Chapter 30: The Appendix

1. Appendicitis is one of the most common surgical emergencies in contemporary medicine, with a yearly incidence rate of about 100 per 100,000 inhabitants. Lifetime risk for appendicitis is 8.6% for males and 6.7% for females, with the highest incidence in the second decade of life.

2. The natural history of appendicitis is unclear, but it appears that progression to perforation is not predictable and that spontaneous resolution is common, suggesting that nonperforated and perforated appendicitis may, in fact, be different diseases.

3. Right lower quadrant pain, gastrointestinal symptoms starting after the onset of pain, and a systemic inflammatory response with leukocytosis and neutrophilia, increased C-reactive protein concentration, and fever are considered diagnostic of appendicitis. The Appendicitis Inflammatory Response Score or Alvarado score can help improve diagnostic accuracy.

4. Computed tomography scan has improved diagnostic accuracy in individual studies. However, in population-wide studies, the rate of misdiagnosis of appendicitis remains constant. Rates of misdiagnosis are highest in female patients of child-bearing age and patients on the extremes of age (i.e., very young and very old).

5. The role of nonoperative treatment for uncomplicated appendicitis remains controversial. Currently, appendectomy remains the standard of care. Laparoscopic appendectomy has a slight benefit over open appendectomy.

6. Perforated or complicated appendicitis is more common in the very young (age <5 years) and very old (age >65 years).

7. Complicated appendicitis without signs of sepsis or generalized peritonitis may benefit from nonoperative management. The role of interval appendectomy in these cases remains controversial.

8. Single-incision appendectomy provides no obvious advantage over standard laparoscopic appendectomy. Natural orifice transluminal endoscopic surgery remains an investigational procedure.

9. The incidence of fetal loss following normal appendectomy in pregnant patients is 4%, and the risk of premature delivery is 10%. The greatest opportunity to improve fetal outcomes may be through improving diagnostic accuracy and reducing the rate of negative appendectomy.

10. Antibiotic prophylaxis is effective in the prevention of postoperative surgical site infection. Postoperative antibiotics are unnecessary following uncomplicated appendicitis. For complicated appendicitis, a treatment duration of 4 to 7 days is recommended.

11. The role of incidental appendectomy is limited to patients at high risk for misdiagnosis of appendicitis (malrotation, patients unable to respond or react normally), patients at high risk for complications with appendicitis (children ready to undergo chemotherapy), and patients with limited access to modern healthcare.

12. The prevalence of appendiceal malignancy remains at or below 1% of appendectomies. Carcinoid and mucinous adenocarcinoma remain the most frequent histologic diagnosis.

Appendiceal disease is a frequent reason for emergency hospital admission, and appendectomy is one of the most common emergency procedures performed in contemporary medicine. Despite the prevalent role this organ plays in healthcare today, the human appendix was not noted until 1492. Leonardo da Vinci depicted the appendix in his anatomic drawings, but these were not published until the eighteenth century.¹ In 1521, Berengario Da Capri and, in 1543, Andreas Vesalius published drawings recognizing the appendix.²

Credit is given to Jean Fernel for first describing appendiceal disease in a paper published in 1544. He reported on a 7-year-old girl whose diarrhea he treated with doses of quince, an apple-like fruit used in folk remedies. She developed abdominal pain and died. At autopsy, the quince was found to have obstructed the lumen of the appendix, causing necrosis and perforation.³ Lorenz Heister provided the first description of classic appendicitis in 1711.¹

The first known appendectomy was performed in 1736 by Claudius Amyand in London. He operated on an 11-year-old boy with a scrotal hernia and a fecal fistula. Within the hernia sac, Amyand found a perforated appendix surrounded by omentum. The appendix and omentum were amputated. The patient was discharged a month later in good condition.⁴

It would be over a century later before appendicitis was widely recognized as a common cause of right lower quadrant pain and early appendectomy advocated as treatment. Throughout this period, there was extensive discussion of typhlitis and perityphlitis as the common etiologies of right lower quadrant pain. Only sporadic cases of right lower quadrant pain were treated with appendectomy. In 1886, Reginald H. Fitz presented his findings regarding appendicitis and recommended consideration for operative treatment. In 1889, Charles McBurney published his landmark paper in the New York State Medical Journal describing the indications for early laparotomy for the treatment of appendicitis.⁵ During the following decade, the role of surgical treatment was discussed intensely between proponents of early appendectomy and of a more expectant management. It was recognized that most instances of appendicitis could resolve without surgical treatment; but, the problem was how to identify early the patients who had the progressive, often lethal form of the disease.⁶ Eventually, early appendectomy became the accepted standard of care, with broad indications in order to prevent perforation. This change in practice resulted in an enormous increase in the number of appendectomies during the first decades of the twentieth century. However, this had almost no impact on the incidence of perforated appendicitis or on the mortality of appendicitis.⁷ In the 1970s, the negative effects of the large number of appendectomies of uninflamed appendices were noted, and the focus gradually shifted toward a more conservative approach to exploration.⁸

Embryology

In the sixth week of human embryonic development, the appendix and cecum appear as outpouchings from the caudal limb of the midgut. The appendiceal outpouching, initially noted in the eighth week, begins to elongate at about the fifth month to achieve a vermiform appearance.^9,10 The appendix maintains its position at the tip of the cecum throughout development. The subsequent unequal growth of the lateral wall of the cecum causes the appendix to find its adult position on the posterior medial wall, just below the ileocecal valve. The base of the appendix can be located by following the longitudinally oriented taeniae coli to their confluence on the cecum. The tip of the appendix can be located anywhere in the right lower quadrant of the abdomen, pelvis, or retroperitoneum.

In patients with midgut malrotation and situs inversus, the cecum (and thus the appendix) will not reside in the usual right lower quadrant location. With midgut malrotation, the midgut (small bowel and proximal colon) incompletely rotates or fails to rotate around the axis of the superior mesenteric artery during fetal development. In this situation, the appendix will remain in the left upper quadrant of the abdomen. Situs inversus is a rare autosomal recessive congenital defect characterized by the transposition of abdominal and/or thoracic organs. In this situation, the appendix is found in the left lower quadrant of the abdomen.¹¹

Anatomy

In the adult, the average length of the appendix is 6 to 9 cm; however, it can vary in length from <1 to >30 cm. The outer diameter varies between 3 and 8 mm, whereas the luminal diameter varies between 1 and 3 mm.⁹

The appendix receives its arterial supply from the appendicular branch of the ileocolic artery. This artery originates posterior to the terminal ileum, entering the mesoappendix close to the base of the appendix.¹² The lymphatic drainage of the appendix flows into lymph nodes that lie along the ileocolic artery. Innervation of the appendix is derived from sympathetic elements contributed by the superior mesenteric plexus (T10-L1) and afferents from the parasympathetic elements via the vagus nerves.¹²

The histologic features of the appendix are contained within the three following layers: the outer serosa, which is an extension of the peritoneum; the muscularis layer, which is not well defined and may be absent in certain locations; and finally, the submucosa and mucosa. Lymphoid aggregates occur in the submucosal layer and may extend into the muscularis mucosa. Lymphatic channels are prominent in regions underlying these lymphoid aggregates. The mucosa is like that of the large intestine, except for the density of the lymphoid follicles. The crypts are irregularly sized and shaped, in contrast to the more uniform appearance of the crypts in the colon. Neuroendocrine complexes composed of ganglion cells, Schwann cells, neural fibers, and neurosecretory cells are positioned just below the crypts.^13,14

Physiology

For many years, the appendix was erroneously believed to be a vestigial organ with no known function. It is now well recognized that the appendix is an immunologic organ that actively participates in the secretion of immunoglobulins, particularly immunoglobulin A.

Although there is no clear role for the appendix in the development of human disease, an inverse association between appendectomy and the development of ulcerative colitis has been reported, suggesting a protecting effect of the appendectomy. However, this association is only seen in patients treated with appendectomy for appendicitis before age 20.^15,16,17

The association between Crohn’s disease and appendectomy is less clear. Although earlier studies suggested that appendectomy increases the risk of developing Crohn’s disease, more recent studies that carefully assessed the timing of appendectomy in relationship to the onset of Crohn’s disease demonstrated no correlation.¹⁷ A recent meta-analysis demonstrated a significant risk of Crohn’s disease early following appendicitis.¹⁸ This risk diminishes later, which suggests that a diagnostic (misidentifying Crohn’s disease as appendicitis) rather than a physiologic relationship exists between appendectomy and Crohn’s disease.

