+++
Etiology and Pathophysiology
++
Appendicitis, diverticular disease, and colorectal carcinoma have been shown to be diseases of developed civilizations. Burkitt14 found an increased incidence of appendicitis in Western countries compared to Africa, as well as in wealthy, urban communities compared to rural areas. He attributed this to the Western diet, which is low in dietary fiber and high in refined sugars and fat, and postulated that low-fiber diets lead to less bulky bowel contents, prolonged intestinal transit time, and increased intraluminal pressure. Burkitt theorized that the combination of firm stool leading to appendiceal obstruction and increased intraluminal pressure causing bacterial translocation across the bowel wall resulted in appendicitis. In examining appendixes removed for reasons other than appendicitis, he found fecaliths to be more prevalent in Canadian (32%) than in South African (4%) adults. In a group of patients with appendicitis, fecaliths were more common in Canadians (52%) than in South Africans (23%).15 He felt this was confirmation that appendiceal obstruction resulted in appendicitis. Of note, however, the majority of patients with appendicitis in his study did not have evidence of a fecalith.
++
Wangensteen extensively studied the structure and function of the appendix and the role of obstruction in appendicitis.16,17 Based on anatomic studies, he postulated that mucosal folds and a sphincter-like orientation of muscle fibers at the appendiceal orifice make the appendix susceptible to obstruction. He proposed the following sequence of events to explain appendicitis: (1) Closed-loop obstruction is caused by a fecalith and swelling of the mucosal and submucosal lymphoid tissue at the base of the appendix; (2) intraluminal pressure rises as the appendiceal mucosa secretes fluid against the fixed obstruction; (3) increased pressure in the appendiceal wall exceeds capillary pressure and causes mucosal ischemia; and (4) luminal bacterial overgrowth and translocation of bacteria across the appendiceal wall result in inflammation, edema, and ultimately necrosis. If the appendix is not removed, perforation can ensue.
++
Although appendiceal obstruction is widely accepted as the primary cause of appendicitis, evidence suggests that this may be only one of many possible etiologies. First, some patients with a fecalith have a histologically normal appendix, and the majority of patients with appendicitis show no evidence for a fecalith.15,18,19 Arnbjornsson and Bengmark20 studied at laparotomy the appendixes of patients with suspected appendicitis. They found the intraluminal pressure of the appendix prior to removal to be elevated in only 8 of 27 patients with nonperforated appendicitis. They found no signs of obstruction in the remaining patients with nonperforated appendicitis, as well as all patients with a normal appendix. Taken together, these studies imply that obstruction is but one of the possible etiologies of acute appendicitis.
+++
Perforated Appendicitis
++
It is a commonly held belief that if left untreated, appendiceal inflammation will progress inevitably to necrosis, and ultimately to perforation. The time course of this progression varies among patients. In one study of the natural history of appendicitis, the authors questioned patients undergoing appendectomy for suspected appendicitis about their duration of symptoms.21 Patients with nonperforated appendicitis reported an average of 22 hours of symptoms prior to presentation to the hospital, while patients with perforated appendicitis reported an average of 57 hours. However, 20% of cases of perforated appendicitis presented within 24 hours of the onset of symptoms; one of those patients had symptoms for only 11 hours. Although concern for perforation should be present when evaluating a patient with more than 24 hours of symptoms, the clinician must remember that perforation can develop more rapidly.
++
Some authors have questioned whether some perforations in acute appendicitis are attributable to delay in diagnosis after a patient seeks medical attention. Velanovich and Satava postulated a surgeon's misdiagnosis rate (the percentage of normal appendixes found at appendectomy) to be inversely related to the perforation rate (the percentage of perforated appendixes found at laparotomy).22 They believed that surgeons are obliged to operate quickly when appendicitis is suspected, thus minimizing the likelihood of perforation in exchange for a higher rate of misdiagnosis. More recent studies suggest that this reasoning is flawed. Temple and colleagues showed that patients with perforated appendicitis were operated on more quickly than those with nonperforated appendicitis (6.5 vs 9 hours), but perforated patients had significantly longer prehospital symptoms (57 vs 22 hours).21 These findings are confirmed by two other studies, both showing that longer duration of prehospital delay is the major contributor to perforation.23,24 Perforation after presenting to surgical attention appears to be uncommon.
