William V. Harford MD, FACP1
1Professor, Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Director, Clinical Gastroenterology Laboratory, Dallas Veterans Affairs Medical Center
The author has no commercial relationships with manufacturers of products or providers of services discussed in this chapter.
Colonic Diverticular Disease
Colonic diverticula are herniations of colonic mucosa and submucosa that extend through the muscularis propria. They occur where perforating arteries traverse the circular muscle layer and form parallel rows between the mesenteric and antimesenteric taenia. Diverticulosis describes the presence of diverticula, whereas diverticulitis refers to the inflammation of diverticula. Diverticulosis is a common condition; of persons with known diverticulosis, about 10% to 20% will develop diverticulitis or diverticular bleeding.1
There are no population-based studies of the prevalence of diverticulosis. About 1% of the United States population reported having diverticulosis in the 1983–1987 National Health Interview Survey (NHIS). Women were two to three times more likely than men to report having diverticulosis, and whites were more likely than African Americans. The prevalence of self-reported diverticulosis increased with age. It was 0.1% at 45 years of age or younger and 4.4% at 75 years of age or older. Unrecognized diverticulosis is more common than known diverticulosis. It is estimated that 10% to 20% of persons older than 50 years have diverticulosis.2 In Western countries, diverticula occur predominantly in the left colon, particularly the sigmoid colon, which is involved in 95% of cases. In the Orient, including Japan, diverticula occur predominantly in the right colon.3,4
About 85% of persons with self-reported diverticulosis in the NHIS were asymptomatic or reported no limitations resulting from diverticulosis. Patients who are asymptomatic at the time of diagnosis are unlikely to develop diverticulitis. In the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study, a cohort of physicians with asymptomatic diverticulosis were followed for a 10-year period. The probability of hospitalization for diverticular disease was less than 1% for physicians who were 25 to 44 years of age at the beginning of the follow-up period and was about 5% for those who were 65 to 74 years of age.2 In English and Finnish populations, the risk of acute diverticulitis was about four per 100,000 population per year.5,6 The risk of diverticulitis increases with age and with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, and opioids.1,5,7
Reduced colonic diameter and reduced colonic wall compliance are felt to predispose persons to diverticulosis. A reduced colonic diameter causes the formation of closed segments during colonic contractions, thereby increasing intraluminal pressure. Diverticulosis is common in countries where a low-fiber diet is consumed, because a low-fiber diet leads to reduced stool volume and colonic diameter, particularly in the sigmoid colon. A high-fiber diet reduces the risk of diverticular disease.8,9 Patients with diverticulosis have an age-related increase in elastin deposition and collagen cross-linking.10 Increased proline absorption from Western diets may be a factor contributing to increased elastin deposition.11 Changes in elastin and collagen lead to thickening and shortening of the taenia and circular muscle layers (myochosis) in many patients with diverticulosis, increasing the possibility of segmentation. These elastin and collagen changes also result in reduced compliance of the colonic wall, so that for any colonic diameter, intraluminal pressure is higher than it is in patients with normal compliance.12 Increased intraluminal pressure leads to herniation of mucosa through the defects in the muscularis of the colon associated with perforating arteries.
Only mucosa and submucosa separate the lumen of diverticula from the colonic serosa. Diverticulitis may result from abrasion of the mucosa by inspissated stool. Changes in bacterial colonic microflora have been reported in patients with diverticulosis. It has been proposed that these changes may lead to low-grade chronic inflammation, predisposing to the development of diverticulitis.13,14 Chronic intermittent use of oral rifaximin, a poorly absorbed antibiotic, and mesalazine, an anti-inflammatory agent, appears to reduce the risk of diverticulitis.15,16
Diverticula form where medium-sized perforating arteries penetrate the muscularis propria to enter the submucosa. Pathologic examination has been reported to reveal evidence of chronic injury to the internal elastic lamina and media of these arteries. This injury can cause arterial rupture into the lumen of the colon. Diverticular bleeding is rarely associated with acute diverticulitis.
Diverticula are most often discovered incidentally during investigation of another condition. Diverticulitis varies in presentation and severity. The diagnosis of acute diverticulitis is often made on the basis of the history and physical examination, which includes abdominal, rectal, and pelvic examinations; imaging studies are used to confirm the diagnosis. Computed tomography has become the optimal method of investigation for patients suspected of having diverticulitis. The modified Hinchey classification, which takes into account both clinical and CT findings, is useful for prognosis and management [see Table 1].17
Table 1 Modified Hinchey Classification of Acute Diverticulitis17
Patients with mild diverticulitis (Hinchey stage 0 or 1a) have limited inflammation or phlegmon in the area of the involved diverticulum. They typically present with left-sided lower abdominal pain and localized tenderness, low-grade fever, anorexia, and nausea without vomiting. They may have mild leukocytosis. Patients with mild diverticulitis can often be managed without hospitalization.4 Patients with more severe diverticulitis usually must be hospitalized. They often have a diverticular abscess (stage 1b or 2), which is usually contained in the pericolic fat, mesentery, or pelvis but may extend beyond the pelvis. Patients with an abscess (or large phlegmon) commonly have systemic toxicity, high fever, severe localized abdominal tenderness, and leukocytosis. The phlegmon or abscess may be palpable. Rupture of a diverticular abscess results in purulent peritonitis (stage 3), which usually leads to diffuse abdominal tenderness. Free perforation of a diverticulum with fecal soiling of the abdominal cavity leads to feculent peritonitis (stage 4). Feculent peritonitis causes severe acute generalized peritonitis and sepsis.