The appendix may function as a reservoir to recolonize the colon with healthy bacteria. One retrospective study demonstrated that prior appendectomy may have an inverse relationship to recurrent Clostridium difficile infections.¹⁹ However, in another retrospective study, prior appendectomy did not affect the rate of C. difficile infections.²⁰ The role of the appendix in recolonizing the colon remains to be elucidated.

Epidemiology

The lifetime risk of developing appendicitis is 8.6% for males and 6.7% for females, with the highest incidence in the second and third decades.²¹ The rate of appendectomy for appendicitis has been decreasing since the 1950s in most countries. In the United States, it reached its lowest incidence rate of about 15 per 10,000 inhabitants in the 1990s.²² Since then, there has been an increase in the incidence rate of nonperforated appendicitis. The reason for this is not clear, but it has been proposed that the increased use of diagnostic imaging has led to a higher detection rate of mild appendicitis that would otherwise resolve undetected.

Etiology and Pathogenesis

The etiology and pathogenesis of appendicitis are not completely understood. Obstruction of the lumen due to fecaliths or hypertrophy of lymphoid tissue is proposed as the main etiologic factor in acute appendicitis. The frequency of obstruction rises with the severity of the inflammatory process. Fecaliths and calculi are found in 40% of cases of simple acute appendicitis,²³ in 65% of cases of gangrenous appendicitis without rupture, and in nearly 90% of cases of gangrenous appendicitis with rupture.²⁴

Traditionally, the belief has been that there is a predictable sequence of events leading to eventual appendiceal rupture. The proximal obstruction of the appendiceal lumen produces a closed-loop obstruction, and continuing normal secretion by the appendiceal mucosa rapidly produces distension. Distension of the appendix stimulates the nerve endings of visceral afferent stretch fibers, producing vague, dull, diffuse pain in the mid-abdomen or lower epigastrium. Distension increases from continued mucosal secretion and from rapid multiplication of the resident bacteria of the appendix. This causes reflex nausea and vomiting, and the visceral pain increases. As pressure in the organ increases, venous pressure is exceeded. Capillaries and venules are occluded but arterial inflow continues, resulting in engorgement and vascular congestion. The inflammatory process soon involves the serosa of the appendix and in turn the parietal peritoneum. This produces the characteristic shift in pain to the right lower quadrant.

The mucosa of the appendix is susceptible to impairment of blood supply; thus, its integrity is compromised early in the process, which allows bacterial invasion. The area with the poorest blood supply suffers the most: ellipsoidal infarcts develop in the antimesenteric border. As distension, bacterial invasion, compromise of the vascular supply, and infarction progress, perforation occurs, usually on the antimesenteric border just beyond the point of obstruction. This sequence is not inevitable, however, and some episodes of acute appendicitis may resolve spontaneously.

Microbiology

Appendicitis may occur in clusters, suggesting an infectious genesis. However, an association with various contagious bacteria and viruses has only been found in a small proportion of appendicitis patients.²⁵ The flora of the inflamed appendix differs from that of the normal appendix. About 60% of aspirates of inflamed appendices have anaerobes compared to 25% of aspirates from normal appendices.²⁶ Tissue specimens from the inflamed appendix wall (not luminal aspirates) virtually all grow Escherichia coli and Bacteroides species on culture.^27,28 Fusobacterium nucleatum/necrophorum, which is not present in the normal cecal flora, has been identified in 62% of inflamed appendices.²⁹ In addition to the other usual species (Peptostreptococcus, Pseudomonas, Bacteroides splanchnicus, Bacteroides intermedius, Lactobacillus), previously unreported fastidious gram-negative anaerobic bacilli have been encountered. Patients with gangrene or perforated appendicitis appear to have more tissue invasion by Bacteroides.

Natural History

Because of the current predilection for surgical treatment, the natural history of appendicitis has not been well described. An increasing amount of circumstantial evidence suggests that not all patients with appendicitis will progress to perforation and that resolution may be a common event.³⁰ Among the strongest evidence are two randomized trials comparing early laparoscopy with conservative management of patients with acute abdominal pain. These studies found three to five times more patients with appendicitis in the group of patients who were randomized to laparoscopy.^31,32 Based on epidemiologic differences, it has been proposed that nonperforated and perforated appendicitis may, in fact, be different diseases.²²

Clinical Presentation

The inflammatory process in the appendix presents as pain, which initially is of a diffuse visceral type and later becomes more localized as the peritoneal lining gets irritated (Table 30-1).³³

Symptoms

Appendicitis usually starts with periumbilical and diffuse pain that eventually localizes to the right lower quadrant (sensitivity, 81%; specificity, 53%).³⁴ Although right lower quadrant pain is one of the most sensitive signs of appendicitis, pain in an atypical location or minimal pain will often be the initial presentation. Variations in the anatomic location of the appendix may account for the differing presentations of the somatic phase of pain.

Appendicitis is also associated with gastrointestinal symptoms like nausea (sensitivity, 58%; specificity, 36%), vomiting (sensitivity, 51%; specificity, 45%), and anorexia (sensitivity, 68%; specificity, 36%). Gastrointestinal symptoms that develop before the onset of pain suggest a different etiology such as gastroenteritis.³⁴ Many patients complain of a sensation of obstipation prior to the onset of pain and feel that defecation will relieve their abdominal pain. Diarrhea may occur in association with perforation, especially in children.

Signs

Early in presentation, vital signs may be minimally altered. The body temperature and pulse rate may be normal or slightly elevated. Changes of greater magnitude may indicate that a complication has occurred or that another diagnosis should be considered.³⁵

Physical findings are determined by the presence of peritoneal irritation and are influenced by whether the organ has already ruptured when the patient is first examined. Patients with appendicitis usually move slowly and prefer to lie supine due to the peritoneal irritation. On abdominal palpation, there is tenderness with a maximum at or near McBurney’s point (Fig. 30-1).⁵ On deep palpation, one can often feel a muscular resistance (guarding) in the right iliac fossa, which may be more evident when compared to the left side. When the pressure of the examining hand is quickly relieved, the patient feels a ­sudden pain, the so-called rebound tenderness. Indirect tenderness (Rovsing’s sign) and indirect rebound tenderness (i.e., pain in the right lower quadrant when the left lower quadrant is palpated) are strong indicators of peritoneal irritation. Rebound tenderness can be very sharp and uncomfortable for the patient. It is therefore recommended to start with testing for indirect rebound tenderness and direct percussion tenderness.

Anatomic variations in the position of the inflamed appendix lead to deviations in the usual physical findings. With a retrocecal appendix, the abdominal findings are less striking, and tenderness may be most marked in the flank. When the appendix hangs into the pelvis, abdominal findings may be entirely absent, and the diagnosis may be missed. Right-sided rectal tenderness is said to help in this situation, but the diagnostic value is low. Pain with extension of the right leg (psoas sign) indicates a focus of irritation in the proximity of the right psoas muscle. Similarly, stretching of the obturator internus through internal rotation of a flexed thigh (obturator sign) suggests inflammation near the muscle.

Laboratory Findings

Appendicitis is associated with an inflammatory response that is strongly related to the severity of the disease. Laboratory examinations are therefore an important part of the diagnosis. Mild leukocytosis is often present in patients with acute, uncomplicated appendicitis and is usually accompanied by a polymorphonuclear prominence. It is unusual for the white blood cell count to be >18,000 cells/mm³ in uncomplicated appendicitis. Counts above this level raise the possibility of a perforated appendix with or without an abscess. An increased C-reactive protein (CRP) concentration is a strong indicator of appendicitis, especially for complicated appendicitis.³⁶

White blood cell counts can be low due to lymphopenia or septic reaction, but in this situation, the proportion of neutrophils is usually very high. Therefore, all inflammatory variables should be viewed together. Appendicitis is very unlikely if the white blood cell count, proportion of neutrophils, and CRP are all normal. The inflammatory response in acute appendicitis is a dynamic process. Early in the process, the inflammatory response can be weak. CRP elevation, in particular, can have up to a 12-hour delay. A decreasing inflammatory response may indicate spontaneous resolution.

