Thursday, January 19, 2012


Anatomy and Function
The appendix first becomes visible in the eighth week of embryologic development as a protuberance off the terminal portion of the cecum. During both antenatal and postnatal development, the growth rate of the cecum exceeds that of the appendix, so that the appendix is displaced medially toward the ileocecal valve. The relationship of the base of the appendix to the cecum remains constant, whereas the tip can be found in a retrocecal, pelvic, subcecal, preileal, or right pericolic position. These anatomic considerations have significant clinical importance in the context of acute appendicitis. The three taeniae coli converge at the junction of the cecum with the appendix and can be a useful landmark to identify the appendix. The appendix can vary in length from <1 cm to >30 cm; most appendices are 6 to 9 cm long. Appendiceal absence, duplication, and diverticula have all been described.1–4

For many years, the appendix was erroneously viewed as 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, recent studies demonstrate a potential correlation between appendectomy and the development of inflammatory bowel disease. There appears to be a negative age-related association between prior appendectomy and subsequent development of ulcerative colitis. In addition, comparative analysis clearly shows that prior appendectomy is associated with a more benign phenotype in ulcerative colitis and a delay in onset of disease. 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 relation to the onset of Crohn's disease demonstrated a negative correlation. These data suggest that appendectomy may protect against the subsequent development of inflammatory bowel disease; however, the mechanism is unclear.
Lymphoid tissue first appears in the appendix approximately 2 weeks after birth. The amount of lymphoid tissue increases throughout puberty, remains steady for the next decade, and then begins a steady decrease with age. After the age of 60 years, virtually no lymphoid tissue remains within the appendix, and complete obliteration of the appendiceal lumen is common

Acute Appendicitis
Historical Background
Although ancient texts have scattered descriptions of surgery being undertaken for ailments sounding like appendicitis, credit for performing the first appendectomy goes to Claudius Amyand, a surgeon at St. George's Hospital in London and Sergeant Surgeon to Queen Ann, King George I, and King George II. In 1736, he operated on an 11-year-old boy with a scrotal hernia and a fecal fistula. Within the hernial sac, Amyand found the appendix perforated by a pin. He successfully removed the appendix and repaired the hernia.5
The appendix was not identified as an organ capable of causing disease until the nineteenth century. In 1824, Louyer-Villermay presented a paper before the Royal Academy of Medicine in Paris. He reported on two autopsy cases of appendicitis and emphasized the importance of the condition. In 1827, François Melier, a French physician, expounded on Louyer-Villermay's work. He reported six autopsy cases and was the first to suggest the antemortem recognition of appendicitis.5 This work was discounted by many physicians of the era, including Baron Guillaume Dupuytren. Dupuytren believed that inflammation of the cecum was the main cause of pathology of the right lower quadrant. The term typhlitis or perityphlitis was used to describe right lower quadrant inflammation. In 1839, a textbook authored by Bright and Addison entitled Elements of Practical Medicine described the symptoms of appendicitis and identified the primary cause of inflammatory processes of the right lower quadrant.6 Reginald Fitz, a professor of pathologic anatomy at Harvard, is credited with coining the term appendicitis. His landmark paper definitively identified the appendix as the primary cause of right lower quadrant inflammation.7
Initial surgical therapy for appendicitis was primarily designed to drain right lower quadrant abscesses that occurred secondary to appendiceal perforation. It appears that the first surgical treatment for appendicitis or perityphlitis without abscess was carried out by Hancock in 1848. He incised the peritoneum and drained the right lower quadrant without removing the appendix. The first published account of appendectomy for appendicitis was by Krönlein in 1886. However, this patient died 2 days after operation. Fergus, in Canada, performed the first elective appendectomy in 1883.5
The greatest contributor to the advancement in the treatment of appendicitis was Charles McBurney. In 1889, he published his landmark paper in the New York State Medical Journal describing the indications for early laparotomy for the treatment of appendicitis. It is in this paper that he described the McBurney point as follows: "maximum tenderness, when one examines with the fingertips is, in adults, one half to two inches inside the right anterior spinous process of the ilium on a line drawn to the umbilicus."8 McBurney subsequently published a paper in 1894 describing the incision that bears his name.9 However, McBurney later credited McArthur with first describing this incision. Semm is widely credited with performing the first successful laparoscopic appendectomy in 1982.10
The surgical treatment of appendicitis is one of the great public health advances of the last 150 years. Appendectomy for appendicitis is the most commonly performed emergency operation in the world. Appendicitis is a disease of the young, with 40% of cases occurring in patients between the ages of 10 and 29 years.11 In 1886, Fitz reported the associated mortality rate of appendicitis to be at least 67% without surgical therapy.7 Currently, the mortality rate for acute appendicitis with treatment is reported to be <1%.

