends on the degree and extent of inflammation. Although anemia is common, massive hemorrhage is rare. Physical findings are often nonspecific.

The diagnosis of ulcerative colitis is almost always made endoscopically. Because the rectum is invariably involved, proctoscopy may be adequate to establish the diagnosis. The earliest manifestation is mucosal edema, which results in a loss of the normal vascular pattern. In more advanced disease, characteristic findings include mucosal friability and ulceration. Pus and mucus may also be present. While mucosal biopsy is often diagnostic in the chronic phase of ulcerative colitis, biopsy in the acute phase will often reveal only nonspecific inflammation. Evaluation with colonoscopy or barium enema during an acute flare is contraindicated because of the risk of perforation.

Barium enema has been used to diagnose chronic ulcerative colitis and to determine the extent of disease. However, this modality is less sensitive than colonoscopy and may not detect early disease. In long-standing ulcerative colitis, the colon is foreshortened and lacks haustral markings (“lead pipe” colon). Because the inflammation in ulcerative colitis is purely mucosal, strictures are highly uncommon. Any stricture diagnosed in a patient with ulcerative colitis must be presumed to be malignant until proven otherwise.

Indications for Surgery

Indications for surgery in ulcerative colitis may be emergent or elective. Emergency surgery is required for patients with massive life-threatening hemorrhage, toxic megacolon, or fulminant colitis who fail to respond rapidly to medical therapy. Patients with signs and symptoms of fulminant colitis should be treated aggressively with bowel rest, hydration, broad-spectrum antibiotics, and parenteral corticosteroids. Colonoscopy and barium enema are contraindicated, and antidiarrheal agents should be avoided. Deterioration in clinical condition or failure to improve within 24 to 48 hours mandates surgery.

Indications for elective surgery include intractability despite maximal medical therapy and high-risk development of major complications of medical therapy such as aseptic necrosis of joints secondary to chronic steroid use. Elective surgery also is indicated in patients at significant risk of developing colorectal carcinoma. The risk of malignancy increases with pancolonic disease and the duration of symptoms and is approximately 2% after 10 years, 8% after 20 years, and 18% after 30 years. Unlike sporadic colorectal cancers, carcinoma developing in the context of ulcerative colitis is more likely to arise from areas of flat dysplasia and may be difficult to diagnose at an early stage. For this reason, it is recommended that patients with long-standing ulcerative colitis undergo colonoscopic surveillance with multiple (40–50), random biopsies to identify dysplasia before invasive malignancy develops. However, the adequacy of this type of screening is controversial. Recently, magnifying chromoendoscopy has been used to improve sensitivity.^46,47 This technique uses topical dyes that are applied to the colonic mucosa at the time of endoscopy (Lugol’s solution, methylene blue, indigo carmine, and others). These dyes highlight contrast between normal and dysplastic epithelium, allowing more precise biopsy of suspicious areas. Surveillance is recommended annually after 8 years in patients with pancolitis, and annually after 15 years in patients with left-sided colitis. Although low-grade dysplasia was long thought to represent minimal risk, more recent studies show that invasive cancer may be present in up to 20% of patients with low-grade dysplasia. For this reason, any patient with dysplasia should be advised to undergo proctocolectomy. Controversy exists over whether prophylactic proctocolectomy should be recommended for patients who have had chronic ulcerative colitis for greater than 10 years in the absence of dysplasia. Proponents of this approach note that surveillance colonoscopy with multiple biopsies samples only a small fraction of the colonic mucosa, and dysplasia and carcinoma are often missed. Opponents cite the relatively low risk of progression to carcinoma (approximately 2.4%) if all biopsies lack dysplasia. Neither approach has been shown definitively to decrease mortality from colorectal cancer.

Operative Management

Emergent Operation

In a patient with fulminant colitis or toxic megacolon, total abdominal colectomy with end ileostomy (with or without a mucus fistula), rather than total proctocolectomy, is recommended. Although the rectum is invariably diseased, most patients improve dramatically after an abdominal colectomy, and this operation avoids a difficult and time-consuming pelvic dissection in a critically ill patient. Rarely, a loop ileostomy and decompressing colostomy may be necessary if the patient is too unstable to withstand colectomy. Definitive surgery may then be undertaken at a later date once the patient has recovered. Complex techniques, such as an ileal pouch–anal reconstruction, generally are contraindicated in the emergent setting. However, massive hemorrhage that includes bleeding from the rectum may necessitate proctectomy and creation of either a permanent ileostomy or an ileal pouch–anal anastomosis.

Elective Operation

Elective resection for ulcerative colitis usually is performed for refractory inflammation and/or the risk of malignancy (dysplasia). Because of the risk of ongoing inflammation, the risk of malignancy, and the availability of restorative proctocolectomy, most surgeons recommend operations that include resection of the rectum. Total proctocolectomy with end ileostomy has been the “gold standard” for treating patients with chronic ulcerative colitis. This operation removes the entire affected intestine and avoids the functional disturbances associated with ileal pouch–anal reconstruction. Most patients function well physically and psychologically after this operation. Total proctocolectomy with continent ileostomy (Kock’s pouch) was developed to improve function and quality of life after total proctocolectomy, but morbidity is significant, and restorative proctocolectomy is generally preferred today. Since its introduction in 1980, restorative proctocolectomy with ileal pouch–anal anastomosis has become the procedure of choice for most patients who require total proctocolectomy but wish to avoid a permanent ileostomy (see Figs. 29-11 and 29-12).⁶ Abdominal colectomy with ileorectal anastomosis may be appropriate for a patient with indeterminate colitis and rectal sparing.

Crohn’s Disease

Similar to ulcerative colitis, Crohn’s disease is characterized by exacerbations and remissions. Crohn’s disease, however, may affect any portion of the intestinal tract, from mouth to anus. Diagnosis may be made by colonoscopy or esophagogastroduodenoscopy or by barium small bowel study or enema, depending on which part of the intestine is most affected. The presence of skip lesions is key in differentiating Crohn’s colitis from ulcerative colitis, and rectal sparing occurs in approximately 40% of patients. The most common site of involvement of Crohn’s disease is the terminal ileum and cecum (ileocolic Crohn’s disease), followed by the small bowel, and then by the colon and rectum. Perianal and anal canal Crohn’s disease manifest by complex anal fistulae and/or abscesses, anal ulcers, and large skin tags may be the initial site of presentation in up to 4% of cases.

Indications for Surgery

Because Crohn’s disease can affect any part of the gastrointestinal tract, the therapeutic rationale is fundamentally different from that of ulcerative colitis. Ulcerative colitis may be cured by removal of the affected intestinal segment (the colon and rectum). In Crohn’s disease, it is impossible to remove all the at-risk intestine; therefore, surgical therapy is reserved for complications of the disease.

Crohn’s disease may present as an acute inflammatory process or as a chronic fibrotic process. During the acute inflammatory phase, patients may present with intestinal inflammation complicated by fistulae and/or intra-abdominal abscesses. Maximal medical therapy should be instituted, including anti-inflammatory medications, bowel rest, and antibiotics. Parenteral nutrition should be considered if the patient is malnourished. Most intra-abdominal abscesses can be drained percutaneously with the use of CT scan guidance. Although the majority of these patients will ultimately require surgery to remove the diseased segment of bowel, these interventions allow the patient’s condition to stabilize, nutrition to be optimized, and inflammation to decrease prior to embarking on a surgical resection. Once an operation is undertaken, fistulae generally require resection of the segment of bowel with active Crohn’s disease; the secondary sites of the fistula are often otherwise normal and do not generally require resection after division of the fistula. Simple closure of the secondary fistula site usually suffices.

Chronic fibrosis may result in strictures in any part of the gastrointestinal tract. Because the fibrotic process is gradual, free perforation proximal to the obstructing stricture is rare. Chronic strictures almost never improve with medical therapy. Optimal timing for surgery should take into account the patient’s underlying medical and nutritional status.

Strictures may be treated with resection or stricturoplasty. Distal ileal strictures are sometimes amenable to colonoscopic balloon dilatation.

Once an operation is undertaken for Crohn’s disease, several principles should guide intraoperative decision making. In general, a laparotomy for Crohn’s disease should be performed through a midline incision because of the possible need for a stoma. Laparoscopy is also increasingly used in this setting. Because many patients with Crohn’s disease often will require multiple operations, the length of bowel removed should be minimized. Bowel should be resected to an area with grossly normal margins; frozen sections are not necessary. Finally, a primary anastomosis may be created safely if the patient is medically stable, nutritionally replete, and taking few immunosuppressive medications. Creation of a stoma should be strongly considered in any patient who is hemodynamically unstable, septic, malnourished, or receiving high-dose immunosuppressive therapy and among patients with extensive intra-abdominal contamination.

Ileocolic and Small Bowel Crohn’s Disease

The terminal ileum and cecum are involved in Crohn’s disease in up to 41% of patients; the small intestine is involved in up to 35% of patients. The most common indications for surgery are internal fistula or abscess (30%–38% of patients) and obstruction (35%–37% of patients). Psoas abscess may result from ileocolic Crohn’s disease. Sepsis should be controlled with percutaneous drainage of abscess(es) and antibiotics, if possible. Parenteral nutrition may be necessary in patients with chronic obstruction. The extent of resection depends on the amount of involved intestine. Short segments of inflamed small intestine and right colon should be resected and a primary anastomosis created if the patient is stable, nutrition is adequate, and immunosuppression is minimal. Isolated chronic strictures should also be resected. In patients with multiple fibrotic strictures that would require extensive small bowel resection, stricturoplasty is a safe and effective alternative to resection. Short strictures are amenable to a transverse stricturoplasty, while longer strictures may be treated with a side-to-side small bowel anastomosis (Fig. 29-18).

Risk of recurrence after resection for ileocolic and small bowel Crohn’s disease is high. More than 50% of patients will experience a recurrence within 10 years, and the majority of these will require a second operation.

Crohn’s Colitis

Crohn’s disease of the large intestine may present as fulminant colitis or toxic megacolon. In this setting, treatment is identical to treatment of fulminant colitis and toxic megacolon secondary to ulcerative colitis. Resuscitation and medical therapy with bowel rest, broad-spectrum antibiotics, and parenteral corticosteroids should be instituted. If the patient’s condition worsens or fails to rapidly improve, total abdominal colectomy with end ileostomy is recommended. An elective proctectomy may be required if the patient has refractory Crohn’s proctitis. Alternatively, if the rectum is spared, an ileorectal anastomosis may be appropriate once the patient has recovered.

Other indications for surgery in chronic Crohn’s colitis are intractability, complications of medical therapy, and risk of or development of malignancy. Unlike ulcerative colitis, Crohn’s colitis may be segmental, and rectal sparing is often observed. A segmental colectomy may be appropriate if the remaining colon and/or rectum appear normal. An isolated colonic stricture may also be treated by segmental colectomy. Although it was long thought that Crohn’s disease did not increase the risk of colorectal carcinoma, it is now recognized that Crohn’s colitis (especially pancolitis) carries nearly the same risk for cancer as ulcerative colitis. Annual surveillance colonoscopy with multiple biopsies is recommended for patients with long-standing Crohn’s colitis (>7 years in duration). As in ulcerative colitis, dysplasia is an indication for total proctocolectomy. Ileal pouch–anal reconstruction is not recommended in these patients because of the risk for development of Crohn’s disease within the pouch and the high risk of complications, such as fistula, abscess, stricture, pouch dysfunction, and pouch failure.

Anal and Perianal Crohn’s Disease

Anal and perianal manifestations of Crohn’s disease are very common and occur in 35% of all patients with Crohn’s disease. Isolated anal Crohn’s disease is uncommon, affecting only 3% to 4% of patients. Detection of anal Crohn’s disease, therefore, should prompt evaluation of the remainder of the gastrointestinal tract.

The most common perianal lesions in Crohn’s disease are skin tags that are minimally symptomatic. Fissures are also common. Typically, a fissure from Crohn’s disease is particularly deep or broad and perhaps better described as an anal ulcer. These fissures are often multiple and located in a lateral position rather than anterior or posterior midline as seen in an idiopathic fissure in ano. A classic-appearing fissure in ano located laterally should raise the suspicion of Crohn’s disease. Perianal abscess and fistulas are common and can be particularly challenging. Fistulas tend to be complex and often have multiple tracts (Fig. 29-19). Hemorrhoids are not more common in patients with Crohn’s disease than in the general population, although many patients tend to attribute any anal or perianal symptom to “hemorrhoids.”

Treatment of anal and perianal Crohn’s disease focuses on alleviation of symptoms. Perianal skin irritation from diarrhea often responds to medical therapy directed at small bowel or colonic disease. In general, skin tags and hemorrhoids should not be excised unless they are extremely symptomatic because of the risk of creating chronic, nonhealing wounds. Fissures may respond to local or systemic therapy; sphincterotomy is relatively contraindicated because of the risk of creating a chronic, nonhealing wound and because of the increased risk of incontinence in a patient with diarrhea from underlying colitis or small bowel disease. Anal ulcers associated with Crohn’s disease are usually not very painful unless there is an underlying abscess. Thus, in patients with significant anal pain, an examination under anesthesia is indicated to exclude an underlying abscess or fistula and to assess the rectal mucosa. In the absence of active Crohn’s proctitis, one can proceed cautiously with a partial internal sphincterotomy if the examination under anesthesia reveals a classic-appearing posterior or anterior fissure and anal stenosis.

Recurrent abscess(es) or complex anal fistulae should raise the possibility of Crohn’s disease. Treatment focuses on control of infection, delineation of complex anatomy, treatment of underlying mucosal disease, and sphincter preservation. Abscesses often can be drained locally, and mushroom catheters are useful for maintaining drainage. Endoanal ultrasound and pelvic MRI are useful for mapping complex fistulous tracts. Liberal use of setons can control many fistulas and avoid division of the sphincter. Many patients with anal Crohn’s disease function well with multiple setons left in place for years. Endoanal advancement flaps may be considered for definitive therapy if the rectal mucosa is uninvolved but will not heal due to rectal inflammation. In 10% to 15% of cases, intractable perianal sepsis requires proctectomy.

Rectovaginal fistula can be a particularly difficult problem in these patients. A rectal or vaginal mucosal advancement flap may be used if the rectal mucosa appears healthy and scarring of the rectovaginal septum is minimal. Occasionally, proctectomy is the best option for women with highly symptomatic rectovaginal fistulae. Although proximal diversion is often employed to protect complex perianal reconstruction, there is no evidence that diversion alone increases healing of anal and perianal Crohn’s disease.

Medical treatment of underlying proctitis with salicylate and/or corticosteroid enemas may be helpful; however, control of infection is the primary goal of therapy. Metronidazole has been used with some success in this setting. Anti-TNF-α agents (infliximab and adalimumab) have shown some efficacy in healing chronic fistulas secondary to Crohn’s disease. The success of these agents has led to a concerted effort to identify other immunomodulators that might prove useful. Proinflammatory cytokines such as interleukin-12 and interferon-γ are potential targets. Inhibition of immune cell migration has also been suggested as an approach.⁴⁸ However, it is of paramount importance to drain any and all abscesses before initiating immunosuppressive therapy such as corticosteroids or anti-TNF-α monoclonal antibodies.

Indeterminate Colitis

Approximately 15% of patients with inflammatory bowel disease manifest clinical and pathologic characteristics of both ulcerative colitis and Crohn’s disease. Endoscopy, barium enema, and biopsy may be unable to differentiate ulcerative colitis from Crohn’s colitis in this setting. The indications for surgery are the same as those for ulcerative colitis: intractability, complications of medical therapy, and risk of or development of malignancy. In the setting of indeterminate colitis in a patient who prefers a sphincter-sparing operation, a total abdominal colectomy with end ileostomy may be the best initial procedure. Pathologic examination of the entire colon may then allow a more accurate diagnosis. If the diagnosis suggests ulcerative colitis, an ileal pouch–anal anastomosis procedure can be performed. If the diagnosis remains in question, the safest surgical option is completion proctectomy with end ileostomy (similar to Crohn’s colitis). Ileal pouch–anal reconstruction may also be considered with the understanding that the pouch failure rate is between 15% and 20%.

Diverticular disease is a clinical term used to describe the presence of symptomatic diverticula. Diverticulosis refers to the presence of diverticula without inflammation. Diverticulitis refers to inflammation and infection associated with diverticula. The majority of colonic diverticula are false diverticula in which the mucosa and muscularis mucosa have herniated through the colonic wall. These diverticula occur between the teniae coli, at points where the main blood vessels penetrate the colonic wall (presumably creating an area of relative weakness in the colonic muscle). They are thought to be pulsion diverticula resulting from high intraluminal pressure. Diverticular bleeding can be massive but usually is self-limited. True diverticula, which comprise all layers of the bowel wall, are rare and are usually congenital in origin.

Diverticulosis is extremely common in the United States and Europe. It is estimated that half of the population older than age 50 years has colonic diverticula. The sigmoid colon is the most common site of diverticulosis (Fig. 29-20). Diverticulosis is thought to be an acquired disorder, but the etiology is poorly understood. The most accepted theory is that a lack of dietary fiber results in smaller stool volume, requiring high intraluminal pressure and high colonic wall tension for propulsion. Chronic contraction then results in muscular hypertrophy and development of the process of segmentation in which the colon acts like separate segments instead of functioning as a continuous tube. As segmentation progresses, the high pressures are directed radially toward the colon wall rather than to development of propulsive waves that move stool distally. The high radial pressures directed against the bowel wall create pulsion diverticula. A loss of tensile strength and a decrease in elasticity of the bowel wall with age have also been proposed etiologies. Although none of these theories has been proven, a high-fiber diet does appear to decrease the incidence of diverticulosis. Although diverticulosis is common, most cases are asymptomatic, and complications occur in the minority of people with this condition.

Inflammatory Complications (Diverticulitis)

Diverticulitis refers to inflammation and infection associated with a diverticulum and is estimated to occur in 10% to 25% of people with diverticulosis. Peridiverticular and pericolic infection results from a perforation (either macroscopic or microscopic) of a diverticulum, which leads to contamination, inflammation, and infection. The spectrum of disease ranges from mild, uncomplicated diverticulitis that can be treated in the outpatient setting, to free perforation and diffuse peritonitis that requires emergency laparotomy. Most patients present with left-sided abdominal pain, with or without fever, and leukocytosis. A mass may be present. Plain radiographs are useful for detecting free intra-abdominal air. CT scan is extremely useful for defining pericolic inflammation, phlegmon, or abscess. Contrast enemas and/or endoscopy are relatively contraindicated because of the risk of perforation. The differential diagnosis includes malignancy, ischemic colitis, infectious colitis, and inflammatory bowel disease.

Uncomplicated Diverticulitis

Uncomplicated diverticulitis is characterized by left lower quadrant pain and tenderness. CT findings include pericolic soft tissue stranding, colonic wall thickening, and/or phlegmon. Most patients with uncomplicated diverticulitis will respond to outpatient therapy with broad-spectrum oral antibiotics and a low-residue diet. Antibiotics should be continued for 7 to 10 days. About 10% to 20% of patients with more severe pain, tenderness, fever, and leukocytosis are treated in the hospital with parenteral antibiotics and bowel rest. Most patients improve within 48 to 72 hours. Failure to improve may suggest abscess formation. CT can be extremely useful in this setting, and many pericolic abscesses can be drained percutaneously (see below). Deterioration in a patient’s clinical condition and the development of peritonitis are indications for laparotomy.

Most patients with uncomplicated diverticulitis will recover without surgery, and 50% to 70% will have no further episodes.⁴⁹ It has long been believed that the risk of complications increases with recurrent disease. For this reason, elective sigmoid colectomy has often been recommended after the second episode of diverticulitis, especially if the patient has required hospitalization. Resection has often been recommended after the first episode in very young patients and is often recommended after the first episode of complicated diverticulitis. These general guidelines have been questioned in recent years, and more recent studies suggest that the risk of complications and/or need for emergent resection does not increase with recurrent disease.^49,50

Many surgeons now will not advise colectomy even after two documented episodes of diverticulitis assuming the patient is completely asymptomatic and that carcinoma has been excluded by colonoscopy. Immunosuppressed patients are generally still advised to undergo colectomy after a single episode of documented diverticulitis. Medical comorbidities should be considered when evaluating a patient for elective resection, and the risks of recurrent disease should be weighed against the risks of the operation. Because colon carcinoma may present in an identical fashion to diverticulitis (either complicated or uncomplicated), all patients must be evaluated for malignancy after resolution of the acute episode. Colonoscopy is recommended 4 to 6 weeks after recovery. Inability to exclude malignancy is another indication for resection.