++
When acute appendicitis has progressed to appendiceal perforation, other symptoms may be present. Patients will often complain of two or more days of abdominal pain, but their duration of symptoms may be shorter, as previously discussed. The pain usually localizes to the right lower quadrant if the perforation has been walled off by surrounding intra-abdominal structures including the omentum, but it may be diffuse if generalized peritonitis ensues. The pain may be so severe that patients do not remember the antecedent colicky pain. Patients with perforation often have rigors and high fevers to 102°F (38.9°C) or above. A history of poor oral intake and dehydration may also be present.
++
Most patients with perforated appendicitis present with symptoms related to the inflamed appendix itself or to a localized intraperitoneal abscess from perforation. Other more rare presentations do occur, however. These are most likely to occur in the very young and very old, who cannot express their symptoms and often present late in the course of their disease. For instance, abscesses can also form in the retroperitoneum due to perforation of a retrocecal appendix, or in the liver from hematogenous spread of infection through the portal venous system. An intraperitoneal abscess could fistulize to the skin, resulting in an enterocutaneous fistula. Pylephlebitis (septic portal vein thrombosis) presents with high fevers and jaundice and can be confused with cholangitis; it is a dreaded complication of acute appendicitis and carries a high mortality.25 On occasion, patients will have bilious vomiting and obstipation due to a small bowel obstruction resulting from appendiceal perforation. Because appendicitis is so common, these rare presentations should alert the surgeon to the possibility of appendicitis.
+++
History and Physical Examination
++
As always, the diagnosis begins with a thorough history and physical examination. The patient should be asked about the classic symptoms of appendicitis, but the surgeon should not be dissuaded by the absence of many of the symptoms. Many patients with acute appendicitis do not have a classic history. Because the differential diagnosis of appendicitis is extensive, patients should be queried about certain symptoms that may suggest an alternative diagnosis. Surgeons must also remember that a previous appendectomy does not definitively exclude the diagnosis of appendicitis, as “stump appendicitis” (appendicitis in the remaining appendiceal stump after appendectomy), although rare, has been described.26
++
On inspection, patients look mildly ill and may have slightly elevated temperature and pulse. They often lie still to avoid the peritoneal irritation caused by movement. The surgeon should systematically examine the entire abdomen, starting in the left upper quadrant away from the patient's described pain. Maximal tenderness is typically in the right lower quadrant, at or near McBurney's point, located one-third of the way from the anterior superior iliac spine to the umbilicus. This tenderness is often associated with localized muscle rigidity and signs of peritoneal inflammation, including rebound, shake, or tap tenderness. RLQ tenderness is most consistent of all signs of acute appendicitis27,28; its presence should always raise the specter of appendicitis, even in the absence of other signs and symptoms. Because of the various anatomic locations of the appendix, however, it is possible for the tenderness to be in the right flank or right upper quadrant, the suprapubic region, or the left lower quadrant. Patients with a retrocecal or pelvic appendix may have no abdominal tenderness whatsoever. In such cases, rectal examination can be helpful to elicit right-sided pelvic tenderness.
++
Multiple signs can be detected on physical examination to contribute to the diagnosis of appendicitis. Rovsing's sign, pain in the right lower quadrant on palpation of the left lower quadrant, results from localized peritoneal inflammation in the right lower quadrant. Psoas sign, pain with flexion of the leg at the right hip, can be seen with a retrocecal appendix due to inflammation adjacent to the psoas muscle. The obturator sign, pain with rotating the flexed right thigh internally, indicates inflammation adjacent to the obturator muscle in the pelvis.
++
In cases of perforated appendicitis, patients can look gravely ill, appearing flushed with dry mucous membranes and considerable elevations in temperature or pulse. If sepsis has developed, blood pressure can be depressed. If the perforation has been walled off by surrounding structures to create an abscess or phlegmon, a mass may be palpable in the right lower quadrant. If free intraperitoneal rupture has occurred, the patient can have signs of generalized peritonitis with diffuse rebound tenderness.