Colonic inflammation associated with diverticulitis may cause either diarrhea or constipation. Acute diverticulitis may lead to colonic or small bowel obstruction. Repeated episodes of diverticulitis with fibrosis may cause colonic stricture.
Diverticulitis may cause fistula formation, most commonly from the sigmoid colon to the bladder. Inflammation adjacent to the bladder may lead to dysuria even if no fistula is present. Overt lower gastrointestinal bleeding is rarely associated with acute diverticulitis. Other causes of bleeding (e.g., angiodysplasia, a neoplasm, or inflammatory bowel disease) must be excluded in patients with diverticulitis who present with overt bleeding or who have positive fecal occult blood tests.
In a large retrospective study of patients who required hospitalization for acute diverticulitis, 72% of patients had no abscess (Hinchey stage 0 or 1a); 19%, an abscess (Hinchey stage 1b or 2); 5%, prurulent peritonitis (Hinchey stage 3); 1%, feculent peritonitis (Hinchey stage 4); 1%, obstruction; and 2%, fistula. Overall, surgery was required in 26% of patients.17 Comparable distribution of stages has been reported in other studies.18,19,20
Diverticulitis in areas other than the sigmoid colon is uncommon in Western countries. In such cases, clinical presentation may be atypical and confusing. Cases of right-sided colonic and cecal diverticulitis are often clinically indistinguishable from appendicitis.21,22,23
Diverticulitis may lead to episodic abdominal pain. In a study of patients previously hospitalized for acute diverticulitis, 70% subsequently experienced new, recurrent episodes of abdominal pain, usually lasting less than 4 hours.24 After the first episode of diverticulitis, 30% to 50% of patients have subsequent episodes. About 20% to 25% of patients have subsequent episodes of complicated diverticulitis within the first several years of follow-up.18,19 Patients who initially have a large diverticular abscess have an increased risk of recurrence of diverticulitis, even if the abscess is treated by antibiotics and drainage by interventional radiology.17
Patients with symptoms and signs of mild, uncomplicated diverticulitis who respond promptly to outpatient medical treatment do not necessarily require an imaging study immediately. Confirmation of the diagnosis can be delayed for 4 to 6 weeks, when active inflammation has resolved. If there is uncertainty about the diagnosis, outpatient CT is performed to exclude conditions that mimic diverticulitis [seeDifferential Diagnosis, below].
On CT, diverticula are seen as collections of gas or contrast measuring 5 to 10 mm and protruding from the wall of the colon. Symmetrical thickening of the colonic wall may be noted. In diverticulitis, a phlegmon is marked by streaky enhancement of pericolic or perirectal soft tissue and the mesentery [see Figure 1]. Perforation and fistula may be visualized by air or contrast. Abscess is seen as one or more discrete fluid collections.25 If the abscess communicates with the colonic lumen, contrast may enter the abscess cavity. CT readily detects remote abscess. When abscess is detected, the feasibility of CT-guided drainage can be determined.8,26,27
Figure 1. CT in Diverticulitis
CT diverticulitis. The wall of the sigmoid colon is thickened (broad arrow). Air is seen within a diverticulum (curved arrow). Streaky enhancement of pericolis fat (horizontal arrow) is caused by inflammation.
The objectives of diagnostic testing in suspected acute diverticulitis are to exclude other important conditions, to confirm the diagnosis of diverticulitis, to determine if complications have occurred, and to plan treatment.
Leukocytosis is usually present in acute diverticulitis. The urine may contain a modest number of white cells or red blood cells. Recurrent or polymicrobial urinary tract infections should suggest the possibility of a colovesical fistula. Plain abdominal x-rays are most useful to exclude other abdominal conditions, such as intestinal obstruction. Occasionally, an inflammatory mass with gas may be noted, confirming the presence of an abscess. Free air in the abdominal cavity is unusual in diverticulitis.
Colonoscopy is generally not required for diagnosis in suspected acute diverticulitis, and air insufflation caused by introduction of air may worsen a contained perforation. Colonoscopy can be performed with relative safety if no fluid or free air is noted on abdominal CT.28 After treatment and resolution of an acute epsisode of diverticulitis, patients should have an elective examination either by colonoscopy or by fiberoptic sigmoidoscopy after barium enema; the purpose of elective colonoscopy is to exclude the presence of colon cancer and inflammatory bowel disease.29 Barium enema should be avoided in suspected acute diverticulitis because of the risk of barium contamination of the peritoneum if a perforation is present.
A number of conditions may mimic acute diverticulitis [see Table 2]; among the differential diagnoses less frequently considered are epiploic appendagitis and omental torsion/infarction, which may be distinguished from diverticulitis by CT. Epiploic appendices are small peritoneal pouches filled with fat that are situated along the margin of the colon. These structures can become inflamed, resulting in acute epiploic appendagitis, which may mimic diverticulitis or appendicitis. The clinical presentation consists of acute abdominal pain and tenderness. Peritoneal signs sometimes occur, as do low-grade fever and mild leukocytosis. On CT scan, epiploic appendagitis has a characteristic appearance: an oval, fatty mass surrounded by mesenteric stranding, and mural thickening of adjacent colon is typically present.30,31,32 In rare cases, the omentum may undergo spontaneous torsion, causing ischemia or infarction. The clinical presentation may mimic acute diverticulitis, appendicitis, or cholecystitis. The diagnosis of omental torsion may be determined preoperatively by the use of abdominal CT.33,34
Table 2 Differential Diagnosis of Acute Diverticulitis
Diverticulitis in Specific Patient Groups
Immunocompromised patients, such as those on glucocorticoids or those who have had an organ transplant, may not manifest the usual signs of diverticulitis, and diagnosis in these patients may therefore be delayed. The severity of diverticulitis may also be underestimated. The threshold for diagnostic evaluation should be low in such patients.
