Acute diverticulitis is the result of micro- or macroscopic perforation of a diverticulum resulting in an inflammatory response. The sigmoid colon is the most common location for diverticula and therefore is the most common location of diverticulitis. The severity of disease can range from mild inflammation localized to a segment of the bowel wall (microperforation) to feculent peritonitis (macroperforation). The majority of patients (75%) present with simple, uncomplicated, diverticulitis. This occurs when microperforation is immediately walled off, resulting in localized inflammation. Complicated diverticulitis occurs in 25% of patients and refers to macro- or gross perforation with abscess or peritonitis, as well as those who develop complications including stricture or fistula.
Patients with acute diverticulitis classically present with abdominal pain and fullness localized to the left-lower quadrant. The average age of presentation is 62 years. The severity of abdominal pain ranges from mild to severe, often described as steady aching or cramping. It often resembles acute appendicitis except that it is situated in the left-lower quadrant. Occasionally, pain is suprapubic, in the right-lower quadrant, or throughout the lower abdomen depending on the location of the sigmoid and the distribution of disease. Changes in bowel habits, including constipation, diarrhea, or both are common. Dysuria is indicative of inflammation adjacent to the bladder. Nausea and vomiting may be present depending on the location and severity of the inflammation. Physical findings characteristically include low-grade fever, mild abdominal distention, and left-lower quadrant tenderness. There may be a palpable mass. Leukocytosis is common.
Acute diverticulitis can also present with other nontypical symptoms. Small bowel obstruction may occur if a loop of small bowel becomes entrapped in inflammatory tissue. Free perforation of a diverticulum can result in generalized peritonitis rather than localized inflammation. Episodes of recurrent diverticulitis may produce mild symptoms until a complication such as stricture or fistula develops that prompts the patient to seek medical attention. The course of diverticulitis may be insidious, particularly in the elderly. Patients may present with vague abdominal pain associated with an abscess or recurrent urinary tract infections from a colovesical fistula. In some cases, pain and inflammatory signs are not marked, but a palpable mass and signs of large bowel obstruction are present, so that carcinoma of the left colon seems the more likely. Diagnosing malignancy can be difficult in the setting of inflammation.
Plain abdominal films are generally not useful unless they show free abdominal air from a diverticulum that has perforated. Other nonspecific findings include ileus, partial colonic obstruction, or left-lower quadrant mass.
CT scan of the abdomen and pelvis with intravenous contrast is the preferred initial imaging study. In most studies, CT has sensitivity, specificity, and accuracy greater than 90%, although 5% of patients will ultimately be found to have cancer as the underlying cause. It is also helpful to rule out other intra-abdominal pathology that may present in a similar fashion. Findings include wall thickening, fat stranding, and diverticula. Complications such as abscess or fistula may be evident (Figure 30–13). Findings on CT scan may also be predictive of the need for surgical intervention or successful nonoperative expectant management. The Hinchey classification was developed in 1978 to help guide clinical decision making for patients with complicated disease and standardize radiographic reporting. These have been updated to reflect improved resolution of CT and currently include the following stages: (0) mild clinical diverticulitis; (1a) pericolic inflammation or phlegmon; (1b) pericolic or mesocolic abscess; (2) pelvic, intra-abdominal, or retroperitoneal abscess resulting from an extension of a pericolic abscess; (3) purulent peritonitis; and (4) feculent peritonitis.
CT scan showing sigmoid colon involved with diverticulitis. Note the pericolonic stranding, bowel wall thickening, and intramural abscess.
Colonoscopy is not needed for the evaluation of a patient presenting with classic signs, symptoms, and imaging. However, differentiating acute diverticulitis from other pathology such as IBD, carcinoma, and ischemic colitis can be difficult. If endoscopy is determined to be necessary for appropriate management, a delayed examination after inflammation has subsided is preferred. If timing is critical, then a sigmoidoscopy with low insufflation is recommended over colonscopy to reduce the risk of perforation.
Acute diverticulitis presents with such variation that the differential diagnosis is broad. It may simulate appendicitis, perforated colonic carcinoma, obstruction with strangulation, colonic ischemia, Crohn disease, cystitis, infectious colitis, and gynecologic disease such as pelvic inflammatory disease, tubal pregnancy, and tubo-ovarian abscess. Differentiation from appendicitis is especially difficult when a redundant sigmoid colon lies in the right-lower quadrant. Free perforation with generalized peritonitis is difficult to differentiate from the other causes of perforation. A thorough history and physical examination as well as imaging studies may be helpful in differentiating these conditions. Colonoscopy is usually deferred upon initial presentation of suspected acute diverticulitis, but may be useful in cases with a high suspicion of carcinoma, vascular insufficiency, or inflammatory disease of the colon. It can be difficult in some cases to rule out carcinoma of the colon, particularly in the more silent forms of diverticulitis that present with a mass or fistula. Occasionally the diagnosis may not be known until the surgical specimen is examined by the pathologist.
The clinical spectrum of diverticulitis includes complications such as free perforation, abscess, fistula, and obstruction. Fecal peritonitis requires immediate surgery. Abscesses can often be drained percutaneously. Fistulas most commonly involve the bladder or colon, but may also extend to involve the ureter, urethra, vagina, uterus, small bowel, ovaries, fallopian tubes, perineum, and abdominal wall. Colonic obstruction is usually slow in onset and incomplete. Small bowel obstruction may result from inflammatory involvement of the small bowel.
Approximately 80% of patients with mild acute diverticulitis (Hinchey 0 and Ia) can be managed on an outpatient basis. However, hospitalization should be considered in patients with mild attacks if they are elderly, immunosuppressed, or have significant comorbidities including diabetes or renal failure. Any patient will need inpatient treatment if there is significant pain, inability to tolerate oral intake, or there is evidence of severe systemic illness. Patients not requiring hospitalization are generally treated with a clear liquid diet, broad spectrum antibiotics (ciprofloxacin and metronidazole or amoxicillin-clavulanate), and close follow up, although this management strategy is largely historical and is being challenged. There is evidence that patients with uncomplicated diverticulitis do not require antibiotics. A recent trial showed no difference in hospital stay, development of complications, or recurrence within 1 year. Patients who were pregnant, immunosuppressed, or septic were excluded.
For those patients requiring hospitalization, treatment depends on the severity of presentation. Generally, patients are managed with bowel rest, intravenous fluids, and systemic broad-spectrum antibiotics. Common regimens cover colonic flora and are chosen based on the patient’s allergies and previous antibiotic exposure. Common regimens include a beta-lactam/beta-lactamase inhibitor, a carbapenem, or the combination of a fluoroquinolone plus metronidazole. As clinical manifestations resolve, oral feeding is resumed gradually, initially with a low residue diet. After recovery, a high fiber diet is prescribed if there is no stricture, although this intervention has not been shown conclusively to reduce recurrence. Conservative management is successful in up to 85% of patients. Repeat CT or intervention is indicated when patients fail to improve or if there is clinical deterioration over the initial 48 hours of medical therapy. This often indicates progression to complicated disease that may require surgery.
Over the last decade, more and more patients are being managed conservatively, which has prompted study into strategies to prevent subsequent episodes. Small randomized trials have been conducted on patients who developed diverticulitis twice in 1 year. Mesalamine and rifaximin taken at 1 week intervals every month decreased symptoms and recurrence compared with rifaximin alone. Two small trials of probiotics have shown no significant improvement. However, it has been shown that avoidance of nuts, popcorn and seeds does not reduce the risk of diverticulitis and thus, patients do not need to be counseled to do so.
Patients with diverticulitis complicated by phlegmon or small abscess without peritonitis (Hinchey Ib) are candidates for conservative treatment. However, large abscesses (> 3 cm) are less likely to resolve with conservative management and should be drained percutaneously if possible. This provides source control and generally results in clinical improvement within days. Percutaneous treatment of an intra-abdominal abscess allows surgical intervention to be performed on an elective basis when there is reduced risk of complications and higher probability of a one-stage operation without a stoma.
Recent studies examining the natural history of diverticulitis have demonstrated that over a period of 10 years, recurrent diverticulitis following nonoperative management is expected in 10%-30% of patients. In patients who have a recurrence, a similar proportion will have a third episode. Recurrences tend to occur with similar severity of the previous episode and patients who require urgent surgery usually do so during the first presentation. In other words, it is rare for a patient with a recurrence to require urgent surgery. This indicates a generally benign course for uncomplicated diverticulitis and calls into question the potential benefits of elective prophylactic surgery for patients with a history of acute diverticulitis.
In addition, elective sigmoid colectomy is not without risks. A retrospective review found that 20% of patients experience fecal incontinence, urgency, or incomplete evacuation after sigmoid resection for diverticulitis. The exact indications for surgery have yet to be defined, but overall there has been a general decrease in elective colon resections for diverticulitis in the past 10 years. The American Society of Colon and Rectal Surgeons (ASCRS) guidelines recommend that surgery is offered on an individual basis. Consideration should be given to the patient’s previous episodes, frailty, reliability, and access to medical resources. Surgery is generally reserved for complicated disease such as abscess, perforation, stricture, fistula, or high risk patients such as those who are immunologically suppressed. Surgery should also be considered in patients in whom an underlying cancer cannot be excluded.
When interval colectomy is recommended, it is generally delayed by 6-8 weeks to allow resolution of acute inflammation that may add difficulty to the operation. There is evidence that delaying surgery increases the rate of a successful laparoscopic resection with primary anastomosis, which is possible in more than 90% of patients. However, delaying surgery comes with the small but significant risk (2%) of interval development of recurrent severe diverticulitis requiring emergency surgery with high morbidity. Further study is required to determine the optimal timing of surgery.
Definitive resection for sigmoid diverticulitis should include the sigmoid colon distally to the uninvolved rectum. The proximal extent of resection should be the point at which the bowel is soft and appears healthy—this generally includes the entire sigmoid colon. It is unnecessary to resect additional bowel proximally; even if it is involved with diverticula, as they are unlikely to become symptomatic (Figure 30–6). Laparoscopy has been shown in randomized trials to decrease hospital stay and postoperative pain without increased complications; however, it is a technically challenging operation that should be undertaken only by surgeons comfortable with the technique. In some cases, even in experienced centers, laparoscopy may not be possible due to persistent inflammation and an open approach is required.
A subset of patients will present with colonic stricture as a result of chronic inflammation and scarring. This generally results in symptoms of partial obstruction. If an inflammatory stricture is diagnosed after radiographic and endoscopic evaluation, elective resection is recommended. The distal extent of resection should always include the rectosigmoid junction so that the proximal colon is anastomosed to healthy proximal rectum.