++
Laboratory studies can be helpful in the diagnosis of appendicitis, but no single test is definitive. A white blood cell count (WBC) is perhaps the most useful laboratory test. Typically, the WBC is slightly elevated in nonperforated appendicitis but may be quite elevated in the presence of perforation. The clinician must remember, however, that the WBC can be normal in patients with acute appendicitis, particularly in early cases. Serial WBC measurements improve the diagnostic accuracy, with a rising value over time commonly seen in patients with appendicitis.29 Urinalysis is performed to diagnose other potential causes for abdominal pain, specifically urinary tract infection and ureteral stone. Significant hematuria with colicky abdominal pain suggests ureterolithiasis, and testing directed at this diagnosis is indicated. A urinary tract infection, on the other hand, is not uncommon in patients with appendicitis. Its presence does not exclude the diagnosis of acute appendicitis, but it should be identified and treated. Although pyuria suggests urinary tract infection, it is not uncommon for the urinalysis in a patient with appendicitis to show a few white blood cells solely due to inflammation of the ureter by the adjacent appendix.
++
In certain patient populations, other laboratory tests are indicated. Measurement of serum liver enzymes and amylase can be helpful in diagnosing liver, gallbladder, or pancreatic disease in patients complaining of midabdominal or RUQ pain. In women of childbearing age, the urine β-human chorionic gonadotropin should be checked to alert the clinician to the possibility of ectopic or concurrent pregnancy. Ectopic pregnancy is another cause of RLQ pain that demands emergent diagnosis and treatment. Concurrent pregnancy should be known before a patient with suspected appendicitis is subjected to ionizing radiation from imaging studies or to general anesthesia.
++
Diagnostic scoring systems have been developed in an attempt to improve the diagnostic accuracy of acute appendicitis.18,30 The most prominent of those scores, developed by Alvarado,30 was based on a retrospective analysis of 305 patients with abdominal pain suspicious for appendicitis. This scoring system gives points for symptoms (migration of pain, anorexia, and nausea), physical signs (RLQ tenderness, rebound tenderness, and pyrexia), and laboratory values (leukocytosis and a left shift). Although these scores can help guide clinical thinking, they do not markedly improve diagnostic accuracy.31 With the recent improvement in imaging studies, these scores play a smaller role in diagnosis.
++
The potential imaging modalities for diagnosis of acute appendicitis include plain radiographs, ultrasound (US), and computed tomography (CT). Prior to the widespread use of modern imaging techniques, plain abdominal films were often obtained in patients with abdominal pain, and a right lower quadrant fecalith (or appendicolith) was considered pathognomonic for acute appendicitis. A number of studies question this teaching, however. Teicher and colleagues18 reviewed the abdominal radiographs of 200 appendectomy patients—100 with pathologically proven appendicitis and 100 with a normal appendix. Of those with appendicitis, 10.5% had an appendicolith on x-ray, compared to 3.3% of those without appendicitis. An extensive review of appendectomy specimens at the Mayo Clinic19 showed that fecaliths or appendiceal calculi were present in 9% of patients with nonperforated appendicitis and 21% of those with perforated appendicitis. Interestingly, fecaliths were also present in 7% of patients with suspected appendicitis who had a pathologically normal appendix and in 2% of patients who had an appendectomy for other reasons.
++
These studies show that fecaliths are not pathognomonic for appendicitis, as some patients with abdominal pain and a fecalith have a normal appendix. In addition, fecaliths are not common enough in patients with appendicitis to be used as a reliable sign. As a result, plain abdominal radiographs are neither helpful nor cost-effective and are not recommended for the diagnosis of acute appendicitis. Plain radiographs are indicated in elderly patients with severe abdominal pain, in whom a perforated viscus is included in the differential diagnosis. In this patient population, an upright chest x-ray can assess for the presence of free air.