Abdominal CT with rapid helical technique is the most useful diagnostic study when complicated acute diverticulitis is suspected or when the diagnosis is not clear. Specificity and sensitivity are reported to be over 95%.35 The colon should be filled with water-soluble contrast given either orally (most commonly) or by gentle enema. CT can confirm the diagnosis, identify complications, and aid in planning of treatment. If the patient does not have acute diverticulitis, abdominal CT will usually lead to the correct diagnosis. Conditions other than diverticulitis are found in up to 25% of CT studies.35
Women suspected of gynecologic conditions
Abdominal ultrasonography may be most useful for women when gynecologic conditions are part of the differential diagnosis. Abdominal ultrasonography may be an alternative test when CT is not readily available or is contraindicated. On ultrasound, diverticula are echogenic and produce acoustic shadowing. On a graded compression ultrasound, the colonic wall in diverticulitis is thickened, noncompressible, and hypoechoic. The involved segment is hypoperistaltic. A phlegmon causes irregular enhancement of pericolic soft tissue, whereas an abscess appears as a fluid collection, within which gas is readily appreciated, if present. When an abscess is identified on ultrasound, a CT scan should be performed to evaluate the potential for radiographic drainage.26,36
Magnetic resonance imaging has been reported to be useful in the diagnosis of acute diverticulitis in pregnant women. MRI has the advantage over CT of avoiding fetal exposure to radiation.37
Fewer than 20% of patients with acute diverticulitis require hospitalization.38 Patients who present with mild diverticulitis should be placed on a regimen of oral fluid/electrolyte solution (e.g., a sports drink) and oral antibiotics. Patients should eat no solid foods during this period. The antibiotic regimen should provide coverage against gram-negative and anaerobic bacteria. For example, amoxicillin-clavulanic acid at a dosage of 875/125 mg twice daily is acceptable monotherapy; a suitable combination therapy is a quinolone (e.g., levofloxacin, 750 mg once daily) combined with metronidazole (500 mg twice daily).39 The patient should be instructed to report back at once if symptoms worsen. Reevaluation is scheduled for 48 to 72 hours after the office visit. If improvement is satisfactory, the diet is advanced to full liquids, antibiotics are continued, and another office visit is scheduled at 7 days. If improvement is evident at 7 days, the patient can resume a regular diet and discontinue antibiotics.4 Patients whose symptoms worsen or who do not have a favorable response within 48 to 72 hours should be hospitalized. If there is uncertainty about the diagnosis, outpatient CT is performed. An elective colonoscopy or sigmoidoscopy and barium enema exam is scheduled for 6 weeks after the acute illness, unless such a study was performed within the past 5 years.
Patients should be hospitalized if there are signs of severe or complicated diverticulitis, such as systemic toxicity, temperature exceeding 101° F (38.3° C), vomiting, an abdominal mass, or signs of peritonitis; patients should also be hospitalized if they fail to respond within 2 to 3 days to outpatient management. Hospitalized patients should be placed on bowel rest and given intravenous fluids and antibiotics. Antibiotic coverage must include both aerobic and anaerobic gram-negative bacteria. An example of a suitable monotherapy regimen is ampicillin-sulbactam (1.5 to 3.0 g every 6 hours); an acceptable combination therapy regimen is levofloxacin (750 mg I.V. once daily) combined with metronidazole (1 g I.V. every 12 hours).39 A surgical consultation should be obtained upon admission. CT scanning should be done promptly. If a phlegmon or small abscess (< 3 cm) is found, antibiotic treatment alone may suffice. Abscesses larger than 5 cm should be drained by interventional radiology, unless radiologic drainage is contraindicated by the location of the abscess or the presence of multiple abscesses.27 Antibiotic treatment and radiologic abscess drainage often allow control of infection in cases of complicated diverticulitis. Control of infection improves the possibility of elective single-stage resection and reanastomosis. Urgent surgery should be considered for patients with large abscesses that are not amenable to radiologic drainage or with multiple abscesses; for patients failing to respond within 48 to 72 hours; and for patients with evidence of free rupture of an abscess or a large perforation with fecal spillage. About 20% to 30% of patients hospitalized for the first time with acute diverticulitis require either urgent or elective surgery.17
The optimal surgical treatment of acute diverticulitis involves resection of the involved segment at the initial operation whenever this is technically possible. Leaving the diseased colon in place and performing only a diverting colostomy is associated with a higher rate of complications than primary resection. Primary reanastomosis is generally possible.40 If there is concern that the anastomosis is at undue risk of disruption, a temporary diverting ileostomy may be performed. Alternatively, the distal rectal segment can be closed (Hartmann procedure) and a descending colostomy created. Patients undergoing surgery for diverticulitis should be informed about the possibility that an ostomy, if created, may be permanent. Because of comorbidities and other issues, about 35% of ostomies performed for diverticulitis will still be in place 4 years after surgery.41 In the case of sigmoid diverticulitis, it is important to extend the resection to the rectum—to include the entire segment involved with diverticula—because failure to do so markedly increases the probability of recurrent diverticulitis.42,43
Laparoscopic surgical techniques are increasingly being used for diverticular disease. Results of laparoscopic resection for diverticulitis are the same as those of open resection if the resection extends to the rectum and no sigmoid colon is left in place.44,45 Laparoscopic resection is safe and effective; its advantages over open surgery include decreased blood loss, faster recovery of bowel function, and shorter hospital stay. There are no differences in operative time or mortality with the two procedures.45 Less than 10% of cases require conversion from laparoscopic to open resection.44