Less than 10% of patients will present with complications requiring urgent surgery. Indications include uncontrolled sepsis and failure to improve with medical therapy or percutaneous drainage. There is a lower threshold for surgery for immunocompromised patients given their greater risk of morbidity and mortality with medical management. These are generally features found in patients with Hinchey III or IV disease.
At laparotomy for severe acute diverticulitis, exploration may reveal an inflammatory mass involving large bowel, mesocolon, mesentery, omentum, and sometimes small bowel. Except in cases of free perforation with generalized fecal peritonitis, the diseased diverticulum is not often visible. The type of operation performed is dependent on the extent of colonic inflammation, the amount of peritonitis, the patient’s general condition, comorbidities, and nutritional status, the extent of blood loss, and the surgeon’s experience and preference.
Ideally, a resection with primary anastomosis is performed as a one-stage procedure. It may not be possible to perform a primary anastomosis if there is gross contamination or infection in the surgical field because of the increased risk of anastomotic leakage. In patients who can tolerate an anastomosis but are still considered high risk, a diverting loop ileostomy is an option.
However, if the risk of an anastomosis is perceived to be too high, two options are available. The standard is the Hartmann procedure, which is a two-stage operation. At the initial operation, the diseased bowel is removed, the proximal end of the colon is brought out as a temporary colostomy, and the distal colonic stump is closed (Figure 30–6). Intestinal continuity is restored in a second operation after the inflammation subsides. There have been reports in the literature of Hinchey III patients having laparoscopic washout and drainage without resection as an alternative to resection. This approach has not been widely adopted and a randomized controlled trial is currently underway to compare this approach with the Hartmann procedure. Increasingly, percutaneous drainage of abscesses avoids the need for staged procedures and allows for primary resection with anastomosis once the inflammation has resolved. However, if percutaneous drainage is unsuccessful, operative drainage is indicated.
A three stage procedure, consisting of diversion and washout followed by resection of the diseased bowel at a second operation, and finally colostomy takedown, is not advised due to the ongoing inflammation of the diseased bowel and associated morbidity despite fecal diversion. However, if the patient will not tolerate a resection, this is an option.
Colonoscopy is recommended 6-8 weeks after the resolution of symptoms and prior to elective surgical resection to rule out other underlying pathology such as IBD and cancer. Although the presence of malignancy is less than 5% in patients with a radiographic diagnosis of acute diverticulitis, it is especially important to exclude malignancy in the presence of rectal bleeding stricture, or mass. The entire colon should be evaluated prior elective resection for presumed diverticular disease.
The mortality for diverticulitis can be divided by Hinchey stage. Patients with stage I or II disease have a mortality of less than 5%, stage III 13%, and stage IV 43%. Approximately 25% of patients hospitalized with acute diverticulitis require surgical treatment. The operative mortality rate is about 5% in recent reports, compared with 25% historically. Some of this improvement is attributable to the greater use of percutaneous drainage.
Diverticulitis recurs in one-third of patients managed conservatively and in 2%-10% of patients after surgical resection. Most of these recurrences develop within the first 5 years and are most commonly in the rectosigmoid junction due to inadequate resection. More study is required prior to the routine use of mesalamine and probiotics to reduce this risk.
et al.: Impact of early or delayed elective resection in complicated diverticulitis. World J Gastroenterol 2011 Dec 28 ;17(48):5274–5279.
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MA: Review of current classifications for diverticular disease and a translation into clinical practice. Int J Colorectal Dis 2012 Feb;27(2):207–214.
et al.: Sigmoidectomy syndrome? Patients’ perspectives on the functional outcomes following surgery for diverticulitis. Dis Colon Rectum 2012 Jan;55(1):10–17.
et al.: A high-fiber diet does not protect against asymptomatic diverticulosis. Gastroenterology 2012 Feb;142(2):266–272.e1.
WD: Practice parameters for sigmoid diverticulitis. Dis Colon Rectum Jul 2006;49(7):939–944.
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LL: Lifestyle factors and the course of diverticular disease. Dig Dis 2012;30(1):35–45.
MA: Systematic review of medical therapy to prevent recurrent diverticulitis. Int J Colorectal Dis 2012 Sep;27(9):1131–1136.
Diverticulitis is the etiology of more than half of all colovesical fistulas. This complication occurs in 2%-4% of cases of patients. Other causes include colon cancer, bladder cancer, Crohn colitis, radiation exposure, trauma, and iatrogenic causes. They occur three times more often in men. This predilection is likely anatomical: in women the uterus and adnexa are situated between the colon and the bladder.
The most common presentation is recurrent urinary tract infection. Pneumaturia is reported by up to 70% of patients and fecaluria in up to 50% depending on the size of the fistula. There are no specific physical examination findings, although some patients may have a palpable pelvic mass. There is usually no leukocytosis. Urine analysis is often indicative of urinary tract infection and cultures are polymicrobial. CT of the pelvis with rectal contrast is the most sensitive imaging study and will often show a segment of inflamed colon and bladder wall with air in the bladder. The fistulous connection is rarely seen. Endoscopy and cystoscopy may reveal inflammation at the site of the fistula, but the fistula is rarely visualized. These tests are useful for ruling out malignancy prior to surgical intervention. If the diagnosis is still in question, ingestion of charcoal or poppy seeds with elimination in urine is diagnostic.
The treatment for symptomatic colovesical fistula is elective surgery. The operation should be delayed until any active inflammation (ie, from diverticulitis) has resolved. Up to 50% of colovesical fistulas will undergo spontaneous closure. In these patients, the decision to proceed with surgery depends on the underlying cause of the fistula. In most patients, surgery involves resection of the involved colon with a primary anastomosis. Large bladder fistulas are closed primarily, but most often they do not require closure but are left to close spontaneously with Foley catheter drainage. However, in malignant fistulas, the tract should be excised en block with the colon and the involved bladder wall, which can be repaired primarily. Omentum is interposed between the anastomosis and the bladder. A urinary catheter is used to decompress the bladder for 5-10 days after surgery. The optimal timing of catheter removal or need for urine cultures or cystogram has not been prospectively validated.
In minimally symptomatic patients at high risk for surgery, conservative management with intermittent antibiotics may be successful. A trial of medical management is also indicated in patients with Crohn colitis, in whom spontaneous closure may be possible.
The prognosis for colovesical fistula is related to the etiology and the general health of the patient. Recurrence is reported to be 4%-5% overall, but is highest in patients with fistulas secondary to radiation therapy and Crohn colitis.
C: Closing fistulas in Crohn’s disease–should the accent be on maintenance or safety? N Engl J Med Feb 26 2004;350(9):934–936.
F: Colovesical fistula caused by diverticulitis of the sigmoid colon: diagnosis and treatment. Urologe A 2012 Jul;51(7):971–974. [Translated to English]
CM: Management and outcomes of colovesical fistula repair. Am Surg 2012 May;78(5):514–518.
RECTOVAGINAL & COLOVAGINAL FISTULA
Colovaginal fistulae are commonly a complication of diverticulitis, especially in women with a history of hysterectomy. The most common cause of rectovaginal fistula is obstetric injury, followed by Crohn colitis, iatrogenic causes, malignancy, radiation, and trauma. Fistula between the lower third of the rectum and lower half of the vagina are classified as low rectovaginal fistulas, while high fistula are defined as those between the middle to upper third of the rectum and the posterior vaginal fornix. The most common presentation is feculent vaginal discharge, which may be mistaken for fecal incontinence. Patients may also report vaginal flatus, recurrent genitourinary infections, and dyspareunia. There is a significant negative impact on quality of life. A fistula may be observed on anoscopy, rigid sigmoidoscopy, and/or vaginal speculum examination in 85% of patients. Endorectal ultrasound (ERUS), CT with rectal contrast, or barium enema may confirm the diagnosis.
The treatment for recto- and colovaginal fistula is surgical. Colovaginal fistulas are often successfully managed with resection of the involved colon. The vaginal defect may be closed, but will generally close spontaneously if this is technically challenging. The optimal surgical treatment for rectovaginal fistula, on the other hand, is less clear. The treatment is largely based on etiology, individual patient factors and surgeon experience. Numerous procedures have been reported, including direct repair, fibrin glue, endorectal advancement flaps, vaginal advancement flaps, biologic mesh, tissue interposition, and rectal resection. Choice of repair depends on the etiology, size, and location of the fistula. However, the recurrence rate is disappointingly high, especially for patients with Crohn disease who have an ongoing source of inflammation. The optimal approach consists of aggressive medical treatment of the colitis and control of pelvic sepsis followed by surgery. However, reported recurrence rates are 25%-50%. Good results have been reported in patients with multiple recurrences using fecal diversion and repair with a gracilis or omental interposition flap or even proctectomy with permanent stoma.
I: A systematic review on advancement flaps for rectovaginal fistula in Crohn’s disease: transrectal vs transvaginal approach. Colorectal Dis 2010 Dec;12(12):1183–1191.
van der Hagen
CG, van Gemert
WG: Laparoscopic fistula excision and omentoplasty for high rectovaginal fistulas: a prospective study of 40 patients. Int J Colorectal Dis 2011 Nov;26(11):1463–1467.
C: Current treatment of rectovaginal fistula in Crohn’s disease. World J Gastroenterol 2011 Feb 28 ;17(8):963–967.
ACUTE LOWER GASTROINTESTINAL BLEEDING
Lower gastrointestinal bleeding refers to bleeding originating distal to the ligament of Treitz and involves the small bowel, colon, or rectum. Unlike upper GI bleeds, it occurs in predominantly elderly patients. It accounts for 20% of all GI bleeds and results in over 300,000 hospitalizations in the United States each year. The incidence appears to be increasing with time. Hematochezia refers to the passage of bright red blood, maroon blood, or clots per rectum. Classically, hematochezia indicates a lower GI source of bleeding, however, the color is a function of time spent in the intestinal tract. The black color of melena is the result of the oxidation of iron in hemoglobin. Bright red blood may stem from brisk esophageal variceal bleeding and melena may be the result of slow blood loss from a right-sided colon cancer.
Lower GI bleeding can originate from numerous sources. In elderly patients common causes include diverticula, angiodysplasia, malignancy, and ischemia. Younger patients are more commonly affected by IBD, solitary rectal ulcer, and infection. In the appropriate patient, bleeding may be related to coagulopathy, radiation injury, chemotherapy, or a recent procedure such as polypectomy. Chronic, low volume bleeding is seen in patients with malignancy, polyps, hemorrhoids, and fissures. The small intestine can be the source of bleeding in 5% of patients. Other more unusual causes include Meckel’s diverticulum (especially with ulceration from ectopic gastric mucosa), and aorto-enteric fistula.