++
Abdominal ultrasonography is a popular imaging modality for acute appendicitis. Findings that suggest appendicitis include thickening of the appendiceal wall, loss of wall compressibility, increased echogenicity of the surrounding fat signifying inflammation, and loculated pericecal fluid (Fig. 31-3). The advantages of ultrasound include its widespread availability, as well as the avoidance of ionizing radiation and the side effects of intravenous contrast such as renal toxicity and allergic reactions. In addition, ultrasound (both abdominal and transvaginal) is particularly useful in assessing obstetric and gynecological causes of abdominal pain in women of childbearing age. Ultrasound is highly operator-dependent, however, and it is frequently unable to visualize the normal appendix.32 A recent meta-analysis of 14 prospective studies showed ultrasound to have a sensitivity of 0.86 and a specificity of 0.81.33
++
++
CT is yet another imaging modality for acute appendicitis. CT benefits from a high diagnostic accuracy for appendicitis33 and visualization and diagnosis of many of the other causes of abdominal pain that can be confused with appendicitis. The radiographic findings of appendicitis on CT include a dilated (>6 mm), thick-walled appendix that does not fill with enteric contrast or air, as well as surrounding fat stranding to suggest inflammation (Fig. 31-4).34 In a meta-analysis of 12 prospective studies, CT demonstrated a sensitivity of 0.94 and a specificity of 0.95.33 CT thus has a high negative predictive value, making it particularly useful in excluding appendicitis in patients for whom the diagnosis is in doubt. Appendicitis is highly unlikely if enteric contrast fills the lumen of the appendix and no surrounding inflammation is present. The clinician must remember, however, that a CT performed early in the course of appendicitis might not show the typical radiographic findings. In confusing cases, it is reasonable to repeat the CT after 24 hours of observation.
++
++
A number of recent prospective studies have compared the accuracy of CT and ultrasound in imaging the appendix (Table 31-1).32,35,36 Balthazar and associates35 performed CT and ultrasound on 100 consecutive patients with suspected appendicitis. The sensitivity of CT was considerably higher (96% for CT, 76% for US), while the specificity was comparable (89% for CT, 91% for US), yielding a higher accuracy for CT (94 vs 83%). CT was also able to provide an alternative diagnosis in more patients and was better able to visualize abscesses or phlegmons (Fig. 31-5). Horton and colleagues36 randomized patients with suspected appendicitis to either CT or ultrasound. Their findings echo those of Balthazar, with both CT and ultrasound having high specificity (100% for CT, 90% for US) but CT having significantly higher sensitivity (97 vs 76%). Yet another prospective study showed similar results, with CT having higher sensitivity (96 vs 62%) and specificity (92 vs 71%) than ultrasound.32 Again, CT was also better able to visualize other intra-abdominal pathology in the absence of appendicitis.
++
++
++
In a study of 100 patients evaluated by CT with rectal and intravenous contrast, Rao and coworkers37 showed that CT can reduce the use of hospital resources and costs. CT changed the management of 59 patients, avoiding 13 unnecessary appendectomies and eliminating a total of 50 inpatient hospital days for observation of unexplained abdominal pain. Even factoring in the cost of the CT scans, the authors calculated a net savings of US$447 per patient.
++
Taken together, these studies suggest an algorithm for evaluation of patients with suspected acute appendicitis. Patients with a history, physical examination, and laboratory studies classic for appendicitis should undergo appendectomy. In those with an evaluation suggestive but not convincing for appendicitis, further imaging is warranted. In women of childbearing age, this should begin with a pelvic ultrasound to evaluate for ovarian pathology. In other patients, transabdominal ultrasound or abdominopelvic CT should be considered, depending on study availability and expertise of the consulting radiologist. CT does have the advantage of improved accuracy in diagnosing both appendiceal and other intra-abdominal pathology. This can be supplemented with rectal contrast CT, if needed, to better visualize the appendix.32,37 Patients with a CT showing nonperforated appendicitis should undergo appendectomy. In many instances, patients with a normal CT do not require hospital admission. If symptoms persist, admission to the hospital for observation, and perhaps a repeat CT scan, is warranted.