Factors considered in the recommendation of elective surgery for diverticulitis include the general health of the patient, the number and severity of episodes, and the degree to which symptoms resolve between episodes. As mentioned, about 20% to 25% of patients will have a subsequent episode of complicated diverticulitis within several years after their first episode.18,20 Surgery is often recommended after one episode of complicated diverticulitis or two episodes of uncomplicated diverticulitis; however, a recent decision analysis study suggested that the best overall outcome—taking into account mortality, morbidity, the number of surgical procedures, and the number of ostomies—may be achieved if elective colectomy is recommended after the fourth episode of uncomplicated diverticulitis, which is a more conservative recommendation than is generally practiced.46
Young, overweight men have been reported in some series to have a higher risk of complicated diverticulitis and recurrent diverticulitis than other patients. Some surgeons therefore recommend surgery after the first episode of diverticulitis in such patients29,47,48; however, this increased risk has not been confirmed in other series, and some surgeons have suggested that the recommendation for surgery after the first episode be tempered.20,49,50
A diet high in insoluble fiber and low in fat and red meat appears to reduce the risk of diverticular disease. Higher levels of physical activity are also associated with reduced risk of diverticulitis.8,9
The intermittent use of rifaximin, a poorly absorbed oral antibiotic, has been reported to provide a greater reduction of symptoms of diverticular disease and risk of recurrence than the use of fiber alone.15 Rifaximin is given in a dosage of 400 mg by mouth twice daily for 1 week of each month. Mesalamine has been used for the same purpose in a dosage of 800 mg by mouth twice daily for 1 week of each month. The combination of rifaximin and mesalamine has been reported to be more effective than mesalamine alone.16
It is prudent to advise patients with a history of diverticular disease to avoid NSAIDs if possible, as these medications have been associated with an increased risk of complications.5,7
COMPLICATIONS OF DIVERTICULAR DISEASE
Fistula is the presenting complication in 10% to 15% of patients who require surgery for diverticular disease. There is often no history of acute diverticulitis. Patients may present with symptoms related primarily to the organ involved with the diverticular fistula, which is the bladder in most cases. Diverticular disease is the most common cause of colovesical fistula, followed by colon cancer and Crohn disease. Colovesical fistulas are much less common in women than in men, presumably because the uterus is interposed between the sigmoid colon and the bladder. Patients with colovesical fistulas usually present with recurrent polymicrobial bladder infections, pneumaturia, or both. Fistulas may also connect with other parts of the colon, the small bowel, the uterus, or the vagina. Colocutaneous fistulas are unusual and generally occur after surgery for diverticulitis.51
Colovesical fistulas are difficult to visualize. CT scanning may be the most useful single study. Even though fistulas are rarely directly visualized, CT is very sensitive for detection of air in the bladder, which is virtually diagnostic of an enterovesical fistula in the absence of prior bladder catheterization. CT demonstrates the presence of diverticula, and thickening of the bladder wall adjacent to an area of diverticulitis supports the diagnosis.52 Colovesical fistulas are often not identified by a barium enema study, although secondary changes of diverticulitis are usually apparent. Cystoscopy often reveals focal mucosal inflammation in the area of a fistula, even though the opening is not apparent. Fistulas may be visualized by contrast cystography.53 Colonoscopy should be done at some point to exclude cancer or inflammatory bowel disease, but it rarely reveals the fistula. CT, barium enema, cystoscopy, and colonoscopy are complementary studies for the evaluation of a suspected colovesical fistula.52 Patients with a diverticular fistula should have elective surgical resection of the involved segment of colon once the acute inflammatory process has been controlled. In the case of colovesical fistulas, the adherent colon can usually be dissected off the bladder and the involved bladder oversewn, rather than resected.54
Obstruction and Stricture
Acute obstruction during an episode of diverticulitis is often self-limited. It may be caused by a large phlegmon or abscess. Secondary ileus may mimic obstruction. Chronic stricture is an uncommon presentation of diverticular disease. It usually occurs after repeated episodes of diverticulitis. A diverticular stricture may be difficult to distinguish from a malignant stricture, particularly by CT or a barium enema study. Colonoscopy with biopsies is the best means of making this distinction, although visualization may be limited even with colonoscopy.
Segmental Colitis Associated with Diverticular Disease
In about 1% of cases, chronic diverticular disease is associated with patchy mucosal hemorrhage, congestion, and granularity in the sigmoid colon. On microscopic examination, a lymphocytic infiltrate, lymphoglandular complexes, mucin depletion, mild cryptitis, crypt distortion, Paneth cell metaplasia, and ulceration can be seen. These changes may mimic Crohn colitis, ulcerative colitis, or ischemic colitis. However, in segmental colitis associated with diverticular disease (SCAD), the changes are limited to areas of diverticulosis.55,56
Risk of Colon Cancer in Diverticular Disease
Some studies have shown an increased risk of sigmoid colon cancer in patients with a history of diverticulitis, but other studies have not confirmed this finding.57,58,59 In addition to the difficulty in distinguishing a diverticular stricture from a malignant stricture, perforated colon cancer can mimic acute diverticulitis accompanied by a phlegmon or abscess. Thus, it seems prudent to recommend elective colonoscopy to patients with diverticular disease.
Diverticular bleeding is less frequent than diverticulitis as a complication of diverticulosis. It is difficult to arrive at a firm estimate of what proportion of major lower gastrointestinal bleeding is caused by colonic diverticula. Estimates have ranged from 15% to 56%.60,61,62 In many cases, the source is presumed to be diverticular when no other cause is found.