Diverticulosis is the most common source of acute lower GI bleeding. Although bleeding occurs in only 5% of patients with diverticulosis, this presentation is common because of the high prevalence of diverticula in the general population. Diverticula form in areas of weakness where vasa recta penetrate the bowel wall. Structural changes in the bowel wall causes damage to the artery, which can lead to rupture. Diverticular bleeding often presents with painless and massive, but self-limited, hemorrhage. There is a dose-related increase in risk in patients who use NSAIDs. The long-term recurrence rate after the first episode is 25%, however, this increases to 50% after the second episode. Therefore surgery is commonly recommended in the elective setting after a patient presents with recurrent bleeding.
Angiodysplasia, or vascular ectasia, is found in 2% of asymptomatic patients on screening colonoscopy. They are generally located in the right colon in elderly patients and the jejunum in younger patients. These lesions are composed of dilated submucosal vessels with a central feeding vein that have a propensity to bleed spontaneously. Bleeding is typically intermittent and low volume. These patients often present in the outpatient setting with iron deficiency anemia and heme-positive stool. The diagnosis is made in some cases by colonoscopy, and colonoscopic therapy is often successful. There is no need to treat incidentally identified ectasias, as it is estimated that only 15% will cause clinically significant bleeding. Surgery is rarely indicated.
Colitis resulting from IBD, ischemia, radiation, or infection is a third cause of hematochezia. These tend to cause mild blood loss rarely requiring transfusion. These should be suspected in patients with abdominal pain and diarrhea. Acute ischemia may be caused by an acute decrease in blood supply from embolism, hypotension, or spasm. The watershed areas, including the splenic flexure and rectosigmoid junction, are most commonly affected. Infectious colitis can be diagnosed by stool culture. The most common organisms causing bloody diarrhea are E coli 0157-H7, Campylobacter, and Shigella. UC and Crohn colitis can also cause hematochezia during periods of acute inflammation. UC is more commonly associated with bleeding, although it can sometimes be difficult to distinguish between these two entities during an initial colonoscopy. However, the management in this setting is the same. Treatment with steroids and immunomodulators depends on the severity of the disease. This is discussed further in the section on colitis.
Chronic rectal bleeding, as seen in patients with colorectal polyps or cancer, and anorectal conditions can be evaluated electively. It is important to include colonoscopy in the evaluation, even if the bleeding can be explained by a benign condition such as hemorrhoids. This is especially true for patients who are more than 50 years of age or have a family history of CRC as it ensures that there is not a more proximal lesion that needs to be addressed.
Acute severe hemorrhage, however, is a potentially life-threatening problem, and prompt evaluation and treatment are critical. The first step in the management of these patients is to evaluate and manage the airway, breathing, and circulation (ABCs). A significant portion of these patients present with hemorrhagic shock. Resuscitation with intravenous fluids and blood products takes priority over initiation of diagnostic procedures. Large bore intravenous catheters should be placed and efforts made to keep the patient warm. Strong consideration should be given to transferring the patient to the intensive care unit or other closely monitored setting. Labs are checked for a coagulation profile, platelet count, and hematocrit. Any coagulation abnormalities should be corrected. Patients should be asked about the recent use of antiplatelet agents and blood thinners. Associated medical conditions should be identified and treated as soon as possible. Digital rectal and anoscopic examinations are performed first to look for an obvious source of bleeding and consideration should be given to the possibility of an upper source. A nasogastric aspirate should be examined to rule out an upper source in most patients. While this is not a perfect test, it can provide quick and useful information in a patient with a life threatening upper GI bleed. If blood is aspirated, there is confirmation of an upper source and EGD should be performed. If bile is aspirated, the source is more likely from the lower GI tract and the diagnostic work up should continue. The next step is determined by patient stability and availability.
A plan of management of acute lower gastrointestinal hemorrhage is outlined in Figure 30–14. Many decisions depend on the rate of bleeding, which is difficult to include in an algorithm. Bleeding stops spontaneously in 90% of patients before transfusion requirements exceed two units, but there are no reliable methods to predict who these patients are or who will have recurrent bleeding. Therefore all brisk GI bleeding must be taken seriously.
Plan for diagnosis and treatment of acute lower gastrointestinal hemorrhage. (NG = nasogastric)
There are a wide range of procedures that can be used for both diagnostic and treatment purposes in the acute setting. These include endoscopy, angiography, and radiographic techniques including radionuclide scintigraphy and CT angiography. There is no current gold standard and prospective trials are lacking.
Colonoscopy can be a very useful first test to localize the bleeding in stable patients in whom the colon is the suspected source. It has the advantages of being able to visualize the entire colon and any potential bleeding lesions, even after active hemorrhage has ceased. The sensitivity is 74%-100% and is limited by the fact that there is often no active hemorrhage at the time of the examination and stigmata of recent bleeding are seen in only 8%-43% of cases. This limits the utility of preventative treatment in cases with multiple possible sources, such as diverticular bleeding. Depending on the lesion, clips, electrocautery, and/or sclerotherapy may be used. If there is a neoplastic lesion, it can be biopsied or removed. From an efficiency standpoint, colonoscopy makes sense as a first step because it is required at some point in all patients with hematochezia. The disadvantages, including availability of the procedure, need for sedation, and bowel preparation, often preclude its use. It is a generally safe procedure with complication rates of 0%-2%. In order to maximize the utility of colonoscopy, it should be done urgently versus electively. Prospective studies show that lesion identification is more common if colonoscopy is performed urgently versus electively (42% versus 22%), which facilitates the use of directed methods to control and prevent recurrent hemorrhage. In addition, early colonoscopy reduces length of stay and overall cost. Although this has not been shown to improve other outcomes, the power of these trials is limited by small sample size. If the patient is stable and EGD and colonoscopy are both normal, a capsule endoscopy or double balloon enteroscopy may be performed to evaluate for a small bowel source.
If there is ongoing active hemorrhage, a radionuclide scan may be considered. It is used as a screening examination to identify patients in whom angiography may be useful. It utilizes 99mTc-labeled red blood cells. The accuracy increases with increased bleeding rates, but has been reported to detect hemorrhage as low as 0.1 mL/min. Radionuclide imaging is particularly useful in patients with intermittent bleeding owing to the long half-life of the tracer. This allows patients to be scanned on multiple occasions during symptomatic periods. In patients with active bleeding, scans are sensitive and specific for identifying the presence of hemorrhage into the GI tract, however they are unable to precisely localize the source in most circumstances. Once bleeding has been confirmed, angiography is performed for localization and possible treatment. This method has been criticized for causing a delay in therapeutic intervention, although it can prevent angiography in patients who are unlikely to benefit.
CT angiography is a newer technique that is growing in popularity as the technology improves. It does require active bleeding, but can identify the location of bleeding in patients with a rate as low as 0.3 mL/min. Unlike radionuclide scanning, CT angiography can localize bleeding, making for a more accurate and timely intervention by formal angiography. The disadvantages include the additional radiation and contrast exposure for a diagnostic test that cannot be used to treat any identified lesion.
If the radionuclide scan or CT angiogram is positive, it can be followed by selective mesenteric angiography, especially if the source appears to be in the small bowel. Angiography requires ongoing hemorrhage of at least 0.5 mL/min and will likely be of no use if the imaging tests are negative. During angiography, if the site of bleeding is demonstrated, which occurs in 40%-86% of patients, vasopressin or embolization can be used to treat the feeding vessel. Embolism is used if possible because re-bleeding is observed in up to 50% of patients treated with vasopressin alone. Embolization is successful 80%-90% of patients when followed for 30 days. Vascular ectasias can be diagnosed by angiography based on a characteristic pattern of an early filling vein, a vascular tuft, and a delayed emptying vein. These lesions should not be treated if bleeding is not demonstrated as they are quite prevalent and usually asymptomatic. The risks of angiography have decreased with the development of super-selective embolization, however, minor complications occur in 26% and major complications (including death and need for surgery) occur in 17%. One must be especially careful in patients with pre-existing renal insufficiency or diabetes, where the combination of hypovolemia and a large dye load creates a high risk for renal failure. In addition, angiography can rarely provide details about the cause of the bleeding and further work up is required after successful treatment.
In patients who have ongoing hemorrhage and a negative the radionuclide scan, colonoscopy should be considered. This can sometimes be performed successfully in the actively bleeding patient without a bowel preparation because blood acts as a cathartic. Even so, colonoscopy in this situation is difficult. However, a complete examination to the cecum is possible in 55%-70% of patients and there is suggestion that the risk of perforation is increased. Endoscopic therapeutic measures can be applied in up to 40% of patients, with success in half of them. Some gastroenterologists favor performing a bowel preparation under urgent conditions. There are multiple regimens, but usually these consist of a large volume preparation (6-8 L) over a short period of time (4 hours) which increases the chances of electrolyte abnormalities, aspiration, and results in a poor to fair prep in more than half of patients.
The majority of lower GI bleeds will stop spontaneously or be controlled by colonoscopy or angiography. However, 10%-25% of patients will have continued or recurrent bleeding and ongoing shock. Surgery should be considered once the transfusion requirement exceeds six units of blood. However, localization of bleeding is critical to the success of the procedure and the reduction of morbidity and mortality. Rarely, the bleeding site has been localized conclusively and the procedure is limited to segmental colonic resection. The mortality rate is less than 10%. When the source is unclear, intraoperative endoscopy can be performed to try to localize the source. If the patient continues to be unstable and the bleeding is suspected to be in the colon, a total abdominal colectomy may be required. This carries a mortality of 10%-30%. This is a fortunately rare occurrence today with improvements in imaging, endoscopy, and interventional techniques.
Up to 90% of lower GI bleeds will stop spontaneously; however, 25% of patients will experience recurrent bleeding. Mortality has been reported in up to 3.6% of patients.
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Volvulus involves rotation of a segment of the intestine on an axis formed by its mesentery (Figure 30–15). This results in a closed-loop obstruction and is therefore a surgical emergency. Luminal obstruction occurs when the bowel rotates 180 degrees. If the bowel rotates 360 degrees, the veins are occluded and arterial flow is interrupted. This leads to ischemia, followed by necrosis and perforation if prompt treatment is not instituted. Sigmoid volvulus can be complicated by the additional development of cecal perforation in patients with a competent ileocecal valve. Physiologically this forms a second closed loop obstruction because the proximal colon is unable to decompress into the small bowel. In this situation, the cecum is at greatest risk of perforation by the law of LaPlace because it has the largest diameter.