In the elective setting, a sigmoid colectomy with a primary anastomosis is the procedure of choice. The resection should always be extended to the rectum distally because the risk of recurrence is high if a segment of sigmoid colon is retained. The proximal extent of the resection should include all thickened or inflamed bowel; however, resection of all diverticula is unnecessary. Increasingly, laparoscopy is being used for elective sigmoid colectomy for diverticular disease.

Complicated Diverticulitis

Complicated diverticulitis includes diverticulitis with abscess, obstruction, diffuse peritonitis (free perforation), or fistulas between the colon and adjacent structures. Colovesical, colovaginal, and coloenteric fistulas are long-term sequelae of complicated diverticulitis. The Hinchey staging system is often used to describe the severity of complicated diverticulitis: Stage I includes colonic inflammation with an associated pericolic abscess; stage II includes colonic inflammation with a retroperitoneal or pelvic abscess; stage III is associated with purulent peritonitis; and stage IV is associated with fecal peritonitis. Treatment depends on the patient’s overall clinical condition and the degree of peritoneal contamination and infection. Small abscesses (<2 cm in diameter) may be treated with parenteral antibiotics. Larger abscesses are best treated with CT-guided percutaneous drainage (Fig. 29-21) and antibiotics. Many of these patients will ultimately require resection, but percutaneous drainage may allow a one-stage, elective procedure and may obviate the need for colectomy if full recovery follows the drainage.

Urgent or emergent laparotomy may be required if an abscess is inaccessible to percutaneous drainage, if the patient’s condition deteriorates or fails to improve, or if the patient presents with free intra-abdominal air or peritonitis. In almost all cases, an attempt should be made to resect the affected segment of bowel. Patients with small, localized pericolic or pelvic abscesses (Hinchey stages I and II) may be candidates for a sigmoid colectomy with a primary anastomosis (a one-stage operation).⁴⁵ Among patients with larger abscesses, peritoneal soiling, or peritonitis, sigmoid colectomy with end colostomy and Hartmann’s pouch is the most commonly used procedure.⁴⁶ Success also has been reported after sigmoid colectomy, primary anastomosis, with or without on-table lavage, and proximal diversion (loop ileostomy). This option may be appropriate in stable patients and offers the great advantage that the subsequent operation to restore bowel continuity is simpler than is takedown of a Hartmann’s pouch. The presence of inflammation and phlegmon may increase the risk of ureteral damage during mobilization of the sigmoid colon, and preoperative placement of ureteral catheters can be invaluable. In extremely unstable patients, or in the presence of such severe inflammation that resection would harm adjacent organs, proximal diversion and local drainage have been employed. However, this approach is generally avoided because of high morbidity and mortality rates, along with the requirement for multiple operations. More recently, several studies have suggested that laparoscopic lavage and drainage without bowel resection may be safe and effective even in the presence of free perforation. Nevertheless, this approach remains controversial and will require additional prospective trials before it can be recommended under most circumstances.

Obstructive symptoms occur in approximately 67% of patients who develop acute diverticulitis, and complete obstruction occurs in 10%. Patients with incomplete obstruction often respond to fluid resuscitation, nasogastric suction, and gentle, low-volume water or Gastrografin enemas. Relief of obstruction allows full bowel preparation and elective resection. A high-volume oral bowel preparation is contraindicated in the presence of obstructive symptoms. Obstruction that does not rapidly respond to medical management mandates laparotomy. Sigmoid colectomy with end colostomy is the safest procedure to perform in this setting. However, colectomy and primary anastomosis, with or without on-table lavage (depending on extent of fecal load in the proximal colon), and proximal diversion may be appropriate if the patient is stable and the proximal and distal bowel appear healthy.

Approximately 5% of patients with complicated diverticulitis develop fistulas between the colon and an adjacent organ. Colovesical fistulas are most common, followed by colovaginal and coloenteric fistulas. Colocutaneous fistulas are a rare complication of diverticulitis. Two key points in the evaluation of fistulas are to define the anatomy of the fistula and exclude other diagnoses. Contrast enema and/or small bowel studies are extremely useful in defining the course of the fistula. CT scan can identify associated abscesses or masses. The differential diagnosis includes malignancy, Crohn’s disease, and radiation-induced fistulas. While Crohn’s disease and radiation injury may be suspected based on the patient’s medical history, colonoscopy or sigmoidoscopy usually is required to rule out malignancy. In addition, in a patient who has received radiation therapy, a fistula must be considered to be recurrent cancer until proven otherwise. Once the anatomy of the fistula has been defined and other diagnoses excluded, operative management should include resection of the affected segment of the colon involved with diverticulitis (usually with a primary anastomosis) and simple repair of the secondarily involved organ. Suspicion of carcinoma may mandate a wider, en bloc resection.

Hemorrhage

Bleeding from a diverticulum results from erosion of the peridiverticular arteriole and may result in massive hemorrhage. Most significant lower gastrointestinal hemorrhage occurs in elderly patients in whom both diverticulosis and angiodysplasia are common. Consequently, the exact bleeding source may be difficult to identify. Fortunately, in 80% of patients, bleeding stops spontaneously. Clinical management should focus on resuscitation and localization of the bleeding site as described for lower gastrointestinal hemorrhage. Colonoscopy may occasionally identify a bleeding diverticulum that may then be treated with epinephrine injection or cautery. Angiography may be diagnostic and therapeutic in this setting. In the rare instance in which diverticular hemorrhage persists or recurs, laparotomy and segmental colectomy may be required.

Giant Colonic Diverticulum

Giant colonic diverticula are extremely rare. Most occur on the antimesenteric side of the sigmoid colon. Patients may be asymptomatic or may present with vague abdominal complaints such as pain, nausea, or constipation. Plain radiographs may suggest the diagnosis. Barium enema is usually diagnostic. Complications of a giant diverticulum include perforation, obstruction, and volvulus. Resection of the involved colon and diverticulum is recommended.

Right-Sided Diverticula

The cecum and ascending colon infrequently are involved in diverticulosis coli. Even more uncommon is a true solitary diverticulum, which contains all layers of the bowel wall and is thought to be congenital in origin. Right-sided diverticula occur more often in younger patients than do left-sided diverticula and are more common in people of Asian descent than in other populations. Most patients with right-sided diverticula are asymptomatic. However, diverticulitis does occur occasionally. Because patients are young and present with right lower quadrant pain, they are often thought to suffer from acute appendicitis, and the diagnosis of right-sided diverticulitis is subsequently made in the operating room. If there is a single large diverticulum and minimal inflammation, a diverticulectomy may be performed, but an ileocecal resection is usually the preferred operation in this setting. Hemorrhage rarely occurs and should be treated in the same fashion as hemorrhage from a left-sided diverticulum.

Incidence

Colorectal carcinoma is the most common malignancy of the gastrointestinal tract. Over 140,000 new cases are diagnosed annually in the United States, and more than 50,000 patients die of this disease each year, making colorectal cancer the third most lethal cancer in the United States.⁵¹

The incidence is similar in men and women and has remained fairly constant over the past 20 years; however, the widespread adoption of current national screening programs is gradually decreasing the incidence of this common and lethal disease. Early detection and improvements in medical and surgical care are thought to be responsible for the decreasing mortality of colorectal cancer observed in recent years.

Epidemiology (Risk Factors)

Identification of risk factors for development of colorectal cancer is essential to establish screening and surveillance programs in appropriately targeted populations.

Aging

Aging is the dominant risk factor for colorectal cancer, with incidence rising steadily after age 50 years. More than 90% of cases diagnosed are in people older than age 50 years. This is the rationale for initiating screening tests of asymptomatic patients at average risk of developing colorectal cancer at age 50 years. However, individuals of any age can develop colorectal cancer, so symptoms such as a significant change in bowel habits, rectal bleeding, melena, unexplained anemia, or weight loss require a thorough evaluation.

Hereditary Risk Factors

Approximately 80% of colorectal cancers occur sporadically, while 20% arise in patients with a known family history of colorectal cancer. Advances in the understanding of these familial disorders have led to interest in early diagnosis using genetic testing. Because of the medical, legal, and ethical considerations that are involved in this type of testing, all patients should be offered genetic counseling if a familial syndrome is suspected.

Environmental and Dietary Factors

The observation that colorectal carcinoma occurs more commonly in populations that consume diets high in animal fat and low in fiber has led to the hypothesis that dietary factors contribute to carcinogenesis. A diet high in saturated or polyunsaturated fats increases risk of colorectal cancer, while a diet high in oleic acid (olive oil, coconut oil, fish oil) does not increase risk. Animal studies suggest that fats may be directly toxic to the colonic mucosa and thus may induce early malignant changes. In contrast, a diet high in vegetable fiber appears to be protective. A correlation between alcohol intake and incidence of colorectal carcinoma has also been suggested. Ingestion of calcium, selenium, vitamins A, C, and E, carotenoids, and plant phenols may decrease the risk of developing colorectal cancer. Obesity and sedentary lifestyle dramatically increase cancer-related mortality in a number of malignancies, including colorectal carcinoma. This knowledge is the basis for primary prevention strategies to eliminate colorectal cancer by altering diet and lifestyle.⁵²

Inflammatory Bowel Disease

Patients with long-standing colitis from inflammatory bowel disease are at increased risk for the development of colorectal cancer. It is hypothesized that chronic inflammation predisposes the mucosa to malignant changes, and there is some evidence that degree of inflammation influences risk. In general, the duration and extent of colitis correlate with risk. Other factors thought to increase risk include the presence of primary sclerosing cholangitis and family history of colorectal cancer.

Other Risk Factors

Cigarette smoking is associated with an increased risk of colonic adenomas, especially after more than 35 years of use. Patients with ureterosigmoidostomy are also at increased risk for both adenoma and carcinoma formation.⁵³

Acromegaly, which is associated with increased levels of circulating human growth hormone and insulin-like growth factor-1, increases risk as well. Pelvic irradiation may increase the risk of developing rectal carcinoma. However, it is unclear whether this represents a direct effect of radiation damage or is instead a correlation between the development of rectal cancer and a history of another pelvic malignancy; for example among patients who develop prostate cancer and are treated with radiation, the risk of rectal cancer increases significantly.⁵⁴

Pathogenesis of Colorectal Cancer

Genetic Defects

Over the past two decades, an intense research effort has focused on elucidating the genetic defects and molecular abnormalities associated with the development and progression of colorectal adenomas and carcinoma. Mutations may cause activation of oncogenes (K-ras) and/or inactivation of tumor suppressor genes (APC, deleted in colorectal carcinoma [DCC], p53). Colorectal carcinoma is thought to develop from adenomatous polyps by accumulation of these mutations in what has come to be known as the adenoma-carcinoma sequence (Fig. 29-22).

Defects in the APC gene were first described in patients with FAP. By investigating these families, characteristic mutations in the APC gene were identified. They are now known to be present in 80% of sporadic colorectal cancers as well.

The APC gene is a tumor suppressor gene. Mutations in both alleles are necessary to initiate polyp formation. The majority of mutations are premature stop codons, which result in a truncated APC protein. In FAP, the site of mutation correlates with the clinical severity of the disease. For example, mutations in either the 3′ or 5′ end of the gene result in attenuated forms of FAP (AFAP), whereas mutations in the center of the gene result in more virulent disease. Thus, knowledge of the specific mutation in a family may help guide clinical decision making.

APC inactivation alone does not result in a carcinoma. Instead, this mutation sets the stage for the accumulation of genetic damage that results in malignancy. Additional mutations may include activation or inactivation of a variety of genes.

One of the most commonly involved genes in colorectal cancer is K-ras. K-ras, a signaling molecule in the epidermal growth factor receptor (EGFR) pathway, is classified as a proto-oncogene because mutation of only one allele will perturb the cell cycle. The K-ras gene product is a G-protein involved in intracellular signal transduction. When active, K-ras binds guanosine triphosphate (GTP); hydrolysis of GTP to guanosine diphosphate (GDP) then inactivates the G-protein. Mutation of K-ras results in an inability to hydrolyze GTP, thus leaving the G-protein permanently in the active form. It is thought that this then leads to uncontrolled cell division. Other EGFR signaling molecules such as BRAF have also been implicated in colorectal cancer pathogenesis and progression, and ongoing research is focusing on elucidating their roles in this disease.

Another common mutation occurs in the MYH gene on chromosome 1p.^55,56 MYH is a base excision repair gene, and biallelic deletion results in changes in other downstream molecules. Since its discovery, MYH mutations have been associated with an AFAP phenotype in addition to sporadic cancers.⁵⁵ Unlike APC gene mutations that are expressed in an autosomal dominant pattern, the requirement for biallelic mutation in MYH results in an autosomal recessive pattern of inheritance.

The tumor suppressor gene p53 has been well characterized in a number of malignancies. The p53 protein appears to be crucial for initiating apoptosis in cells with irreparable genetic damage. Mutations in p53 are present in 75% of colorectal cancers.

Deletion of the tumor suppressor phosphatase and tensin homolog (PTEN) appears to be involved in a number of hamartomatous polyposis syndromes. Deletions in PTEN have been identified in juvenile polyposis, Peutz-Jeghers syndrome, Cowden’s syndrome, and PTEN hamartoma syndrome, in addition to multiple endocrine neoplasia type IIB.¹²

Genetic Pathways

The mutations involved in colorectal cancer pathogenesis and progression are now recognized to accumulate via one of three major genetic pathways: the loss of heterozygosity (LOH; chromosomal instability) pathway, the microsatellite instability (MSI) pathway, and the CpG island methylation (CIMP; serrated methylated) pathway.

The Loss of Heterozygosity Pathway

The LOH pathway is characterized by chromosomal deletions and tumor aneuploidy. Eighty percent of colorectal carcinomas appear to arise from mutations in the LOH pathway. This pathway was first described in patients with FAP in whom mutations of the APC gene were found to be inherited.

Another example of LOH occurs in the region of chromosome 18q. This region has been found to be deleted in up to 70% of colorectal cancers. Two tumor suppressor genes, DCC and SMAD4, are located in this region, and as such, deletion of 18q may result in the loss of one or both of these genes. DCC is a tumor suppressor gene, and loss of both alleles is required for malignant degeneration. The main role of this molecule appears to be in the central nervous system, where it is involved in neural differentiation and axonal migration. This observation has led to the hypothesis that DCC may be involved in differentiation and cellular adhesion in colorectal cancer, but this theory remains unproven.⁵⁷ DCC mutations are present in more than 70% of colorectal carcinomas and may negatively impact prognosis. SMAD4 functions in the signaling cascade of transforming growth factor beta and beta-catenin (also a downstream effector of the APC gene). Loss of either of these genes is thought to promote cancer progression.

The Microsatellite Instability Pathway

Many of the remaining colorectal carcinomas are thought to arise from mutations in the MSI pathway, which is characterized by errors in mismatch repair during DNA replication. These errors in mismatch repair were first described in HNPCC (Lynch’s syndrome), but are now recognized to be present in many sporadic tumors as well. A number of genes have been identified that appear to be crucial for recognizing and repairing DNA replication errors. These mismatch repair genes include MSH2, MLH1, PMS1, PMS2, and MSH6/GTBP. A mutation in one of these genes predisposes a cell to mutations, which may occur in proto-oncogenes or tumor suppressor genes. Accumulation of these errors then leads to genomic instability and ultimately to carcinogenesis.

Microsatellites are regions of the genome in which short base-pair segments are repeated several times, regions that are particularly prone to replication error. Consequently, a mutation in a mismatch repair gene produces variable lengths of these repetitive sequences, a finding that has been described as MSI.

Tumors associated with MSI appear to have different biologic characteristics than do tumors that result from the LOH pathway. Tumors with MSI are more likely to be in the right colon and possess diploid DNA and are associated with a better prognosis than tumors that arise from the LOH pathway that are microsatellite stable. Tumors arising from the LOH pathway tend to occur in the more distal colon, often have chromosomal aneuploidy, and are associated with a poorer prognosis.

CpG Island Methylation Pathway

In the recently described CIMP pathway, genes do not accumulate mutations (deletions or insertions of bases), but instead are activated or inactivated by methylation. This process has been called epigenetic alteration to differentiate it from the more traditional genetic alterations or true mutations. In normal cells, methylation is critical for regulation of gene expression. In cancer, aberrant methylation (either hyper- or hypomethylation), usually of a promoter region, results in abnormal activation or inactivation of genes. This gene silencing or, alternatively, activation results in a phenotype similar to that present with a true gene mutation. This pathway has also been called the serrated methylated pathway because of the observation that serrated polyps often harbor aberrant methylation in contrast to adenomatous polyps that are more often associated with mutations in the APC gene (LOH pathway).⁵⁸

Although these classifications are useful for understanding the mechanisms underlying carcinogenesis, they are not mutually exclusive. For example, a mismatch repair gene may be inactivated by methylation. Errors in mismatch repair may then allow mutations to inactivate a tumor suppressor gene. In addition, there is considerable interest in targeting molecules in each of these pathways in order to design better anticancer agents. Finally, ongoing research is focusing on the utility of molecular profiling in predicting prognosis and/or response to treatment.

Polyps

It is now well accepted that the majority of colorectal carcinomas evolve from adenomatous polyps; this sequence of events is the adenoma-carcinoma sequence. Polyp is a nonspecific clinical term that describes any projection from the surface of the intestinal mucosa regardless of its histologic nature. Colorectal polyps may be classified as neoplastic (tubular adenoma, villous adenoma, tubulovillous adenomas, serrated adenomas/polyps), hyperplastic, hamartomatous (juvenile, Peutz-Jeghers, Cronkite-Canada), or inflammatory (pseudopolyp, benign lymphoid polyp).

Neoplastic Polyps

Adenomatous polyps are common, occurring in up to 25% of the population older than 50 years of age in the United States. By definition, these lesions are dysplastic. The risk of malignant degeneration is related to both the size and type of polyp. Tubular adenomas are associated with malignancy in only 5% of cases, whereas villous adenomas may harbor cancer in up to 40%. Tubulovillous adenomas are at intermediate risk (22%). Invasive carcinomas are rare in polyps smaller than 1 cm; the incidence increases with size. The risk of carcinoma in a polyp larger than 2 cm is 35% to 50%. Although most neoplastic polyps do not evolve to cancer, most colorectal cancers originate as a polyp. It is this fact that forms the basis for secondary prevention strategies to eliminate colorectal cancer by targeting the neoplastic polyp for removal before malignancy develops.

Polyps may be pedunculated or sessile. Most pedunculated polyps are amenable to colonoscopic snare excision. Removal of sessile polyps is often more challenging. Special colonoscopic techniques, including saline lift, piecemeal snare excision, and endoscopic mucosal resection facilitate successful removal of many sessile polyps. For rectal sessile polyps, transanal operative excision is preferred because it produces an intact, single pathology specimen that can be used to determine the need for further therapy. Interpretation of the precise depth of invasion of a cancer arising in a sessile polyp after piecemeal excision is often impossible. The site of sessile polypectomies should be marked by injection of India ink to guide follow-up colonoscopy sessions to ensure that the polyp has been completely removed and to facilitate identification of the involved bowel segment should operative resection be necessary. Colectomy is reserved for cases in which colonoscopic removal is impossible, such as large, flat lesions, or if a focus of invasive cancer is confirmed in the specimen.

Complications of polypectomy include perforation and bleeding. A small perforation (microperforation) in a fully prepared, stable patient may be managed with bowel rest, broad-spectrum antibiotics, and close observation. Signs of sepsis, peritonitis, or deterioration in clinical condition are indications for laparotomy. Bleeding may occur immediately after polypectomy or may be delayed. The bleeding will usually stop spontaneously, but colonoscopy may be required to resnare a bleeding stalk or cauterize the lesion. Occasionally angiography and infusion of vasopressin may be necessary. Rarely, colectomy is required.

Hyperplastic Polyps

Hyperplastic polyps are extremely common in the colon. These polyps are usually small (<5 mm) and show histologic characteristics of hyperplasia without any dysplasia. They are not considered premalignant, but cannot be distinguished from adenomatous polyps colonoscopically and are therefore often removed. In contrast, large hyperplastic polyps (>2 cm) may have a slight risk of malignant degeneration. Moreover, large polyps may harbor foci of adenomatous tissue and dysplasia. Hyperplastic polyposis is a rare disorder in which multiple large hyperplastic polyps occur in young adults. These patients are at slightly increased risk for the development of colorectal cancer.