The lifetime rate of appendectomy is 12% for men and 25% for women, with approximately 7% of all people undergoing appendectomy for acute appendicitis during their lifetime. Over the 10-year period from 1987 to 1997, the overall appendectomy rate decreased in parallel with a decrease in incidental appendectomy.11,13 However, the rate of appendectomy for appendicitis has remained constant at 10 per 10,000 patients per year.14 Appendicitis is most frequently seen in patients in their second through fourth decades of life, with a mean age of 31.3 years and a median age of 22 years. There is a slight male:female predominance (1.2 to 1.3:1).
Despite the increased use of ultrasonography, computed tomography (CT), and laparoscopy, the rate of misdiagnosis of appendicitis has remained constant (15.3%), as has the rate of appendiceal rupture. The percentage of misdiagnosed cases of appendicitis is significantly higher among women than among men (22.2 vs. 9.3%). The negative appendectomy rate for women of reproductive age is 23.2%, with the highest rates in women aged 40 to 49 years. The highest negative appendectomy rate is reported for women >80 years of age

Etiology and Pathogenesis
Obstruction of the lumen is the dominant etiologic factor in acute appendicitis. Fecaliths are the most common cause of appendiceal obstruction. Less common causes are hypertrophy of lymphoid tissue, inspissated barium from previous x-ray studies, tumors, vegetable and fruit seeds, and intestinal parasites. The frequency of obstruction rises with the severity of the inflammatory process. Fecaliths are found in 40% of cases of simple acute appendicitis, in 65% of cases of gangrenous appendicitis without rupture, and in nearly 90% of cases of gangrenous appendicitis with rupture.
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 distention. The luminal capacity of the normal appendix is only 0.1 mL. Secretion of as little as 0.5 mL of fluid distal to an obstruction raises the intraluminal pressure to 60 cm H2O. Distention of the appendix stimulates the nerve endings of visceral afferent stretch fibers, producing vague, dull, diffuse pain in the midabdomen or lower epigastrium. Peristalsis also is stimulated by the rather sudden distention, so that some cramping may be superimposed on the visceral pain early in the course of appendicitis. Distention increases from continued mucosal secretion and from rapid multiplication of the resident bacteria of the appendix. Distention of this magnitude usually causes reflex nausea and vomiting, and the diffuse visceral pain becomes more severe. As pressure in the organ increases, venous pressure is exceeded. Capillaries and venules are occluded, but arteriolar inflow continues, resulting in engorgement and vascular congestion. The inflammatory process soon involves the serosa of the appendix and in turn parietal peritoneum in the region, which produces the characteristic shift in pain to the right lower quadrant.
The mucosa of the GI tract, including the appendix, is susceptible to impairment of blood supply; thus its integrity is compromised early in the process, which allows bacterial invasion. As progressive distention encroaches on first the venous return and subsequently the arteriolar inflow, the area with the poorest blood supply suffers most: ellipsoidal infarcts develop in the antimesenteric border. As distention, bacterial invasion, compromise of vascular supply, and infarction progress, perforation occurs, usually through one of the infarcted areas on the antimesenteric border. Perforation generally occurs just beyond the point of obstruction rather than at the tip because of the effect of diameter on intraluminal tension.
This sequence is not inevitable, however, and some episodes of acute appendicitis apparently subside spontaneously. Many patients who are found at operation to have acute appendicitis give a history of previous similar, but less severe, attacks of right lower quadrant pain. Pathologic examination of the appendices removed from these patients often reveals thickening and scarring, suggesting old, healed acute inflammation. The strong association between delay in presentation and appendiceal perforation supported the proposition that appendiceal perforation is the advanced stage of acute appendicitis; however, recent epidemiologic studies have suggested that nonperforated and perforated appendicitis may, in fact, be different diseases
The bacterial population of the normal appendix is similar to that of the normal colon. The appendiceal flora remains constant throughout life with the exception of Porphyromonas gingivalis. This bacterium is seen only in adults.18 The bacteria cultured in cases of appendicitis are therefore similar to those seen in other colonic infections such as diverticulitis. The principal organisms seen in the normal appendix, in acute appendicitis, and in perforated appendicitis are Escherichia coli and Bacteroides fragilis.18–21 However, a wide variety of both facultative and anaerobic bacteria and mycobacteria may be present (Table 30-1). Appendicitis is a polymicrobial infection, with some series reporting the culture of up to 14 different organisms in patients with perforation.18
Table 30-1 Common Organisms Seen in Patients with Acute Appendicitis
Aerobic and Facultative Anaerobic
Gram-negative bacilli Gram-negative bacilli
  Escherichia coli    Bacteroides fragilis 
  Pseudomonas aeruginosa    Other Bacteroides species 
  Klebsiella species    Fusobacterium species 
Gram-positive cocci Gram-positive cocci
  Streptococcus anginosus    Peptostreptococcus species 
  Other Streptococcus species  Gram-positive bacilli
  Enterococcus species    Clostridium species 