Volvulus of the sigmoid colon. The twist is counterclockwise in most cases of sigmoid volvulus.
Most cases of volvulus in the United States involve the cecum or sigmoid colon. A minority of patients present with volvulus of the transverse colon or splenic flexure. Volvulus accounts for 5% of all cases of large bowel obstruction in the United States. In pregnant women, volvulus accounts for 25% of intestinal obstructions; most commonly in the third trimester. This may be secondary to the displacement of the colon by the enlarging uterus.
Cecal volvulus often occurs in patients with a hypermobile cecum as a result of incomplete embryologic fixation. The average age of presentation is 53 years. This is in contrast to sigmoid volvulus, which tends to occur in elderly or institutionalized patients who experience high rates of constipation and associated motility disorders. It is thought that a long sigmoid colon with an associated narrow-based mesentery is a risk factor. In parts of Africa and the Middle East, sigmoid volvulus accounts for about 50% of bowel obstructions and tends to effect younger, healthy, male patients. In South America, it is seen in association with megacolon in patients with Chagas disease.
Cecal bascule accounts for 10% of cecal volvulus. It involves anterior-superior movement of the cecum, causing obstruction at the site of the transverse fold in the ascending colon. Patients may describe intermittent bloating, pain, and obstructive symptoms improved by lying down and massaging the abdomen. Mesenteric blood flow is not compromised because there is no twist in the mesentery. However, without treatment these patients are still at risk of gangrene and perforation as a result of the closed loop obstruction.
The cecum and terminal ileum are involved in the rotation, so the symptoms generally include those of distal small bowel obstruction. Severe intermittent colicky pain begins in the right abdomen. Pain eventually becomes continuous, and the patient will experience the classic symptoms of obstruction: vomiting, distention, and obstipation. Patients may report a history of similar but milder attacks.
Imaging studies are the key to diagnosis. In the early stages, a plain film of the abdomen may show single fluid level that may be mistaken for gastric dilation. In later stages there may be a hugely dilated ovoid cecum that favors the epigastrium or left-upper quadrant. It is classically described as the “coffee bean” sign. In cecal volvulus, the dilated loop points toward the right-lower abdominal quadrant. If a film is taken later in the course, the x-ray may show classic findings of small bowel obstruction superimposed on the cecal volvulus. The distal colon will be decompressed. The success rate of diagnosis based on plain abdominal films is extremely variable, ranging from 5% to 90%. CT shows a distended cecum, often with a mesenteric swirl sign, indicating the rotation of the mesentery. Ischemia and necrosis can be identified by a lack of bowel wall enhancement.
Sigmoid volvulus presents in a similar fashion to cecal volvulus. Symptoms include intestinal colic, nausea, and obstipation. Distention tends to be more pronounced in sigmoid volvulus. There may be a history of chronic constipation and dysmotility or transient attacks in which spontaneous reduction of the volvulus has occurred. Abdominal x-rays show a markedly distended loop of bowel like a “bent inner tube” that has lost its haustral markings rising up out of the pelvis extending towards the diaphragm. Barium enema reveals a pathognomonic “bird’s beak” deformity with spiral narrowing of the upper end of the lower segment (Figure 30–16). CT should be performed in cases where the diagnosis is unclear as it can demonstrate a dilated sigmoid loop with a mesenteric swirl sign, indicating the mesenteric twist. As with cecal volvulus, the pattern of bowel wall enhancement may help identify patients with ischemia and necrosis of the bowel wall.
Volvulus of the sigmoid colon. Barium enema taken with the patient in the supine position. Note the massively dilated sigmoid colon. The distinct vertical crease, which represents juxtaposition of adjacent walls of the dilated loop, points toward the site of torsion. The barium column resembles a “bird’s beak” or “ace of spades” because of the way in which the lumen tapers toward the volvulus.
Cecal volvulus must be differentiated from colonic pseudo-obstruction and from other causes of small bowel and colonic obstruction. Sigmoid volvulus mimics other types of large bowel obstruction. Although x-ray examinations can be helpful, they are often not diagnostic for volvulus, and often a CT is performed which eliminates other causes of the abdominal pain and can provide additional information about the presence of complications.
Early diagnosis and treatment are imperative because the involved segment of colon is at risk of gangrene and perforation. The first step in the management of these patients is fluid resuscitation and correction of electrolyte imbalances. Vital signs and urine output should be monitored and a nasogastric tube placed. If there is evidence of ischemia, necrosis, or perforation, antibiotics should be administered as the patient is prepared for emergency surgery.
Many techniques have been described for managing patients with cecal volvulus and cecal bascule, but the recommended treatment is ileocecectomy. This can be done via the laparoscopic or open technique depending on the clinical scenario and surgeon preference. If there is necrotic bowel, the blood supply is ideally controlled prior to releasing the volvulus in an attempt to reduce the systemic release of the potentially infected, acidotic, and hyperkalemic fluid that can cause cardiac arrest. In unstable patients, the bowel can be left in discontinuity and anastomosis performed at a second look laparotomy. However, a primary ileocolic anastomosis is almost always possible. This approach is associated with less than 5% mortality. Cecopexy (suture fixation of the bowel to the parietal peritoneum) and tube cecostomy (placement of a decompressive transabdominal drain) has been used to avoid a resection and anastomosis in the acute setting, however, these techniques have generally been abandoned due to high rates of both recurrence (30%) and complications (50%). Colonoscopic decompression may be attempted if an expert is available, especially in patients who have serious comorbidities that would make operation hazardous. However, this is successful in less than half of patients. This treatment is contraindicated in patients with suspected strangulation, which occurs in about 20% of cases.
In contrast, sigmoid volvulus without strangulation is more commonly treated initially by urgent endoscopy. A flexible sigmoidoscope or colonoscope is advanced to the obstruction. Under direct visualization, the colon is insufflated and the tip of the scope is used to apply gentle pressure. In 70%-90% of patients, decompression is achieved with the immediate release of gas and stool. The mucosa can then be inspected for signs of ischemia. If there is no evidence of ischemia, the patients is ideally scheduled for resection of the affected bowel with primary anastomosis during the same admission. Half of patients managed with decompression alone will have a recurrence within the first year. However, in patients with severe comorbidities, surgery may need to be delayed or may not be an option. Urgent surgery is indicated if strangulation or perforation is suspected or if endoscopic decompression is unsuccessful. In this case, primary anastomosis is not usually possible and a Hartmann’s procedure with washout is performed.
The outcome for patients with volvulus depends on comorbidities, the urgency of the surgery, and the presence of strangulation or perforation. The mortality rate for patients with cecal and sigmoid volvulus is less than 10%, but this increases to 30%-50% if strangulation or perforation has occurred. Patients who undergo semi-elective resection after endoscopic decompression have a mortality rate less than 10%.
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et al.: Colonic volvulus: presentation and management in metropolitan Minnesota, United States. Dis Colon Rectum 2012;55:444–449.
J: Management of sigmoid volvulus: is early surgery justifiable? ANZ J Surg 2013 Jan;83(1-2):74–78.
INFLAMMATORY BOWEL DISEASE
Inflammatory bowel disease (IBD) refers to UC, Crohn disease (CD), and indeterminate colitis. The cause of IBD is not known. The disease is likely the result of a combination of genetic, environmental, and host immune response factors.
There is a positive family history of IBD in 15%-40% of patients. Crohn disease seems to have a stronger genetic link than UC. Genome-wide association studies initially identified normal variants of multiple loci associated with the development of IBD; however, these associations are still poorly understood. These genetic associations are heterogeneous and have precluded the development of a useful screening test.
It is postulated that the interplay between the immune system, normal microflora, and colonic epithelium is a factor in the development of IBD, but this is still being investigated. Patients with UC are known to have an increased concentration of normal bacterial flora compared to healthy controls; however, it is not known if this contributes to the disease process. The mucosal immune system has been implicated by the finding that patients with CD have a predominantly Th1 mucosal population, whereas patients with UC have a Th2 predominance. An autoimmune component is suggested by circulating perinuclear antineutrophil cytoplasmic antibody (pANCA) and abnormally high levels of auto-IgG1 antibodies. These antibodies cross react with the epithelium of the colon, biliary tract, skin, eye, and cartilage and have been hypothesized to contribute to extraintestinal manifestations.
Environmental factors are also important. The use of NSAIDs has been associated with flares in patients with CD. Smoking has been shown to be a protective factor for UC. Smokers are less likely to develop the disease, and smoking cessation leads to worsening of disease in smokers with UC. For unclear reasons, this disease is also less common in patients who have undergone appendectomy.
UC has a bimodal age distribution, with the first peak between ages 15 and 30 years and a second, smaller peak in the sixth to eighth decades. The annual incidence varies from 1 to 20 per 100,000, and the prevalence is 8-246 per 100,000. UC is more common than CD in adults but less common in children. The disease is found worldwide but is more common in Western countries and the incidence is increasing in Asia. This finding has also contributed to the theory of bacterial flora contributing to the development of the disease.
UC is a diffuse but contiguous mucosal inflammatory disease. Abscesses form in the crypts of Lieberkühn and penetrate the superficial submucosa. In the acute setting, neutrophils predominate whereas in the chronic setting, the infiltrate is largely composed of lymphocytes and plasma cells. There are no granulomas. The overlying mucosa sloughs as the inflammation spreads. Vascular congestion and hemorrhage are prominent, and there is often diffuse thickening of the muscularis mucosa. The normal tissues surrounding the ulcerated areas appear endoscopically protruberant and thus are called pseudopolyps. Except in the most severe forms, the muscular layers are spared. In fulminant disease, the full thickness of the colon wall can be involved, which leads to dilation and ultimately perforation. In patients with long standing or severe disease, the colon becomes shortened and loses its normal haustral markings.
UC classically starts at the rectum and extends proximally without skip lesions. The disease is confined to the rectum (proctitis) or up to the rectosigmoid region (proctosigmoiditis) in at least half of patients. The disease is classified as left-sided colitis if it involves the descending colon, extensive colitis if it extends proximal to the splenic flexure, and pancolitis if the cecum is involved. In patients with pancolitis, a few centimeters of terminal ileum may be involved by proximity in patients with an incompetent ileocecal valve. This is termed backwash ileitis and can make the differentiation of UC from CD challenging. There are no strict diagnostic criteria, but generally a clinical and histologic appearance of UC without evidence of CD is enough to establish a diagnosis and initiate treatment.