Serrated Polyps

Serrated polyps are a recently recognized, histologically distinct group of neoplastic polyps. These lesions were long thought to be similar to hyperplastic polyps with minimal malignant potential. However, it has become clear that some of these polyps will develop into invasive cancers. In addition, a familial serrated polyposis syndrome has recently been described. Serrated polyps should be treated like adenomatous polyps.⁵⁹

Hamartomatous Polyps (Juvenile Polyps)

In contrast to adenomatous and serrated polyps, hamartomatous polyps (juvenile polyps) usually are not premalignant. These lesions are the characteristic polyps of childhood but may occur at any age. Bleeding is a common symptom, and intussusception and/or obstruction may occur. Because the gross appearance of these polyps is identical to adenomatous polyps, these lesions should also be treated by polypectomy. In contrast to adenomatous polyposis syndromes, these conditions are often associated with mutation in PTEN.

Familial juvenile polyposis is an autosomal dominant disorder in which patients develop hundreds of polyps in the colon and rectum. Unlike solitary juvenile polyps, these lesions may degenerate into adenomas and eventually carcinoma. Annual screening should begin between the ages of 10 and 12 years. Treatment is surgical and depends in part on the degree of rectal involvement. If the rectum is relatively spared, a total abdominal colectomy with ileorectal anastomosis may be performed with subsequent close surveillance of the retained rectum. If the rectum is carpeted with polyps, total proctocolectomy is the more appropriate operation. These patients are candidates for ileal pouch–anal reconstruction to avoid a permanent stoma.

Peutz-Jeghers syndrome is characterized by polyposis of the small intestine and, to a lesser extent, polyposis of the colon and rectum. Characteristic melanin spots are often noted on the buccal mucosa and lips of these patients. The polyps of Peutz-Jeghers syndrome are generally considered to be hamartomas and are not thought to be at significant risk for malignant degeneration. However, carcinoma may occasionally develop. Because the entire length of the gastrointestinal tract may be affected, surgery is reserved for symptoms such as obstruction or bleeding or for patients in whom polyps develop adenomatous features. Screening consists of a baseline colonoscopy and upper endoscopy at age 20 years, followed by annual flexible sigmoidoscopy thereafter.

Cronkite-Canada syndrome is a disorder in which patients develop gastrointestinal polyposis in association with alopecia, cutaneous pigmentation, and atrophy of the fingernails and toenails. Diarrhea is a prominent symptom, and vomiting, malabsorption, and protein-losing enteropathy may occur. Most patients die of this disease despite maximal medical therapy, and surgery is reserved for complications of polyposis such as obstruction.

Cowden’s syndrome is an autosomal dominant disorder with hamartomas of all three embryonal cell layers. Facial trichilemmomas, breast cancer, thyroid disease, and gastrointestinal polyps are typical of the syndrome. Patients should be screened for cancers. Treatment is otherwise based on symptoms.

Inflammatory Polyps (Pseudopolyps)

Inflammatory polyps occur most commonly in the context of inflammatory bowel disease, but may also occur after amebic colitis, ischemic colitis, and schistosomal colitis. These lesions are not premalignant, but they cannot be distinguished from adenomatous polyps based on gross appearance and therefore should be removed. Microscopic examination shows islands of normal, regenerating mucosa (the polyp) surrounded by areas of mucosal loss. Polyposis may be extensive, especially in patients with severe colitis, and may mimic FAP.

Inherited Colorectal Carcinoma

Many of the genetic defects originally described in hereditary cancers have subsequently been found in sporadic tumors. Although the majority of colorectal cancer is sporadic, several hereditary syndromes provide paradigms for the study of this disease. Insight gained from studying inherited colorectal cancer syndromes has led to better understanding of the genetics of colorectal carcinoma.

Familial Adenomatous Polyposis

This rare autosomal dominant condition accounts for only about 1% of all colorectal adenocarcinomas. Nevertheless, this syndrome has provided tremendous insight into the molecular mechanisms underlying colorectal carcinogenesis. The genetic abnormality in FAP is a mutation in the APC gene, located on chromosome 5q. Of patients with FAP, APC mutation testing is positive in 75% of cases. While most patients with FAP will have a known family history of the disease, up to 25% present without other affected family members. Clinically, patients develop hundreds to thousands of adenomatous polyps shortly after puberty. The lifetime risk of colorectal cancer in FAP patients approaches 100% by age 50 years.

Flexible sigmoidoscopy of first-degree relatives of FAP patients beginning at age 10 to 15 years has been the traditional mainstay of screening. Today, following genetic counseling, APC gene testing may be used to screen family members, providing an APC mutation has been identified. If APC testing is positive in a relative of a patient with a known APC mutation, annual flexible sigmoidoscopy beginning at age 10 to 15 years is done until polyps are identified. If APC testing is negative, the relative can be screened starting at age 50 years per average-risk guidelines. If APC testing is refused or unavailable, or if a mutation cannot be identified, annual flexible sigmoidoscopy beginning at age 10 to 15 years is performed until age 24 years. Screening flexible sigmoidoscopy is then done every 2 years until age 34 years, every 3 years until age 44 years, and then every 3 to 5 years.

FAP patients are also at risk for the development of adenomas anywhere in the gastrointestinal tract, particularly in the duodenum. Periampullary carcinoma is a particular concern. Upper endoscopy is therefore recommended for surveillance every 1 to 3 years beginning at age 25 to 30 years.

Once the diagnosis of FAP has been made and polyps are developing, treatment is surgical. Four factors affect the choice of operation: age of the patient; presence and severity of symptoms; extent of rectal polyposis; and presence and location of cancer or desmoid tumors. Three operative procedures can be considered: total proctocolectomy with an end (Brooke) ileostomy; total abdominal colectomy with ileorectal anastomosis; and restorative proctocolectomy with ileal pouch–anal anastomosis with or without a temporary ileostomy. Most patients elect to have an ileal pouch–anal anastomosis in the absence of a distal rectal cancer, a mesenteric desmoid tumor that prevents the ileum from reaching the anus, or poor sphincter function. Mucosectomy has been advocated in patients with FAP undergoing ileal pouch–anal anastomosis because of the risk of neoplasia in the anal transition zone, but the requirement for this procedure remains controversial. Although patient satisfaction with this procedure remains high, function may not be ideal, and up to 50% of patients experience some degree of incontinence. Total abdominal colectomy with an ileorectal anastomosis is also an option in these patients, but requires vigilant surveillance of the retained rectum for development of rectal cancer. There is increasing data suggesting that the administration of cyclooxygenase-2 (COX-2) inhibitors (celecoxib, sulindac) may slow or prevent the development of polyps.⁶⁰

FAP may be associated with extraintestinal manifestations such as congenital hypertrophy of the retinal pigmented epithelium, desmoid tumors, epidermoid cysts, mandibular osteomas (Gardner’s syndrome), and central nervous system tumors (Turcot’s syndrome). Desmoid tumors in particular, can make surgical management difficult and are a source of major morbidity and mortality in these patients. Desmoid tumors are often hormone responsive, and growth may be inhibited in some patients with tamoxifen. COX-2 inhibitors and nonsteroidal, anti-inflammatory drugs may also be beneficial in this setting.

Attenuated Familial Adenomatous Polyposis

AFAP is a recognized variant of FAP. Patients present later in life with fewer polyps (usually 10–100) predominantly located in the right colon, when compared to classic FAP. Colorectal carcinoma develops in more than 50% of these patients, but occurs later (average age, 55 years). Patients are also at risk for duodenal polyposis. However, in contrast to FAP, APC gene mutations are present in only about 30% of patients with AFAP. When present, these mutations are expressed in an autosomal dominant pattern.

Mutations in MYH also result in the AFAP phenotype but are expressed in an autosomal recessive pattern. It has been suggested that MYH mutations may be responsible for AFAP in patients who do not have a detectable APC gene mutation.⁶¹

Genetic testing is often offered to patients with suspected AFAP. When positive, genetic counseling and testing may be used to screen at-risk family members. If the family mutation is unknown, screening colonoscopy is recommended beginning at age 13 to 15 years, then every 4 years to age 28 years, and then every 3 years. These patients are often candidates for a total abdominal colectomy with ileorectal anastomosis because the limited polyposis in the rectum can usually be treated by colonoscopic snare excision.^62,63 Prophylaxis with COX-2 inhibitors also may be appropriate. Because of the more subtle phenotype in these patients, it is important to rule out other familial syndromes such as HNPCC (Lynch’s syndrome) and the more common familial colorectal cancer.

Hereditary Nonpolyposis Colon Cancer (Lynch’s Syndrome)

HNPCC (Lynch’s syndrome) is more common than FAP, but is still extremely rare (1%–3% of all colon cancers). The genetic defects associated with HNPCC arise from errors in mismatch repair, the phenotypic result being MSI. HNPCC is inherited in an autosomal dominant pattern and is characterized by the development of colorectal carcinoma at an early age (average age, 40–45 years). Approximately 70% of affected individuals will develop colorectal cancer. Cancers appear in the proximal colon more often than in sporadic colorectal cancer and have a better prognosis regardless of stage. The risk of synchronous or metachronous colorectal carcinoma is 40%. HNPCC may also be associated with extracolonic malignancies, including endometrial carcinoma, which is most common, and ovarian, pancreas, stomach, small bowel, biliary, and urinary tract carcinomas. The diagnosis of HNPCC is made based on family history. The Amsterdam criteria for clinical diagnosis of HNPCC are three affected relatives with histologically verified adenocarcinoma of the large bowel (one must be a first-degree relative of one of the others) in two successive generations of a family with one patient diagnosed before age 50 years. The presence of other HNPCC-related carcinomas should raise the suspicion of this syndrome. In a patient with an established diagnosis of colorectal cancer, tumor testing for presence of mismatch repair gene products (immunohistochemistry) and/or MSI can sometimes serve as screening for this syndrome.^64,65

HNPCC results from mutations in mismatch repair genes, and like FAP, specific mutations are associated with different phenotypes. For example, mutations in PMS2 or MSH6 result in a more attenuated form of HNPCC when compared to mutations in other genes. MSH6 inactivation also appears to be associated with a higher risk for endometrial cancer. Further significance of these specific mutations remains to be determined.

Screening colonoscopy is recommended annually for at-risk patients beginning at either age 20 to 25 years or 10 years younger than the youngest age at diagnosis in the family, whichever comes first.⁶⁶ Because of the high risk of endometrial carcinoma, transvaginal ultrasound or endometrial aspiration biopsy is also recommended annually after age 25 to 35 years. Because there is a 40% risk of developing a second colon cancer, total colectomy with ileorectal anastomosis is recommended once adenomas or a colon carcinoma is diagnosed. Annual proctoscopy is necessary because the risk of developing rectal cancer remains high. Similarly, prophylactic hysterectomy and bilateral salpingo-oophorectomy should be considered in women who have completed childbearing.

Familial Colorectal Cancer

Nonsyndromic familial colorectal cancer accounts for 10% to 15% of patients with colorectal cancer. The lifetime risk of developing colorectal cancer increases with a family history of the disease. The lifetime risk of colorectal cancer in a patient with no family history of this disease (average-risk population) is approximately 6%, but rises to 12% if one first-degree relative is affected and to 35% if two first-degree relatives are affected. Age of onset also impacts risk, and a diagnosis before the age of 50 years is associated with a higher incidence in family members. Screening colonoscopy is recommended every 5 years beginning at age 40 years or beginning 10 years before the age of the earliest diagnosed patient in the pedigree. While there are no specific genetic abnormalities that are associated with familial colorectal cancer, any of the defects found in either the LOH pathway or MSI pathway may be present in these patients.

Prevention: Screening and Surveillance

Because the majority of colorectal cancers are thought to arise from adenomatous polyps, preventive measures focus on identification and removal of these premalignant lesions. In addition, many cancers are asymptomatic, and screening may detect these tumors at an early and curable stage (Table 29-1). Although screening for colorectal cancer decreases the incidence of cancer and cancer-related mortality, the optimal method of screening remains controversial. Screening guidelines are meant for asymptomatic patients.^61,66,67,68 Any patient with a gastrointestinal complaint (bleeding, change in bowel habits, pain, etc.) requires a complete evaluation, usually by colonoscopy.

Fecal Occult Blood Testing

FOBT is known to reduce colorectal cancer mortality by 33% and metastatic disease by 50%. However, FOBT is relatively insensitive, missing up to 50% of cancers and the majority of adenomas. Its specificity is low because 90% of patients with positive tests do not have colorectal cancer. Compliance with annual testing is low and costs are significant if one includes the colonoscopy examinations done to evaluate patients with positive FOBT. Nonetheless, the direct evidence that FOBT screening is efficacious and decreases both the incidence and mortality of colorectal cancer is so strong that national guidelines recommend annual FOBT screening for asymptomatic, average-risk Americans older than 50 years of age as one of several accepted strategies. Newer immunohistochemical methods for detecting human globin may prove to be more sensitive and specific.⁶⁹ A positive FOBT test should be followed by colonoscopy.

Flexible Sigmoidoscopy

Screening by flexible sigmoidoscopy every 5 years may lead to a 60% to 70% reduction in mortality from colorectal cancer, chiefly by identifying high-risk individuals with adenomas. However, it is important to recognize that lesions in the proximal colon cannot be identified, and for this reason, flexible sigmoidoscopy has often been paired with air-contrast barium enema to detect transverse and right colon lesions. Patients found to have a polyp, cancer, or other lesion on flexible sigmoidoscopy will require colonoscopy.⁷⁰

Fecal Occult Blood Testing and Flexible Sigmoidoscopy

Several trials have shown that FOBT screening is least effective at detecting rectosigmoid cancers.^69,71 This is precisely the area screened by flexible sigmoidoscopy; thus, the combination of the two tests has been suggested as a reasonable screening strategy. Winawer and colleagues, in a study of 12,479 subjects, showed that the combination of FOBT annually with flexible sigmoidoscopy every 5 years resulted in lower mortality from colorectal cancer and better survival in patients with colorectal cancer.⁷² Such data led to the American Cancer Society recommendations that one of the acceptable screening regimens for average-risk Americans is the combination of FOBT annually and flexible sigmoidoscopy every 5 years; this combination was preferred over either test alone. The addition of air-contrast barium enema to assess the proximal colon may improve sensitivity as well.

Colonoscopy

Colonoscopy is currently the most accurate and most complete method for examining the large bowel. This procedure is highly sensitive for detecting even small polyps (<1 cm) and allows biopsy, polypectomy, control of hemorrhage, and dilation of strictures. However, colonoscopy does require mechanical bowel preparation, and the discomfort associated with the procedure requires conscious sedation in most patients. Colonoscopy is also considerably more expensive than other screening modalities and requires a well-trained endoscopist. The risk of a major complication after colonoscopy (perforation and hemorrhage) is extremely low (0.2%–0.3%). Nevertheless, deaths have been reported.

Air-Contrast Barium Enema

Air-contrast barium enema is also highly sensitive for detecting polyps greater than 1 cm in diameter (90% sensitivity). Unfortunately, there are no studies proving its efficacy for screening large populations. Accuracy is greatest in the proximal colon but may be compromised in the sigmoid colon if there is significant diverticulosis. The major disadvantages of barium enema are the need for mechanical bowel preparation and the requirement for colonoscopy if a lesion is discovered.

Computed Tomography Colonography (Virtual Colonoscopy)

Advances in imaging technology have created a number of less invasive, but highly accurate tools for screening. CT colonography makes use of helical CT technology and three-dimensional reconstruction to image the intraluminal colon. A present, patients require a mechanical bowel preparation. The colon is then insufflated with air, a spiral CT is performed, and both two-dimensional and three-dimensional images are generated. In the hands of a qualified radiologist, sensitivity appears to be as good as colonoscopy for colorectal cancers and polyps greater than 1 cm in size.⁷³ Colonoscopy is required if a lesion is identified. CT colonography is also useful for imaging the proximal colon in cases of obstruction or if a colonoscopy cannot be completed. Limitations of this technique include false-positive results from retained stool, diverticular disease, haustral folds, motion artifacts, and an inability to detect flat adenomas.

Guidelines for Screening

Current American Cancer Society guidelines advocate screening for the average-risk population (asymptomatic, no family history of colorectal carcinoma, no personal history of polyps or colorectal carcinoma, no familial syndrome) beginning at age 50 years. Recommended procedures include yearly FOBT, flexible sigmoidoscopy every 5 years, FOBT and flexible sigmoidoscopy in combination, air-contrast barium enema every 5 years, or colonoscopy every 10 years.⁶⁶ Patients with other risk factors should be screened earlier and more frequently (Table 29-2).

Routes of Spread and Natural History

Carcinoma of the colon and rectum arises in the mucosa. The tumor subsequently invades the bowel wall and eventually adjacent tissues and other viscera. Tumors may become bulky and circumferential, leading to colon obstruction. Local extension (especially in the rectum) may occasionally cause obstruction of other organs such as the ureter.

Regional lymph node involvement is the most common form of spread of colorectal carcinoma and usually precedes distant metastasis or the development of carcinomatosis. The likelihood of nodal metastasis increases with tumor size, poorly differentiated histology, lymphovascular invasion, and depth of invasion. The T stage (depth of invasion) is the single most significant predictor of lymph node spread. Carcinoma in situ (Tis) in which there is no penetration of the muscularis mucosa (basement membrane) has also been called high-grade dysplasia and should carry no risk of lymph node metastasis. Small lesions confined to the bowel wall (T1 and T2) are associated with lymph node metastasis in 5% to 20% of cases, whereas larger tumors that invade through the bowel wall or into adjacent organs (T3 and T4) are likely to have lymph node metastasis in more than 50% of cases. The number of lymph nodes with metastases correlates with the presence of distant disease and inversely with survival. Four or more involved lymph nodes predict a poor prognosis. In colon cancer, lymphatic spread usually follows the major venous outflow from the involved segment of the colon. Lymphatic spread from the rectum follows two routes. In the upper rectum, drainage ascends along the superior rectal vessels to the inferior mesenteric nodes. In the lower rectum, lymphatic drainage may course along the middle rectal vessels. Nodal spread along the inferior rectal vessels to the internal iliac nodes or groin is rare unless the tumor involves the anal canal or the proximal lymphatics are blocked with tumor (Fig. 29-23).

The most common site of distant metastasis from colorectal cancer is the liver. These metastases arise from hematogenous spread via the portal venous system. Like lymph node metastasis, the risk of hepatic metastasis increases with tumor size and tumor grade. However, even small tumors may produce distant metastasis. The lung is also a site of hematogenous spread, but this rarely occurs in isolation. Carcinomatosis (diffuse peritoneal metastases) occurs by peritoneal seeding and has a dismal prognosis.

Staging and Preoperative Evaluation

Clinical Presentation

Symptoms of colon and rectal cancers are nonspecific and generally develop when the cancer is locally advanced. The classic first symptoms are a change in bowel habits and rectal bleeding. Abdominal pain, bloating, and other signs of obstruction typically occur with larger tumors and suggest more advanced disease. Because of the caliber of the bowel and the consistency of the stool, left-sided tumors are more likely to cause obstruction than are right-sided tumors. Rectal tumors may cause bleeding, tenesmus, and pain. Alternatively, patients may be asymptomatic and/or present with unexplained anemia, weight loss, or poor appetite.

Staging

Colorectal cancer staging is based on tumor depth and the presence or absence of nodal or distant metastases. Older staging systems, such as the Dukes’ Classification and its Astler-Coller modification, have been replaced by the tumor-node-metastasis (TNM) staging system (Table 29-3).⁷⁴ Stage I disease includes adenocarcinomas that are invasive through the muscularis mucosa but are confined to the submucosa (T1) or the muscularis propria (T2) in the absence of nodal metastases. Stage II disease consists of tumors that invade through the bowel wall into the subserosa or nonperitonealized pericolic or perirectal tissues (T3) or into other organs or tissues or through the visceral peritoneum (T4) without nodal metastases. Stage III disease includes any T stage with nodal metastases, and stage IV disease denotes distant metastases.