Urinalysis can be useful to rule out the urinary tract as the source of infection; however, several white or red blood cells can be present from irritation of the ureter or bladder. Bacteriuria is generally not seen.

Clinical Scoring Systems

The clinical diagnosis of appendicitis is a subjective estimate of the probability of appendicitis based on multiple variables that individually are weak discriminators; however, used in conjunction, they possess a high predictive value. This process can be made more objective by the use of clinical scoring systems, which are based on variables with proven discriminating power and assigned a proper weight. The Alvarado score is the most widespread scoring system. It is especially useful for ruling out appendicitis and selecting patients for further diagnostic workup.³⁷ The Appendicitis Inflammatory Response Score resembles the Alvarado score but uses more graded variables and includes CRP (Table 30-2).^38,39 Studies have shown it to perform better than the Alvarado score in accurately predicting appendicitis.^38,39 However, clinical scoring systems have not gained widespread acceptance in making the diagnosis of appendicitis.

Imaging Studies

Plain films of the abdomen can show the presence of a fecalith and fecal loading in the cecum associated with appendicitis but are rarely helpful in diagnosing acute appendicitis⁴⁰; however, they may be of benefit in ruling out other pathology. A chest radiograph is helpful to rule out referred pain from a right lower lobe pneumonic process. If the appendix fills on barium enema, appendicitis is unlikely⁴¹; however, this test is not indicated in the acute setting. Technetium-99m–labeled leukocyte scan has been reported for use in diagnosing appendicitis with good results but has not gained widespread use due to its relative unavailability and impracticality in daily use.⁴²

Ultrasonography and computed tomography (CT) scan are the most commonly used imaging tests in patients with abdominal pain, particularly in evaluation of possible appendicitis. Multiple meta-analyses have been performed comparing the two imaging modalities (Table 30-3).^{43,44,45,46,47} Overall, CT scan is more sensitive and specific than ultrasonography in diagnosing appendicitis.

Graded compression ultrasonography is inexpensive, can be performed rapidly, does not require a contrast medium, and can be used in pregnant patients. Sonographically, the appendix is identified as a blind-ending, nonperistaltic bowel loop originating from the cecum. With maximal compression, the diameter of the appendix is measured in the anterior-posterior direction. Thickening of the appendiceal wall and the presence of periappendiceal fluid are highly suggestive of appendicitis. Demonstration of an easily compressible appendix measuring <5 mm in diameter excludes the diagnosis of appendicitis. The sonographic diagnosis of acute appendicitis has a reported sensitivity of 55% to 96% and a specificity of 85% to 98%. Ultrasonography is similarly effective in children and pregnant women, although its application is limited in late pregnancy. Ultrasonography has its limitations, particularly the operator-dependent nature of results. In the adult population, ultrasonography remains limited in its use.

With high-resolution helical CT, the inflamed appendix appears dilated (>5 mm), and the wall is thickened. There is often evidence of inflammation, which can include periappendiceal fat stranding, thickened mesoappendix, periappendiceal phlegmon, and free fluid. Fecaliths can be often visualized; however, their presence is not pathognomonic of appendicitis. CT scanning is also an excellent technique for identifying other inflammatory processes masquerading as appendicitis. Several CT techniques have been used, including focused and nonfocused CT scans and contrast and noncontrast scans. Surprisingly, all of these techniques have yielded essentially identical rates of diagnostic accuracy: 92% to 97% sensitivity, 85% to 94% specificity, 90% to 98% accuracy, 75% to 95% positive predictive value, and 95% to 99% negative predictive value. The additional use of rectal contrast does not improve the results of CT scanning.

A number of studies have documented improvement in diagnostic accuracy with the liberal use of CT scanning in the workup of suspected appendicitis. CT lowered the rate of negative appendectomies from 19% to 12% in one study⁴⁸ and the incidence of negative appendectomies in women from 24% to 5% in another study.⁴⁹ Use of CT altered the care of 24% of patients studied and provided an alternative diagnosis in half of the patients with normal appendices on CT scan.

Despite the potential usefulness of CT, there are significant disadvantages. CT scanning is expensive, exposes the patient to significant radiation, and has limited use during pregnancy. Allergy to iodine or contrast limits the administration of contrast agents in some patients, and others cannot tolerate the oral ingestion of luminal dye.

The role of CT scanning in patients who present with right lower quadrant pain is unclear. One rationale is universal CT scanning. There is, however, an argument that indiscriminate diagnostic imaging can increase the detection of clinically nonsignificant appendicitis that would resolve without treatment. Alternatively, selective CT scanning based on the likelihood of appendicitis takes advantage of the clinical skills of the surgeon and, when indicated, adds the expertise of the radiologist.

Despite the increased use of ultrasonography and CT, the rate of misdiagnosis of appendicitis has remained constant (15%). The percentage of misdiagnosed cases of appendicitis is significantly higher among women than men (22% vs. 9.3%).^50,51 The negative appendectomy rate is highest in women of reproductive age.

Differential Diagnosis

The differential diagnosis of acute appendicitis is essentially the diagnosis of acute abdomen. An identical clinical picture can result from a wide variety of acute processes within the peritoneal cavity that produce the same physiologic alterations as acute appendicitis.

The accuracy of preoperative diagnosis should be higher than 85%. If it is consistently less, it is likely that unnecessary operations are being performed and a more rigorous preoperative differential diagnosis is needed.

The most common findings in the case of an erroneous preoperative diagnosis of appendicitis—together accounting for more than 75% of cases—are, in descending order of frequency, acute mesenteric adenitis, no organic pathologic condition, acute pelvic inflammatory disease, twisted ovarian cyst or ruptured graafian follicle, and acute gastroenteritis.

The differential diagnosis of acute appendicitis depends on four major factors: the anatomic location of the inflamed appendix; the stage of the process (uncomplicated or complicated); the patient’s age; and the patient’s gender.^{52,53,54,55,56}

Pediatric Patient

Acute mesenteric adenitis is the disease most often confused with acute appendicitis in children. Almost invariably, an upper respiratory tract infection is present or has recently subsided. The pain usually is diffuse, and tenderness is not as sharply localized as in appendicitis. Voluntary guarding is sometimes present, but true rigidity is rare. Generalized lymphadenopathy may be noted. Laboratory procedures are of little help in arriving at the correct diagnosis, although a relative lymphocytosis, when present, suggests mesenteric adenitis. Observation for several hours is appropriate if the diagnosis of mesenteric adenitis is suspected, as it is a self-limited disease.

Elderly Patient

Diverticulitis or perforating carcinoma of the cecum or of a portion of the sigmoid that overlies the right lower abdomen may be impossible to distinguish from appendicitis. These entities should be considered, particularly in older patients. CT scanning is often helpful in making a diagnosis in older patients with right lower quadrant pain and atypical clinical presentations. In patients successfully managed conservatively, interval surveillance of the colon (colonoscopy or barium enema) may be warranted.

Female Patient

Diseases of the female internal reproductive organs that may erroneously be diagnosed as appendicitis are, in approximate descending order of frequency, pelvic inflammatory disease, ruptured graafian follicle, twisted ovarian cyst or tumor, endometriosis, and ruptured ectopic pregnancy. As a result, the rate of misdiagnosis remains higher among female patients.

In pelvic inflammatory disease, the infection is usually bilateral but, if confined to the right tube, may mimic acute appendicitis. Nausea and vomiting are present in patients with appendicitis but in only approximately 50% of those with pelvic inflammatory disease. Pain and tenderness are usually lower, and motion of the cervix is exquisitely painful. Intracellular diplococci may be demonstrable on smear of the purulent vaginal discharge. The ratio of cases of appendicitis to cases of pelvic inflammatory disease is low in females in the early phase of the menstrual cycle and high during the luteal phase. The careful clinical use of these features has reduced the incidence of negative findings on laparoscopy in young women to 15%.