Patients commonly report frequent, small volume watery stools mixed with blood, pus, and mucus accompanied by tenesmus, rectal urgency, and even fecal incontinence. Many patients will report crampy abdominal pain and variable degrees of fever, vomiting, weight loss, malaise, and dehydration. The symptoms can be episodic with periods of spontaneous improvement or severe and unrelenting. Mild disease may be manifested only by loose or frequent stools, or occasionally constipation. In isolated instances, the only symptoms may be from extraintestinal manifestations such as arthropathy or pyoderma.
If the disease is mild, physical examination may be normal, but in severe disease the abdomen is tender and distended. Severe rectal inflammation may result in considerable tenderness and spasticity of the anus during digital rectal examination. The examining finger may be covered with blood, mucus, or pus. Perianal disease can occur in UC patients as they do in the general population, but signs of anal disease should prompt a workup for CD.
A simple classification of the severity of an attack was devised by Truelove and Witt in 1955. The assessment of disease severity is based on six simple clinical signs including stool frequency, hematochezia, pulse, temperature, hemoglobin, and erythrocyte sedimentation rate (Table 30–8).
Table 30–8.Ulcerative colitis disease severity (based on the Truelove and Witt classification). ||Download (.pdf) Table 30–8. Ulcerative colitis disease severity (based on the Truelove and Witt classification).
|Symptoms ||Mild ||Severe ||Fulminant |
|Stools (per day) ||< 4 ||> 6 ||> 10 |
|Hematochezia ||Intermittent ||Frequent ||Continuous |
|Temperature ||Normal ||> 37.5°C || |
|Pulse (beats/min) ||Normal ||> 90 || |
|Hemoglobin ||Normal ||< 75% of normal ||Requires transfusion |
|ESR ||< 30 mm/h ||> 30 mm/h || |
There is no single diagnostic test for UC, although in unclear cases, serum antibody tests can help differentiate UC from CD. Serum pANCA are found in 60%-70% of patients with UC but also are found in up to 40% of patients with CD. In patients with IBD for whom the differentiation between UC and CD is unclear, the combination of a positive pANCA and negative anti-saccharomyces cerevisiae antibodies (ASCA) has a specificity of 97%, sensitivity of 48%, and a positive predictive value of 75% for UC. A negative pANCA and positive ASCA has a positive predictive value of 86% for CD. Thus serologic testing in patients with IBD may be helpful when considered in the context of other clinical factors.
During an acute flare, basic laboratory tests are used to assist in determining the severity of disease. Anemia, leukocytosis, and an elevated sedimentation rate or C reactive protein is usually present. Severe disease leads to hypoalbuminemia, dehydration, and electrolyte abnormalities. There is often evidence of steatorrhea. To look for signs of superinfection, the stool should be sent for ova and parasite examination, culture (E. coli 0157:H7 and Campylobacter), and C difficile toxin assay.
In the acute setting, colonoscopy and barium enema should be avoided due to the risk of perforation. If needed for diagnosis, biopsies obtained by proctoscopy should be sufficient. Abdominal x-rays may show dilation of the colon, and can be used to detect free air when perforation is suspected. CT scan has become the most common imaging modality during an acute episode. CT will often show thickened rectum and colon with associated inflammatory changes, however, it does not often lend much to the clinical management of these patients.
Barium enema, which is now infrequently used, shows mucosal irregularity that varies from fine serrations to extensive ulceration with pseudopolyps. As the disease progresses, haustrations are gradually effaced, and the colon narrows and shortens because of muscular rigidity (Figure 30–17). Widening of the space between the sacrum and rectum is due either to periproctitis or to shortening of the bowel. The presence of a stricture should always arouse suspicion of cancer or CD.
Ulcerative colitis. Barium enema x-ray of colon. Note shortening of colon, loss of haustral markings (“lead pipe” appearance), and fine serrations at the edges of the bowel wall that represent multiple small ulcers.
In cases where the diagnosis is unclear, a small bowel series or CT enterography may be performed to look for involvement suggestive of CD.
Colonoscopy is an essential part of diagnosis and surveillance. The characteristic mucosal changes include loss of vascular pattern, granularity, friability, hyperemia, and ulceration. Pseudopolyps represent islands of normal mucosa against a background of inflamed, denuded bowel wall. These findings begin in the distal rectum and proceed proximally in a continuous fashion. In more advanced disease, the mucosa is purplish-red, velvety, and extremely friable. Blood mixed with mucus is evident in the lumen. If the mucosa is not grossly diseased, biopsy may be helpful to confirm the diagnosis. In the recovery phase, mucosal hyperemia and edema subside. The healing mucosa is typically dull and granular and has a neovascular pattern of telangiectatic vessels that differs from the normal pink mucosa. Patients with disease distal to the splenic flexure may have a “cecal patch,” an inflammatory lesion at the appendiceal orifice, that can be misidentified as a skip lesion associated with CD. In the acute setting, colonoscopy is important in determining the severity of disease and response to treatment. These patients are at increased risk for CRC. Screening colonoscopy begins 8-10 years after the initial diagnosis of pancolitis and 12 years after left-sided colitis. Surveillance for dysplasia should be done every 1-2 years. At least 30 random biopsies should be taken throughout the colon to detect dysplasia.
The differential diagnosis of patients presenting with new onset UC is extremely broad and includes all forms of colitis. Cancer and diverticulitis should also be considered. Infectious colitis can mimic UC but can also be superimposed on patients with underlying UC. Salmonellosis and other bacillary dysenteries are diagnosed by repeated stool cultures. Shigellosis may be suspected on the basis of a positive methylene blue stain for fecal leukocytes. Campylobacter jejuni is a common cause of bloody diarrhea; the organisms can be cultured from the stool, and serum antibody titers rise during the illness. Hemorrhagic colitis—a syndrome of bloody diarrhea and abdominal cramps but no fever—is associated with infection by E coli O157:H7. Legionella infections can mimic UC. Gonococcal proctitis is detected by culture of rectal swabs. Herpes simplex virus is the most common cause of nongonococcal proctitis in homosexual men. In patients with suspected amoebiasis, corticosteroids should be held until amebiasis is excluded by microscopic examination of stool, rectal swabs, rectal biopsies, or serologic tests.
Cases of histoplasmosis, tuberculosis, cytomegalovirus disease, schistosomiasis, amyloidosis, or Behçet disease may be very difficult to diagnose. Drug-induced colitis may be suspected based on the patient’s history. NSAIDs can cause mucosal inflammation and even strictures in the large intestine. Collagenous colitis may or may not be related to NSAID use. Watery diarrhea is the main symptom of this syndrome, endoscopy is grossly normal, and biopsies show a thickened band of collagen just beneath the mucosa. Ischemic colitis has a segmental pattern of involvement quite unlike the contiguous distribution of UC. Functional diarrhea can mimic colitis, but organic disease must be excluded before it can be concluded that the diarrhea is functional. Diversion colitis refers to inflammation of a previously normal segment of colon or rectum following construction of a temporary colostomy. Deficiency of mucosal nutrients may be responsible, and inflammation may be treated with topical application of short-chain fatty acids or restoration of intestinal continuity.
The most difficult differential diagnosis is between mucosal UC and Crohn colitis (Table 30–9). None of the features are specific for one disease, and often the differentiation can be made only after all the data have been assembled. Luckily, in the acute phase, the medical treatment is similar, however, the differentiation is important because it can dictate appropriate surgical therapy. About 10% of cases cannot be classified (indeterminate colitis).
Table 30–9.Comparison of various features of ulcerative colitis with those of Crohn colitis. ||Download (.pdf) Table 30–9. Comparison of various features of ulcerative colitis with those of Crohn colitis.
| ||Ulcerative (Mucosal) Colitis ||Crohn Colitis |
|Signs and symptoms || || |
|Diarrhea ||Marked ||Present; less severe |
|Gross bleeding ||Characteristic ||Infrequent |
|Perianal lesions ||Infrequent, mild ||Frequent, complex; may precede diagnosis of intestinal disease |
|Toxic dilatation ||Yes (3%-10%) ||Yes (2%-5%) |
|Perforation ||Free ||Localized |
|Systemic manifestations (arthritis, uveitis, pyoderma, hepatitis) ||Common ||Common |
|X-ray studies ||Confluent, diffuse ||Skip areas. Longitudinal ulcers, transverse ridges, “cobblestone” appearance |
| ||Tiny serrations, coarse mucosa, mucosal tags || |
| ||Concentric involvement ||Eccentric involvement |
| ||Internal fistulas very rare ||Internal fistula common |
| ||Colon only except in backwash ileitis; may be limited to left side ||Any portion of intestinal tract may be involved; may be limited to ileum and right colon |
|Morphology || || |
|Gross ||Confluent involvement ||Segmental involvement with or without skip areas |
| ||Rectum usually involved ||Rectum often not involved |
| ||Mesocolon not involved; nodes enlarged ||Thickened mesocolon; pronounced lymph node enlargement |
| ||Widespread, ragged, superficial ulceration ||Large longitudinal ulcers or transverse fissures |
| ||Inflammatory polyps (pseudopolyps) common ||Inflammatory polyps not prominent |
| ||No thickening of bowel wall ||Thickened bowel wall |
|Microscopic ||Inflammatory reaction usually limited to mucosa and submucosa; only in severe disease are muscle coats involved; no fibrosis ||Chronic inflammation of all layers of bowel wall; damage to muscle layers usual; submucosal fibrosis |
| ||Granulomas rare ||Granulomas frequent |
|Natural history ||Exacerbations, remissions; may be explosive, lethal ||Indolent, recurrent |
|Treatment || || |
|Response to medical treatment ||Good response in 85% of cases ||Difficult to evaluate; less well controlled over long term |
|Type of surgical treatment and response ||Colectomy with ileoanal anastomosis; proctocolectomy with ileostomy ||Segmental colectomy; total colectomy with ileorectal anastomosis; proctocolectomy if rectum severely diseased |
| ||No recurrence ||Recurrence common |
A. Extraintestinal Manifestations
Extraintestinal manifestations (EM) occur in approximately 21% of patients with UC. They are more common in women and patients with pancolitis. The pathogenesis is unknown, but it is thought that they may be a result of a systemic autoimmune process. A genetic component is suggested by the fact that they tend to cluster in families. Nearly 80% of patients who develop EM do so after the development of colonic symptoms, but a minority will present with EM prior to symptomatic colonic disease that may lead to a diagnosis of UC. The most common EMs are musculoskeletal (arthralgias, arthritis, ankylosing spondylitis), anterior ocular chamber inflammation (uveitis, iritis, scleritis, and conjunctivitis), skin (erythema nodosum, pyoderma gangrenosum), and primary sclerosing cholangitis (PSC) in order of decreasing frequency. PSC can lead to cirrhosis requiring liver transplant and puts the patient at increased risk for cholangiocarcinoma. For unclear reasons, patients with PSC also develop colorectal cancer at an increased rate. PSC is not improved with treatment of the colonic disease and may develop or progress after curative proctocolectomy. However, arthritis, ocular disease, and skin manifestations are known for paralleling disease activity. Most patients will develop only one EM, but a subset will develop multiple.