Diverticular bleeding is usually sudden and painless. Typically, moderate to large amounts of bright-red blood, clots, or maroon stool are passed. Bleeding stops spontaneously in 70% to 80% of cases; bleeding eventually recurs in 25% to 35% of cases.63,64 Lower gastrointestinal bleeding (occult bleeding in particular) should not be attributed to diverticulosis unless other causes have been excluded. The most common causes of lower gastrointestinal bleeding in adults are diverticulosis, inflammatory bowel disease, neoplasm, angioectasias, benign anorectal disease, and upper gastrointestinal sources.65
Practice guidelines for the evaluation and management of lower gastrointestinal bleeding have been published.64
Emergent Management and Evaluation
The first priority in lower gastrointestinal bleeding is volume restoration with intravenous fluids and blood. During resuscitation, a directed history is taken and a physical examination is performed; the physical examination includes anoscopy and proctoscopy to exclude an anorectal source. A nasogastric aspirate should be obtained, because about 10% to 15% of apparent major lower gastrointestinal bleeding is, in actuality, from an upper gastrointestinal source.61 Lack of blood in the nasogastric aspirate, however, is not conclusive proof of a lower gastrointestinal source. Bleeding from an upper gastrointestinal source may have stopped, and the stomach may have evacuated residual blood. Blood from a duodenal source may not reflux into the stomach. Some clinicians perform an upper gastrointestinal endoscopy before colonoscopy even if the nasogastric aspirate is negative for blood, particularly for apparent major lower gastrointestinal bleeding.
Many clinicians consider colonoscopy to be the most useful initial study for the evaluation of patients presenting with major lower gastrointestinal bleeding of unknown cause.66 Lower gastrointestinal bleeding is usually intermittent and often stops before hospital admission or shortly thereafter. Adequate colonic purging followed by colonoscopy is almost always possible even in spite of moderate active lower gastrointestinal bleeding.61,66 The most important contribution of colonoscopy is to establish a presumptive diagnosis of diverticular bleeding by excluding other causes and to determine the distribution of diverticula, which is important if colonic resection becomes necessary. Some authors recommend urgent colonoscopy and report a high success rate in localizing and treating diverticula responsible for bleeding.66 In another report, however, there was no correlation between the timing of colonoscopy and success in localizing the bleeding diverticulum over an interval of 7 to 29 hours.67 If active bleeding or an adherent clot is found at the time of colonoscopy, endoscopic therapy can be performed with epinephrine injection, cautery, hemostatic clips, or banding.68,69
Labeled blood cell scintigraphy
Technetium-99m (99mTc)-labeled red blood cell scintigraphy is another tool for the evaluation of acute lower gastrointestinal bleeding. After injection with 99mTc, imaging is done continuously for 60 to 120 minutes. Dynamic scans are viewed in a computer-generated cinematic format. Continuous scanning improves the probability of detecting intermittent bleeding.70 The radioactive label remains active for over 24 hours; thus, if the scan is not positive initially, scanning can be repeated at any time during the first day if there are indications of recurrent bleeding. A scan is considered positive if there is a focus of increased activity that changes in location and intensity over time [seeFigures 2a and 2b]. 99mTc-labeled red blood cell scanning is the most sensitive study for detection of acute gastrointestinal bleeding. It can theoretically detect bleeding rates as low as 0.5 ml/min. Localization of bleeding to the small bowel, right colon, or left colon is generally possible, but reports of the accuracy of 99mTc-labeled red blood cell scanning have been inconsistent.70,71,72 False positive readings may occur with vascular neoplasms, inflammatory conditions, vascular grafts, varices, splenosis, and bladder or penile activity.
Figure 2a. Technetium-99m Scan of Hepatic Flexure
Technetium-99m red cell scanning shows increased tracer activity in the area of the hepatic flexure (arrow).
Progression of Tracer Activity Later, tracer activity has progressed to the transverse colon (broad arrow), as well as the splenic flexure and descending colon (small arrow), confirming that the right colon is the source of the bleeding.
99mTc scanning does not elucidate the cause of bleeding; rather, it demonstrates active bleeding and the approximate location of its source. Colonoscopy is still necessary to determine the presence of diverticula and exclude other potential colonic sources. Once diverticula have been established as the probable cause of bleeding, scanning has a role in detecting recurrent bleeding. A positive 99mTc scan also provides prognostic information; patients with positive scans are much more likely to have positive arteriograms and are more likely to require surgery than those with negative scans.72
Visceral angiography and vasopressin infusion
Visceral angiography may be useful in persistent moderate to severe lower gastrointestinal bleeding, particularly when the site has not been discovered by colonoscopy and upper gastrointestinal endoscopy or when colonoscopy is not feasible. Angiography can provide precise localization of bleeding in patients who have a positive bleeding scan. If active bleeding is detected and localized, it may then be treated with intra-arterial vasopressin infusion. Rebleeding occurs in 25% of patients when the vasopressin infusion is stopped. Even temporary control may provide time to stabilize the patient and prepare for elective surgery.64,71
Arterial embolization of the bleeding artery has been reported, but it is associated with a substantial risk of intestinal infarction, particularly if followed by vasopressin infusion.71 Bowel or myocardial ischemia, as well as other complications inherent to contrast arteriography, may complicate both vasopressin infusion and embolization.