Ovulation commonly results in the spillage of sufficient amounts of blood and follicular fluid to produce brief, mild lower abdominal pain. If the amount of fluid is unusually copious and is from the right ovary, appendicitis may be simulated. Pain and tenderness may be rather diffuse, and leukocytosis and fever minimal or absent. Because this pain occurs at the midpoint of the menstrual cycle, it is often called mittelschmerz.

Serous cysts of the ovary are common and generally remain asymptomatic. When right-sided cysts rupture or undergo torsion, the manifestations are similar to those of appendicitis. Patients develop right lower quadrant pain, tenderness, rebound, fever, and leukocytosis. Both transvaginal ultrasonography and CT scanning can be diagnostic.

Torsion requires emergent operative treatment. If the torsion is complete or longstanding, the pedicle undergoes thrombosis, and the ovary and tube become gangrenous and require resection. However, simple detorsion, fenestration of the cyst, and fixation of the ovary as a primary intervention, followed by a laparoscopy a few days later, can be recommended because it is often difficult to preoperatively determine the viability of the ovary.

Blastocysts may implant in the fallopian tube (usually the ampullary portion) and in the ovary. Rupture of right tubal or ovarian pregnancies can mimic appendicitis. Patients may give a history of abnormal menses, either missing one or two periods or noting only slight vaginal bleeding. Unfortunately, patients do not always realize they are pregnant. The development of right lower quadrant or pelvic pain may be the first symptom. The diagnosis of ruptured ectopic pregnancy should be relatively easy. The presence of a pelvic mass and elevated levels of human chorionic gonadotropin are characteristic. Although the leukocyte count rises slightly, the hematocrit level falls as a consequence of the intra-abdominal hemorrhage. Vaginal examination reveals cervical motion and adnexal tenderness, and a more definitive diagnosis can be established by culdocentesis. The presence of blood and particularly decidual tissue is pathognomonic. The treatment of ruptured ectopic pregnancy is emergency surgery.

Immunosuppressed Patient

The incidence of acute appendicitis in patients infected with human immunodeficiency virus (HIV) is reported to be 0.5%. This is higher than the 0.1% to 0.2% incidence reported for the general population.⁵⁷ The presentation of acute appendicitis in HIV-infected patients is similar to that in noninfected patients. The majority of HIV-infected patients with appendicitis have fever, periumbilical pain radiating to the right lower quadrant (91%), right lower quadrant tenderness (91%), and rebound tenderness (74%). HIV-infected patients do not manifest an absolute leukocytosis; however, if a baseline leukocyte count is available, nearly all HIV-infected patients with appendicitis demonstrate a relative leukocytosis.⁵⁷

The risk of appendiceal rupture appears to be increased in HIV-infected patients. In one large series of HIV-infected patients who underwent appendectomy for presumed appendicitis, 43% of patients were found to have perforated appendicitis at laparotomy.⁵⁸ The increased risk of appendiceal rupture may be related to the delay in presentation seen in this patient population.^57,58 A low CD4 count is also associated with an increased incidence of appendiceal rupture.⁵⁷

The differential diagnosis of right lower quadrant pain is expanded in HIV-infected patients compared with the general population. In addition to the conditions discussed elsewhere in this chapter, opportunistic infections should be considered as a possible cause of right lower quadrant pain.^57,58 Neutropenic enterocolitis (typhlitis) should also be considered in the differential diagnosis of right lower quadrant pain in HIV-infected patients.^57,58

Initial Management

Uncomplicated Appendicitis

Operative versus Nonoperative Management of Uncomplicated Appendicitis

In patients with uncomplicated appendicitis, surgical treatment has been the standard of treatment since McBurney reported his experiences. The concept of nonoperative treatment for uncomplicated appendicitis developed from two lines of observations. First, for patients in an environment where surgical treatment is not available (e.g., submarines, expeditions in remote areas), treatment with antibiotics alone was noted to be effective. Second, many patients with signs and symptoms consistent with appendicitis who did not pursue medical treatment would occasionally have spontaneous resolution of their illness.

A handful of observational studies and controlled trials have reported the outcomes of nonoperative versus operative treatment of presumed uncomplicated appendicitis (Table 30-4).^{59,60,61,62,63,64} Overall, there is a reported 9% short-term (<30 days) failure rate with nonoperative management of appendicitis (13% if evaluated per protocol). In patients in whom nonoperative treatment fails, nearly half of patients have complicated (perforated or gangrenous) appendicitis. After 1 month, about 1% of patients in the trials underwent an interval appendectomy, and 13% of patients who initially were successfully treated with nonoperative measures developed recurrent appendicitis, with an 18% rate of complicated appendicitis. Follow-up was not longer than 1 year in any study. In addition, one-third of patients declined or dropped out from nonoperative management of appendicitis.

In comparison, operative appendectomy demonstrated a relatively low dropout rate (2%), lower proportion of complicated appendicitis (25%), small proportion of a normal appendix (5%), and low rates of superficial surgical site infection (3.7%) and intra-abdominal abscess (1.3%).

The results in these studies must viewed with caution due to unclear selection of patients, incomplete diagnostic workup in the nonoperated patients, unclear gold standard for the operated patients, and high rates of crossover between the treatment arms. The consequences in terms of use of hospital beds, length of hospital stay, morbidity of delayed surgical treatment after failed nonsurgical treatment, delayed diagnosis for patients with an underlying cancer in the appendix or cecum, and risk of increased antibiotic resistance need to be further investigated. Thus, operative treatment of presumed uncomplicated appendicitis still remains the standard of care. Certain subgroups with uncomplicated appendicitis may do well with nonoperative therapy. Patients pursuing nonoperative management should be carefully counseled regarding the risks of treatment failure and recurrent appendicitis.

Urgent versus Emergent Appendectomy for Uncomplicated Appendicitis

Traditionally, appendicitis has been considered a surgical emergency. Once diagnosed, a patient was emergently taken to the operating room for surgical treatment. However, delays in diagnosis, lack of access to available operating suites, and nonoperative management of appendicitis have challenged the notion that uncomplicated appendicitis is a surgical emergency.

Three retrospective studies have evaluated the role of emergent or urgent surgery for uncomplicated appendicitis; the emergent group had a time from presentation to the operating room of <12 hours, whereas the urgent group had a time from presentation to the operating room of 12 to 24 hours (Table 30-5).^65,66,67 There was no statistically significant increase in the number of complicated appendicitis cases in the urgent group when compared to the emergent group. Similarly, rates of surgical site infection, intra-abdominal abscesses, conversion to an open procedure, or operative time showed no difference between the two groups. While length of stay was longer for the urgent group, it was not statistically or clinically different from the emergent group. Important caveats in consideration of urgent as opposed to emergent surgical care include the patient’s clinical examination, time of presentation from onset of symptoms, and duration of “delay” in surgery. Patients with clinical signs of perforation, patients with delayed presentation of greater than 48 hours from onset of symptoms, and patients whose definitive therapy may be delayed for more than 12 hours were beyond the scope of these studies.

Emergent versus urgent operation for uncomplicated appendicitis is dependent on each institution and surgeon. Institutions without readily available operating rooms and staff may consider performing appendectomy in an urgent fashion as opposed to emergently.

Complicated Appendicitis

Complicated appendicitis typically refers to perforated appendicitis commonly associated with an abscess or phlegmon. The yearly incidence rate of perforated appendicitis is about 2 per 10,000 persons and has remarkable little variance over time, geographic region, and age.^51,68,69 The proportion of perforated appendicitis, commonly around 25%, is often used as an indicator of quality of care. Differences in this proportion are almost entirely related to differences in the incidence of nonperforated appendicitis. A low proportion of perforations may therefore be the consequence of a higher rate of detection and treatment of early or resolving appendicitis.

Children less than 5 years of age and patients more than 65 years of age have the highest rates of perforation (45% and 51%, respectively). The proportion of perforation increases with increasing duration of symptoms. There is, however, no association of in-hospital delay with perforation. This suggests that most perforations occur early, before the patient arrives to hospital. It has also been proposed that the increasing proportion of perforations with time is explained by selection due to spontaneous resolution of noncomplicated appendicitis.