Patients with UC also develop symptoms as a result of the disease process in the colon, including iron deficiency anemia and malnutrition. They are at high risk for thrombosis, especially during flares. Patients are also at risk of developing complications from medical treatment using long-term corticosteroids such as diabetes, osteoporosis, cataracts, and adrenal insufficiency.
Gross hematochezia is common during acute flares of UC. In the chronic setting, patients frequently develop a chronic iron deficiency anemia. Ten percent of patients will require blood transfusion for bleeding during a flare. Massive hemorrhage is a potentially life threatening complication that occurs in up to 5% of patients. This is an indication for urgent colectomy and accounts for approximately 10% of all urgent colectomies in patients with UC.
Fulminant colitis occurs in less than 10% of all patients with UC, but in up to 50% of these patients, it develops during their initial presentation. This represents the most severe, acute form of the disease. Patients are systemically ill and develop inflammation extending into the muscular layer of the bowel. Electrolyte disturbances, especially hypokalemia, may contribute to toxicity and should be treated aggressively. Opioids and anticholinergics should be avoided. These patients should be fluid resuscitated and treated with broad spectrum antibiotics. Electrolyte disturbances should be corrected. A nasogastric tube is placed for patients with significant signs of distension. A CT scan can detect perforation or ischemia, as well as other causes of abdominal sepsis. Serial abdominal x-rays can trend colonic distention. However, if there is clinical deterioration or no improvement with maximal medical therapy over the course of 48-72 hours, surgery should be considered. Although barium enema is no longer used to diagnose toxic colon, one can see the classic findings in Figure 30–18. These include a thickened bowel wall and dilation of the lumen greater than 6 cm. Luminal air can be seen outlining irregular nodular pseudopolyps. However, patients do not need to have colonic dilatation to have toxic colitis.
Barium enema showing acute colonic dilation in ulcerative colitis. Note dilation of the transverse colon, the multiple irregular densities in the lumen that represent pseudopolyps, and the loss of haustral markings.
Colonic perforation is the most dreaded complication of severe acute UC and occurs in 3% of hospitalized patients. It is responsible for more deaths than any other complication. The risk of perforation is highest during the initial attack of the disease and correlates well with its extent and severity. It may also occur as a complication of endoscopy or barium enema in acutely ill patients. Patients with toxic colitis are especially vulnerable. Perforation is most common in the sigmoid or splenic flexure and may result in a localized abscess or generalized fecal peritonitis. Systemic therapy (corticosteroids and antibiotics) may mask the development of this complication. Therefore, serial abdominal examinations, laboratory tests, and abdominal imaging are important in detecting this complication.
Colorectal cancer risk increases above that of the general population 10 years after the onset of UC, although the rates vary widely between studies. The risk increases with the duration and severity of disease, and is higher in patients with a family history of CRC, extensive colitis, and PSC. Decreased risk in recent reports may be associated with improved medical treatment of colitis. Cancers in UC tend to be multicentric and broadly infiltrating. They are difficult to recognize endoscopically because they arise from small, flat areas of dysplasia located in a background of ulceration and inflammation. They do not follow the typical adenoma-carcinoma sequence seen in sporadic CRC in the general population. Newer techniques, including narrow-band imaging and chromoendoscopy may improve detection.
Colonoscopic surveillance is recommended beginning 8-12 years after the onset of colitis and continues at 1-2 year intervals. Ideally, approximately 48 random biopsies are taken throughout the colon and rectum to screen for dysplasia. Synchronous CRC is found in 20% of patients undergoing proctocolectomy for low-grade dysplasia, 40%-60% of patients with high-grade dysplasia, and 40%-85% of patients with dysplasia-associated lesion or mass (DALM) regardless of the degree of dysplasia. Low-grade dysplasia places the patient at a ninefold increased risk of developing CRC compared to UC patients without dysplasia. In addition, low-grade dysplasia has been reported to progress to carcinoma without progressing to high-grade dyplasia. IBD-associated cancers account for 1%-2% of all CRCs but occur in younger patients and confer a poorer prognosis. High-grade dysplasia and DALM are clear indications for proctocolectomy, and consideration should be given to patients with low-grade dysplasia. Intensive study is ongoing to identify more sensitive screening methods.
The goals of medical therapy are to stop an acute flare as rapidly as possible and to maintain remission of mucosal inflammation. Traditionally, medical management has been approached in a “step up” fashion, with treatment depending on the severity of disease (classified as mild, moderate, severe, or fulminant), the extent of colonic involvement, and history of previous response to treatment. However, a new paradigm of “top down” treatment has evolved for patients with severe disease as research has shown improved outcomes with more aggressive treatment. The endpoints of therapy have shifted away from symptomatic improvement to objective mucosal healing and steroid free remission. Mild to moderate disease usually can be treated on an outpatient basis. If the disease flare is refractory or progressive, hospitalization may be required. Patients with severe or fulminant disease may require inpatient treatment for supportive therapy (IV hydration, antibiotics, blood transfusion, and monitoring).
Mild to moderate disease is treated with sulfasalazine or 5-aminosalicylates, such as mesalamine, olsalazine, or balsalazide. Sulfasalazine is cheaper, but associated with more side effects and should not be given to sulfa-allergic patients. These drugs can be administered orally or topically in the form of suppositories or enemas in patients with disease limited to the rectum or sigmoid. Seventy percent of patients will respond to this regimen within 1 month. The remaining 30% are started on prednisone 40-60 mg/d. In patients who do not exhibit objective evidence of response or who remain steroid dependent, azathioprine, 6 mercaptopurine, infliximab, and adalimumab are additional options to induce and maintain remission.
In patients with severe disease, these initial steps are bypassed and treatment with intravenous glucocorticoids is initiated. In addition, biologic agents or immunomodulators are added. Infliximab, an anti-TNF antibody, tacrolimus and cyclosporine have been shown in randomized controlled trials to be effective for treatment of severe flares.
If these regimens are not successful, additional medications or surgery are considered. Multiple new drugs show promise in the treatment of patients with refractory disease. Newer biologic agents, such as certolizumab and natilizumab, as well as Tofacitinib, an oral Janus kinase inhibitor have been shown to be effective in inducing remission in patients with steroid refractory moderate to severe UC. Other treatments, such as stem cells and fecal transplants, are currently under investigation.
Once remission has been obtained, a maintenance regimen is required to prevent relapse in most patients. These regimens should be individualized based on the response to the induction regimen and revised as clinically indicated. For mild disease, mesalamine is commonly used. Patients unable to wean from steroids require intensified treatment. Azathioprine, 6 mercaptopurine, methotrexate, infliximab, adalimumab, or newer immunomodulators may be needed to successfully wean patients off steroids.
Indications for surgery fall under three broad categories: patients who require urgent or emergency surgery due to severe illness or complications during a flare, patients who have chronic intractable disease or medication intolerance, and those who require treatment for dysplasia or carcinoma. Twenty percent of patients who present with fulminant colitis will go on to require surgery. There have been no trials comparing medical therapy to surgery for any of these indications. Crohn disease should be ruled out in any patient in whom surgery is being considered, as a proctocolectomy, especially with J-pouch reconstruction, is inappropriate for these patients.
In the acute setting, emergency surgery is indicated for colonic perforation. Other complications, such as toxic megacolon, fulminant colitis, or uncontrolled hemorrhage are initially managed medically. However, if there is no improvement with aggressive medical therapy, surgery is warranted. There are no firm guidelines for how long patients should be treated medically prior to considering surgery. These patients are monitored closely for 48-72 hours. If there is clinical deterioration or no improvement, surgery is indicated.
Another group of patients in whom surgery is considered are those with intractable disease despite maximal medical therapy or those who cannot wean off steroids due to worsening symptoms. In children this may present with growth retardation. Adults may become physically debilitated, psychosocially limited, and experience poor quality of life. There may be medication intolerance, especially in those patients who are steroid dependent. Surgery is also considered for patients with severe extraintestinal manifestations that have developed in parallel with the UC flares such as peripheral arthritis, pyoderma gangrenosum, and ocular manifestations. These may respond to colectomy.
Patients who have biopsy-proven carcinoma are offered proctocolectomy as opposed to standard oncologic resection because this treats both the UC and the cancer. Further, colitis-related CRC tends to be widely infiltrative, multicentric, and difficult to visualize making standard oncologic resection dangerous. Patients with dysplasia or dysplasia-associated lesion or mass are also candidates for surgery as the risk for a synchronous or metachronous malignancy is high as discussed previously.
In the elective setting there are two surgical options. Proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the operation of choice in most patients because it provides intestinal continuity (Figure 30–19). However, total proctocolectomy with a permanent end ileostomy is indicated in a subset of patients. Factors include preoperative sphincter function, presence of carcinoma low rectal cancer, and the patient’s age, general health, and preferences. IPAA is contraindicated in patients with poor baseline sphincter tone or in whom a diagnosis of CD cannot be excluded. Both procedures are now increasingly performed laparoscopically with equivalent functional results and improved short-term outcomes.
View of the pelvis after colectomy and ileoanal anastomosis in a male. The J-pouch, shown here, is one of several types of reservoirs and is most commonly utilized. The pouch is anastomosed to the anal canal just above the dentate line.
A permanent end ileostomy may be desired by patients who have concerns about the postoperative complications or anticipate difficulty managing the changes in bowel function associated with the ileoanal pouch. Patients frequently experience greater than 10 bowel movements per day during the first 3 months. This eventually decreases to an average of 5-7 bowel movements per day. Twenty percent of patients experience nocturnal seepage or incontinence 1 year after surgery. The most common complications after surgery include small bowel obstruction, infertility, sexual dysfunction, and pelvic sepsis as a result of anastomotic or pouch leaks. Pelvic sepsis occurs in 25% of patients and is the most common cause of pouch failure. Pouchitis affects 40% of patients in the first 10 years after surgery. This is an idiopathic inflammation of the ileoanal pouch that causes abdominal pain, increased bowel movements, and bleeding. It is treated with antibiotics.