About 20% of patients hospitalized for diverticular bleeding require surgery during that hospitalization.63 Patients who initially require four units or more of blood have a 50% risk of continued bleeding, as compared with a 2% risk of continued bleeding for patients who require two or more units of blood. Persistent instability despite aggressive resuscitation demands surgical intervention.63
Elective surgery for recurrent bleeding
The risk of recurrent diverticular bleeding after the first episode is about 10% after 2 years and 25% after 4 years.60 The risk is higher after a second episode. Elective surgery is usually recommended after two or more episodes of bleeding. If diverticula are limited to the left side of the colon, left hemicolectomy is appropriate. The decision regarding the extent of resection is more difficult when diverticula are distributed throughout the colon. If all previous episodes of diverticular bleeding have been localized to either the right or the left side by scintigraphy or angiography, some clinicians would advocate a corresponding hemicolectomy. The risk of recurrent bleeding from diverticula in the remaining colon is not known. Other clinicians would recommend a subtotal colectomy. Occasionally, persistent or recurrent severe lower gastrointestinal bleeding cannot be localized. Blind segmental resection is associated with an unacceptable recurrence rate, and subtotal colectomy is the favored procedure.61
The lifetime risk of appendicitis is about 9% for males and 7% for females.73 Appendicitis rarely occurs in infants; it increases in frequency between the ages of 2 and 4; and it reaches a peak between the ages of 10 and 20. About 80% of cases occur before the age of 45. Nevertheless, there is a steady low incidence in older individuals. The mortality associated with acute appendicitis declined between 1945 and 1960, coincident with advances in antibiotic treatment. In 1990, the mortality associated with acute uncomplicated appendicitis was approximately equal to that associated with general anesthesia. However, the mortality associated with gangrenous appendicitis is about 0.5 %, and that of perforated appendicitis is 5%. Most deaths from acute appendicitis occur in persons older than 65 years.73
ANATOMY AND PATHOGENESIS
The adult appendix is a tubular structure that is 4 to 25 cm long and arises from the medial posterior wall of the cecum several centimeters below the ileocecal valve. Its location in the peritoneal cavity varies. Atypical locations, such as the pelvis, retrocecal area, and right upper quadrant, lead to atypical clinical presentations [see Atypical Presentations, below].
Appendicitis is generally caused by obstruction of the lumen of the appendix, followed by infection. The appendix has abundant lymphoid tissue. Appendicitis increases in frequency during the period of lymphoid hyperplasia in childhood. During periods of childhood enteric infection, lymphoid tissue may obstruct the appendiceal lumen. About one third of cases of appendicitis are associated with obstruction by fecaliths. Foreign bodies, tumor (e.g., carcinoid or cecal adenocarcinoma), barium, and adhesions may also cause obstruction. Obstruction leads to bacterial overgrowth. Mucus accumulates in the lumen proximal to the obstruction, and intraluminal pressure increases. Impairment of lymphatic and venous drainage leads to mucosal ulceration, bacterial invasion, transmural inflammation, and ischemia. During the first 24 hours after obstruction, most patients have only inflammation. The incidence of necrosis and perforation increases markedly after that. Patients who present with a history of symptoms for 48 hours should be strongly suspected of having perforation and abscess. Free perforation causes generalized peritonitis.
Appendicitis usually causes a distinctive sequence of symptoms and signs. More than 90% of patients with appendicitis complain of pain. The pain of appendicitis is initially caused by obstruction of the appendiceal lumen. It has the qualities of midgut visceral pain and is referred to the periumbilical or epigastric areas. It may be cramping or aching in nature, but it is often difficult for patients to describe. Within 12 to 24 hours, inflammation becomes transmural, involving the adjacent parietal peritoneum. Pain then becomes somatic in quality: sharper and more localized. At this time, patients may note exacerbation of pain by coughing, sneezing, or movement.
Anorexia is present in 80% to 90% of patients. Vomiting, when it occurs, does not occur initially but follows the onset of pain. Prominent vomiting is unusual and suggests the possibility of another diagnosis, such as gastroenteritis or small bowel obstruction. Fever is usually low grade. High fever or rigors suggest perforation.
Tenderness in the right lower quadrant can be elicited in more than 90% of patients. Proximity of the inflammatory process to the retroperitoneal muscles produces the psoas and obturator signs. The psoas sign is present when pain occurs as the patient raises the right leg against resistance or, alternatively, when the physician passively extends the right hip with the patient lying on the left side. The obturator sign is present when pain occurs upon internal rotation of the hip. Local hyperesthesia of the skin in the right lower quadrant may be noted. Voluntary guarding progresses to involuntary muscle rigidity as the inflammatory process worsens. Diffuse abdominal tenderness and rigidity suggest perforation. An abdominal mass suggests phlegmon or abscess formation.
The presentation of appendicitis may mimic a broad range of diseases [see Table 3].
Table 3 Differential Diagnosis of Appendicitis
There is evidence that appendicitis may resolve spontaneously and recur. Occasionally, the patient history includes previous episodes of acute appendicitis that resolved without treatment. Examination of appendixes removed incidentally at surgery or at autopsy sometimes show fibrosis and obliteration of a portion of the lumen, suggesting previous episodes of appendicitis.74,75
Atypical presentations of appendicitis are as common as the classic presentation. Atypical location of the appendix leads to atypical symptoms and signs. An inflamed retrocecal appendix is relatively shielded from the parietal peritoneum. Pain may be less severe and abdominal tenderness less pronounced. The characteristic shift in pain location to the right lower quadrant may be delayed. A pelvic appendix may cause symptoms resulting from inflammation of the bladder or rectum, such as dysuria or tenesmus. In such cases, tenderness may be best elicited on pelvic or rectal examination. Incomplete intestinal rotation and third-trimester pregnancy displace the appendix toward the right upper quadrant, causing confusion with cholecystitis or perforated peptic ulcer.