Perforated appendicitis has been suggested to increase the risk of female infertility due to impaired tubal function, but this has not been shown in epidemiologic studies.⁷⁰

Rupture should be suspected in the presence of generalized peritonitis and a strong inflammatory response. In many cases, rupture is contained and patients display localized peritonitis. In 2% to 6% of cases, a palpable mass is detected on physical examination. This could represent a phlegmon, which consists of matted loops of bowel adherent to the adjacent inflamed appendix or a periappendiceal abscess. Patients who present with a mass have experienced symptoms for a longer duration, usually 5 to 7 days. Distinguishing acute, uncomplicated appendicitis from acute appendicitis with perforation based on clinical findings is often difficult, but it is important to make the distinction because the treatments may differ. CT scan may be beneficial in establishing a diagnosis and guiding therapy.

Operative versus Nonoperative Management of Complicated Appendicitis

Patients who present with signs of sepsis and generalized peritonitis should be taken to the operating room immediately with concurrent resuscitation. The surgical approach is based on the surgeon’s level of comfort; however, open appendectomy through a lower midline incision may be necessary to treat these complicated cases.

In patients with complicated appendicits and a contained abscess or phlegmon but limited peritonitis (focal right lower quadrant pain), the treatment options become more complicated. Often, these patients will require a challenging procedure with a high risk for development of a postoperative intra-abdominal abscess. Options include operative management versus conservative management (antibiotics, bowel rest, fluids, and possible percutaneous drainage).

There have been no prospective randomized controlled studies comparing operative versus conservative management of complicated appendicitis in adults; all studies have been retrospective cohort studies. Two meta-analyses have been performed. In Andersson and Petzold’s 2007 analysis of 61 studies evaluating this issue, they noted that initial nonoperative management had superior outcomes.⁷⁰ Nonoperative management included intravenous fluids, minimizing gastrointestinal stimulation, parenteral antibiotics, and percutaneous drainage where deemed appropriate. The morbidity of immediate operative treatment was 36.5%, whereas the morbidity of conservative management was 11%. Of patients undergoing conservative treatment, 7.6% failed conservative treatment and underwent operative management. This subgroup had an overall complication rate of 13.5%. The recurrence rate was 7.4%, which does not necessitate interval appendectomy. The authors concluded that conservative treatment was favored over early operation in complicated appendicitis.³⁰

Simillis and colleagues performed a meta-analysis of 17 studies.⁷¹ They noted that conservative treatment was associated with fewer overall complications (odds ratio, 0.24; 95% confidence interval [CI], 0.13 to 0.44), intra-abdominal abscesses (odds ratio, 0.19; 95% CI, 0.07 to 0.58), bowel obstructions (odds ratio, 0.35; 95% CI, 0.17 to 0.71), and reoperations (odds ratio, 0.17; 95% CI, 0.04 to 0.75).⁷¹ The authors concluded that conservative treatment was favored over early operation in complicated appendicitis.

In the pediatric literature, there have been two prospective randomized controlled trials^72,73 demonstrating that early operative intervention had equivalent or superior outcomes to conservative management, but these studies included interval appendectomy for all patients in their calculations. St. Peter and colleagues⁷² demonstrated that 20% of patients failed conservative treatment. Early surgical intervention had equivalent results to interval appendectomy. Alternatively, Blakely and colleagues⁷³ noted that interval appendectomy, versus early appendectomy, had a higher incidence of adverse events (50% vs. 30%, P = .003), intra-abdominal abscesses (37% vs. 19%, P = .02), small bowel obstruction (10.4% vs. 0%, P = .01), and readmissions (31% vs. 8%, P = .06). In addition, Blakely and colleagues noted that 9% of the group treated conservatively developed recurrent appendicitis. The authors concluded that immediate surgical treatment was superior to conservative treatment with interval appendectomy.

Interval Appendectomy Following Nonoperative Management of Complicated Appendicitis

Interval appendectomy is defined as performing an appendectomy following initial successful nonoperative management in patients with no further symptoms. The major argument against interval appendectomy is that many patients treated conservatively never develop manifestations of appendicitis, and those who do generally can be treated without additional morbidity. The major argument for interval appendectomy is to prevent future attacks of appendicitis or to identify other disease, such as appendiceal malignancy.

There has only been one small prospective randomized controlled trial (n = 40) investigating this subject. The literature is largely populated with small case series and retrospective cohort studies; there is no meta-analysis evaluating the subject (Table 30-6).^{74,75,76,77,78,79,80,81} Of the 1434 patients who had presumed complicated appendicitis and were successfully treated conservatively, 8.8% developed recurrent appendicitis with a median follow-up of 35 months. The incidence of complicated appendicitis following recurrence was low (2.4%). Malignancy was noted in 1.3% of cases where pathology was reported. Many of the patients were excluded from these studies due to persistent symptoms, persistent infections, or note of malignancy on screening colonoscopy.

Alternatively, of the 344 patients who had presumed complicated appendicitis, were successfully treated conservatively, and subsequently underwent interval appendectomy, surgical complications occurred in 9.4% of the patients. Most patients underwent interval appendectomy 2 to 4 months after their acute presentation. Although operative and pathologic details were not uniformly reported in these patients, many continued to have evidence of appendicitis or abscess at the time of interval appendectomy; 3.6% of patients had malignancy in cases where pathology was reported.

The role of interval appendectomy following successful management of conservative treatment of complicated appendicitis is unclear. Close clinical follow-up, a complete history searching for persistent symptoms, and screening colonoscopy (when age appropriate) should all be used to help guide the discussion with the patient on the role of interval appendectomy following conservative management of complicated appendicitis.

Open Appendectomy

Typically performed with a patient under general anesthesia, the patient is placed in supine position. The entire abdomen should be prepped and draped in case a larger incision is needed. For early nonperforated appendicitis, a right lower quadrant incision at McBurney’s point (one-third of the distance from the anterior superior iliac spine to the umbilicus) is commonly used. A McBurney (oblique) or Rocky-Davis (transverse) right lower quadrant muscle splitting incision is made. If perforated appendicitis is suspected or the diagnosis is in doubt, a lower midline laparotomy can be considered. Although it has been reported that the position of the base of the appendix can change with pregnancy, prospective studies have demonstrated that pregnancy does not change the proportion of patients with the appendiceal base within 2 cm of McBurney’s point.⁸²

Following entry into the abdomen, the patient should be placed in slight Trendelenburg position with rotation of the bed to the patient’s left. If the appendix is not easily identified, the cecum should be located. Tracing the taenia libera (anterior taenia), the most visible of the three taeniae coli, distally, the base of the appendix can be identified.

The appendix will often have attachments to the lateral wall or pelvis that can be dissected free. Dividing the mesentery of the appendix first will often allow improved exposure of the base of the appendix. The appendiceal stump can be managed by simple ligation or by ligation and inversion. As long as the stump is clearly visible and the base of the cecum is not involved with the inflammatory process, the stump can be safely ligated. Obliteration of the mucosa with electrocautery with the intention to obviate the development of a mucocele is recommended by some surgeons; however, no data have evaluated the risk or benefit of this surgical maneuver. Inversion of the stump with plication of the cecum has also been described. Placement of surgical drains for both uncomplicated⁸³ and complicated appendicitis,^84,85,86,87 practiced by many surgeons, has not been supported in clinical trials. Pus in the abdomen should be aspirated, but irrigation in complicated appendicitis is not recommended.⁸⁸ The skin can also be closed primarily in patients with perforated appendicitis.

If appendicitis is not found, a methodical search must be made for an alternative diagnosis. The cecum and mesentery should be inspected. The small bowel should be evaluated in a retrograde fashion beginning at the ileocecal valve. Concerns for Crohn’s disease or Meckel’s diverticulum should be of priority. In female patients, the reproductive organs should be closely inspected. If purulent or bilious fluid is encountered, it is imperative that the source be identified. For example, Valentino’s appendicitis, or a perforated duodenal ulcer presenting as appendicitis, should be excluded in such cases. A medial extension of the incision (Fowler-Weir) or superior extension of the lateral incision is appropriate if further evaluation of the lower abdomen or right colon is warranted. Selective laparoscopy through a right lower quadrant incision has also been described.⁸⁹ If upper abdominal pathology is encountered, a midline incision should be made.

Laparoscopic Appendectomy

The first reported laparoscopic appendectomy was performed in 1983 by Semm; however, the laparoscopic approach did not come into widespread use until much later, following the success of laparoscopic cholecystectomy. This may be due to the small incision already commonly used with open appendectomy.