Proctocolectomy with IPAA can be performed as a one-, two-, or three-stage procedure. In the elective setting, a two stage procedure is most common, involving proctocolectomy with IPAA and diverting loop ileostomy at the first surgery followed by ileostomy reversal as a second surgery. A single stage operation (without diverting loop ileostomy) is performed only in the most ideal candidates. This approach eliminates the ileostomy-associated complications and avoids a second surgery at the increased risk of the potentially significant consequences of pelvic sepsis from an undiverted anastomotic leak. The three stage procedure is reserved for ill patients who would not tolerate the IPAA during the first surgery secondary to malnutrition or severe active disease. It is also useful in patients with indeterminate colitis in whom confirmation of UC may be made after pathologic evaluation of the surgical specimen allowing the safe formation of the IPAA. The first procedure is a subtotal colectomy with end ileostomy, followed by completion proctectomy, and IPAA. At the time of this procedure, an ileostomy may be avoided in selected patients, otherwise the ileostomy is reversed at a third operation. In the interval between subtotal colectomy and proctectomy, the residual disease in the rectal remnant improves with fecal diversion and if symptoms persist, it can be treated locally with suppositories or enemas.
Proctocolectomy involves mobilizing and resecting the entire colon and rectum. If IPAA is planned, the anal sphincter complex is left in place. The ileum is made into a reservoir most commonly with a “J” configuration (although multiple configurations have been described) and an anastomosis is created just above the dentate line (Figure 30–19). A diverting loop ileostomy is used to protect the anastomosis if there is any intraoperative concern about the anastomosis or if the patient has risk factors for impaired healing such as steroid exposure, anemia, diabetes, or malnutrition. Most of these patients will have been treated with immunosuppressants or immunomodulators in the preoperative period. Although these medications theoretically impact healing, there is no clear evidence to suggest that they increase surgical complications in the setting of diversion.
The continent ileostomy, which was first reported by Kock in 1969 is plagued by complications requiring reoperation in 50% of patients. It has largely been replaced with the IPAA and is mainly mentioned for historical purposes.
The mortality rate of UC has dropped sharply in the past two decades. First attacks are seldom fatal when treated by specialists. In one large series, emergency colectomy was required in 25% of patients with severe first attacks; 60% responded rapidly to medical therapy; and 15% improved slowly on medications alone. Overall, the colitis-related mortality rate during the year after onset is about 1%. Emergency colectomy has a mortality rate of 6%; most of these deaths occur in patients with preoperative perforation, a complication that has a fatal outcome in 40% of cases.
Compared to pancolitis, the long-term prognosis of ulcerative proctitis is excellent; only 10% of patients will develop colonic disease by 10 years, and the mortality rate is very low. In patients with pancolitis, the likelihood of operation during the first year is about 25% and the mortality rate is 5% over 10 years. Colorectal cancer in UC is more often diagnosed at an advanced stage than is sporadic cancer, but the stage-for-stage prognosis is the same. Screening with colonoscopy and biopsies seems to have reduced the cancer mortality rate, but there are still many patients who escape detection until the malignancy has progressed to an advanced stage. The operative mortality rate is less than 1% for elective colectomy.
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Approximately 45% of patients with CD have diffuse involvement of the GI tract; 30% have disease limited to the small bowel, 20% have disease limited to the colon, and another 5% have isolated anorectal involvement. Symptoms, including diarrhea, abdominal pain, constitutional effects, and extraintestinal manifestations are approximately the same in colonic and enteric disease. Fistulas, abscesses, and intestinal obstruction are more often complications of small bowel disease. Anorectal complications such as anal fistula, fissure, abscess, rectal stricture, as well as hemorrhage occur more commonly in patients with disease affecting the large bowel.
Patients present with abdominal pain, diarrhea, and systemic signs such as low-grade fevers, weight loss, and malaise. Symptoms are generally dictated by the distribution of disease, but patients with Crohn colitis may report urgency or mucous, blood, or pus per rectum. Patients with perianal disease may present with perianal pain or discharge. If the inflammatory process has caused structuring, partial obstructive symptoms may be present.
Radiographic features include sparing of the rectum, right colonic and ileal involvement, skip areas, transverse fissures, longitudinal ulcers, strictures, and fistulas. Typical anal lesions of CD include fissures, abscesses or fistulas. Large external skin tags are also common. The differential diagnosis is broad and includes all forms of colitis including UC, infectious and ischemic. Features differentiating CD from UC are summarized in Table 30–9.
Colonoscopy is indicated for diagnosis, evaluation for severity of disease, determining response to treatment, and screening for colorectal cancer. Colonoscopy with biopsy is a mainstay in diagnosis. Patients with Crohn colitis have rectal sparing about 50% of the time. Skip lesions are common, with irregular ulcerations separated by edematous or even normal-appearing mucosa. Patients with pancolitis appear to have similar risk profile for cancer as their UC counterparts. The risk of colorectal cancer in Crohn colitis patients is 4 to 20 times that of the general population. The 25-year risk of dysplasia in patients with Crohn colitis is 12%-25%. Data to support surveillance and management strategies for patients with Crohn colitis are limited and often extrapolated from UC patients. Routine annual colonoscopy with random biopsies is recommended beginning 8 years after the diagnosis. Surveillence should include high risk areas, such as segments of intestine excluded from the fecal stream, strictures, and fistulas with focused biopsies performed as needed.
Steroids are effective for acute attacks in up to 70% of patients, but they are not used for maintenance therapy because of the associated side effects and complications. Up to 45% of patients who initially improve with steroids will relapse upon tapering or withdrawal. Oral 5-aminosalicylates (sulfasalazine, 4 g/d; or mesalamine, 2-5 g/d) are effective treatment for Crohn colitis. Topical 5-aminosalicylates are beneficial for disease of the rectum and sigmoid and are often used to wean patients off steroids. Anal abscesses and fistulas require surgical drainage and seton placement to treat local sepsis, but healing is improved with biologic agents.
Immunosuppressants (azathioprine, mercaptopurine, methotrexate) are steroid-sparing drugs that seem to control Crohn colitis well enough that surgery is delayed or avoided. Biologic agents including infliximab and other anti-TNF therapies are effective for inflammatory CD and also specifically indicated for fistulizing or refractory disease. Patients who respond to infliximab induction should receive maintenance therapy. Adalimumab is an effective therapy for patients who are refractory or intolerant to infliximab. Newer human monoclonal antibodies, such as the anti-TNF natalizumab and anti-interleukin ustekinumab have shown promising results in preliminary clinical trials and are now being used more frequently for patients who initially responded to other agents.
Failure of medical therapy, neoplasia, and complications of CD are indications for surgery. Patients whose symptoms do not respond to medical treatment, are unable to achieve remission, have intractable weight loss, or have unmanageable side effects should be considered. The choice of operation depends on the severity and distribution of disease, but the general principle is bowel preservation, with resection of only diseased, actively symptomatic areas. In contrast to UC, CD is not cured surgically, and procedures are performed with palliation in mind. However, patients who have distal colon and rectal disease or multiple segments of disease often do better with a proctocolectomy. Disease tends to recur, especially at areas of intestinal anastomosis and short bowel syndrome is a major concern. Cigarette smoking is an independent risk factor for recurrence of CD after resection.
Strictures are more common in patients with longstanding disease. The use of CT or MR enterography is useful to localize the lesion. If the lesion is symptomatic and unresponsive to medical therapy, resection is indicated. If the lesion is asymptomatic, malignancy should be ruled out with biopsies or brushings. Lesions not amenable to surveillance should be considered for resection, as 7% are malignant.
Intra-abdominal abscesses may be managed with percutaneous drainage and antibiotics. Those who do not respond to conservative management may need an operation. Patients with CD are at risk of developing enterocutaneous and enteroenteric fistulas spontaneously or after surgical intervention, and if diagnosed, nutritional optimization and control of sepsis are of utmost importance.
Five percent of patients will develop severe or fulminant colitis. These patients should be treated in a similar fashion as patients with UC including bowel rest, intravenous fluids, broad spectrum antibiotics, and aggressive CD therapy. They should be closely monitored with serial abdominal examinations, laboratory tests, and imaging as indicated. Patients with CD more commonly respond to medical management than patients with UC. When patients require surgery, total abdominal colectomy with end ileostomy is the most common operation performed in the acute setting, although if by operative inspection the disease is limited to a specific part of the large bowel, this can be resected with creation of a colostomy and Hartmann’s pouch or mucous fistula. Isolated perforation without toxic megacolon is preferentially treated with segmental resection, as simple closure is associated with a higher mortality rate. Diversion is commonly performed in colonic perforations and occasionally for perforation of small bowel depending on the clinical status of the patient and the intraoperative findings.
Perianal complications include perianal abscess, fistula, ulcer, and fissure. These processes are treated using the same methods as are used in non-IBD patients, although these problems tend to be more complicated and chronic, requiring dedicated surgical follow-up. The key elements to treatment are elimination of sepsis and protection of the anal sphincter.
Dysplasia or cancer of the colon requires surgical treatment. Depending on the location and extent of disease, proctocolectomy or segmental resection is performed for high-grade dysplasia, dysplasia-associated lesions or mass lesions. Twenty percent of patients with high grade dysplasia are found to have carcinoma in the surgical specimen, and half of patients known to have cancer preoperatively are found to have remote dysplasia upon pathologic review. For this reason, total proctocolectomy with end ileostomy should be considered in patients found to have cancer or high grade dysplasia on surveillance colonoscopy.
Surgical procedures—like medical therapy—should be regarded as palliative, not curative, in patients with CD. Although recurrence rates are high and chronic disease is common, a productive life is usually possible with the aid of combined medical and surgical management. The mortality rate is about 15% over 30 years.
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Pseudomembranous colitis is caused by C difficile. C. difficile colitis was first reported in 1978 but the incidence and severity of infection is increasing with time. Of particular concern is the increasing virulence, with reports of antibiotic resistance and mutant strains with uncontrolled toxin production. Infection causes a range of illness from mild diarrhea to fulminant, life threatening colitis and is particularly dangerous in frail or immunocompromised patients.
Clostridium difficile is a spore-forming organism that is ubiquitous in the environment. It is a commensal gut organism that exists in 5%-15% of the general population and up to 57% of patients in long-term care facilities. The spores are dormant and extremely resistant to disinfectants and extreme environments. Spread by health care practitioners is reduced significantly by the use of standard contact precautions including disposable gowns and gloves and hand washing with water and soap. Alcohol-based hand sanitizers are not effective. Once ingested, the spore is reactivated after contact with bile salts in the small intestine.
The bacterium exists in both toxin-producing and nonproducing forms. Only the toxin-producing bacterium is capable of causing colitis. Toxins A, B, and binary toxin induce apoptosis and provoke inflammation. The epidemic-associated 027 strain is thought to have a mutation causing increased production of toxins A and B, as well as enhanced sporulation making it particularly virulent and transmittable. These toxins as well as a variety of nontoxin virulence factors cause pseudomembranous colitis.