+++
Differential Diagnosis
++
Because many of its signs and symptoms are nonspecific, the differential diagnosis of acute appendicitis is extensive and includes virtually all possible abdominal sources of pain, as well as some nonabdominal sources (Table 31-2). However, some diagnoses are more likely than others in certain patient groups. For instance, in young males with a suggestive history and physical examination, acute appendicitis is the most likely cause of RLQ pain. Meckel's diverticulitis causes similar symptoms but is relatively uncommon.38 Gastroenteritis is considerably more common and should be expected when nausea and vomiting precede the abdominal pain, or when diarrhea is a prominent symptom. Crohn's disease affecting the terminal ileum may resemble appendicitis in its initial presentation, but on further questioning the patient typically describes a subacute course, including fever, weight loss, and pain.
++
++
In middle-aged and older adults, other inflammatory conditions should be considered, including peptic or duodenal ulcer (with fluid tracking into the right paracolic gutter), cholecystitis, and pancreatitis. In addition, cecal or sigmoid diverticulitis can be confused with acute appendicitis. Cecal diverticulitis is quite similar in pathogenesis and presentation to appendicitis, because cecal diverticula, like the appendix, are true diverticula containing all layers of the intestinal wall. Because a redundant, floppy sigmoid colon can extend to the right side of the abdomen, patients with sigmoid diverticulitis can sometimes present with RLQ pain. Those patients typically describe a quicker progression to localized tenderness, as well as a prodrome of an alteration in bowel habits. Malignancies can present with acute RLQ pain due to perforation of a cecal carcinoma or appendicitis caused by a mass obstructing the appendiceal orifice.39 These patients will also typically have guaiac-positive stools, anemia, and a history of weight loss.
++
In women of childbearing years, the diagnosis of RLQ pain can be even more difficult. In addition to the causes of RLQ pain mentioned for young men, young women can also have pain from obstetric and gynecological causes such as ruptured ovarian cyst or follicle, ovarian torsion, ectopic pregnancy, acute salpingitis, and tubo-ovarian abscess. A complete history including recent menstrual history, as well as pelvic examination, can be helpful in differentiating these causes of pain from acute appendicitis. Nonetheless, appendicitis can be difficult to diagnose in this patient population, and higher rates of misdiagnosis have been described in women of childbearing age.40
+++
Special Considerations
++
Appendicitis most commonly affects children age 10–19, with an overall incidence of approximately 20 cases per 10,000 population annually.13 Among those younger than 20, infants aged 0–4 have the lowest incidence of appendicitis (2 cases per 10,000 annually), but up to two-thirds will present with perforation.41 Perforation is common because infants often present later in their disease course and because of the difficulty in obtaining an accurate history. The diagnosis is further complicated by diseases of childhood that can mimic appendicitis. For instance, mesenteric adenitis, an inflammation of the mesenteric lymph nodes secondary to upper respiratory tract infection, can present with fever and RLQ pain. Streptococcal pharyngitis and bacterial meningitis can also present with fever, nausea, and abdominal pain. These diagnoses and others including ovarian cysts, ovarian torsion, urinary tract infection, pelvic inflammatory disease, and complications of a Meckel's diverticulum should be considered when evaluating children or adolescents for suspected appendicitis.
++
In children with an equivocal history and physical examination, imaging with either a CT scan or US can significantly reduce the negative appendectomy rate from 14 to 37% down to 2 to 10%.42 The pertinent question is which study is preferable. As with adults, both CT and US have been shown to be highly accurate in diagnosing appendicitis in children, although CT scan is believed to have a higher specificity and sensitivity. In an early study Garcia Pena and associates compared ultrasonography and rectal contrast CT in 139 children with suspected appendicitis and found CT to be more sensitive (97% for CT, 44% for US), more specific (94% for CT, 93% for US), and more accurate (94% for CT, 76% for US).43 CT correctly changed the management of 73% of patients, while ultrasound correctly changed 19%. More recent meta-analysis and reviews evaluating CT and/or ultrasound in pediatric populations found the specificity of the two imaging modalities to be similar (92–95%) but the sensitivity of ultrasound (88–90%) to be less than that of CT scan (94–95%).42,44 An important determinant in the diagnostic success of ultrasound is the body mass index (BMI) of the child. The sensitivity of ultrasound has been reported by some to be 76% in children with a BMI below 25, 37% in children with a BMI greater than 25, and 82% in one study in which the patient population had a mean BMI of 17.42,45,46
++
The use of CT can be recommended for children with one caveat. The radiation from a CT in childhood theoretically causes a small increase in the lifetime risk of certain cancers.47 Based on estimated radiation exposure from a CT scan, studies have hypothesized that a 1-year-old and 15-year-old would have a 0.18 and 0.11% lifetime risk, respectively, of fatal radiation-induced malignancy following a CT scan.42 Therefore, clinicians should consider the risks and benefits of CT, and efforts should be directed toward reducing radiation dose when imaging children.48 In the pediatric patients with suspected appendicitis, an algorithm starting with an ultrasound, especially in low BMI children and females, followed by CT scan if the ultrasound is equivocal may allow the maximum benefit of radiologic imaging while minimizing potential deleterious radiation effects. The use of magnetic resonance imaging (MRI) in the evaluation of children has only recently begun to be investigated. Although its ability to identify the appendix has been established, the use of MRI in the diagnosis of appendicitis in children requires further study.