Laparoscopic appendectomy is performed under general anesthesia. An oro- or nasogastric tube and urinary catheter are placed. The patient should be placed supine with his or her left arm tucked and securely strapped to the operating table. Both surgeon and assistant should be standing on the patient’s left facing the appendix. The laparoscopic screens should be positioned on the patient’s right or at the foot of the bed. Standard laparoscopic appendectomy typically uses three ports. Typically, a 10- or 12-mm port is placed at the umbilicus, whereas two 5-mm ports are placed suprapubic and in the left lower quadrant. The patient should be placed in Trendelenburg and tilted to the left (Fig. 30-2).

The appendix should be identified similarly as in open surgery by tracking the taenia libera/coli to the appendiceal base. Through the suprapubic port, the appendix should be grasped securely and elevated to the 10 o’clock position. An “appendiceal critical view” should be obtained where the taenia libera is at the 3 o’clock position, the terminal ileum at the 6 o’clock position, and the retracted appendix at the 10 o’clock position to allow proper identification of the base of the appendix (Fig. 30-3).⁹⁰ Through the infraumbilical port, the mesentery should be gently dissected from the base of the appendix and a window created. Typically the base of the appendix is stapled, followed by stapling of the mesentery. Alternatively, the mesentery may be divided by an energy device or clipped and the base of the appendix secured with an Endoloop. The stump should be carefully examined to ensure hemostasis, complete transection, and ensure that no stump is left behind. The appendix is removed through the infraumbilical trocar in a retrieval bag.

Laparoscopic versus Open Appendectomy

There have been multiple prospective, randomized controlled trials comparing laparoscopic and open appendectomy outcomes. A number of meta-analyses have been performed evaluating the cumulative outcomes (Table 30-7).^{91,92,93,94,95,96,97,98,99}

Laparoscopic appendectomy is associated with fewer incisional surgical site infections compared to open appendectomy. However, laparoscopic appendectomy may be associated with increased risk of intra-abdominal abscess compared to open appendectomy. There is less pain, shorter length of stay, and quicker return to normal activity with laparoscopic appendectomy when compared to open appendectomy. Laparoscopic appendectomy is associated with increased operative duration and increased operating rooms costs; however, overall costs are likely similar when compared to open appendectomy. Patients tend to have improved satisfaction scores with laparoscopic appendectomy. Many of the differences, while statistically significant, have nominal clinical difference, such as length of stay where differences are measured in hours.^{91,92,93,94,95,96,97,98,99}

In addition, laparoscopic appendectomy may provide a benefit when the diagnosis is in question, such as in female patients of reproductive age, older patients in whom malignancy is suspected, and morbidly obese patients for whom larger open appendectomy incisions may be required.

Laparoscopic Single-Incision Appendectomy

There has been growing interest in laparoscopic single-incision appendectomy. Instead of two or three incisions, a single incision is made, typically periumbilical. The first published laparoscopic-assisted, single-incision appendectomy was reported by Inoue in 1994, where the appendix was identified laparoscopically and grasped and pulled through the laparoscopic incision and the appendectomy completed in an open manner. The first reports of a pure laparoscopic single-incision appendectomy were described in 2009 by multiple surgical groups. By this time, industry had designed multiple options for true single-port access as opposed to makeshift single-incision access.

With laparoscopic single-incision appendectomy, the patient is prepared similarly to laparoscopic appendectomy. Under general anesthesia, the patient is secured in a supine position with the left arm tucked. The surgeon and assistant stand on the left side facing the appendix and the screen. When performing laparoscopic single-incision appendectomy, the surgeon’s hands perform the opposite function that they would normally in standard laparoscopic surgery. The surgeon’s right hand will grasp the appendix and retract it to the right lower quadrant at the 10 o’clock position.⁹⁰ The surgeon’s left hand will dissect the mesenteric window and, upon identifying the appendiceal critical view, staple across the base of the appendix and mesentery. If the base of the appendix cannot be definitively identified or the appendiceal critical view cannot be obtained, additional ports can be placed to perform a “plus one” or even standard laparoscopic appendectomy. The appendix may be placed in a retrieval bag or removed through the single incision.

There have been multiple small trials evaluating the efficacy of laparoscopic single-incision appendectomy compared to standard appendectomy; however, there has only been one prospective randomized study (in the pediatric population) and one meta-analysis. Gill and colleagues, in 2012, reviewed nine studies for a total of 275 laparoscopic single-incision appendectomies and 348 standard laparoscopic appendectomy procedures. In this meta-analysis, there was no difference in operative time (57 ± 10 vs. 55 ± 13 minutes), complications (11% vs. 8.3%), incisional surgical site infections (5.6% vs. 4.9%), intra-abdominal abscesses (1.8% vs. 1.4%), or length of stay (3 ± 2 vs. 4 ± 1 days). Cases were converted to open or additional ports were placed in 4% of laparoscopic single-incision appendectomies and 0.9% of standard laparoscopic procedures. There was no difference in return to bowel function, postoperative pain, or return to normal activity. There was no difference in overall cost. The incidence of hernia formation following the laparoscopic single-incision appendectomy procedure compared to standard laparoscopy has not been reported.¹⁰⁰

Although further study is needed, it appears that in laparoscopic appendectomy, laparoscopic single-incision appendectomy conveys no discernible advantage or disadvantage with short-term outcomes. Late outcomes and patient quality-of-life outcomes remain to be investigated.

Natural Orifice Transluminal Endoscopic Surgery

Natural orifice transluminal endoscopic surgery (NOTES) is a new surgical procedure using flexible endoscopes in the abdominal cavity. In this procedure, access is gained by way of organs that are reached through a natural, already-existing external orifice. The hoped-for advantages associated with this method include the reduction of postoperative wound pain, shorter convalescence, avoidance of wound infection and abdominal wall hernias, and the absence of scars.

One hundred thirteen NOTES appendectomies in human patients have been reported in the medical literature. Eighty-seven were performed transvaginally, and 26 were performed transgastrically.¹⁰¹ The vast majority of these cases are hybrid procedures (NOTES plus laparoscopic assist port) with only 14 cases of pure NOTES appendectomies (three transvaginal and 11 transgastric). Although reported complication rates appear low, conversion rates (to hybrid procedures) remain high.

The main concern with NOTES has been complications with closure of the enterotomy. To date, there is no reliable method of closure of the gastrotomy site, and there has been significant morbidity reported with this approach.

Although the transvaginal approach appears to be more promising, in women surveyed on their perception of NOTES, three-quarters were either neutral or unhappy about the prospects of NOTES.¹⁰²

Much work remains to demonstrate whether NOTES is able to provide the theoretical benefits purported. Great care must be taken to prevent significant morbidity or mortality en route to studying these procedures.

Acute Appendicitis in the Young

The establishment of a diagnosis of acute appendicitis is more difficult in young children than in the adult. The inability of young children to give an accurate history, diagnostic delays by both parents and physicians, and the frequency of gastrointestinal distress in children are all contributing factors to the misdiagnosis and delay in diagnosis.¹⁰³ In children, the physical examination findings of maximal tenderness in the right lower quadrant, the inability to walk or walking with a limp, and pain with percussion, coughing, and hopping were found to have the highest sensitivity for appendicitis.¹⁰⁴

The more rapid progression to rupture and the inability of the underdeveloped greater omentum to contain a rupture lead to significant morbidity rates in children. Children <5 years of age have a negative appendectomy rate of 25% and an appendiceal perforation rate of 45%. These rates may be compared with a negative appendectomy rate of <10% and a perforated appendix rate of 20% in children 5 to 12 years of age.^50,51 The incidence of major complications after appendectomy in children is correlated with appendiceal rupture. The wound infection rate after the treatment of nonperforated appendicitis in children is 2.8%, compared with a rate of 11% after the treatment of perforated appendicitis. The incidence of intra-abdominal abscess also is higher after the treatment of perforated appendicitis than after nonperforated appendicitis (6% vs. 3%).¹⁰⁵ The treatment regimen for perforated appendicitis generally includes immediate appendectomy. Antibiotic coverage is limited to 24 to 48 hours in cases of nonperforated appendicitis. For perforated appendicitis, intravenous antibiotics usually are given until the white blood cell count is normal and the patient is afebrile for 24 hours. Laparoscopic appendectomy has been shown to be safe and effective for the treatment of appendicitis in children.¹⁰⁶