Tip appendicitis and stump appendicitis
In appendicitis that involves only the tip of the appendix, inflammation may be less severe and may resolve spontaneously; cases of recurrent appendicitis may involve such a pathophysiology. Partial visualization of the appendix on CT may be mistaken for complete filling and lead to a false negative reading.76 Appendicitis has been reported to occur in the stump of the appendix that is left behind after a previous appendectomy; this can lead to confusion and a delay in diagnosis.77
Appendicitis and appendiceal tumors
Tumor of the appendix, such as carcinoids, may obstruct the lumen and lead to appendicitis. In elderly men with appendicitis, there is a relatively high incidence of appendiceal tumors.13,69
Appendicitis in special groups of patients
The diagnosis of appendicitis is difficult in certain groups of patients. Young children, for example, often do not express their symptoms clearly; they may present with only lethargy, irritability, and anorexia.78 Elderly patients may have a reduced inflammatory reaction; in such cases, pain may be vague, and there may be less fever or abdominal tenderness.79 Consideration of other diagnoses, such as diverticulitis, may delay surgery. Delayed diagnosis of appendicitis contributes to an incidence of perforation that is close to 20% in the elderly and small children.80
In women of childbearing age, gynecologic conditions and pregnancy cause difficulty in diagnosing appendicitis.81 In one study, the preoperative diagnosis was incorrect in 25% of cases.82 Complications of pregnancy attributable to appendicitis are considerable. Appendicitis in pregnancy has been reported to result in fetal loss in 33% of first-trimester cases and 14% of second-trimester cases.82
Diagnosis of appendicitis may also be difficult in immunosuppressed patients; for example, patients on glucocorticoids often have attenuated symptoms, leading to delay in presentation and a high incidence of complications. In patients with AIDS, symptoms may be typical, but concerns about a multiplicity of other diagnoses may delay surgery.
In the management of suspected appendicitis, it is important to minimize the delay to surgery—and thus reduce the risk of perforation—while at the same time minimizing the number of unnecessary appendectomies. Taking into account the serious consequences of progression to perforation and the relatively low morbidity of appendectomy, most surgeons adopt a relatively aggressive approach to early surgery, accepting a 10% to 15% rate of negative appendectomies (i.e., negative exploration in patients with clinically suspected acute appendicitis).
Some factors that lead to a delay in diagnosis are not under physician control, such as a patient's delay in seeking medical care. Factors that are under physician control include decisions to perform additional diagnostic studies or to observe the patient for the purpose of improving diagnostic accuracy and reducing the number of unnecessary appendectomies. Clinical scoring systems have generally not been found to improve preoperative diagnostic accuracy.83
The abdominal examination is very important for the diagnosis of appendicitis. This has led some physicians to delay the administration of narcotic analgesics until a surgeon has had the opportunity to examine the patient. It has been proved that this practice is unnecessary: morphine does not change the physical examination in acute appendicitis, and early pain relief does not affect the decision for surgery in adults.84,85
The role of diagnostic studies for suspected appendicitis depends on the particular clinical presentation. In cases characterized by a classic presentation, it is standard practice to base the decision to operate primarily on the history and physical examination. A complete blood count, a urinalysis, and plain x-rays of the chest and abdomen may be obtained, but these serve the purpose of excluding other conditions rather than confirming the diagnosis of appendicitis. The total white blood cell count, the differential count, or both are abnormal in more than 90% of cases, but the decision to perform surgery should not be delayed if the white blood cell count is not elevated.86
In women of childbearing age, a pregnancy test is mandatory. In many cases, no further diagnostic studies are performed. Among women of childbearing age, the rate of negative appendectomy can be as high as 40%.81 In other patients, particularly young children or the elderly, the presentation may be atypical and the diagnosis uncertain. In such patients, additional diagnostic studies may be appropriate and helpful.
Examination by transabdominal or transvaginal ultrasound or both is useful in pregnant and nonpregnant women of childbearing age to exclude a gynecologic cause of symptoms.81,87 Ultrasound examination is also useful for evaluation of children in cases in which the diagnosis is doubtful. Sonography is widely available, fast, safe, and inexpensive.
On graded compression ultrasonography, the inflamed appendix is a noncompressible, aperistaltic tubular structure that is greater than 6 mm in diameter and located in the right lower quadrant. It has a target appearance, and the lumen is filled with anechoic or hyperechoic material. An appendicolith may be visualized in up to 30% of cases. Pericecal inflammation or phlegmon is seen as prominent fat; abscess appears as loculated fluid. In experienced hands, the sensitivity and specificity for the diagnosis of appendicitis are 85% and 95%, respectively.88 Despite abdominal tenderness, most patients find the examination tolerable if it is performed gently. Marked peritonitis or abdominal gas may compromise the examination.
Abdominal ultrasound is not as accurate as CT for the diagnosis of appendicitis in adults and adolescents; in addition, it is not as useful as CT for the evaluation of phlegmon or abscess.89
Abdominal CT scanning can increase diagnostic accuracy in many cases of suspected appendicitis. The development of rapid scanning techniques has made CT readily available and practical even in emergency room settings. CT is useful when the diagnosis is unclear, as in elderly patients in whom diverticulitis and perforated colon cancer are important considerations. Abdominal CT may be helpful in women if pregnancy has been ruled out.90 The routine use of appendiceal CT in the emergency room setting has been reported to reduce both the number of unnecessary appendectomies and delays before necessary appendectomies.91 CT is helpful when an appendiceal abscess is suspected. It provides information about the size, location, and number of abscesses, as well as the feasibility of percutaneous drainage under radiologic guidance.92
CT for suspected appendicitis has been reported to have an accuracy of about 95%.93,94 CT scan for appendicitis is best done using thin collimation helical scanning. The terminal ileum and cecum must be opacified with contrast that is administered by mouth or by rectum. Rectal administration of contrast has been reported to have advantages over oral contrast for assessing appendiceal filling.84 The diagnosis of appendicitis is established when pericecal inflammation, phlegmon, or abscess is seen with either an appendicolith or an abnormal appendix. In appendicitis, the appendix is enlarged to more than 6 mm in diameter and fails to fill with contrast. If intravenous contrast has been given, the inflamed appendix will also show enhancement.71 CT is useful for the evaluation of the degree and extent of periappendiceal inflammation [see Figure 3]. Inflammation may cause thickening of the adjacent cecum or ileum. Streakiness of periappendiceal fat is seen with phlegmon. Loculated fluid and, sometimes, gas bubbles are seen with abscess; if gas bubbles are not present, an air-fluid level may be apparent.