++
Although appendicitis is more common in younger age groups, it is still an important cause of abdominal pain in the elderly. Perhaps because of a diminished inflammatory response, the elderly can present with less impressive symptoms and physical signs, longer duration of symptoms, and decreased leukocytosis compared to younger patients.49 Perforation is thus more common, occurring in as many as 50% of patients older than 65.13 These patients may have cardiac, pulmonary, and renal conditions, resulting in considerable morbidity and mortality from perforation. In one series, the mortality from perforated appendicitis in patients older than 80 was 21%.50 These factors argue that RLQ pain in elderly patients must be aggressively investigated. Because of the multiple other possible causes of abdominal pain in this patient population (including malignancy, diverticulitis, and perforated peptic ulcer disease), prompt CT scan is advocated when the diagnosis is in question.
++
The diagnosis of acute appendicitis in the pregnant patient can be particularly challenging, as nausea, anorexia, and abdominal pain may be symptoms of both appendicitis and normal pregnancy. In addition, the gravid uterus can displace the abdominal viscera, shifting the location of the appendix from the right lower quadrant. Appendicitis affects 1 in every 1400 pregnancies, an incidence similar to that of the nonpregnant female population.51 It can occur in any trimester, with perhaps a slight increase in frequency during the second trimester.51,52 Perforation is more common in the third trimester, however, and results from a longer duration from the onset of symptoms to operation.53 The differential diagnosis of appendicitis includes not only the conditions possible in nonpregnant women but also certain conditions specific to pregnancy: ectopic pregnancy, chorioamnionitis, preterm labor, placental abruption, and round ligament pain.
++
In the first and early second trimesters, the presentation of appendicitis is similar to that seen in nonpregnant women. In the third trimester, women may not present with RLQ pain due to displacement of the appendix by the gravid uterus. Baer and associates performed barium enemas on normal pregnant women and found the appendix to migrate superiorly toward the right upper quadrant in later stages of pregnancy.54 Their findings suggest that appendicitis should present with RUQ or flank pain in late pregnancy. Two retrospective studies contradict this, however, showing that even in the third trimester, pain and tenderness are more common in the right lower than the right upper quadrant.51,52 Nonetheless, RUQ pain did predominate in some third-trimester patients with appendicitis in each study,51,52 reminding the clinician that right upper quadrant and right flank symptoms could be due to appendicitis in an appendix displaced by the gravid uterus. Recent studies highlight the difficulty of assigning a clinical picture to a pregnant patient with appendicitis. Brown et al55 reviewed case-control studies attempting to correlate preoperative signs and symptoms with the postoperative diagnosis of appendicitis in pregnant patients. Although patients presented with RUQ pain, RLQ pain, and fevers, only nausea, vomiting, and peritonitis were found to significantly correlate with the diagnosis of appendicitis.