The routine culture of intraperitoneal samples in patients with either perforated or nonperforated appendicitis is questionable. As discussed earlier, the flora is known, and therefore broad-spectrum antibiotics are indicated. By the time culture results are available, the patient often has recovered from the illness. In addition, the number of organisms cultured and the ability of a specific laboratory to culture anaerobic organisms vary greatly. Peritoneal culture should be reserved for patients who are immunosuppressed, as a result of either illness or medication, and for patients who develop an abscess after the treatment of appendicitis.20–22 Antibiotic prophylaxis is effective in the prevention of postoperative wound infection and intra-abdominal abscess.23 Antibiotic coverage is limited to 24 to 48 hours in cases of nonperforated appendicitis. For perforated appendicitis, 7 to 10 days of therapy is recommended. IV antibiotics are usually given until the white blood cell count is normal and the patient is afebrile for 24 hours. Antibiotic irrigation of the peritoneal cavity and the use of transperitoneal drainage through the wound are controversial

Clinical Manifestations
Abdominal pain is the prime symptom of acute appendicitis. Classically, pain is initially diffusely centered in the lower epigastrium or umbilical area, is moderately severe, and is steady, sometimes with intermittent cramping superimposed. After a period varying from 1 to 12 hours, but usually within 4 to 6 hours, the pain localizes to the right lower quadrant. This classic pain sequence, although usual, is not invariable. In some patients, the pain of appendicitis begins in the right lower quadrant and remains there. Variations in the anatomic location of the appendix account for many of the variations in the principal locus of the somatic phase of the pain. For example, a long appendix with the inflamed tip in the left lower quadrant causes pain in that area. A retrocecal appendix may cause principally flank or back pain; a pelvic appendix, principally suprapubic pain; and a retroileal appendix, testicular pain, presumably from irritation of the spermatic artery and ureter. Intestinal malrotation also is responsible for puzzling pain patterns. The visceral component is in the normal location, but the somatic component is felt in that part of the abdomen where the cecum has been arrested in rotation.
Anorexia nearly always accompanies appendicitis. It is so constant that the diagnosis should be questioned if the patient is not anorectic. Although vomiting occurs in nearly 75% of patients, it is neither prominent nor prolonged, and most patients vomit only once or twice. Vomiting is caused by both neural stimulation and the presence of ileus.
Most patients give a history of obstipation beginning before the onset of abdominal pain, and many feel that defecation would relieve their abdominal pain. Diarrhea occurs in some patients, however, particularly children, so that the pattern of bowel function is of little differential diagnostic value.
The sequence of symptom appearance has great significance for the differential diagnosis. In >95% of patients with acute appendicitis, anorexia is the first symptom, followed by abdominal pain, which is followed, in turn, by vomiting (if vomiting occurs). If vomiting precedes the onset of pain, the diagnosis of appendicitis should be questioned.
Physical findings are determined principally by what the anatomic position of the inflamed appendix is, as well as by whether the organ has already ruptured when the patient is first examined.
Vital signs are minimally changed by uncomplicated appendicitis. Temperature elevation is rarely >1°C (1.8°F) and the pulse rate is normal or slightly elevated. Changes of greater magnitude usually indicate that a complication has occurred or that another diagnosis should be considered.25
Patients with appendicitis usually prefer to lie supine, with the thighs, particularly the right thigh, drawn up, because any motion increases pain. If asked to move, they do so slowly and with caution.