Acute Appendicitis in the Elderly

Compared with younger adults, elderly patients with appendicitis often pose a more difficult diagnostic problem because of the atypical presentation, expanded differential diagnosis, and communication difficulty. These factors may be responsible for the disproportionately high perforation rate seen in the elderly. In the general population, perforation rates range from 20% to 30%, compared with 50% to 70% in the elderly.¹⁰⁷ In addition, the perforation rate appears to increase with age greater than 80 years.¹⁰⁸

Elderly patients usually present with lower abdominal pain, but on clinical examination, localized right lower quadrant tenderness is not as common as in younger patients. A ­history of periumbilical pain migrating to the right lower quadrant is reported infrequently. Although currently there are no criteria that definitively identify elderly patients with acute ­appendicitis who are at risk of rupture, prioritization should be given to patients with a temperature of greater than 38°C (100.4°F) and a shift to the left in leukocyte count of more than 76%, especially if they are male, are anorexic, or have had pain of long duration before admission.⁶⁵

As a result of increased comorbidities and an increased rate of perforation, postoperative morbidity, mortality, and hospital length of stay are increased in the elderly compared with younger populations with appendicitis. Although no randomized trials have been conducted, it appears that elderly patients benefit from a laparoscopic approach to treatment of appendicitis. The use of laparoscopy in the elderly has significantly increased in recent years. In general, laparoscopic appendectomy offers elderly patients with appendicitis a shorter length of hospital stay, a reduction in complication and mortality rates, and a greater chance of discharge to home (independent of further nursing care or rehabilitation).¹⁰⁹

Acute Appendicitis during Pregnancy

Appendectomy for presumed appendicitis is the most common surgical emergency during pregnancy. The incidence is approximately 1 in 766 births. Acute appendicitis can occur at any time during pregnancy but is rare in the third trimester.¹¹⁰ The overall negative appendectomy rate during pregnancy is approximately 25% and appears to be higher than the rate seen in nonpregnant women.^110,111 A higher rate of negative appendectomy is seen in the second trimester, whereas the lowest rate is in the third trimester. The diversity of clinical presentations and the difficulty in making the diagnosis of acute appendicitis in pregnant women are well established. This is particularly true in the late second trimester and the third trimester, when many abdominal symptoms may be considered pregnancy related. In addition, during pregnancy, there are anatomic changes in the appendix and increased abdominal laxity that may further complicate clinical evaluation.

Appendicitis in pregnancy should be suspected when a pregnant woman complains of abdominal pain of new onset. The most consistent sign encountered in acute appendicitis during pregnancy is pain in the right side of the abdomen. Seventy-four percent of patients report pain located in the right lower abdominal quadrant, with no difference between early and late pregnancy. Only 57% of patients present with the classic history of diffuse periumbilical pain migrating to the right lower quadrant. Laboratory evaluation is not helpful in establishing the diagnosis of acute appendicitis during pregnancy. The physiologic leukocytosis of pregnancy has been defined as high as 16,000 cells/mm³. In one series, only 38% of patients with appendicitis had a white blood cell count of more than 16,000 cells/mm³.¹¹⁰ Recent data suggest that the incidence of perforated or complex appendicitis is not increased in pregnant patients.¹¹¹

When the diagnosis is in doubt, abdominal ultrasound may be beneficial. Another option is magnetic resonance imaging, which has no known deleterious effects on the fetus. The American College of Radiology recommends the use of nonionizing radiation techniques for front-line imaging in pregnant women.⁷⁰ Laparoscopy has been advocated in equivocal cases, especially early in pregnancy; however, laparoscopic appendectomy may be associated with an increase in pregnancy-related complications. In an analysis of outcomes in California using administrative databases, laparoscopy was found to be associated with a 2.31 times increased risk of fetal loss compared with open surgery.¹¹¹

The overall incidence of fetal loss after appendectomy is 4%, and the risk of early delivery is 7%. Rates of fetal loss are considerably higher in women with complicated appendicitis than in those with a negative appendectomy or with simple appendicitis. It is important to note that a negative appendectomy is not a benign procedure. Removing a normal appendix is associated with a 4% risk of fetal loss and 10% risk of early delivery. Maternal mortality after appendectomy is extremely rare (0.03%). Because the incidence of complicated appendix is similar in pregnant and nonpregnant women and because maternal mortality is so low, it appears that the greatest opportunity to improve fetal outcomes is by improving diagnostic accuracy and reducing the rate of negative appendectomy.^{110,111,112,113}

Following uncomplicated appendectomy, complication rates are low,¹¹⁴ and most patients can quickly be started on a diet and discharged home the same day or the following day.¹¹⁵ Postoperative antibiotic therapy is unnecessary.¹¹⁶

Alternatively, with complicated appendectomy, complication rates are increased compared to uncomplicated appendicitis.¹¹⁴ Patients should be continued on broad-spectrum antibiotics for 4 to 7 days.^117,118 Postoperative ileus may occur, so diet should be started based on daily clinical evaluation. These patients are at increased risk for surgical site infections.

Surgical Site Infection

In patients with incisional (superficial or deep) surgical site infection, treatment should be opening of the incision and obtaining a culture. Following laparoscopic appendectomy, the extraction port site is the most common site of surgical site infection. Patients with cellulitis can be started on antibiotics. The cultured organisms are typically bowel flora, as opposed to skin flora.¹¹⁹

Patients with postoperative intra-abdominal abscesses can present in a variety of ways. Although fever, leukocytosis, and abdominal pain are common presentations, patients with ileus, bowel obstruction, diarrhea, and tenesmus may also harbor intra-abdominal abscesses. Small abscesses can be simply treated with antibiotics; however, larger abscesses require drainage. Most commonly, percutaneous drainage with CT or ultrasound guidance is effective. For abscesses not amenable to percutaneous drainage, laparoscopic abscess drainage is a viable option.

Stump Appendicitis

Incomplete appendectomy represents a failure of removing the entire appendix on the initial procedure. A review of literature has revealed only 60 reports of this phenomenon. Likely, incomplete appendectomy is underreported, and the true prevalence is much higher. Reported as “stump appendicitis,” patients typically present with recurrent symptoms of appendicitis approximately 9 years after their initial surgery. There was no difference in initial surgery between laparoscopic and open procedures. However, there were more complicated appendectomies on initial surgery. Patients ­presenting with stump appendicitis are more likely to have complicated appendicitis, have an open procedure, and undergo colectomy.

The key to avoiding stump appendicitis is prevention. Use of the “appendiceal critical view” (appendix placed at 10 o’clock, taenia coli/libera at 3 o’clock, and terminal ileum at 6 o’clock) and identification of where the taeniae coli merge and disappear is paramount to identifying and ligating the base of the appendix during the initial operation. The remaining stump should be no longer than 0.5 cm, as stump appendicitis has only been noted in stumps ≥0.5 cm in the literature.

In patients who have had prior appendectomy, a low index of suspicion is important to prevent delay in diagnosis and complications. Prior appendectomy should not be an absolute criterion in ruling out acute appendicitis.

Decisions regarding the efficacy of incidental appendectomy should be based on the epidemiology of appendicitis. The best data were published by the Centers for Disease Control and Prevention based on the period from 1979 to 1984.¹²⁰ During this period, an average of 250,000 cases of appendicitis and 310,000 incidental appendectomies occurred annually in the United States. It was estimated that 36 incidental appendectomies had to be performed to prevent one patient from developing appendicitis.¹²¹ In view of the added costs and risk of morbidity for each extension of a surgical intervention, this does not seem to justify incidental appendectomy.

The financial aspects of the decision to perform incidental appendectomy were assessed.¹²² For open appendectomy, there was a financial disincentive to perform incidental appendectomy. On an annual basis, $20,000,000 had to be spent to save the $6,000,000 cost of appendicitis. With the laparoscopic approach, it was cost-effective to perform incidental appendectomy only in patients less than 25 years of age and only if the reimbursement for surgeons was 10% of the usual and customary charges. At a higher rate of reimbursement, incidental appendectomy was not cost-effective in any age group.