The preoperative evaluation usually identifies stage IV disease. In colon cancer, differentiating stages I, II, and III depends on examination of the resected specimen. In rectal cancer, endorectal ultrasound or MRI may predict the stage (ultrasound stage, uTxNx) preoperatively, but the final determination depends on pathologic examination of the resected tumor and adjacent lymph nodes (pathologic stage, pTxNx). Disease stage correlates with 5-year survival. Patients with stages I and II disease can expect excellent survival rates. The presence of nodal metastases (stage III) decreases survival (Table 29-4). The 5-year survival rate with stage IV disease is less than 16%. However, in well-selected patients, metastasectomy, especially of isolated liver or lung lesions, can result in cure. In rectal cancer, staging has been further refined, and outcomes suggest that subgroups of patients within each stage may have very different prognoses (Table 29-5). If the mesorectum around a rectal cancer is involved or threatened (only 1–2 mm of clearance), there is a very high likelihood of local recurrence and a poor prognosis. This circumferential or radial margin is probably best assessed preoperatively by MRI. Although nodal involvement is the single most important prognostic factor in colorectal carcinoma, tumor characteristics, such as degree of differentiation, mucinous or signet-ring cell histology, vascular invasion, and DNA aneuploidy, also adversely affect prognosis. Molecular profiling is currently being studied in an effort to further improve prognostic indicators.

Preoperative Evaluation

Once a colon or rectal carcinoma has been diagnosed, a staging evaluation should be undertaken. The colon must be evaluated for synchronous tumors, usually by colonoscopy. Synchronous disease will be present in up to 5% of patients. For rectal cancers, digital rectal examination and rigid or flexible proctoscopy with biopsy should be performed to assess tumor size, location, morphology, histology, and fixation. Endorectal ultrasound or MRI can be invaluable in staging rectal cancer and is used to classify the ultrasound T and N stage of rectal cancers (Fig. 29-24). A chest/abdominal/pelvic CT scan should be obtained to evaluate for distant metastases. Pelvic CT scan, and sometimes MRI, can be useful in large rectal tumors and in recurrent disease to determine the extent of local invasion. Among patients with obstructive symptoms, a water-soluble contrast study (Gastrografin enema) may be useful for delineating the degree of obstruction. It is important to avoid mechanical bowel preparation (for either colonoscopy or surgery) in a patient who appears to be obstructed. PET scan may be useful in evaluating lesions seen on CT scan and in patients in whom a risky or highly morbid operation is planned (pelvic exenteration, sacrectomy). Preoperative CEA is often obtained and may be useful for postoperative follow-up.

Therapy for Colonic Carcinoma

Principles of Resection

The objective in treatment of carcinoma of the colon is to remove the primary tumor along with its lymphovascular supply. Because the lymphatics of the colon accompany the main arterial supply, the length of bowel resected depends on which vessels are supplying the segment involved with the cancer. Any adjacent organ or tissue, such as the omentum, that has been invaded should be resected en bloc with the tumor. If all of the tumor cannot be removed, a palliative procedure should be considered, although it important to note that “debulking” is rarely effective in colorectal adenocarcinoma.

The presence of synchronous cancers or adenomas or a strong family history of colorectal neoplasms suggests that the entire colon is at risk for carcinoma (often called a field defect), and a subtotal or total colectomy should be considered. Metachronous tumors (a second primary colon cancer) identified during follow-up studies should be treated similarly. However, the surgeon must be aware of which mesenteric vessels have been ligated at the initial colectomy because that may influence the choice of procedure.

The number of lymph nodes recovered in the surgical specimen has long served as a proxy for the oncologic adequacy of resection. A number of studies previously have suggested that a minimum of 12 lymph nodes in the resected specimen are necessary for adequate staging. In addition, patients in whom more nodes are harvested have better long-term outcome.^76,77 As such, a 12-node minimum has been suggested as an appropriate benchmark for assessing quality of care. However, several investigators recently have called this into question, noting that the number of lymph nodes examined does not correlate with staging, use of adjuvant chemotherapy, or patient survival.⁷⁰ Others have suggested that the number of negative lymph nodes and/or the lymph node ratio (positive lymph nodes to total lymph nodes) may further improve staging.^77,78,79

If unexpected metastatic disease is encountered at the time of a laparotomy, the decision about whether to proceed with resection of the primary tumor depends on the volume of distant disease, location and size of the primary tumor, the operation required to remove the primary tumor, and the operative approach. If the metastatic disease is low volume (isolated or potentially resectable liver lesions) and the resection of the primary tumor is straightforward (segmental abdominal colectomy), it is probably reasonable to proceed with resection. On the other hand, if the metastatic disease is high volume (carcinomatosis), especially if the primary tumor is minimally symptomatic, the operation should be aborted in order to facilitate early systemic chemotherapy. Some centers favor starting the operation with a diagnostic laparoscopy in cases where risk of discovering metastasis is high in order to minimize the magnitude of the operation should surgery be aborted. With recent advances in chemotherapy, many of these patients will never develop a complication from the primary tumor requiring surgical intervention.⁸¹

Other palliative approaches include a bypass or proximal stoma for obstructing lesions.

Stage-Specific Therapy

Stage 0 (Tis, N0, M0)

Polyps containing carcinoma in situ (high-grade dysplasia) carry no risk of lymph node metastasis. However, the presence of high-grade dysplasia increases the risk of finding an invasive carcinoma within the polyp. For this reason, these polyps should be excised completely, and pathologic margins should be free of dysplasia. Most pedunculated polyps and many sessile polyps may be completely removed endoscopically. These patients should be followed with frequent colonoscopy to ensure that the polyp has not recurred and that an invasive carcinoma has not developed. In cases where the polyp cannot be removed entirely, a segmental resection is recommended.

Stage I: The Malignant Polyp (T1, N0, M0)

Occasionally a polyp that was thought to be benign will be found to harbor invasive carcinoma after polypectomy. Treatment of a malignant polyp is based on the risk of local recurrence and the risk of lymph node metastasis.⁶⁴ The risk of lymph node metastases depends primarily on the depth of invasion. Invasive carcinoma in the head of a pedunculated polyp with no stalk involvement carries a low risk of metastasis (<1%) and may be completely resected endoscopically. However, lymphovascular invasion, poorly differentiated histology, or tumor within 1 mm of the resection margin greatly increases the risk of local recurrence and metastatic spread. Segmental colectomy is then indicated. Invasive carcinoma arising in a sessile polyp extends into the submucosa and is usually best treated with segmental colectomy (Fig. 29-25).

Stages I and II: Localized Colon Carcinoma (T1-3, N0, M0)

The majority of patients with stages I and II colon cancer will be cured with surgical resection. Few patients with completely resected stage I disease will develop either local or distant recurrence, and adjuvant chemotherapy does not improve survival in these patients. However, up to 46% of patients with completely resected stage II disease will ultimately die from colon cancer. For this reason, adjuvant chemotherapy has been suggested for selected patients with stage II disease (young patients, tumors with “high-risk” histologic findings). It remains controversial as to whether chemotherapy improves survival rates in these patients. Molecular profiling holds promise for improving patient selection in these early cancers.

Stage III: Lymph Node Metastasis (Tany, N1, M0)

Patients with lymph node involvement are at significant risk for both local and distant recurrence, and adjuvant chemotherapy has been recommended routinely in these patients. 5-Fluorouracil–based regimens (with leucovorin) and oxaliplatin (FOLFOX) reduce recurrences and improve survival in this patient population.⁶⁹ It is important to note, however, that a subgroup of patients with stage III disease will do well without chemotherapy. MSI status in particular predicts good prognosis. Subset analysis from the CRYSTAL trial has shown that patients with MSI-high stage III disease do not benefit from 5-fluorouracil–based chemotherapy. Molecular profiling, therefore, may be helpful in determining which stage III patients can safely avoid systemic chemotherapy.⁸²

Stage IV: Distant Metastasis (Tany, Nany, M1)

Survival is extremely limited in stage IV colon carcinoma. However, unlike many other malignancies, highly selected patients with isolated, resectable metastases may benefit from resection (metastasectomy). The most common site of metastasis is the liver. Of patients with systemic disease, approximately 15% will have metastases limited to the liver. Of these, 20% are potentially resectable for cure. Survival is improved in these patients (20% –40% 5-year survival) when compared to patients who do not undergo resection. Hepatic resection of synchronous metastases from colorectal carcinoma may be performed as a combined procedure or in two stages. All patients require adjuvant chemotherapy. The second most common site of metastasis is the lung, occurring in approximately 20% of patients with colorectal carcinoma. Although very few of these patients will be potentially resectable, among those who are (about 1%–2% of all colorectal cancer patients), long-term survival benefit is approximately 30% to 40%.⁸³ There are limited reports of successful resection of metastases in other sites (ovary and retroperitoneum are most common).

The remainder of patients with stage IV disease cannot be cured surgically, and therefore, the focus of treatment should be palliation.⁸⁴ Methods such as colonic stenting for obstructing lesions of the left colon also provide good palliation. More limited surgical intervention such as a diverting stoma or bypass procedure may be appropriate in patients with stage IV disease who develop obstruction. Hemorrhage in an unresectable tumor can sometimes be controlled with angiographic embolization. External beam radiation also has been used for palliation.

Therapy for Rectal Carcinoma

Principles of Resection

The biology of rectal adenocarcinoma is thought to be identical to the biology of colonic adenocarcinoma, and the operative principles of complete resection of the primary tumor, its lymphatic bed, and any other involved organ apply to surgical resection of rectal carcinoma. However, the anatomy of the pelvis and proximity of other structures (ureters, bladder, prostate, vagina, iliac vessels, and sacrum) make resection more challenging and often require a different approach than for colonic adenocarcinoma. Moreover, it is more difficult to achieve negative radial margins in rectal cancers that extend through the bowel wall because of the anatomic limitations of the pelvis. Therefore, local recurrence is higher than with similar stage colon cancers. However, unlike the intraperitoneal colon, the relative paucity of small bowel and other radiation-sensitive structures in the pelvis makes it easier to treat rectal tumors with radiation. Therapeutic decisions, therefore, are based on the location and depth of the tumor and its relationship to other structures in the pelvis.

Local Therapy

The distal 10 cm of the rectum are accessible transanally. For this reason, several local approaches have been proposed for treating rectal neoplasms. Transanal excision (full thickness or mucosal) is an excellent approach for noncircumferential, benign, villous adenomas of the rectum. Transanal endoscopic microsurgery (TEM) and transanal minimally invasive surgery (TAMIS) make use of a specially designed proctoscope, magnifying system, and instruments similar to those used in laparoscopy to allow local excision of lesions higher in the rectum (up to 15 cm). Although this technique has been used for selected T1, and some T2, carcinomas, local excision does not allow pathologic examination of the lymph nodes and might therefore understage patients. Moreover, local recurrence rates are high after transanal excision, and salvage surgery, while often curative, is associated with poorer survival than with initial radical surgery. Local excision of any rectal neoplasm should be considered an excisional biopsy because final pathologic examination of the specimen may reveal an invasive carcinoma that then mandates more radical therapy.

Ablative techniques, such as electrocautery or endocavitary radiation, also have been used. The disadvantage of these techniques is that no pathologic specimen is retrieved to confirm the tumor stage. Fulguration is generally reserved for extremely high-risk patients with a limited life span who cannot tolerate more radical surgery.

Radical Resection

Radical resection is preferred to local therapy for most rectal carcinomas. Radical resection involves removal of the involved segment of the rectum along with its lymphovascular supply. Although any microscopically negative margin has been suggested to be adequate, most surgeons still attempt to obtain a 2-cm distal mural margin for curative resections.

Total mesorectal excision (TME) is a technique that uses sharp dissection along anatomic planes to ensure complete resection of the rectal mesentery during low and extended low anterior resections. For upper rectal or rectosigmoid resections, a partial mesorectal excision of at least 5 cm distal to the tumor appears adequate. TME both decreases local recurrence rates and improves long-term survival rates. Moreover, this technique is associated with less blood loss and less risk to the pelvic nerves and presacral plexus than is blunt dissection. The principles of TME should be applied to all radical resections for rectal cancer.

Recurrence of rectal cancer generally has a poor prognosis. Extensive involvement of other pelvic organs (usually occurring in the setting of tumor recurrence) may require a pelvic exenteration. The rectal and perineal portions of this operation are similar to an APR, but en bloc resection of the ureters, bladder, and prostate or uterus and vagina are also performed. A permanent colostomy and an ileal conduit to drain the urinary tract may be necessary. The sacrum may also be resected if necessary (sacrectomy) up to the level of the S2-S3 junction. These operations are best performed in tertiary centers with multidisciplinary teams consisting of a colon and rectal surgeon, urologist, neurosurgeon, and plastic surgeon.

Stage-Specific Therapy

(Fig. 29-26).

Pretreatment staging of rectal carcinoma often relies on endorectal ultrasound to determine the T and N status of a rectal cancer. Ultrasound is highly accurate at assessing tumor depth, but less accurate in diagnosing nodal involvement. Ultrasound evaluation can guide choice of therapy in most patients. MRI is useful to assess mesorectal involvement. When the radial margin is threatened or involved, neoadjuvant chemoradiation is recommended.

Stage 0 (Tis, N0, M0)

Villous adenomas harboring carcinoma in situ (high-grade dysplasia) are ideally treated with local excision. A 1-cm margin should be obtained. Rarely, radical resection will be necessary if transanal excision is not technically possible (large circumferential lesions).

Stage I: Localized Rectal Carcinoma (T1-2, N0, M0)

Although local excision has been used for small, favorable sessile uT1N0 and uT2N0 rectal cancers, local recurrence rates may be as high as 20% and 40%, respectively. For this reason, radical resection is strongly recommended in all good-risk patients. Lesions with unfavorable histologic characteristics and those located in the distal third of the rectum, in particular, are prone to recurrence. In high-risk patients and in patients who refuse radical surgery because of the risk of need for a permanent colostomy, local excision may be adequate, but strong consideration should be given to adjuvant or neoadjuvant chemoradiation to improve local control. The efficacy of adjuvant or neoadjuvant chemoradiation followed by transanal excision in patients who can tolerate radical surgery has been controversial. Early results from ACOSOG Z6041, in which patients with T2 rectal cancers received neoadjuvant chemoradiation followed by transanal excision, showed a pathologic complete response rate of 44%. Long-term outcomes, however, are not yet known.⁸⁵

Locally Advanced Rectal Cancer (Stages II and III)

Stage II: Localized Rectal Carcinoma (T3-4, N0, M0)

Larger rectal tumors, especially if located in the distal rectum, are more likely to recur locally. There are two schools of thought, each differing in their approach to control local recurrences. Advocates of total mesorectal resection suggest that optimization of operative technique will obviate the need for any adjuvant chemoradiation to control local recurrence after resection of stages I, II, and III rectal cancers. The opposing school suggests that stages II and III rectal cancers will benefit from chemoradiation. They argue that such therapy reduces local recurrences and prolongs survival whether given preoperatively or postoperatively. The advantages of preoperative chemoradiation include tumor shrinkage, increased likelihood of resection and of a sphincter-sparing procedure, tumor downstaging by treating locally involved lymph nodes, and decreased risk to the small intestine. Disadvantages include possible overtreatment of early-stage tumors, impaired wound healing, and pelvic fibrosis increasing the risk of operative complications. Postoperative radiation allows accurate pathologic staging of the resected tumor and lymph nodes and avoids the wound healing problems associated with preoperative radiation. However, bulky tumors, tumors involving adjacent organs, and very low rectal tumors may be much more difficult to resect without preoperative radiation and may require a more extensive operation.

Stage III: Lymph Node Metastasis (Tany, N1, M0)

Many surgeons now recommend chemotherapy and radiation either pre- or postoperatively for node-positive rectal cancers. The advantages and disadvantages are similar to those listed for stage II disease, except that the likelihood of overtreating an early-stage lesion is considerably less.

Over the past two decades, a wide variety of studies have addressed the issue of adjuvant and neoadjuvant therapy for locally advanced rectal cancer. Many of these studies demonstrated both improved local control and prolonged survival and resulted in the 1990 National Institutes of Health (NIH) consensus conference recommendation for postoperative chemoradiation therapy in these patients. There is little controversy regarding chemoradiation therapy for stage III (node-positive) disease. However, advances in surgical technique, such as TME, for locally advanced node-negative cancers (T3-4, N0; stage II) have improved local control with surgery alone, prompting some to abandon adjuvant chemoradiation in these patients, especially for those with cancers in the proximal rectum. Although the data from these studies are intriguing, other reports have shown that chemoradiation improves local control and survival even in patients who undergo TME. Thus, most colorectal surgeons in the United States continue to recommend adjuvant or neoadjuvant therapy for patients with locally advanced disease. Many European surgeons now rely heavily on MRI staging to determine the need for neoadjuvant chemoradiation. They use neoadjuvant chemoradiation if the radial margin is threatened or involved by the cancer or if anal sphincter or other local organ invasion is present. In the United States, chemoradiation therapy is still recommended for all patients with stage III disease and the majority of patients with stage II disease. In select patients with T3 tumors, favorable histology, and negative radial margins, chemoradiation may not be necessary, but larger prospective studies are required before this approach can be recommended.

Appropriate timing of chemoradiation for locally advanced rectal cancer has been debated. Historically, preoperative chemoradiation has been advocated based on tumor shrinkage/downstaging, improved resectability, and the possibility of performing a sphincter-sparing operation in some patients. In addition, the absence of small bowel adhesions in the pelvis may decrease toxicity. However, preoperative radiation therapy may increase operative complications and impairs wound healing. Although preoperative endorectal ultrasound and MRI have improved our ability to stage rectal cancer, clinical “overstaging” can be problematic, and neoadjuvant therapy may therefore overtreat patients with pT1-2, N0 tumors. Advocates of postoperative radiation therapy cite more accurate pathologic staging and fewer operative/postoperative complications. However, large, bulky tumors may be unresectable or require a more extensive operation (APR, pelvic exenteration) without preoperative therapy. In addition, postoperative pelvic radiation may compromise function of the neorectum.

Comparisons of perioperative toxicity and oncologic outcome have been addressed by the German CAO/ARO/AIO-94 trial. In this study, pre- and postoperative chemoradiation were associated with equivalent acute toxicity and equivalent postoperative complication rates. Postoperative chemoradiation, however, doubled the risk of postoperative stricture formation. In addition, preoperative chemoradiation halved the risk of local recurrence (6% vs. 12%). Based on these data, most surgeons consider preoperative chemoradiation to be the most appropriate therapy for locally advanced rectal cancer.⁸⁶

Stage IV: Distant Metastasis (Tany, Nany, M1)

Like stage IV colon carcinoma, survival is limited in patients with distant metastasis from rectal carcinoma. Isolated hepatic and/or pulmonary metastases are rare, but when present may be resected for cure in selected patients.⁸³ Some patients will require palliative procedures. Radical resection may be required to control pain, bleeding, or tenesmus, but highly morbid procedures such as pelvic exenteration and sacrectomy should generally be avoided in this setting. Local therapy using cautery, endocavitary radiation, or laser ablation may be adequate to control bleeding or prevent obstruction. Intraluminal stents may be useful in the uppermost rectum but often cause pain and tenesmus lower in the rectum. Occasionally, a proximal diverting colostomy will be required to alleviate obstruction. A mucus fistula should be created if possible to vent the distal colon. It is critical that the morbidity of any procedure be realistically weighed against potential benefit in these patients with limited life expectancy. The assistance of a palliative care team can be invaluable in this setting.⁸⁴

Follow-Up and Surveillance

Patients who have been treated for one colorectal cancer are at risk for the development of recurrent disease (either locally or systemically) or metachronous disease (a second primary tumor). In theory, metachronous cancers should be preventable by using surveillance colonoscopy to detect and remove polyps before they progress to invasive cancer. For most patients, a colonoscopy should be performed within 12 months after the diagnosis of the original cancer (or sooner if the colon was not examined in its entirety prior to the original resection). If that study is normal, colonoscopy should be repeated every 3 to 5 years thereafter.