Figure 3. CT of Appendicitis
CT of appendicitis. A calcified appendicolith is noted within a complex abscess containing fluid and air (broad arrow). The abscess involves the soft tissues of the abdominal wall (small arrow)
Since the advent of abdominal ultrasound and CT examination, barium enema has had little place in the evaluation of suspected appendicitis. Appendicitis is most likely to be discovered on barium enema exam when the study is done for determination of another diagnosis. In acute appendicitis, the appendix fails to fill with contrast on barium enema exam; this finding is more valuable in children than in adults, because the appendix fails to fill with contrast in 15% to 20% of normal adults. Partial filling of the appendix is often difficult to distinguish from complete filling, given the marked anatomic variations in the length of the appendix. Appendicitis may produce a mass effect or inflammatory changes in the adjacent cecum or ileum that can be appreciated by barium enema, but CT provides much more information than barium enema in this regard. Barium enema exam may be helpful in the evaluation of chronic or recurrent right lower quadrant abdominal conditions that mimic “chronic” appendicitis, such as Crohn disease.
The treatment of appendicitis is prompt appendectomy. Preoperative preparation consists of intravenous volume repletion and antibiotics. For simple appendicitis, one dose of a broad-spectrum antibiotic given before surgery and one dose given postoperatively is sufficient.95 One example of an appropriate regimen for adults is cefazolin (1.5 g I.V.) preoperatively and metronidazole (500 mg I.V.) postoperatively.39
If perforated appendicitis is suspected, antibiotic coverage should be broadened. An example of an acceptable regimen for adults is levofloxacin (750 mg I.V. once daily) combined with metronidazole (1 g I.V. every 12 hours).39 If the presence of a phlegmon or abscess is confirmed, antibiotics are customarily continued for 7 to 14 days postoperatively. However, a prospective, randomized study found that adding a 7-day regimen of oral antibiotics after a course of intravenous antibiotics made no difference in outcome, either in complicated or uncomplicated appendicitis.96
Patients with free, unconfined perforation should have abdominal saline lavage during surgery. A prolonged ileus should be anticipated.
Appendectomy can be performed by a traditional open incision or by laparoscopy. Compared to open appendectomy, laparoscopic appendectomy results in decreased wound infections but slightly increased intra-abdominal infections. Postoperative pain is reduced in laparoscopic appendectomy, and patients return to normal activity sooner. Overall, the benefits of laparoscopic appendectomy over open appendectomy are modest; the greatest benefits occur in women and obese patients.97,98,99 The laparoscopic approach is useful in women because it allows for accurate diagnosis of gynecologic conditions if appendicitis is not responsible for the symptoms.100,101
Complications occur in fewer than 5% of cases of simple appendicitis but can be anticipated in 30% to 50% of cases of appendicitis after perforation. The most common complications are wound infections, intra-abdominal abscess, intestinal obstruction, and prolonged ileus. Postoperative abscesses are heralded by recurrent malaise, anorexia, and fever, and they are best evaluated by CT.
Some patients with a contained perforation can be managed by interval appendectomy after treatment with antibiotics or CT-guided percutaneous drainage. The information from preoperative CT or sonography is useful in planning therapy. If imaging shows a phlegmon or small abscess and the patient responds to antibiotic treatment within 48 hours, appendectomy may be postponed for 6 weeks, until the inflammatory process has subsided. If the abscess is large but well circumscribed and accessible, CT-guided percutaneous catheter drainage may be used to reduce the abscess before surgery. The catheter is placed in the abscess and left until drainage from the abscess becomes minimal.92 If drainage is successful, appendectomy can be postponed for 6 weeks. However, if a patient with a contained perforation does not respond promptly to antibiotic treatment or drainage, surgery should not be delayed. Catheter drainage is not possible if imaging shows a poorly defined or multilocular abscess or if the abscess is not accessible to percutaneous drainage.
If a patient is operated on for suspected appendicitis and the appendix is found to be normal at surgery, it should be removed to prevent future confusion. The cecum and terminal ileum should be examined for evidence of Crohn disease or other acute inflammatory bowel disease, for tumor, or for Meckel diverticulitis. Lymph nodes in the area should be inspected for evidence of mesenteric adenitis, and biopsies should be performed if the lymph nodes appear abnormal. The gallbladder and duodenum should be palpated. If necessary, the incision should be extended to permit wider exposure. Before closing, the surgeon must feel confident that the cause of the clinical presentation has been explained and that there is no other acute abdominal condition.
Incidental appendectomy, performed during surgery for another cause, may be justified in individuals younger than 30 years if the primary surgery would not be compromised. Appendectomy does not increase morbidity when performed under these circumstances.102
Editors: Dale, David C.; Federman, Daniel D.