Although incidental appendectomy is generally neither clinically nor economically appropriate, there are some special patient groups in whom it should be performed during laparotomy or laparoscopy for other indications. These include children about to undergo chemotherapy, the disabled who cannot describe symptoms or react normally to abdominal pain, patients with Crohn’s disease in whom the cecum is free of macroscopic disease, and individuals who are about to travel to remote places where there is no access to medical or surgical care.¹²³

Appendectomy is routinely carried out during the performance of Ladd’s procedure for malrotation because displacement of the cecum into the left upper quadrant would complicate the diagnosis of subsequent appendicitis.

Prevalence of Neoplasms

Multiple studies have evaluated the prevalence of mass lesions present in appendectomy specimens (Table 30-8).^{124,125,126,127,128,129,130,131,132} The prevalence of identifying a mass within the appendix is less than 1%. Appendiceal carcinoid and appendiceal adenomas are the most common lesions identified. There is no clear age relationship associated with the identification of these masses.

In older patients, the prevalence of identifying colon cancer appearing as appendicitis has been reported in a single study with a prevalence of less than 1%. The mean age in this case series was 69 years (range, 42 to 89 years).

Carcinoid

The finding of a firm, yellow, bulbar mass in the appendix should raise the suspicion of an appendiceal carcinoid. The appendix is the most common site of gastrointestinal carcinoid, followed by the small bowel and rectum. Carcinoid syndrome is rarely associated with appendiceal carcinoid unless widespread metastases are present, which occur in 2.9% of cases. Symptoms attributable directly to the carcinoid are rare, although the tumor can occasionally obstruct the appendiceal lumen much like a fecalith and result in acute ­appendicitis.^131,133,134

The majority of carcinoids are located in the tip of the appendix. Malignant potential is related to size, with tumors <1 cm rarely resulting in extension outside of the appendix or adjacent to the mass. The mean tumor size for carcinoids is 2.5 cm.¹³³ Carcinoid tumors usually present with localized disease (64%). Treatment for tumors ≤1 cm is appendectomy. For tumors larger than 1 to 2 cm located at the base, involving the mesentery, or with lymph node metastases, right hemicolectomy is indicated. Despite these recommendations, surveillance, epidemiology, and end results data indicate that proper surgery for carcinoids is not performed at least 28% of the time.¹³³

Adenocarcinoma

Primary adenocarcinoma of the appendix is a rare neoplasm with three major histologic subtypes: mucinous adenocarcinoma, colonic adenocarcinoma, and adenocarcinoid.¹³⁵ The most common mode of presentation for appendiceal carcinoma is that of acute appendicitis. Patients also may present with ascites or a palpable mass, or the neoplasm may be discovered during an operative procedure for an unrelated cause. The recommended treatment for all patients with adenocarcinoma of the appendix is a formal right hemicolectomy. Appendiceal adenocarcinomas have a propensity for early perforation, although they are not clearly associated with a worsened prognosis.¹³⁴ Overall 5-year survival is 55% and varies with stage and grade. Patients with appendiceal adenocarcinoma are at significant risk for both synchronous and metachronous neoplasms, approximately half of which will originate from the gastrointestinal tract.¹³⁵

Mucocele

A mucocele of the appendix is an obstructive dilatation by intraluminal accumulation of mucoid material. Mucoceles may be caused by one of four processes: retention cysts, mucosal hyperplasia, cystadenomas, and cystadenocarcinomas. The clinical presentation of a mucocele is nonspecific, and often it is an incidental finding at operation for acute appendicitis. An intact mucocele presents no future risk for the patient; however, the opposite is true if the mucocele has ruptured and epithelial cells have escaped into the peritoneal cavity. As a result, when a mucocele is visualized at the time of laparoscopic examination, conversion to open laparotomy is recommended. Conversion from a laparoscopic approach to a laparotomy ensures that a benign process will not be converted to a malignant one through mucocele rupture. In addition, laparotomy allows for thorough abdominal exploration to rule out the presence of mucoid fluid accumulations.¹³⁵

The presence of a mucocele of the appendix does not mandate performance of a right hemicolectomy. The principles of surgery include resection of the appendix, wide resection of the mesoappendix to include all the appendiceal lymph nodes, collection and cytologic examination of all intraperitoneal mucus, and careful inspection of the base of the appendix. Right hemicolectomy or, preferably, ileocecectomy is reserved for patients with a positive margin at the base of the appendix or positive periappendiceal lymph nodes. Recently, a more aggressive approach to ruptured appendiceal neoplasms has been advocated. This approach includes a thorough but minimally aggressive approach at initial laparotomy, as described earlier, with subsequent referral to a specialized center for consideration of reexploration and hyperthermic intraperitoneal chemotherapy.¹³⁴

Pseudomyxoma Peritonei

Pseudomyxoma peritonei is a rare condition in which diffuse collections of gelatinous fluid are associated with mucinous implants on peritoneal surfaces and omentum. Pseudomyxoma is two to three times more common in females than in males. Recent immunocytologic and molecular studies suggest that the appendix is the site of origin for the overwhelming majority of cases of pseudomyxoma. Pseudomyxoma is invariably caused by neoplastic mucus-secreting cells within the peritoneum. These cells may be difficult to classify as malignant because they may be sparse, widely scattered, and have a low-grade cytologic appearance. Patients with pseudomyxoma usually present with abdominal pain, distention, or a mass. Primary pseudomyxoma usually does not cause abdominal organ dysfunction. However, ureteral obstruction and obstruction of venous return can be seen.¹³⁶ Pseudomyxoma is a disease that progresses slowly and in which recurrences may take years to develop or become symptomatic.¹³⁶ In a series from the Mayo Clinic, 76% of patients developed recurrences within the abdomen.¹³⁷ Lymph node metastasis and distant metastasis are uncommon.

The use of imaging before surgery is advantageous to plan surgery. CT scanning is the preferred imaging modality. At surgery, a variable volume of mucinous ascites is found together with tumor deposits involving the right hemidiaphragm, right retrohepatic space, left paracolic gutter, ligament of Treitz, and the ovaries in women. Peritoneal surfaces of the bowel are usually free of tumor. Thorough surgical debulking is the mainstay of treatment. All gross disease and the omentum should be removed. If not done previously, appendectomy is routinely performed. Hysterectomy with bilateral salpingo-oophorectomy is performed in women. Survival is better in patients who undergo R0 or R1 resection than in patients who undergo R2 resection (visible gross disease remaining).¹³⁸ Because 5-year survival of mucinous appendiceal neoplasms is only 30%, adjuvant intraperitoneal hyperthermic chemotherapy is advocated as a standard adjunct to radical cytoreductive surgery.¹³⁹ ­Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy is a long, tedious procedure with operative times of 300 to 1020 minutes reported. In addition, morbidity (38%) and mortality (6%) are high. Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy is associated with a 5-year survival rate of 53% to 78%. Survival is associated with initial patient performance status.^138,139,140

Any recurrence should be investigated completely. Recurrences are usually treated by additional surgery. It is important to note that surgery for recurrent disease is usually difficult and is associated with an increased incidence of enterotomies, anastomotic leaks, and fistulas.^136,137

Lymphoma

Lymphoma of the appendix is extremely uncommon. The gastrointestinal tract is the most frequently involved extranodal site for non-Hodgkin’s lymphoma.¹⁴¹ Other types of appendiceal lymphoma, such as Burkitt’s lymphoma, as well as leukemia, have also been reported.¹⁴² Primary lymphoma of the appendix accounts for 1% to 3% of gastrointestinal lymphomas. Appendiceal lymphoma usually presents as acute appendicitis and is rarely suspected preoperatively. Findings on CT scan of an appendiceal diameter ≥2.5 cm or surrounding soft tissue thickening should prompt suspicion of an appendiceal lymphoma. The management of appendiceal lymphoma confined to the appendix is appendectomy. Right hemicolectomy is indicated if tumor extends beyond the appendix onto the cecum or mesentery. A postoperative staging workup is indicated before ­initiating adjuvant therapy. Adjuvant therapy is not indicated for lymphoma confined to the appendix.^142,143