The optimal method of following patients for recurrent cancer remains controversial. The goal of close follow- up observation is to detect resectable recurrence and to improve survival. Re-resection of local recurrence and resection of distant metastasis to liver, lung, or other sites are often technically challenging and highly morbid, with only a limited chance of achieving long-term survival. Thus, only selected patients who would tolerate such an approach should be followed intensively. Because most recurrences occur within 2 years of the original diagnosis, surveillance focuses on this time period. Patients who have undergone local resection of rectal tumors probably also should be followed with frequent endoscopic examinations (every 3–6 months for 3 years, then every 6 months for 2 years). CEA is often followed every 3 to 6 months for 2 years. CT scans are often performed annually for 5 years, but there are few data to support this practice. More intensive surveillance is appropriate in high-risk patients such as those with possible HNPCC syndrome or T3, N+ cancers. Although intensive surveillance improves detection of resectable recurrences, it is important to note that a survival benefit has never been proven. Therefore, the risks and benefits of intensive surveillance must be weighed and treatment individualized.

Treatment of Recurrent Colorectal Carcinoma

Between 20% and 40% of patients who have undergone curative intent surgery for colorectal carcinoma will eventually develop recurrent disease. Most recurrences occur within the first 2 years after the initial diagnosis, but preoperative chemoradiation therapy may delay recurrence. While most of these patients will present with distant metastases, a small proportion will have isolated local recurrence and may be considered for salvage surgery. Recurrence after colon cancer resection usually occurs at the local site within the abdomen or in the liver or lungs. Resection of other involved organs may be necessary. Recurrence of rectal cancer can be considerably more difficult to manage because of the proximity of other pelvic structures. If the patient has not received chemotherapy and radiation, then adjuvant therapy should be administered prior to salvage surgery. Radical resection may require extensive resection of pelvic organs (pelvic exenteration with or without sacrectomy). Ideally, the aim of a salvage operation should be to resect all of the tumor with negative margins. However, if the ability to achieve a negative margin is in question, the addition of intraoperative radiation therapy (usually brachytherapy) can help improve local control. Pelvic MRI is useful for identifying tumor extension that would prevent successful resection (extension of tumor into the pelvic sidewall, involvement of the iliac vessels or bilateral sacral nerves, sacral invasion above the S2-S3 junction). Patients should also undergo a thorough preoperative evaluation to identify distant metastases (CT of chest, abdomen, and pelvis, and PET scan) before undergoing such an extensive procedure. Nevertheless, radical salvage surgery can prolong survival in selected patients.

Minimally Invasive Techniques For Resection

Laparoscopic colectomy for cancer has been controversial. Early reports of high port site recurrence dampened enthusiasm for this technique.⁸⁷ The ability to perform an adequate oncologic resection for cancer has also been questioned. Several trials have laid to rest many of these fears. The Clinical Outcomes of Surgical Therapy Study Group (COST), the Colon Carcinoma Laparoscopic or Open Resection (COLOR) trial, and the United Kingdom Medical Research Council Conventional versus Laparoscopic-Assisted Surgery in Colorectal Cancer (CLASSICC) trial all have shown oncologic equivalence between open and laparoscopic techniques. In these multi-institutional studies, the rates of cancer recurrence, survival, and quality of life were similar, suggesting that, in the hands of an appropriately trained surgeon, laparoscopic colectomy is appropriate for cancer.^87,88,89 The recent introduction of robotic surgery offers an additional minimally invasive approach. Early studies suggest that robotic surgery may be the oncologic equivalent to laparoscopic surgery for colorectal cancer. A prospective, randomized, multicenter trial, Robotic versus Laparoscopic Resection for Rectal Cancer (ROLARR) is under way in hopes of answering this question.⁹¹

Rare Colorectal Tumors

Carcinoid Tumors

Carcinoid tumors occur most commonly in the gastrointestinal tract, and up to 25% of these tumors are found in the rectum. Most small rectal carcinoids are benign, and overall survival is greater than 80%. However, the risk of malignancy increases with size, and more than 60% of tumors greater than 2 cm in diameter are associated with distant metastases. Rectal carcinoids appear to be less likely to secrete vasoactive substances than carcinoids in other locations, and carcinoid syndrome is uncommon in the absence of hepatic metastases. Small carcinoids can be locally resected transanally. Larger tumors or tumors with obvious invasion into the muscularis require more radical surgery. Carcinoid tumors in the proximal colon are less common and are more likely to be malignant. Size also correlates with risk of malignancy, and tumors less than 2 cm in diameter rarely metastasize. However, the majority of carcinoid tumors in the proximal colon present as bulky lesions, and up to two thirds of patients will have metastatic spread at the time of diagnosis. These tumors should usually be treated with radical resection. Because carcinoid tumors are typically slow growing, patients with distant metastases may expect reasonably long survival. Symptoms of carcinoid syndrome can often be alleviated with somatostatin analogues (octreotide) and/or interferon-α. Tumor debulking can offer effective palliation in selected patients.

Carcinoid Carcinomas

Composite carcinoid carcinomas (adenocarcinoids) have histologic features of both carcinoid tumors and adenocarcinomas. The natural history of these tumors more closely parallels that of adenocarcinomas than carcinoid tumors, and regional and systemic metastases are common. Carcinoid carcinoma of the colon and rectum should be treated according to the same oncologic principles as followed for management of adenocarcinoma.

Lipomas

Lipomas occur most commonly in the submucosa of the colon and rectum. They are benign lesions, but rarely may cause bleeding, obstruction, or intussusception, especially when greater than 2 cm in diameter. Small asymptomatic lesions do not require resection. Larger lipomas should be resected by colonoscopic techniques or by a colotomy and enucleation or limited colectomy.

Lymphoma

Lymphoma involving the colon and rectum is rare but accounts for about 10% of all gastrointestinal lymphomas. The cecum is most often involved, probably as a result of spread from the terminal ileum. Symptoms include bleeding and obstruction, and these tumors may be clinically indistinguishable from adenocarcinomas. Bowel resection is the treatment of choice for isolated colorectal lymphoma. Adjuvant therapy may be given based on the stage of disease.

Leiomyoma and Leiomyosarcoma

Leiomyomas are benign tumors of the smooth muscle of the bowel wall and occur most commonly in the upper gastrointestinal tract. Most patients are asymptomatic, but large lesions can cause bleeding or obstruction. Because it is difficult to differentiate a benign leiomyoma from a malignant leiomyosarcoma, these lesions should be resected. Recurrence is common after local resection, but most small leiomyomas can be adequately treated with limited resection. Lesions larger than 5 cm should be treated with radical resection because the risk of malignancy is high.

Leiomyosarcoma is rare in the gastrointestinal tract. When this malignancy occurs in the large intestine, the rectum is the most common site. Symptoms include bleeding and obstruction. A radical resection is indicated for these tumors.

Gastrointestinal Stromal Tumor

These rare tumors occur most commonly in the stomach and small intestine, but 5% to 10% arise in the colon or rectum. They are often mistaken for leiomyomas. Thirty percent to 50% are malignant; thus all lesions should be resected.

Retrorectal/Presacral Tumors

Tumors occurring in the retrorectal space are rare. This region lies between the upper two thirds of the rectum and the sacrum above the rectosacral fascia. It is bound by the rectum anteriorly, the presacral fascia posteriorly, and the endopelvic fascia laterally (lateral ligaments). The retrorectal space contains multiple embryologic remnants derived from a variety of tissues (neuroectoderm, notochord, and hindgut). Tumors that develop in this space are often heterogeneous.

Congenital lesions are most common, comprising almost two thirds of retrorectal lesions. The remainder are classified as neurogenic, osseous, inflammatory, or miscellaneous lesions. Malignancy is more common in the pediatric population than in adults, and solid lesions are more likely to be malignant than are cystic lesions. Inflammatory lesions may be solid or cystic (abscess) and usually represent extensions of infection either in the perirectal space or in the abdomen.

Developmental cysts constitute the majority of congenital lesions and may arise from all three germ cell layers. Dermoid and epidermoid cysts are benign lesions that arise from the ectoderm. Enterogenous cysts arise from the primitive gut. Anterior meningocele and myelomeningocele arise from herniation of the dural sac through a defect in the anterior sacrum. A “scimitar sign” (sacrum with a rounded, concave border without any bony destruction) is the pathognomonic radiographic appearance of this condition.

Solid lesions include teratomas, chordomas, neurologic tumors, or osseous lesions. Teratomas are true neoplasms and contain tissue from each germ cell layer. They often contain both cystic and solid components. Teratomas are more common in children than in adults, but when found in adults, 30% are malignant. Chordomas arise from the notochord and are the most common malignant tumor in this region. These are slow-growing, invasive cancers that show characteristic bony destruction. Neurogenic tumors include neurofibromas and sarcomas, neurilemomas, ependymomas, and ganglioneuromas. Osseous lesions include osteomas and bone cysts, as well as neoplasms such as osteogenic sarcoma, Ewing’s tumor, chondromyxosarcoma, and giant cell tumors.

Patients may present with pain (lower back, pelvic, or lower extremity), gastrointestinal symptoms, or urinary tract symptoms. Most lesions are palpable on digital rectal examination. While plain X-rays and CT scans often are used to evaluate these lesions, pelvic MRI is the most sensitive and specific imaging study. Myelogram is occasionally necessary if there is central nervous system involvement. Treatment is almost always surgical resection. The approach depends in part on the nature of the lesion and its location. Lesions high in the pelvis may be approached via a transabdominal route, whereas low lesions may be resected transsacrally. Intermediate lesions may require a combined abdominal and sacral operation. Although survival is excellent after resection of benign lesions, local recurrence is not uncommon. Prognosis after resection of malignant lesions is highly variable and reflects the biology of the underlying tumor.

The role of biopsy in this setting has been controversial. Historically, the recommendation was to avoid biopsy because of the risk of infection or needle tract seeding. This recommendation has recently been challenged, especially for large and/or unusual tumors that would be better treated with multimodality neoadjuvant therapy (sarcomas, for example). A recent study confirmed the utility of needle biopsy of solid lesions and refuted concerns about needle tract seeding.⁹² As such, most solid lesions should be biopsied regardless of resectability. Biopsy of cystic lesions, especially meningoceles, should still be avoided because of the risk of infection.

Anal Canal and Perianal Tumors

Cancers of the anal canal are uncommon and account for approximately 2% of all colorectal malignancies. Neoplasms of the anal canal have traditionally been divided into those affecting the anal margin (distal to the dentate line) and those affecting the anal canal (proximal to the dentate line) based on lymphatic drainage patterns. Lymphatics from the anal canal proximal to the dentate line drain cephalad via the superior rectal lymphatics to the inferior mesenteric nodes and laterally along both the middle rectal vessels and inferior rectal vessels through the ischiorectal fossa to the internal iliac nodes. Lymph from the anal canal distal to the dentate line usually drains to the inguinal nodes. It can also drain to the superior rectal lymph nodes or along the inferior rectal lymphatics to the ischiorectal fossa if primary drainage routes are blocked with tumor (Fig. 29-27).

A more clinically useful classification divides anal lesions into those that are perianal (can be completely visualized with gentle eversion of the buttocks) and those that are intra-anal (cannot be completely visualized with gentle eversion of the buttocks). In many cases, therapy depends on whether the tumor is perianal or intra-anal.

Squamous Intraepithelial Lesions

Anal canal and perianal dysplasia have long had a potpourri of nomenclature. Anal intraepithelial neoplasia (AIN), Bowen’s disease, and carcinoma in situ all refer to human papillomavirus (HPV)–induced dysplasia. Because these entities are pathologically identical, there has been a recent effort to standardize nomenclature. High-grade squamous intraepithelial lesions (HSIL) include high- and intermediate-grade dysplasia, AIN2 and AIN3, Bowen’s disease, and carcinoma in situ. Low-grade squamous intraepithelial lesions (LSIL) include low-grade dysplasia and AIN1.⁹³

HSIL is a precursor to an invasive squamous cell carcinoma (epidermoid carcinoma). HSIL may appear as a plaque-like lesion or may only be apparent with high-resolution anoscopy and application of acetic acid or Lugol’s iodine solution. Both HSIL and LSIL are associated with infection with HPV, especially types 16 and 18. The incidence of both squamous intraepithelial lesions and epidermoid carcinoma of the anus has increased dramatically among human immunodeficiency virus (HIV)–positive, homosexual men. This increase is thought to result from increased rates of HPV infection along with HIV-induced immunosuppression. Treatment of HSIL is ablation. Because of a high recurrence and/or reinfection rate, these patients require extremely close surveillance. High-risk patients should be followed with frequent anal Papanicolaou (Pap) smears every 3 to 6 months. An abnormal Pap smear should be followed by an examination under anesthesia and anal mapping using high-resolution anoscopy. High-resolution anoscopy shows areas with abnormal telangiectasias that are consistent with high-grade dysplasia (HSIL). Many centers now consider this technique for repeated ablation of HSIL to be the optimal method for following these patients. It should be noted, however, that the practice has not been universally adopted, and it is unclear whether close surveillance in lower risk (nonimmunosuppressed) patients is necessary. Rarely, extensive disease may require resection with flap closure. Medical therapy for HPV has also been proposed. Topical immunomodulators such as imiquimod (Aldara) have been shown to induce regression in some series.⁹⁴ Topical 5-fluorouracil has also been used in this setting. Finally, the introduction of a vaccine against HPV may help decrease the incidence of this disease in the future.

Epidermoid Carcinoma

Epidermoid carcinoma of the anus includes squamous cell carcinoma, cloacogenic carcinoma, transitional carcinoma, and basaloid carcinoma. The clinical behavior and natural history of these tumors are similar. Epidermoid carcinoma is a slow-growing tumor and usually presents as an intra-anal or perianal mass. Pain and bleeding may be present. Perianal epidermoid carcinoma may be treated in a similar fashion as squamous cell carcinoma of the skin in other locations because wide local excision can usually be achieved without resecting the anal sphincter. Intra-anal epidermoid carcinoma cannot be excised locally, and first-line therapy relies on chemotherapy and radiation (the Nigro protocol: 5-fluorouracil, mitomycin C, and 30 Gy of external beam radiation). More than 80% of these tumors can be cured by using this regimen. Recurrence usually requires radical resection (APR). Metastasis to inguinal lymph nodes is a poor prognostic sign.

Verrucous Carcinoma (Buschke-Lowenstein Tumor, Giant Condyloma Acuminata)

Verrucous carcinoma is a locally aggressive form of condyloma acuminata. Although these lesions do not metastasize, they can cause extensive local tissue destruction and may be grossly indistinguishable from epidermoid carcinoma. Wide local excision is the treatment of choice when possible, but radical resection may sometimes be required. Very large lesions may respond to external beam radiation, but resection is almost always required.

Basal Cell Carcinoma

Basal cell carcinoma of the anus is rare and resembles basal cell carcinoma elsewhere on the skin (raised, pearly edges with central ulceration). This is a slow-growing tumor that rarely metastasizes. Wide local excision is the treatment of choice, but recurrence occurs in up to 30% of patients. Radical resection and/or radiation therapy may be required for large lesions.

Adenocarcinoma

Adenocarcinoma of the anus is extremely rare and usually represents downward spread of a low rectal adenocarcinoma. Adenocarcinoma may occasionally arise from the anal glands or may develop in a chronic fistula. Radical resection with or without adjuvant chemoradiation is usually required.

Extramammary perianal Paget’s disease is adenocarcinoma in situ arising from the apocrine glands of the perianal area. The lesion is typically plaque-like and may be indistinguishable from HSIL. Characteristic Paget’s cells are seen histologically. These tumors are often associated with a synchronous gastrointestinal adenocarcinoma, so a complete evaluation of the intestinal tract should be performed. Wide local excision is usually adequate treatment for perianal Paget’s disease.

Melanoma

Anorectal melanoma is rare, comprising less than 1% of all anorectal malignancies and 1% to 2% of melanomas. Despite many advances in the treatment of melanoma, prognosis for patients with anorectal disease remains poor. Overall 5-year survival is less than 10%, and many patients present with systemic metastasis and/or deeply invasive tumors at the time of diagnosis. A few patients with anorectal melanoma, however, present with isolated local or locoregional disease that is potentially resectable for cure, and both radical resection (APR) and wide local excision have been advocated. Recurrence is common and usually occurs systemically regardless of the initial surgical procedure. Local resection with free margins does not increase the risk of local or regional recurrence, and APR offers no survival advantage over local excision. Because of the morbidity associated with APR, wide local excision is recommended for initial treatment of localized anal melanoma. In some patients, wide local excision may not be technically feasible, and APR may be required if the tumor involves a significant portion of the anal sphincter or is circumferential. The addition of adjuvant chemotherapy, biochemotherapy, vaccines, or radiotherapy may be of benefit in some patients, but efficacy remains unproven.⁹⁵

Rectal Prolapse and Solitary Rectal Ulcer Syndrome

Rectal Prolapse

Rectal prolapse refers to a circumferential, full-thickness protrusion of the rectum through the anus and has also been called “first-degree” prolapse, “complete” prolapse, or procidentia. Internal prolapse occurs when the rectal wall intussuscepts but does not protrude and is probably more accurately described as internal intussusception. Mucosal prolapse is a partial-thickness protrusion often associated with hemorrhoidal disease and is usually treated with banding or hemorrhoidectomy.

In adults, this condition is far more common among women, with a female-to-male ratio of 6:1. Prolapse becomes more prevalent with age in women and peaks in the seventh decade of life. In men, prevalence is unrelated to age. Symptoms include tenesmus, a sensation of tissue protruding from the anus that may or may not spontaneously reduce, and a sensation of incomplete evacuation. Mucus discharge and leakage may accompany the protrusion. Patients also present with a myriad of functional complaints, from incontinence and diarrhea to constipation and outlet obstruction.

A thorough preoperative evaluation, including colonic transit studies, anorectal manometry, tests of pudendal nerve terminal motor latency, EMG, and cinedefecography, may be useful. The colon should be evaluated by colonoscopy, air-contrast barium enema, or CT colonography to exclude neoplasms or diverticular disease. Cardiopulmonary condition should be thoroughly evaluated because comorbidities may influence the choice of surgical procedure.

The primary therapy for rectal prolapse is surgery, and more than 100 different procedures have been described to treat this condition. Operations can be categorized as either abdominal or perineal. Abdominal operations have taken three major approaches: (a) reduction of the perineal hernia and closure of the cul-de-sac (Moschowitz repair); (b) fixation of the rectum, either with a prosthetic sling (Ripsten and Wells rectopexy) or by suture rectopexy; or (c) resection of redundant sigmoid colon (Fig. 29-28). In some cases, resection is combined with rectal fixation (resection rectopexy). Abdominal rectopexy with or without resection also is increasingly performed laparoscopically or robotically. Perineal approaches have focused on tightening the anus with a variety of prosthetic materials, reefing the rectal mucosa (Delorme procedure), or resecting the prolapsed bowel from the perineum (perineal rectosigmoidectomy or Altemeier procedure) (Fig. 29-29).

Because rectal prolapse occurs most commonly in elderly women, the choice of operation depends in part on the patient’s overall medical condition. Abdominal rectopexy (with or without sigmoid resection) offers the most durable repair, with recurrence occurring in less than 10% of patients. Perineal rectosigmoidectomy avoids an abdominal operation and may be preferable in high-risk patients but is associated with a higher recurrence rate. Reefing the rectal mucosa is effective for patients with limited prolapse. Anal encirclement procedures generally have been abandoned.

Solitary Rectal Ulcer Syndrome

Solitary rectal ulcer syndrome and colitis cystica profunda are commonly associated with internal intussusception. Patients may complain of pain, bleeding, mucus discharge, or outlet obstruction. In solitary rectal ulcer syndrome, one or more ulcers are present in the distal rectum, usually on the anterior wall. In colitis cystica profunda, nodules or a mass may be found in a similar location. Evaluation should include anorectal manometry, defecography, and either colonoscopy or barium enema to exclude other diagnoses. Biopsy of an ulcer or mass is mandatory to exclude malignancy or infection due to cytomegalovirus (CMV) in an immunosuppressed patient. Nonoperative therapy (high-fiber diet, defecation training to avoid straining, and laxatives or enemas) is effective in the majority of patients. Biofeedback has also been reported to be effective in some patients. Surgery (either abdominal or perineal repair of prolapse as described earlier) is reserved for highly symptomatic patients who have failed all medical interventions.⁷²

Volvulus

Volvulus occurs when an air-filled segment of the colon twists about its mesentery. The sigmoid colon is involved in up to 90% of cases, but volvulus can involve the cecum (<20%) or transverse colon. A volvulus may reduce spontaneously, but more commonly produces bowel obstruction, which can progress to strangulation, gangrene, and perforation. Chronic constipation may produce a large, redundant colon (chronic megacolon) that predisposes to volvulus, especially if the mesenteric base is narrow.