++
Ultrasound is accurate in pregnancy56 and is a useful first radiological study because it has no known adverse fetal effects.57 Rectal contrast CT has also been shown to be highly accurate in the pregnant population.58 Although ionizing radiation has risks to the fetus, the radiation from a typical abdominopelvic CT is below the threshold of 5 rad at which teratogenic effects are seen.59 When the diagnosis is in doubt, the risk of radiation should be weighed against the risk of spontaneous abortion from an unnecessary laparotomy or from undiagnosed appendicitis progressing to perforation. Hospital admission with close observation for progression of symptoms is a viable alternative if the risks of radiation from CT scan are deemed excessive. Additionally, MRI has been recently used to aid in the diagnosis of appendicitis in the pregnant patient when ultrasound results are equivocal. In those pregnant patients with a normal or inconclusive ultrasound, MRI is a diagnostic option, with accuracy that rivals CT; MRI has a sensitivity of 80% and specificity of 99%, compared with 85.7 and 97.4% for CT. Although MRI does not carry a risk of radiation, it does have theoretical risks of static and time-varying magnetic fields, heating effects of the radiofrequency pulses and acoustic noise generated by the spatial encoding gradients do exist. To date, however, no adverse effects of MRI on the developing fetus have been reported.60
++
The pregnant patient should proceed directly to appendectomy if appendicitis is suspected. A normal appendix is not an uncommon finding, as negative appendectomy has been reported in approximately one-third of cases due to the difficulty of diagnosis in this population.51,52,61 Negative appendectomy should not be considered an error in diagnosis, because the risk to the fetus varies directly with the severity of appendicitis. In one series, fetal loss occurred in only 1 (3%) of 30 negative laparotomies.51 Fetal mortality rises to 5% in cases of nonperforated appendicitis and increases to 20–35% when the appendix perforates.55,61 These data warrant an aggressive approach to appendectomy. Early negative exploration is justified to minimize the likelihood of progression to perforation.
++
As laparoscopic appendectomy has become increasingly popular, it has been utilized more frequently during pregnancy.62 Pregnancy can increase the complexity of the procedure, as the gravid uterus can make laparoscopic visualization difficult, particularly if the appendix is located in the pelvis. In addition, carbon dioxide insufflation of the abdomen results in fetal hypercarbia and decreased placental blood flow, the effects of which have not been completely studied.63 Recent case series, however, have supported the safety of laparoscopic appendectomy in the pregnant patient. In a retrospective review of 45 cases, Lemieux et al64 demonstrated that 4% of patients had a major complication (uterine perforation, intra-abdominal abscess), 4% of patients had a minor complication (cystitis, ileus), 18% delivered before 37 weeks gestation, and there was no fetal loss. There was also no difference in complications, preterm delivery, or operative time associated with performing the appendectomy during the first, second, or third trimester. A retrospective review directly comparing laparoscopic to open appendectomy in 42 pregnant women found no intra- or postoperative complications in either group and one fetal loss in both groups.65 Thus, the feasibility and safety of laparoscopy during pregnancy are supported by these studies, but larger studies are required for it to become fully accepted.
++
The immunocompromised state alters the normal response to acute infection and wound healing. Appendicitis affects all types of patients and must be considered in those who have undergone organ transplant, are receiving chemotherapy, have hematological malignancy, or are infected with the human immunodeficiency virus (HIV). The differential diagnosis of abdominal pain in this population is broad and includes hepatitis, pancreatitis (from medications or cytomegalovirus infection), acalculous cholecystitis, intra-abdominal opportunistic infections (cytomegalovirus colitis or mycobacterial ileitis), secondary malignancies (lymphoma or Kaposi's sarcoma), graft-versus-host disease, and typhlitis. This broad differential diagnosis often results in delay in diagnosis and late presentation to surgical evaluation, at which time perforation may be more likely.66,67
++
Appendicitis in patients with HIV and acquired immunodeficiency syndrome (AIDS) presents unique challenges. Abdominal pain is not an uncommon symptom in these patients, making differentiation between surgical and nonsurgical causes difficult. Nonetheless, immunocompromised patients with appendicitis present with symptoms similar to those of the general population,66 and RLQ pain, nausea, and anorexia. Fever and WBC may not be helpful in this population, so imaging studies, particularly CT, have been supported by some authors.67 There is no specific contraindication to operation in immunocompromised patients, so once diagnosed with appendicitis, appendectomy should be performed promptly.