The classic right lower quadrant physical signs are present when the inflamed appendix lies in the anterior position. Tenderness often is maximal at or near the McBurney point.8 Direct rebound tenderness usually is present. In addition, referred or indirect rebound tenderness is present. This referred tenderness is felt maximally in the right lower quadrant, which indicates localized peritoneal irritation.25 The Rovsing sign—pain in the right lower quadrant when palpatory pressure is exerted in the left lower quadrant—also indicates the site of peritoneal irritation. Cutaneous hyperesthesia in the area supplied by the spinal nerves on the right at T10, T11, and T12 frequently accompanies acute appendicitis. In patients with obvious appendicitis, this sign is superfluous, but in some early cases, it may be the first positive sign. Hyperesthesia is elicited either by needle prick or by gently picking up the skin between the forefinger and thumb.
Muscular resistance to palpation of the abdominal wall roughly parallels the severity of the inflammatory process. Early in the disease, resistance, if present, consists mainly of voluntary guarding. As peritoneal irritation progresses, muscle spasm increases and becomes largely involuntary, that is, true reflex rigidity due to contraction of muscles directly beneath the inflamed parietal peritoneum.
Anatomic variations in the position of the inflamed appendix lead to deviations in the usual physical findings. With a retrocecal appendix, the anterior abdominal findings are less striking, and tenderness may be most marked in the flank. When the inflamed appendix hangs into the pelvis, abdominal findings may be entirely absent, and the diagnosis may be missed unless the rectum is examined. As the examining finger exerts pressure on the peritoneum of Douglas' cul-de-sac, pain is felt in the suprapubic area as well as locally within the rectum. Signs of localized muscle irritation also may be present. The psoas sign indicates an irritative focus in proximity to that muscle. The test is performed by having the patient lie on the left side as the examiner slowly extends the patient's right thigh, thus stretching the iliopsoas muscle. The test result is positive if extension produces pain. Similarly, a positive obturator sign of hypogastric pain on stretching the obturator internus indicates irritation in the pelvis. The test is performed by passive internal rotation of the flexed right thigh with the patient supine.
Laboratory Findings
Mild leukocytosis, ranging from 10,000 to 18,000 cells/mm3, usually is present in patients with acute, uncomplicated appendicitis and often is accompanied by a moderate polymorphonuclear predominance. White blood cell counts are variable, however. It is unusual for the white blood cell count to be >18,000 cells/mm3 in uncomplicated appendicitis. White blood cell counts above this level raise the possibility of a perforated appendix with or without an abscess. Urinalysis can be useful to rule out the urinary tract as the source of infection. Although several white or red blood cells can be present from ureteral or bladder irritation as a result of an inflamed appendix, bacteriuria in a urine specimen obtained via catheter generally is not seen in acute appendicitis
Imaging Studies
Plain films of the abdomen, although frequently obtained as part of the general evaluation of a patient with an acute abdomen, rarely are helpful in diagnosing acute appendicitis. However, plain radiographs can be of significant benefit in ruling out other pathology. In patients with acute appendicitis, one often sees an abnormal bowel gas pattern, which is a nonspecific finding. The presence of a fecalith is rarely noted on plain films but, if present, is highly suggestive of the diagnosis. A chest radiograph is sometimes indicated to rule out referred pain from a right lower lobe pneumonic process.