The symptoms of volvulus are those of acute bowel obstruction. Patients present with abdominal distention, nausea, and vomiting. Symptoms rapidly progress to generalized abdominal pain and tenderness. Fever and leukocytosis are heralds of gangrene and/or perforation. Occasionally, patients will report a long history of intermittent obstructive symptoms and distention, suggesting intermittent chronic volvulus.

Sigmoid Volvulus

Sigmoid volvulus can often be differentiated from cecal or transverse colon volvulus by the appearance of plain X-rays of the abdomen. Sigmoid volvulus produces a characteristic bent inner tube or coffee bean appearance, with the convexity of the loop lying in the right upper quadrant (opposite the site of obstruction). Gastrografin enema shows a narrowing at the site of the volvulus and a pathognomonic bird’s beak (Fig. 29-30).

Unless there are obvious signs of gangrene or peritonitis, the initial management of sigmoid volvulus is resuscitation followed by endoscopic detorsion. Detorsion is usually most easily accomplished by using a rigid proctoscope, but a flexible sigmoidoscope or colonoscope may also be effective. A rectal tube may be inserted to maintain decompression. Although these techniques are successful in reducing sigmoid volvulus in the majority of patients, the risk of recurrence is high (up to 40%). For this reason, an elective sigmoid colectomy should be performed after the patient has been stabilized and undergone an adequate bowel preparation.

Clinical evidence of gangrene or perforation mandates immediate surgical exploration without an attempt at endoscopic decompression. Similarly, the presence of necrotic mucosa, ulceration, or dark blood noted on endoscopy examination suggests strangulation and is an indication for operation. If dead bowel is present at laparotomy, a sigmoid colectomy with end colostomy (Hartmann’s procedure) may be the safest operation to perform.

Cecal Volvulus

Cecal volvulus results from nonfixation of the right colon. In the majority of cases, rotation occurs around the ileocolic blood vessels and vascular impairment occurs early, although 10% to 30% of the cecum folds upon itself (cecal bascule). Plain X-rays of the abdomen show a characteristic kidney-shaped, air-filled structure in the left upper quadrant (opposite the site of obstruction), and a Gastrografin enema confirms obstruction at the level of the volvulus.

Unlike sigmoid volvulus, cecal volvulus can almost never be detorsed endoscopically. Moreover, because vascular compromise occurs early in the course of cecal volvulus, surgical exploration is necessary when the diagnosis is made. Right hemicolectomy with a primary ileocolic anastomosis can usually be performed safely and prevents recurrence. Simple detorsion or detorsion and cecopexy are associated with a high rate of recurrence.

Transverse Colon Volvulus

Transverse colon volvulus is extremely rare. Nonfixation of the colon and chronic constipation with megacolon may predispose to transverse colon volvulus. The radiographic appearance of transverse colon volvulus resembles sigmoid volvulus, but Gastrografin enema will reveal a more proximal obstruction. Although colonoscopic detorsion is occasionally successful in this setting, most patients require emergent exploration and resection.

Megacolon

Megacolon describes a chronically dilated, elongated, hypertrophied large bowel. Megacolon may be congenital or acquired and is usually related to chronic mechanical or functional obstruction. In general, the degree of megacolon is related to the duration of obstruction. Evaluation must always include examination of the colon and rectum (either endoscopically or radiographically) to exclude a surgically correctable mechanical obstruction.

Congenital megacolon caused by Hirschsprung’s disease results from the failure of migration of neural crest cells to the distal large intestine. The resulting absence of ganglion cells in the distal colon results in a failure of relaxation and causes a functional obstruction. The proximal, healthy bowel becomes progressively dilated. Surgical resection of the aganglionic segment is curative. Although Hirschsprung’s disease primarily is a disease of infants and children, it occasionally presents later in adulthood, especially if an extremely short segment of the bowel is affected (ultrashort-segment Hirschsprung’s disease).

Acquired megacolon may result from infection or chronic constipation. Infection with the protozoan Trypanosoma cruzi (Chagas’ disease) destroys ganglion cells and produces both megacolon and megaesophagus. Chronic constipation from slow transit or secondary to medications (especially anticholinergic medications) or neurologic disorders (paraplegia, poliomyelitis, amyotrophic lateral sclerosis, multiple sclerosis) may produce progressive colonic dilatation. Diverting ileostomy or subtotal colectomy with an ileorectal anastomosis is occasionally necessary in these patients.

Colonic Pseudo-obstruction (Ogilvie’s Syndrome)

Colonic pseudo-obstruction (Ogilvie’s syndrome) is a functional disorder in which the colon becomes massively dilated in the absence of mechanical obstruction. Pseudo-obstruction most commonly occurs in hospitalized patients and is associated with the use of narcotics, bed rest, and comorbid disease. Pseudo-obstruction is thought to result from autonomic dysfunction and severe adynamic ileus. The diagnosis is made based on the presence of massive dilatation of the colon (usually predominantly the right and transverse colon) in the absence of a mechanical obstruction. Initial treatment consists of cessation of narcotics, anticholinergics, or other medications that may contribute to ileus. Strict bowel rest and intravenous hydration are crucial. Most patients will respond to these measures. In patients who fail to improve, colonoscopic decompression often is effective. However, this procedure is technically challenging, and great care must be taken to avoid causing perforation. Up to 40% of patients recur. Intravenous neostigmine (an acetylcholinesterase inhibitor) also is extremely effective in decompressing the dilated colon and is associated with a low rate of recurrence (20%). However, neostigmine may produce transient but profound bradycardia and may be inappropriate in patients with cardiopulmonary disease. Because the colonic dilatation is typically greatest in the proximal colon, placement of a rectal tube is rarely effective. It is crucial to exclude mechanical obstruction (usually with a Gastrografin enema) prior to medical or endoscopic treatment.

Ischemic Colitis

Intestinal ischemia occurs most commonly in the colon. Unlike small bowel ischemia, colonic ischemia rarely is associated with major arterial or venous occlusion. Instead, most colonic ischemia appears to result from low flow and/or small vessel occlusion. Risk factors include vascular disease, diabetes mellitus, vasculitis, hypotension, and tobacco use. In addition, ligation of the inferior mesenteric artery during aortic surgery predisposes to colonic ischemia. Occasionally, thrombosis or embolism may cause ischemia. Although the splenic flexure is the most common site of ischemic colitis, any segment of the colon may be affected. The rectum is relatively spared because of its rich collateral circulation.

Signs and symptoms of ischemic colitis reflect the extent of bowel ischemia. In mild cases, patients may have diarrhea (usually bloody) without abdominal pain. With more severe ischemia, intense abdominal pain (often out of proportion to the clinical examination), tenderness, fever, and leukocytosis are present. Peritonitis and/or systemic toxicity are signs of full-thickness necrosis and perforation.

The diagnosis of ischemic colitis is often based on the clinical history and physical examination. Plain films may reveal thumb printing, which results from mucosal edema and submucosal hemorrhage. CT often shows nonspecific colonic wall thickening and pericolic fat stranding. Angiography is usually not helpful because major arterial occlusion is rare. While sigmoidoscopy may reveal characteristic dark, hemorrhagic mucosa, the risk of precipitating perforation is high. For this reason, sigmoidoscopy is relatively contraindicated in any patient with significant abdominal tenderness. Contrast studies (Gastrografin or barium enema) are similarly contraindicated during the acute phase of ischemic colitis.

Treatment of ischemic colitis depends on clinical severity. Unlike ischemia of the small bowel, the majority of patients with ischemic colitis can be treated medically. Bowel rest and broad-spectrum antibiotics are the mainstay of therapy, and 80% of patients will recover with this regimen. Hemodynamic parameters should be optimized, especially if hypotension and low flow appear to be the inciting cause. Long-term sequelae include stricture (10%–15%) and chronic segmental ischemia (15%–20%). Colonoscopy should be performed after recovery to evaluate strictures and to rule out other diagnoses such as inflammatory bowel disease or malignancy. Failure to improve after 2 to 3 days of medical management, progression of symptoms, and deterioration in clinical condition are indications for surgical exploration. In this setting, all necrotic bowel should be resected. Primary anastomosis should be avoided. Occasionally, repeated exploration (a second-look operation) may be necessary.

Infectious Colitis

Pseudomembranous Colitis (Clostridium difficile Colitis)

Pseudomembranous colitis is caused by C. difficile, a gram-positive anaerobic bacillus. C. difficile colitis is extremely common and is the leading cause of nosocomially acquired diarrhea.^6,88 The spectrum of disease ranges from watery diarrhea to fulminant, life-threatening colitis. C. difficile is carried in the large intestine of many healthy adults. Colitis is thought to result from overgrowth of this organism after depletion of the normal commensal flora of the gut with the use of antibiotics. Although clindamycin was the first antimicrobial agent associated with C. difficile colitis, almost any antibiotic may cause this disease. Moreover, although the risk of C. difficile colitis increases with prolonged antibiotic use, even a single dose of an antibiotic may cause the disease. Immunosuppression, medical comorbidities, prolonged hospitalization or nursing home residence, and bowel surgery increase the risk.

The pathogenic changes associated with C. difficile colitis result from production of two toxins: toxin A (an enterotoxin) and toxin B (a cytotoxin). Diagnosis of this disease was traditionally made by culturing the organism from the stool. Detection of one or both toxins (either by cytotoxic assays or by immunoassays) has proven to be more rapid, sensitive, and specific. The diagnosis may also be made endoscopically by detection of characteristic ulcers, plaques, and pseudomembranes.

Management should include immediate cessation of the offending antimicrobial agent. Patients with mild disease (diarrhea but no fever or abdominal pain) may be treated as outpatients with a 10-day course of oral metronidazole. Oral vancomycin is a second-line agent used in patients allergic to metronidazole or in patients with recurrent disease. More severe diarrhea associated with dehydration and/or fever and abdominal pain is best treated with bowel rest, intravenous hydration, and oral metronidazole or vancomycin. Proctosigmoiditis may respond to vancomycin enemas. Recurrent colitis occurs in up to 20% of patients and may be treated by a longer course of oral metronidazole or vancomycin (up to 1 month) or rifaximin (a rapamycin derivative). Reintroduction of normal flora by ingestion of probiotics or stool transplantation has been suggested as a possible treatment for recurrent or refractory disease. Fulminant colitis, characterized by septicemia and/or evidence of perforation, requires emergent laparotomy. A total abdominal colectomy with end ileostomy may be lifesaving. Over the past decade, C. difficile colitis has increased in prevalence, and new, more virulent strains have appeared, making this disease increasingly challenging to treat.⁹⁶

Other Infectious Colitides

A variety of other infections with bacteria, parasites, fungi, or viruses may cause colonic inflammation. Common bacterial infections include enterotoxic E. coli, Campylobacter jejuni, Yersinia enterocolitica, Salmonella typhi, Shigella, and N. gonorrhoeae. Less commonly, Mycobacterium tuberculosis, Mycobacterium bovis, Actinomycosis israelii, or Treponema pallidum (syphilis) may cause colitis or proctitis. Parasitic infections such as amebiasis, cryptosporidiosis, and giardiasis are also relatively common. Fungal infections (Candida species, histoplasmosis) are extremely rare in otherwise healthy individuals. The most common viral infections that produce colitic symptoms are HIV, herpes simplex viruses, and CMV.

Most symptoms are nonspecific and consist of diarrhea (with or without bleeding), crampy abdominal pain, and malaise. A thorough history may offer clues to the etiology (other medical conditions, especially immunosuppression; recent travel or exposures; and ingestions). Diagnosis is usually made by identification of a pathogen in the stool, either by microscopy or culture. Serum immunoassays may also be useful (amebiasis, HIV, CMV). Occasionally, endoscopy with biopsy may be required. Treatment is tailored to the infection.

Any patient with anal/perianal symptoms requires a careful history and physical, including a digital rectal examination. Other studies such as defecography, manometry, CT scan, MRI, contrast enema, endoscopy, endoanal ultrasound, or exam under anesthesia may be required to arrive at an accurate diagnosis.

Hemorrhoids

Hemorrhoids are cushions of submucosal tissue containing venules, arterioles, and smooth muscle fibers that are located in the anal canal (see Fig. 29-4). Three hemorrhoidal cushions are found in the left lateral, right anterior, and right posterior positions. Hemorrhoids are thought to function as part of the continence mechanism and aid in complete closure of the anal canal at rest. Because hemorrhoids are a normal part of anorectal anatomy, treatment is only indicated if they become symptomatic. Excessive straining, increased abdominal pressure, and hard stools increase venous engorgement of the hemorrhoidal plexus and cause prolapse of hemorrhoidal tissue. Bleeding, thrombosis, and symptomatic hemorrhoidal prolapse may result.

External hemorrhoids are located distal to the dentate line and are covered with anoderm. Because the anoderm is richly innervated, thrombosis of an external hemorrhoid may cause significant pain. It is for this reason that external hemorrhoids should not be ligated or excised without adequate local anesthetic. A skin tag is redundant fibrotic skin at the anal verge, often persisting as the residua of a thrombosed external hemorrhoid. Skin tags are often confused with symptomatic hemorrhoids. External hemorrhoids and skin tags may cause itching and difficulty with hygiene if they are large. Treatment of external hemorrhoids and skin tags is only indicated for symptomatic relief.

Internal hemorrhoids are located proximal to the dentate line and covered by insensate anorectal mucosa. Internal hemorrhoids may prolapse or bleed, but rarely become painful unless they develop thrombosis and necrosis (usually related to severe prolapse, incarceration, and/or strangulation). Internal hemorrhoids are graded according to the extent of prolapse. First-degree hemorrhoids bulge into the anal canal and may prolapse beyond the dentate line on straining. Second-degree hemorrhoids prolapse through the anus but reduce spontaneously. Third-degree hemorrhoids prolapse through the anal canal and require manual reduction. Fourth-degree hemorrhoids prolapse but cannot be reduced and are at risk for strangulation.

Combined internal and external hemorrhoids straddle the dentate line and have characteristics of both internal and external hemorrhoids. Hemorrhoidectomy is often required for large, symptomatic, combined hemorrhoids. Postpartum hemorrhoids result from straining during labor, which results in edema, thrombosis, and/or strangulation. Hemorrhoidectomy is often the treatment of choice, especially if the patient has had chronic hemorrhoidal symptoms. Portal hypertension was long thought to increase the risk of hemorrhoidal bleeding because of the anastomoses between the portal venous system (middle and upper hemorrhoidal plexuses) and the systemic venous system (inferior rectal plexuses). It is now understood that hemorrhoidal disease is no more common in patients with portal hypertension than in the normal population. Rectal varices, however, may occur and may cause hemorrhage in these patients. In general, rectal varices are best treated by lowering portal venous pressure. Rarely, suture ligation may be necessary if massive bleeding persists. Surgical hemorrhoidectomy should be avoided in these patients because of the risk of massive, difficult-to-control variceal bleeding.

Treatment

Medical Therapy

Bleeding from first- and second-degree hemorrhoids often improves with the addition of dietary fiber, stool softeners, increased fluid intake, and avoidance of straining. Associated pruritus often may improve with improved hygiene. Many over-the-counter topical medications are desiccants and are relatively ineffective for treating hemorrhoidal symptoms.

Rubber Band Ligation

Persistent bleeding from first-, second-, and selected third-degree hemorrhoids may be treated by rubber band ligation.

Mucosa located 1 to 2 cm proximal to the dentate line is grasped and pulled into a rubber band applier. After firing the ligator, the rubber band strangulates the underlying tissue, causing scarring and preventing further bleeding or prolapse (Fig. 29-31). In general, only one or two quadrants are banded per visit. Severe pain will occur if the rubber band is placed at or distal to the dentate line where sensory nerves are located. Other complications of rubber band ligation include urinary retention, infection, and bleeding. Urinary retention occurs in approximately 1% of patients and is more likely if the ligation has inadvertently included a portion of the internal sphincter. Necrotizing infection is an uncommon, but life-threatening complication. Severe pain, fever, and urinary retention are early signs of infection and should prompt immediate evaluation of the patient usually with an exam under anesthesia. Treatment includes débridement of necrotic tissue, drainage of associated abscesses, and broad-spectrum antibiotics. Bleeding may occur approximately 7 to 10 days after rubber band ligation, at the time when the ligated pedicle necroses and sloughs. Bleeding is usually self-limited, but persistent hemorrhage may require exam under anesthesia and suture ligation of the pedicle.

Infrared Photocoagulation

Infrared photocoagulation is an effective office treatment for small first- and second-degree hemorrhoids. The instrument is applied to the apex of each hemorrhoid to coagulate the underlying plexus. All three quadrants may be treated during the same visit. Larger hemorrhoids and hemorrhoids with a significant amount of prolapse are not effectively treated with this technique.

Sclerotherapy

The injection of bleeding internal hemorrhoids with sclerosing agents is another effective office technique for treatment of first-, second-, and some third-degree hemorrhoids. One to 3 mL of a sclerosing solution (phenol in olive oil, sodium morrhuate, or quinine urea) is injected into the submucosa of each hemorrhoid. Few complications are associated with sclerotherapy, but infection and fibrosis have been reported.

Excision of Thrombosed External Hemorrhoids

Acutely thrombosed external hemorrhoids generally cause intense pain and a palpable perianal mass during the first 24 to 72 hours after thrombosis. The thrombosis can be effectively treated with an elliptical excision performed in the office under local anesthesia. Because the clot is usually loculated, simple incision and drainage is rarely effective. After 72 hours, the clot begins to resorb, and the pain resolves spontaneously. Excision is unnecessary, but sitz baths and analgesics are often helpful.

Operative Hemorrhoidectomy

A number of surgical procedures have been described for elective resection of symptomatic hemorrhoids. All are based on decreasing blood flow to the hemorrhoidal plexuses and excising redundant anoderm and mucosa.

Closed Submucosal Hemorrhoidectomy

The Parks or Ferguson hemorrhoidectomy involves resection of hemorrhoidal tissue and closure of the wounds with absorbable suture. The procedure may be performed in the prone or lithotomy position under local, regional, or general anesthesia. The anal canal is examined and an anal speculum inserted. The hemorrhoid cushions and associated redundant mucosa are identified and excised using an elliptical incision starting just distal to the anal verge and extending proximally to the anorectal ring. It is crucial to identify the fibers of the internal sphincter and carefully brush these away from the dissection in order to avoid injury to the sphincter. The apex of the hemorrhoidal plexus is then ligated and the hemorrhoid excised. The wound is then closed with a running absorbable suture. All three hemorrhoidal cushions may be removed using this technique; however, care should be taken to avoid resecting a large area of perianal skin in order to avoid postoperative anal stenosis (Fig. 29-32).

Open Hemorrhoidectomy

This technique, often called the Milligan and Morgan hemorrhoidectomy, follows the same principles of excision described earlier, but the wounds are left open and allowed to heal by secondary intention.

Whitehead’s Hemorrhoidectomy

Whitehead’s hemorrhoidectomy involves circumferential excision of the hemorrhoidal cushions just proximal to the dentate line. After excision, the rectal mucosa is then advanced and sutured to the dentate line. While some surgeons still use Whitehead’s hemorrhoidectomy, most have abandoned this approach because of the risk of ectropion (Whitehead’s deformity).