Although C. difficile is commensal and the spores are easily transmitted, the presence of normal colonic flora is usually enough to prevent infection. Symptoms generally only occur when the normal flora is disrupted. Therefore, pseudomembranous colitis most often occurs in patients taking antibiotics. Clindamycin is historically the most common cause, but all antibiotics that alter the gut flora have the potential to cause infection. Pseudomembranous colitis may develop as early as 2 days after exposure to antibiotics but has been reported many weeks after they are discontinued. Other risk factors include surgery of the gastrointestinal tract, immunosuppression, and use of proton pump inhibitors and H2 blockers.
The most common symptom is diarrhea, which is usually watery, occasionally bloody, and has a characteristic foul odor. Other symptoms include colicky abdominal pain, vomiting, and fever. C. difficile infection may also cause a paralytic ileus and therefore, can present without diarrhea. Depending on the severity, patients may present with abdominal distention, tenderness, dehydration, and sepsis. The stool is usually positive for leukocytes. Radiographic studies may reveal colonic wall thickening due to submucosal edema. On abdominal films, this may appear as a “target sign.” CT scanning is reserved for patients with complicated disease. It may show colonic wall thickening, ascites, colonic dilation, or perforation.
Changes in the colonic mucosa depend on the severity of the infection. Endoscopy performed for mild to moderate cases will show erythema and edema of the mucosa, with occasional hemorrhage. In severe cases, findings include elevated whitish-green or yellow plaques like “pseudomembranes” overlying inflamed mucosa. The pseudomembrane is made up of leukocytes, necrotic epithelial cells, and fibrin. The rectum is spared in about one-fourth of cases.
The gold standard for diagnosis of C. difficile colitis was a cytotoxin neutralization assay. This has largely been abandoned owing to its technical difficulty and length of time required to obtain a result (24-48 hours). Instead, the 2013 American College of Gastroenterology (ACG) guidelines recommends using PCR amplification of the genes for toxins A and B from a stool sample. This test has high sensitivity (87%) and specificity (97%) and is cost effective. It can be used as a sole diagnostic test or as part of a two-step approach using a glutamine dehydrogenase (GDH) screening assay, and if positive, following with the PCR confirmatory test. The guidelines recommend against the popular enzyme-linked immunoassay for toxins A and B owing to a cited lack of sensitivity and specificity (75%-95% and 83%-98% respectively); however, the test is still widely used for its ease of performance, low cost, and some studies show similar effectiveness. Stool culture is limited to use in epidemiologic studies. Finally, retesting stool for cure is not recommended because there is a high rate of positive tests after clinical cure, which may lead to prolonged and unnecessary treatment.
After discontinuing the inciting antibiotic agent, which is the first step in treatment for any patient, management is determined by severity of disease. In the United States, vancomycin and metronidazole are the drugs of choice. ACG guidelines recommend treatment of mild to moderate infections with Metronidazole 500 mg three times daily for 10 days. If there is no clinical improvement by day 5, vancomycin is started at a dose of 125 mg orally four times daily for 10 days. Both antibiotics have similar efficacy in patients with mild to moderate disease, but metronidazole is cheaper ($2/d vs. $71-$143/d). A third agent, fidaxomicin, was FDA approved for treatment in 2011 after phase III trials showed non-inferiority for clinical cure and decreased rates of relapse compared to vancomycin in mild-moderate disease. However, this drug is more expensive than vancomyin ($280/d) and post-marketing clinical trials are still underway. There is some evidence that teicoplanin, a bacteriocidal antibiotic, is more effective than vancomycin. However, its use is limited as it is extremely expensive and not available in the United States.
Severe infections (serum albumin < 3 with either a WBC > 15,000 or abdominal tenderness) are treated initially with vancomycin, 125 mg orally four times daily for 10 days, which has been shown to be more effective in patients with severe disease. Patients with complicated disease (admission to ICU, hypotension, fever > 38.5, abdominal distention, altered mental status, WBC > 35,000 or < 2000, lactate > 2.2, or organ failure) are treated with combination therapy consisting of vancomycin 500 mg orally four times daily, vancomycin enemas, and metronidazole 500 mg IV every 8 hours.
Recurrent disease is less well studied, however, ACG guidelines recommend standard treatment if symptoms are mild to moderate. If the patient has more severe illness, treatment should be stepped up as indicated. Oral vancomycin should be administered as a first line treatment and there is some evidence to suggest that pulsed vancomycin can be helpful in patients with multiple recurrences. There is mounting evidence, including a small randomized clinical trial, showing superior clinical efficacy in patients treated with vancomycin plus fecal transplant as opposed to vancomycin alone.
Although most patients will respond to initial medical management, a subset will develop complicated or “fulminant” colitis. Risk factors include patients with IBD, recent gastrointestinal surgery, and WBC greater than 16,000. These patients are critically ill and have a mortality rate of 35%-80%. An abdominal CT scan is indicated to look for complications of C. difficile colitis, such as toxic megacolon and perforation, and exclude other intra-abdominal pathology. Surgical evaluation is recommended for patients with shock (altered mental status, organ dysfunction, lactic acidosis) peritonitis, significant leukocytosis, or failure to improve on medical therapy for 5 days. Although there have been no randomized controls, timely surgery for these patients provides a substantial decrease in mortality. Given the diffuse involvement of the colon and the severity of the illness, a subtotal colectomy with end ileostomy is recommended. Residual rectal disease may be treated with vancomycin enemas if needed. Intestinal continuity is restored at a later operation.
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Ischemic colitis refers to colonic inflammation caused by inadequate perfusion. It is more common in elderly patients and has a mortality of 13%. It occurs as a result of an occlusive or non-occlusive insult. Examples of occlusive ischemic colitis include embolism, thrombosis (arterial or venous), atherosclerosis, trauma, and postsurgical causes such as patients with loss of inferior mesenteric blood supply after aortic aneurysm repair and those with inadequate perfusion to colonic anastomoses. Nonocclusive injury may occur as a result of shock, vasopressors, vasospasm, mechanical obstruction of the lumen, or systemic vasculitides.
An important clinical distinction that must be made when evaluating patients is assessing the colon for gangrenous and non-gangrenous ischemic colitis. Patients with gangrenous forms have transmural, nonreversible injury that is rapidly fatal without surgery. The non-gangrenous type is divided into transient reversible and chronic forms. The chronic form involves the muscularis propria and is prone to stricture development. Transient reversible ischemia involves the submucosa and heals without sequelae. Most cases of ischemic colitis are idiopathic and attributed to a nonocclusive state.
Patients with ischemic colitis present with diarrhea (90%), hematochezia (65%), and abdominal pain (58%). A history of atrial fibrillation, thrombophilia, atherosclerotic arterial disease, recent trauma or surgery, or systemic vasculitis should be sought. Recent severe systemic illness with shock is a common suspected cause. There may be localized or diffuse peritonitis. Blood tests may reveal leukocytosis, hyperamylasemia, and acidosis, as well as electrolyte derangements. The most common location is the sigmoid colon (40%) followed by the transverse colon (17%), splenic flexure (11%), ascending colon (12%), and the rectum (6%).
The most useful diagnostic tests are endoscopy and abdominal CT. Colonoscopy is the diagnostic modality of choice (although contraindicated in critically ill patients with peritonitis) as it allows diagnostic confirmation, determination of severity, and can rule out other types of colitis. The mucosa of the involved segment is edematous, hemorrhagic, friable, and sometimes ulcerated. A grayish membrane may be present, resembling pseudomembranous colitis, but the presence of hyalinized, hemorrhagic lamina on biopsy will differentiate colonic ischemia from C difficile colitis. Serial endoscopy can be used to identify patients with progression of mucosal lesions who require surgery. Abdominal CT with contrast shows a thickened colonic wall, decreased wall enhancement, pneumatosis, and occasionally a disruption in the arterial circulation. It is also useful to exclude other conditions.
Initial treatment for patients without gangrene suspected to have reversible ischemic colitis consists of intravenous fluids, bowel rest, broad spectrum antibiotics, and observation with serial abdominal examinations. Approximately 20% of patients will have irreversible disease, whether gangrenous from the beginning, becoming more severe over several days, or just failing to resolve after treatment. These patients need surgery. The extent of the resection is based on the amount of necrotic or severely diseased colon. Most commonly a segmental resection is required, although a subtotal or total colectomy is performed in 20% of patients. Depending on the etiology of the ischemia and the appearance of the remaining bowel, a second-look laparotomy may be planned 12-24 hours later. Primary anastomosis is rarely performed and intestinal continuity is restored during a subsequent operation.
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Neutropenic colitis, also referred to as neutropenic enterocolitis, necrotizing enteropathy, ileocecal syndrome, and typhlitis, is a syndrome of colonic necrosis occurring in neutropenic patients. The cause is poorly understood, but likely involves mucosal injury and unimpeded bacterial translocation as a result of profound immunosuppression. Neutropenic colitis should be on the differential diagnosis for any immunosuppressed patient with abdominal pain; however, it is most common in neutropenic patients undergoing chemotherapy with cytotoxic agents such as the vinca alkaloids and doxorubicin. There are reports in patients with acquired immunodeficiency syndrome (AIDS), aplastic anemia, cyclic neutropenia, and those being treated with a variety of immunosuppressants for other conditions.
The clinical presentation ranges from mild to life-threatening and overall mortality is 30%-50%. Symptoms include fever, nausea, abdominal pain, distention, and watery or bloody diarrhea. These patients often present late and with deceptively benign findings on physical examination owing to the inability to mount a normal inflammatory response. The cecum and right colon are most often affected; however, any part of the small or large bowel, including the appendix, can be involved. Patients are commonly bacteremic and/or fungemic. Causative organisms include gram-negative rods, gram positive cocci, anaerobes, and candida.
Diagnosis is confirmed using abdominal CT scan, which demonstrates bowel wall thickening, distention, and may show pneumatosis or perforation. Initial management consists of bowel rest, intravenous fluids, and broad spectrum antibiotics. Antifungals are started if there is evidence of fungemia or persistent fevers on antibiotics. Resolution of neutropenia is an important prognostic factor, therefore, discontinuation of immunosuppressants, chemotherapeutics, and administration of granulocyte colony stimulating factor (G-CSF) should be considered. Surgery is recommended for patients with perforation, persistent bleeding, or who do not improve with medical management. Most patients undergo segmental resection with proximal diversion.
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