Procedure for Prolapse and Hemorrhoids/Stapled Hemorrhoidectomy

Procedure for prolapse and hemorrhoids (PPH) has been proposed as an alternative surgical approach. The term PPH has largely replaced stapled hemorrhoidectomy because the procedure does not involve excision of hemorrhoidal tissue, but instead pexes the redundant mucosa above the dentate line. PPH removes a short circumferential segment of rectal mucosa proximal to the dentate line using a circular stapler. This effectively ligates the venules feeding the hemorrhoidal plexus and fixes redundant mucosa higher in the anal canal. Several studies suggest that this procedure is safe and effective, is associated with less postoperative pain and disability, and has an equivalent risk of postoperative complications when compared to traditional hemorrhoidectomy.^97,98 Nevertheless, with increased use of this technique, serious and occasionally life-threatening complications have been described.⁹⁹

Doppler-Guided Hemorrhoidal Artery Ligation

Another recent approach to treating symptomatic hemorrhoids is Doppler-guided hemorrhoidal artery ligation (also called transanal hemorrhoidal dearterioalization). In this procedure, a Doppler probe is used to identify the artery or arteries feeding the hemorrhoidal plexus. These vessels are then ligated. Early reports have shown promise, but long-term durability remains to be determined.¹⁰⁰

Complications of Hemorrhoidectomy

Postoperative pain following excisional hemorrhoidectomy requires analgesia usually with oral narcotics. Nonsteroidal anti-inflammatory drugs, muscle relaxants, topical analgesics, and comfort measures, including sitz baths, are often useful as well. Urinary retention is a common complication following hemorrhoidectomy and occurs in 10% to 50% of patients. The risk of urinary retention can be minimized by limiting intraoperative and perioperative intravenous fluids and by providing adequate analgesia. Pain can also lead to fecal impaction. Risk of impaction may be decreased by preoperative enemas or a limited mechanical bowel preparation, liberal use of laxatives postoperatively, and adequate pain control. While a small amount of bleeding, especially with bowel movements, is to be expected, massive hemorrhage can occur after hemorrhoidectomy. Bleeding may occur in the immediate postoperative period (often in the recovery room) as a result of inadequate ligation of the vascular pedicle. This type of hemorrhage mandates an urgent return to the operating room where suture ligation of the bleeding vessel will often solve the problem. Bleeding may also occur 7 to 10 days after hemorrhoidectomy when the necrotic mucosa overlying the vascular pedicle sloughs. While some of these patients may be safely observed, others will require an exam under anesthesia to ligate the bleeding vessel or to oversew the wounds if no specific site of bleeding is identified. Infection is uncommon after hemorrhoidectomy; however, necrotizing soft tissue infection can occur with devastating consequences. Severe pain, fever, and urinary retention may be early signs of infection. If infection is suspected, emergent examination under anesthesia, drainage of abscess, and/or débridement of all necrotic tissue are required.

Long-term sequelae of hemorrhoidectomy include incontinence, anal stenosis, and ectropion (Whitehead’s deformity). Many patients experience transient incontinence to flatus, but these symptoms are usually short-lived, and few patients have permanent fecal incontinence. Anal stenosis may result from scarring after extensive resection of perianal skin. Ectropion may occur after Whitehead’s hemorrhoidectomy.

Anal Fissure

A fissure in ano is a tear in the anoderm distal to the dentate line. The pathophysiology of anal fissure is thought to be related to trauma from either the passage of hard stool or prolonged diarrhea. A tear in the anoderm causes spasm of the internal anal sphincter, which results in pain, increased tearing, and decreased blood supply to the anoderm. This cycle of pain, spasm, and ischemia contributes to development of a poorly healing wound that becomes a chronic fissure. The vast majority of anal fissures occur in the posterior midline. Ten percent to 15% occur in the anterior midline. Less than 1% of fissures occur off midline.

Symptoms and Findings

Anal fissure is extremely common. Characteristic symptoms include tearing pain with defecation and hematochezia (usually described as blood on the toilet paper). Patients may also complain of a sensation of intense and painful anal spasm lasting for several hours after a bowel movement. On physical examination, the fissure can often be seen in the anoderm by gently separating the buttocks. Patients are often too tender to tolerate digital rectal examination, anoscopy, or proctoscopy. An acute fissure is a superficial tear of the distal anoderm and almost always heals with medical management. Chronic fissures develop ulceration and heaped-up edges with the white fibers of the internal anal sphincter visible at the base of the ulcer. There often is an associated external skin tag and/or a hypertrophied anal papilla internally. These fissures are more challenging to treat and may require surgery. A lateral location of a chronic anal fissure may be evidence of an underlying disease such as Crohn’s disease, HIV, syphilis, tuberculosis, or leukemia. If the diagnosis is in doubt or there is suspicion of another cause for the perianal pain such as abscess or fistula, an examination under anesthesia may be necessary.

Treatment

Therapy focuses on breaking the cycle of pain, spasm, and ischemia thought to be responsible for development of fissure in ano. First-line therapy to minimize anal trauma includes bulk agents, stool softeners, and warm sitz baths. The addition of 2% lidocaine jelly or other analgesic creams can provide additional symptomatic relief. Nitroglycerin ointment has been used locally to improve blood flow but often causes severe headaches. Both oral and topical calcium channel blockers (diltiazem and nifedipine) have also been used to heal fissures and may have fewer side effects than topical nitrates.⁹⁷ Newer agents, such as arginine (a nitric oxide donor) and topical bethanechol (a muscarinic agonist), have also been used to treat fissures. Medical therapy is effective in most acute fissures, but will heal only approximately 50% of chronic fissures.

Botulinum toxin (Botox) causes temporary muscle paralysis by preventing acetylcholine release from presynaptic nerve terminals. Injection of botulinum toxin is used in some centers as an alternative to surgical sphincterotomy for chronic fissure. Although there are few long-term complications from the use of botulinum toxin, healing appears to be equivalent to other medical therapies.^98,101

Surgical therapy has traditionally been recommended for chronic fissures that have failed medical therapy, and lateral internal sphincterotomy is the procedure of choice. The aim of this procedure is to decrease spasm of the internal sphincter by dividing a portion of the muscle. Approximately 30% of the internal sphincter fibers are divided laterally by using either an open (Fig. 29-33) or closed (Fig. 29-34) technique. Healing is achieved in more than 95% of patients using this technique, and most patients experience immediate pain relief. Recurrence occurs in less than 10% of patients, and the risk of incontinence (usually to flatus) ranges from 5% to 15%. Advancement flaps (VY) with or without sphincterotomy have also been reported to successfully treat chronic fissures.

Anorectal Sepsis and Cryptoglandular Abscess

Relevant Anatomy

The majority of anorectal suppurative disease results from infections of the anal glands (cryptoglandular infection) found in the intersphincteric plane. Their ducts traverse the internal sphincter and empty into the anal crypts at the level of the dentate line. Infection of an anal gland results in the formation of an abscess that enlarges and spreads along one of several planes in the perianal and perirectal spaces. The perianal space surrounds the anus and laterally becomes continuous with the fat of the buttocks. The intersphincteric space separates the internal and external anal sphincters. It is continuous with the perianal space distally and extends cephalad into the rectal wall. The ischiorectal space (ischiorectal fossa) is located lateral and posterior to the anus and is bounded medially by the external sphincter, laterally by the ischium, superiorly by the levator ani, and inferiorly by the transverse septum. The ischiorectal space contains the inferior rectal vessels and lymphatics. The two ischiorectal spaces connect posteriorly above the anococcygeal ligament but below the levator ani muscle, forming the deep postanal space. The supralevator spaces lie above the levator ani on either side of the rectum and communicate posteriorly. The anatomy of these spaces influences the location and spread of cryptoglandular infection (Fig. 29-35).

As an abscess enlarges, it spreads in one of several directions. A perianal abscess is the most common manifestation and appears as a painful swelling at the anal verge. Spread through the external sphincter below the level of the puborectalis produces an ischiorectal abscess. These abscesses may become extremely large and may not be visible in the perianal region. Digital rectal exam will reveal a painful swelling laterally in the ischiorectal fossa. Intersphincteric abscesses occur in the intersphincteric space and are notoriously difficult to diagnose, often requiring an examination under anesthesia. Pelvic and supralevator abscesses are uncommon and may result from extension of an intersphincteric or ischiorectal abscess upward or extension of an intraperitoneal abscess downward (Fig. 29-36).

Diagnosis

Severe anal pain is the most common presenting complaint. A palpable mass is often detected by inspection of the perianal area or by digital rectal examination. Occasionally, patients will present with fever, urinary retention, or life-threatening sepsis. The diagnosis of a perianal or ischiorectal abscess can usually be made with physical exam alone (either in the office or in the operating room). However, complex or atypical presentations may require imaging studies such as CT or MRI to fully delineate the anatomy of the abscess.

Treatment

Anorectal abscesses should be treated by drainage as soon as the diagnosis is established. If the diagnosis is in question, an examination and drainage under anesthesia are often the most expeditious ways both to confirm the diagnosis and to treat the problem. Delayed or inadequate treatment may occasionally cause extensive and life-threatening suppuration with massive tissue necrosis and septicemia. Antibiotics are only indicated if there is extensive overlying cellulitis or if the patient is immunocompromised, has diabetes mellitus, or has valvular heart disease. Antibiotics alone are ineffective at treating perianal or perirectal infection.

Perianal Abscess

Most perianal abscesses can be drained under local anesthesia in the office, clinic, or emergency room. Larger, more complicated abscesses may require drainage in the operating room. A skin incision is created, and a disk of skin excised to prevent premature closure. No packing is necessary, and sitz baths are started the next day (Fig. 29-37).

Ischiorectal Abscess

An ischiorectal abscess causes diffuse swelling in the ischiorectal fossa that may involve one or both sides, forming a “horseshoe” abscess. Simple ischiorectal abscesses are drained through an incision in the overlying skin. Horseshoe abscesses require drainage of the deep postanal space and often require counterincisions over one or both ischiorectal spaces (Fig. 29-38).

Intersphincteric Abscess

Intersphincteric abscesses are notoriously difficult to diagnose because they produce little swelling and few perianal signs of infection. Pain is typically described as being deep and “up inside” the anal area and is usually exacerbated by coughing or sneezing. The pain is so intense that it usually precludes a digital rectal examination. The diagnosis is made based on a high index of suspicion and usually requires an examination under anesthesia. Once identified, an intersphincteric abscess can be drained through a limited, usually posterior, internal sphincterotomy.

Supralevator Abscess

This type of abscess is uncommon and can be difficult to diagnose. Because of its proximity to the peritoneal cavity, supralevator abscesses can mimic intra-abdominal conditions. Digital rectal examination may reveal an indurated, bulging mass above the anorectal ring. It is essential to identify the origin of a supralevator abscess prior to treatment. If the abscess is secondary to an upward extension of an intersphincteric abscess, it should be drained through the rectum. If it is drained through the ischiorectal fossa, a complicated, suprasphincteric fistula may result. If a supralevator abscess arises from the upward extension of an ischiorectal abscess, it should be drained through the ischiorectal fossa. Drainage of this type of abscess through the rectum may result in an extrasphincteric fistula. If the abscess is secondary to intra-abdominal disease, the primary process requires treatment and the abscess is drained via the most direct route (transabdominally, rectally, or through the ischiorectal fossa).

Perianal Sepsis in the Immunocompromised Patient

The immunocompromised patient with perianal pain presents a diagnostic dilemma. Because of leukopenia, these patients may develop serious perianal infection without any of the cardinal signs of inflammation. While broad-spectrum antibiotics may cure some of these patients, an exam under anesthesia should not be delayed because of neutropenia. An increase in pain or fever and/or clinical deterioration mandates an exam under anesthesia. Any indurated area should be incised and drained, biopsied to exclude a leukemic infiltrate, and cultured to aid in the selection of antimicrobial agents.¹⁰²

Necrotizing Soft Tissue Infection of the Perineum

Necrotizing soft tissue infection of the perineum is a rare, but lethal, condition. Most of these infections are polymicrobial and synergistic. The source of sepsis is commonly an undrained or inadequately drained cryptoglandular abscess or a urogenital infection. Occasionally, these infections may be encountered postoperatively (e.g., after hemorrhoidectomy). Immunocompromised patients and diabetic patients are at increased risk.

Physical examination may reveal necrotic skin, bullae, or crepitus. Patients often have signs of systemic toxicity and may be hemodynamically unstable. A high index of suspicion is necessary because perineal signs of severe infection may be minimal and prompt surgical intervention can be lifesaving.

Surgical débridement of all nonviable tissue is required to treat all necrotizing soft tissue infections. Multiple operations may be necessary to ensure that all necrotic tissue has been resected. Broad-spectrum antibiotics are frequently employed, but adequate surgical débridement remains the mainstay of therapy. Colostomy may be required if extensive resection of the sphincter is required or if stool contamination of the perineum makes wound management difficult. Despite early recognition and adequate surgical therapy, the mortality of necrotizing perineal soft tissue infections remains approximately 50%.

Fistula In Ano

Drainage of an anorectal abscess results in cure for about 50% of patients. The remaining 50% develop a persistent fistula in ano. The fistula usually originates in the infected crypt (internal opening) and tracks to the external opening, usually the site of prior drainage. The course of the fistula can often be predicted by the anatomy of the previous abscess.

While the majority of fistulas are cryptoglandular in origin, trauma, Crohn’s disease, malignancy, radiation, or unusual infections (tuberculosis, actinomycosis, and chlamydia) may also produce fistulas. A complex, recurrent, or nonhealing fistula should raise the suspicion of one of these diagnoses.

Diagnosis

Patients present with persistent drainage from the internal and/or external openings. An indurated tract is often palpable. Although the external opening is often easily identifiable, identification of the internal opening may be more challenging. Goodsall’s rule can be used as a guide in determining the location of the internal opening (Fig. 29-39). In general, fistulas with an external opening anteriorly connect to the internal opening by a short, radial tract. Fistulas with an external opening posteriorly track in a curvilinear fashion to the posterior midline. However, exceptions to this rule often occur if an anterior external opening is greater than 3 cm from the anal margin. Such fistulas usually track to the posterior midline.

Fistulas are categorized based on their relationship to the anal sphincter complex, and treatment options are based on these classifications. An intersphincteric fistula tracks through the distal internal sphincter and intersphincteric space to an external opening near the anal verge (Fig. 29-40A). A transsphincteric fistula often results from an ischiorectal abscess and extends through both the internal and external sphincters (Fig. 29-40B). A suprasphincteric fistula originates in the intersphincteric plane and tracks up and around the entire external sphincter (Fig. 29-40C). An extrasphincteric fistula originates in the rectal wall and tracks around both sphincters to exit laterally, usually in the ischiorectal fossa (Fig. 29-40D).

Treatment

The goal of treatment of fistula in ano is eradication of sepsis without sacrificing continence. Because fistulous tracks encircle variable amounts of the sphincter complex, surgical treatment is dictated by the location of the internal and external openings and the course of the fistula. The external opening is usually visible as a red elevation of granulation tissue with or without concurrent drainage. The internal opening may be more difficult to identify. Injection of hydrogen peroxide or dilute methylene blue may be helpful. Care must be taken to avoid creating an artificial internal opening (thus often converting a simple fistula into a complex fistula).

Simple intersphincteric fistulas can often be treated by fistulotomy (opening the fistulous tract), curettage, and healing by secondary intention (see Fig. 29-40A). “Horseshoe” fistulas usually have an internal opening in the posterior midline and extend anteriorly and laterally to one or both ischiorectal spaces by way of the deep postanal space. Treatment of a transsphincteric fistula depends on its location in the sphincter complex. Fistulas that include less than 30% of the sphincter muscles can often be treated by sphincterotomy without significant risk of major incontinence (see Fig. 29-40B). High transsphincteric fistulas, which encircle a greater amount of muscle, are more safely treated by initial placement of a seton (see below). Similarly, suprasphincteric fistulas are usually treated with seton placement (see Fig. 29-40C). Extrasphincteric fistulas are rare, and treatment depends on both the anatomy of the fistula and its etiology. In general, the portion of the fistula outside the sphincter should be opened and drained. A primary tract at the level of the dentate line may also be opened if present. Complex fistulas with multiple tracts may require numerous procedures to control sepsis and facilitate healing. Liberal use of drains and setons is helpful. Failure to heal may ultimately require fecal diversion (see Fig. 29-40D). Complex and/or nonhealing fistulas may result from Crohn’s disease, malignancy, radiation proctitis, or unusual infection. Proctoscopy should be performed in all cases of complex and/or nonhealing fistulas to assess the health of the rectal mucosa. Biopsies of the fistula tract should be taken to rule out malignancy.

A seton is a drain placed through a fistula to maintain drainage and/or induce fibrosis. Cutting setons consist of a suture or a rubber band that is placed through the fistula and intermittently tightened in the office. Tightening the seton results in fibrosis and gradual division of the sphincter, thus eliminating the fistula while maintaining continuity of the sphincter. A noncutting seton is a soft plastic drain (often a vessel loop) placed in the fistula to maintain drainage. The fistula tract may subsequently be laid open with less risk of incontinence because scarring prevents retraction of the sphincter. Alternatively, the seton may be left in place for chronic drainage. Higher fistulas may be treated by an endorectal advancement flap (see below). Fibrin glue and a variety of collagen-based plugs also have been used to treat persistent fistulas with variable results. A more recent technique, ligation of the intersphincteric fistula tract (LIFT), also shows promise. In this procedure, the fistula is identified in the intersphincteric plane (usually by placement of a lacrimal probe), divided, and the two ends ligated. Early reports have shown success with this technique, but long-term outcome is not yet known.^103,104

Rectovaginal Fistula

A rectovaginal fistula is a connection between the vagina and the rectum or anal canal proximal to the dentate line. Rectovaginal fistulas are classified as low (rectal opening close to the dentate line and vaginal opening in the fourchette), middle (vaginal opening between the fourchette and cervix), or high (vaginal opening near the cervix). Low rectovaginal fistulas are commonly caused by obstetric injuries or trauma from a foreign body. Mid-rectovaginal fistulas may result from more severe obstetric injury, but also occur after surgical resection of a mid-rectal neoplasm, radiation injury, or extension of an undrained abscess. High rectovaginal fistulas result from operative or radiation injury. Complicated diverticulitis may cause a colovaginal fistula. Crohn’s disease can cause rectovaginal fistulas at all levels, as well as colovaginal and enterovaginal fistulas.

Diagnosis

Patients describe symptoms varying from the sensation of passing flatus from the vagina to the passage of solid stool from the vagina. Most patients experience some degree of fecal incontinence. Contamination may result in vaginitis. Large fistulas may be obvious on anoscopic and/or vaginal speculum examination, but smaller fistulas may be difficult to locate. Occasionally, a barium enema or vaginogram may identify these fistulas. Endorectal ultrasound may also be useful. With the patient in the prone position, installation of methylene blue into the rectum while a tampon is in the vagina may confirm the presence of a small fistula.

Treatment

The treatment of rectovaginal fistula depends on the size, location, etiology, and condition of surrounding tissues. Because up to 50% of fistulas caused by obstetric injury heal spontaneously, it is prudent to wait 3 to 6 months before embarking on surgical repair in these patients. If the fistula was caused by a cryptoglandular abscess, drainage of the abscess may allow spontaneous closure.

Low and mid-rectovaginal fistulas are usually best treated with an endorectal advancement flap. The principle of this procedure is based on the advancement of healthy mucosa, submucosa, and circular muscle over the rectal opening (the high-pressure side of the fistula) to promote healing (Fig. 29-41). If a sphincter injury is present, an overlapping sphincteroplasty should be performed concurrently. Fecal diversion is rarely required. High rectovaginal, colovaginal, and enterovaginal fistulas are usually best treated via a transabdominal approach. The diseased tissue, which caused the fistula (upper rectum, sigmoid colon, or small bowel), is resected and the hole in the vagina closed. Healthy tissue, such as omentum or muscle, frequently is interposed between the bowel anastomosis and the vagina to prevent recurrence.

Rectovaginal fistulas caused by Crohn’s disease, radiation injury, or malignancy almost never heal spontaneously. In Crohn’s disease, treatment is based on adequate drainage of perianal sepsis and nutritional support. An endorectal advancement flap may be performed if the rectum is spared from active Crohn’s disease. Fistulas resulting from radiation damage are not amenable to local repair with an advancement flap because of damage to the surrounding rectal and vaginal tissues. Such mid- and high rectovaginal fistulas are occasionally repaired successfully with a transabdominal approach in which healthy tissue (omentum, muscle, or nonradiated bowel) is interposed between the damaged rectum and vagina. Fistulas caused by malignancy should be treated with resection of the tumor. Because differentiating radiation damage from malignancy can be extremely difficult, all fistulas resulting from radiation should be biopsied to rule out the presence of cancer.

Perianal Dermatitis

Pruritus Ani

Pruritus ani (severe perianal itching) is a common problem with a multitude of etiologies. Surgically correctable (anatomic) causes include prolapsing hemorrhoids, ectropion, fissure, fistula, and neoplasms. Perianal infection may also present with pruritus ani. Infections may be caused by fungus (Candida species and Epidermophyton organisms), parasites (Enterobius vermicularis [pinworms], Pediculus pubis [a louse], and Sarcoptes scabiei [scabies]), bacteria (Corynebacterium minutissimum [erythrasma] and T. pallidum [syphilis]), or viruses (HPV [condyloma acuminata]). Antibiotic use may also cause itching, usually by precipitating fungal infection. Noninfectious dermatologic causes include seborrhea, psoriasis, and contact dermatitis. Contact dermatitis can be particularly troublesome because many over-the-counter topical agents used by patients to relieve itching may exacerbate the problem. Occasionally, systemic diseases such as jaundice and diabetes may present with pruritus ani.

Despite the myriad of causes, the majority of pruritus ani is idiopathic and probably related to local hygiene, neurogenic, or psychogenic causes. Treatment focuses on removal of irritants, improving perianal hygiene, dietary adjustments, and avoiding scratching. Biopsy and/or culture may be required to rule out an infectious or dermatologic cause. Hydrocortisone ointment 0.5% to 1.0% can provide symptomatic relief but should not be used for prolonged periods of time because of the risk of dermal atrophy. Skin barriers such as Calmoseptine can also provide relief. Systemic antihistamines or tricyclic antidepressants have also been used with some success.

Nonpruritic Lesions

Several perianal skin conditions may present with perianal skin changes. Leprosy, amebiasis, actinomycosis, and lymphogranuloma venereum produce characteristic perianal lesions. Neoplasms such as squamous intraepithelial lesions, Paget’s disease, and invasive carcinomas may also appear first in the perianal skin. Biopsy can usually distinguish these diagnoses.

Sexually Transmitted Diseases

Bacterial Infections

Proctitis is a common symptom of anorectal bacterial infection. N. gonorrhoeae is the most common bacterial cause of proctitis and causes pain, tenesmus, rectal bleeding, and mucus discharge. Chlamydia trachomatis infection may be asymptomatic or may produce similar symptoms. T. pallidum, the microbe causing syphilis, causes a chancre at the site of inoculation, which may be asymptomatic or may present as an atypical fissure (primary syphilis). Condyloma lata are characteristic of secondary syphilis. Chancroid, caused by Haemophilus ducreyi, is a disease manifested by multiple painful, bleeding lesions. Inguinal lymphadenopathy and fluctuant, draining lymph nodes are characteristic. Donovania granulomatis infection produces shiny, red masses on the perineum (granuloma inguinale). Diarrheal illnesses caused by organisms such as Campylobacter or Shigella may also be sexually transmitted. Treatment consists of antimicrobial agents directed against the infecting organism.

Parasitic Infections

Entamoeba histolytica is an increasingly common sexually transmitted disease. Amebas produce ulcerations in the gastrointestinal mucosa and can infect any part of the gut. Symptoms include diarrhea, abdominal pain, and tenesmus. Giardia lamblia is also common and produces diarrhea, abdominal pain, and malaise.

Viral Infections

Herpes Simplex Virus

Herpes proctitis is extremely common. Proctitis is usually caused by type 2 herpes simplex virus and less commonly by type 1 herpes simplex virus. Patients complain of severe, intractable perianal pain and tenesmus. Pain often precedes the development of characteristic vesicles, and these patients may require an examination under anesthesia to exclude another diagnosis such as an intersphincteric abscess. Diagnosis is confirmed by viral culture of tissue or vesicular fluid.

Human Papillomavirus

HPV causes condyloma acuminata (anogenital warts) and is associated with squamous intraepithelial lesions and squamous cell carcinoma (see previous section, “Anal Canal and Perianal Tumors”). Condylomas occur in the perianal area or in the squamous epithelium of the anal canal. Occasionally, the mucosa of the lower rectum may be affected. There are approximately 30 serotypes of HPV. As previously mentioned, HPV types 16 and 18, in particular, appear to predispose to malignancy and often cause flat dysplasia in skin unaffected by warts. In contrast, HPV types 6 and 11 commonly cause warts, but do not appear to cause malignant degeneration.

Treatment of anal condyloma depends on the location and extent of disease. Small warts on the perianal skin and distal anal canal may be treated in the office with topical application of bichloracetic acid or podophyllin. Although 60% to 80% of patients will respond to these agents, recurrence and reinfection are common. Imiquimod (Aldara) is an immunomodulator that was recently introduced for topical treatment of several viral infections, including anogenital condyloma.¹⁰⁵ Initial reports suggest that this agent is highly effective in treating condyloma located on the perianal skin and distal anal canal. Larger and/or more numerous warts require excision and/or fulguration in the operating room. Excised warts should be sent for pathologic examination to rule out dysplasia or malignancy. It is important to note that prior use of podophyllin may induce histologic changes that mimic dysplasia. The recent introduction of a vaccine against HPV holds promise for preventing anogenital condylomas.

Human Immunodeficiency Virus

See later section, “The Immunocompromised Patient.”

Pilonidal Disease

Pilonidal disease (cyst, infection) consists of a hair-containing sinus or abscess occurring in the intergluteal cleft. Although the etiology is unknown, it is speculated that the cleft creates a suction that draws hair into the midline pits when a patients sits. These ingrown hairs may then become infected and present acutely as an abscess in the sacrococcygeal region. Once an acute episode has resolved, recurrence is common.

An acute abscess should be incised and drained as soon as the diagnosis is made. Because these abscesses are usually very superficial, this procedure can often be performed in the office, clinic, or emergency room under local anesthetic. Because midline wounds in the region heal poorly, some surgeons recommend using an incision lateral to the intergluteal cleft. A number of procedures have been proposed to treat a chronic pilonidal sinus. The simplest method involves unroofing the tract, curetting the base, and marsupializing the wound. The wound must then be kept clean and free of hair until healing is complete (often requiring weekly office visits for wound care). Alternatively, a small lateral incision can be created and the pit excised. This method is effective for most primary pilonidal sinuses. In general, extensive resection should be avoided. Complex and/or recurrent sinus tracts may require more extensive resection and closure with a Z-plasty, advancement flap, or rotational flap.

Hidradenitis Suppurativa

Hidradenitis suppurativa is an infection of the cutaneous apocrine sweat glands. Infected glands rupture and form subcutaneous sinus tracts. The infection may mimic complex anal fistula disease, but stops at the anal verge because there are no apocrine glands in the anal canal. Treatment involves incision and drainage of acute abscesses and unroofing of all chronically inflamed fistulas and débridement of granulation tissue. Radical excision and skin grafting are almost never necessary.

Penetrating Colorectal Injury

Colorectal injury is common following penetrating trauma to the abdomen and has historically been associated with high mortality. In the first half of the twentieth century, the mortality rate from colorectal injury was as high as 90%. The introduction of exteriorization of colonic injuries and fecal diversion during World War II dramatically decreased mortality, and this principle has governed the management of large bowel injury for over 50 years. Recently, however, this practice was challenged, and trauma surgeons are increasingly performing primary repairs in selected patients.

Management of colonic injury depends on the mechanism of injury, the delay between the injury and surgery, the overall condition and stability of the patient, the degree of peritoneal contamination, and the condition of the injured colon. A primary repair may be considered in hemodynamically stable patients with few additional injuries and minimal contamination if the colon appears otherwise healthy. Contraindications to primary repair include shock, injury to more than two other organs, mesenteric vascular damage, and extensive fecal contamination. A delay of greater than 6 hours between the injury and the operation also is associated with increased morbidity and mortality and is a relative contraindication to primary repair. Injuries caused by high-velocity gunshot wounds or blast injuries are often associated with multiple intra-abdominal injuries and tissue loss and therefore are usually treated by fecal diversion after débridement of all nonviable tissue. Patient factors, such as medical comorbidities, advanced age, and the presence of tumor or radiation injury, must also be considered (Table 29-6).

Like injuries to the intraperitoneal colon, penetrating trauma to the rectum traditionally has been associated with high morbidity and mortality. Primary repair of the rectum is more difficult than primary repair of the colon, however, and most rectal injuries are associated with significant contamination. For that reason, the majority of penetrating rectal injuries should be treated with proximal fecal diversion and copious irrigation of the rectum (distal rectal washout). Small, clean rectal injuries may be closed primarily without fecal diversion in an otherwise stable patient. Intractable rectal bleeding may require angiographic embolization. Very rarely, hemorrhage or extensive tissue loss (especially if the anal sphincter is severely damaged) may require an emergent APR. However, this operation should be avoided, if at all possible, because of the morbidity associated with an extensive pelvic dissection in a severely injured patient.

Blunt Colorectal Injury

Blunt injury to the colon and rectum is considerably less common than penetrating injury. Nevertheless, blunt trauma can cause colon perforation, and shear injury to the mesentery can devascularize the intestine. Management of these injuries should follow the same principles outlined for management of penetrating injuries. Small perforations with little contamination in a stable patient may be closed primarily; more extensive injury requires fecal diversion. A serosal hematoma alone does not mandate resection, but the bowel should be carefully inspected to ensure that there is not an associated perforation or significant bowel ischemia.

Blunt injury to the rectum may result from significant trauma, such as a pelvic crush injury, or may result from local trauma caused by an enema or foreign body. Crush injuries, especially with an associated pelvic fracture, are often associated with significant rectal damage and contamination. These patients require débridement of all nonviable tissue, proximal fecal diversion, and a distal rectal washout, with or without drain placement. Blunt trauma from an enema or foreign body may produce a mucosal hematoma, which requires no surgical treatment if the mucosa is intact. Small mucosal tears may be closed primarily if the bowel is relatively clean and there is little contamination.

Iatrogenic Injury

Intraoperative Injury

The colon and rectum are at risk for inadvertent injury during other procedures, especially during pelvic operations. The key to managing these injuries is early recognition. The vast majority of iatrogenic colorectal injuries may be closed primarily if there is little contamination and if the patient is otherwise stable. Delayed recognition of colorectal injuries may result in significant peritonitis and life-threatening sepsis. In these cases, fecal diversion is almost always required, and the patient may need repeated exploration for drainage of abscesses.

Injury from Barium Enema

Colorectal injury from a barium enema is an extremely rare complication associated with a high rate of morbidity and mortality. Perforation with spillage of barium, especially above the peritoneal reflection, may result in profound peritonitis, sepsis, and a systemic inflammatory response. If the perforation is recognized early, it may be closed primarily and the abdomen irrigated to remove stool and barium. However, if the patient has developed sepsis, fecal diversion (with or without bowel resection) is almost always required. Rarely, a small mucosal injury to the extraperitoneal rectum may be managed with bowel rest, broad-spectrum antibiotics, and close observation.

Colonoscopic Perforation

Perforation is the most common major complication after either diagnostic or therapeutic colonoscopy. Fortunately, this complication is rare and occurs in less than 1% of procedures. Perforation may result from trauma from the tip of the instrument, from shear forces related to the formation of a “loop” in the colonoscope, or from barotrauma from insufflation. Biopsy or fulguration can also cause perforation. Polypectomy using electrocautery may produce a full-thickness burn, resulting in postpolypectomy syndrome in which a patient develops abdominal pain, fever, and leukocytosis without evidence of diffuse peritonitis.

Management of colonoscopic perforation depends on the size of the perforation, the duration of time since the injury, the overall condition of the patient, and the underlying diagnosis. A large perforation recognized during the procedure requires surgical exploration. Because the bowel has almost always been prepared prior to the colonoscopy, there is usually little contamination associated with these injuries, and most can be repaired primarily. If there is significant contamination, if there has been a delay in diagnosis with resulting peritonitis, or if the patient is hemodynamically unstable, proximal diversion with or without resection is the safest approach. It is also important to know the indication for and findings at the time of colonoscopy. If the patient has an underlying neoplasm and is stable, definitive resection is best. Occasionally, a patient will develop abdominal pain and localized signs of perforation after what was thought to be an uneventful colonoscopy. Many of these patients will have a “microperforation,” which will resolve with bowel rest, broad-spectrum antibiotics, and close observation. Evidence of peritonitis or any deterioration in clinical condition mandates exploration. Similarly, free retroperitoneal or intraperitoneal air may be discovered incidentally after colonoscopy. In a completely asymptomatic patient, this finding is thought to result from barotrauma and dissection of air through tissue planes without a free perforation. Many of these patients can be successfully treated with bowel rest and broad-spectrum antibiotics. Surgical exploration is indicated if any clinical deterioration occurs.

Anal Sphincter Injury and Incontinence

The most common cause of anal sphincter injury is obstetric trauma during vaginal delivery. The risk of sphincter injury is increased by a laceration that extends into the rectum (fourth-degree tear), infection of an episiotomy or laceration repair, prolonged labor, and possibly by use of a midline episiotomy. Sphincter damage may also result from hemorrhoidectomy, sphincterotomy, abscess drainage, or fistulotomy. Patients with incontinence and a suspected sphincter injury can be evaluated with anal manometry, EMG, pudendal nerve motor latency, and endoanal ultrasound. Mild incontinence, even in the presence of a sphincter defect, may respond to dietary changes and/or biofeedback. More severe incontinence may require surgical repair.

The anal sphincter can also be injured by penetrating or blunt mechanisms (impalement, blast injury, crush injuries of the pelvis). Because damage to the anal sphincter is not life-threatening, definitive repair of the sphincter is often deferred until other injuries have been repaired and the patient’s clinical condition is stable. Isolated sphincter injuries that do not involve the rectum may be repaired primarily. Rectal injury accompanied by sphincter injury should be treated with fecal diversion and distal rectal washout, with or without drain placement. Significant perineal tissue loss may require extensive débridement and a diverting colostomy.

Surgical Repairs

The most common method of repair of the anal sphincter is a wrap-around sphincteroplasty (Fig. 29-42).¹⁰⁶ The procedure involves mobilization of the divided sphincter muscle and reapproximation without tension. The internal and external sphincters may be overlapped together or separately. Postanal intersphincteric levatorplasty is less commonly used to repair sphincter defects but may be useful for incontinence caused by prolapse and/or loss of the anorectal angle (see “Continence”). The approach is via the intersphincteric plane posteriorly. It may be performed concomitantly with a perineal repair of rectal prolapse. The levator ani muscle is approximated to restore the anorectal angle, and the puborectalis and external sphincter muscle are tightened with sutures. These elective procedures usually do not require a diverting colostomy.

In cases where there has been significant loss of sphincter muscle or in which prior repairs have failed, more complex techniques, such as gracilis muscle transposition with or without chronic, low-frequency electrostimulation, have been used with some success.¹⁰⁷ In this procedure, the gracilis muscle is mobilized from the thigh, detached from its insertion on the tibial tuberosity, tunneled through the perineum, and wrapped around the anal canal. Another alternative in patients who have failed other repairs is the artificial anal sphincter. This device consists of an inflatable silastic cuff, a pressure-regulating balloon, and a control pump. Patients deflate the cuff manually to open the anal canal; the cuff then reinflates spontaneously to maintain closure of the anal canal. Sacral nerve stimulation via an implanted pulse generator is a technique used for neurogenic incontinence when the sphincter is intact.^16,27 In some patients, an end stoma provides the best relief for intractable incontinence.¹⁰⁸

Foreign Body

Foreign body entrapment in the rectum is not uncommon. Depending on the level of entrapment, a foreign body may cause damage to the rectum, rectosigmoid, or descending colon. Generalized abdominal pain suggests intraperitoneal perforation. Evaluation of the patient includes inspection of the perineum and a careful abdominal examination to detect any evidence of perforation. Plain films of the abdomen are mandatory to detect free intra-abdominal air.

Foreign bodies lodged low in the rectum may often be removed under conscious sedation with or without a local anesthetic block. Objects impacted higher in the rectum may require regional or general anesthesia for removal. Only rarely will a laparotomy be required to remove the object. After removal of the foreign body, it is crucial to evaluate the rectum and sigmoid colon for injury. Proctoscopy and/or flexible sigmoidoscopy should be performed. A hematoma without evidence of perforation requires no surgical treatment. Perforation of the rectum or sigmoid colon should be managed as described in the preceding sections.

Human Immunodeficiency Virus

Patients infected with HIV may present with a myriad of gastrointestinal symptoms. Diarrhea, in particular, is extremely common. The severity of gastrointestinal disease depends in part on the degree of immunosuppression; however, both ordinary and opportunistic pathogens may affect patients at any stage of the disease. Opportunistic infections with bacteria (Salmonella, Shigella, Campylobacter, Chlamydia, and Mycobacterium species), fungi (histoplasmosis, coccidiosis, Cryptococcus), protozoa (toxoplasmosis, cryptosporidiosis, isosporiasis), and viruses (CMV, herpes simplex virus) can cause diarrhea, abdominal pain, and weight loss. CMV in particular may cause severe enterocolitis and is the most common infectious cause of emergency laparotomy in acquired immunodeficiency syndrome (AIDS) patients. C. difficile colitis is a major concern in these patients, especially because many patients are maintained on suppressive antibiotic therapy. The incidence of gastrointestinal malignancy is also increased in patients with HIV infection.¹⁰⁹ Kaposi’s sarcoma is the most common malignancy in AIDS patients and can affect any part of the gastrointestinal tract. Patients may be asymptomatic or may develop bleeding or obstruction. Gastrointestinal lymphoma (usually non-Hodgkin’s lymphoma) is also common. The incidence of colorectal carcinoma may also be increased in this population, although definitive data are lacking.

Perianal disease is extremely common in patients with HIV infection. Because HIV is sexually transmitted, it is common to find concomitant infection with other sexually transmitted diseases such as Chlamydia, herpes simplex virus, and HPV (anal condyloma). Anal condyloma in particular are very common, and the incidence of dysplasia (HSIL) is high in the HIV-infected population.¹¹⁰ Abscesses and fistulas may be more difficult to diagnose in these patients and may be complex. Many patients require an examination under anesthesia with biopsy and cultures to determine the etiology of many of these perianal problems. The introduction of highly active antiretroviral therapy (HAART) has changed the natural history of HIV infection, but it remains to be seen how these medications will affect the incidence and outcome of colorectal disease in this patient population.

The gastrointestinal tract is a common site for posttransplantation complications that are responsible for significant morbidity and mortality. In these patients, infection and medication are the most common causes of diarrhea. Immunosuppressant medications, in particular, may cause diarrhea. CMV infection is common and may be severe. C difficile colitis also occurs commonly. Diverticulitis appears to be more common in some populations of transplant patients and may be more likely to present with abscess or free perforation. Elective resection after recovery from one episode of confirmed diverticulitis may be indicated in the transplant population. Graft-versus-host disease is unique to transplant patients and often requires endoscopy and biopsy to diagnose gastrointestinal involvement. Patients are subject to the same opportunistic infections outlined earlier; however, sexually transmitted infections and Kaposi’s sarcoma are somewhat less prevalent. Perianal disease is somewhat less common in the transplant population than in patients infected with HIV; however, similar infections may occur, and immunosuppression often makes diagnosis and treatment challenging.

With increasing long-term survival among transplant recipients, the development of posttransplant malignancy has become a major concern. Posttransplant lymphoproliferative disease is increasingly common and may occur anywhere in the gastrointestinal tract. The risk of colorectal carcinoma is increased in patients with predisposing conditions such as ulcerative colitis. However, immunosuppression alone does not appear to increase the incidence of colorectal cancer, and current screening recommendations are similar to those for the average risk population. In contrast, the incidence of anal squamous cell carcinoma is dramatically increased in transplant patients, and patients with known HPV infection should undergo more vigorous screening.

Neutropenic enterocolitis (typhlitis) is a life-threatening problem with a mortality rate of greater than 50%. This syndrome is characterized by abdominal pain and distention, fever, diarrhea (often bloody), nausea, and vomiting in a patient with fewer than 1000 neutrophils/μL blood from any cause (bone marrow transplantation, solid-organ transplantation, or chemotherapy). CT scan of the abdomen often shows a dilated cecum with pericolic stranding. However, a normal-appearing CT scan does not exclude the diagnosis. Some patients will respond to bowel rest, broad-spectrum antibiotics, parenteral nutrition, and granulocyte infusion or colony-stimulating factors. Evidence of perforation, generalized peritonitis, and deterioration in clinical condition are indications for operation.

Neutropenic patients often develop perianal pain, and diagnosis may be difficult because of a lack of inflammatory response to infection. While broad-spectrum antibiotics may cure some of these patients, an examination under anesthesia should not be delayed because of neutropenia. An increase in pain or fever and/or clinical deterioration mandates an exam under anesthesia. Any indurated area should be incised and drained, biopsied to exclude a leukemic infiltrate, and cultured to aid in the selection of antimicrobial agents.