Additional radiographic studies include barium enema examination and radioactively labeled leukocyte scans. If the appendix fills on barium enema, appendicitis is excluded. On the other hand, if the appendix does not fill, no determination can be made.27 To date, there has not been enough experience with radionuclide scans to assess their utility.
Graded compression sonography has been suggested as an accurate way to establish the diagnosis of appendicitis. The technique is inexpensive, can be performed rapidly, does not require a contrast medium, and can be used even 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 anteroposterior dimension. Scan results are considered positive if a noncompressible appendix ≥6 mm in the anteroposterior direction is demonstrated (Fig. 30-3). The presence of an appendicolith establishes the diagnosis. Thickening of the appendiceal wall and the presence of periappendiceal fluid is highly suggestive. Sonographic demonstration of a normal appendix, which is an easily compressible, blind-ending tubular structure measuring ≤5 mm in diameter, excludes the diagnosis of acute appendicitis. The study results are considered inconclusive if the appendix is not visualized and there is no pericecal fluid or mass. When the diagnosis of acute appendicitis is excluded by sonography, a brief survey of the remainder of the abdominal cavity should be performed to establish an alternative diagnosis. In females of childbearing age, the pelvic organs must be adequately visualized either by transabdominal or endovaginal ultrasonography to exclude gynecologic pathology as a cause of acute abdominal pain. The sonographic diagnosis of acute appendicitis has a reported sensitivity of 55 to 96% and a specificity of 85 to 98%.28–30 Sonography is similarly effective in children and pregnant women, although its application is somewhat limited in late pregnancy.
The rational approach is the selective use of CT scanning. This has been documented by several studies in which imaging was performed based on an algorithm or protocol.48 The likelihood of appendicitis can be ascertained using the Alvarado scale (Table 30-2).49 This scoring system was designed to improve the diagnosis of appendicitis and was devised by giving relative weight to specific clinical manifestation. Table 30-2 lists the eight specific indicators identified. Patients with scores of 9 or 10 are almost certain to have appendicitis; there is little advantage in further work-up, and they should go to the operating room. Patients with scores of 7 or 8 have a high likelihood of appendicitis, whereas scores of 5 or 6 are compatible with, but not diagnostic of, appendicitis. CT scanning is certainly appropriate for patients with Alvarado scores of 5 and 6, and a case can be built for imaging for those with scores of 7 and 8. On the other hand, it is difficult to justify the expense, radiation exposure, and possible complications of CT scanning in patients whose scores of 0 to 4 make it extremely unlikely (but not impossible) that they have appendicitis.
Table 30-2 Alvarado Scale for the Diagnosis of Appendicitis
  Manifestations Value
Symptoms Migration of pain 1
  Anorexia 1
  Nausea and/or vomiting 1
Signs Right lower quadrant tenderness 2
  Rebound 1
  Elevated temperature 1
Laboratory values Leukocytosis 2
  Left shift in leukocyte count 1
    Total points 10

Source: Reproduced with permission from Alvarado.49
Selective CT scanning based on the likelihood of appendicitis takes advantage of the clinical skill of the experienced surgeon and, when indicated, adds the expertise of the radiologist and his or her imaging study. Figure 30-5 proposes a treatment algorithm addressing the rational use of diagnostic testing

Laparoscopy can serve as both a diagnostic and therapeutic maneuver for patients with acute abdominal pain and suspected acute appendicitis. Laparoscopy is probably most useful in the evaluation of females with lower abdominal complaints, because appendectomy is performed on a normal appendix in as many as 30 to 40% of these patients. Differentiating acute gynecologic pathology from acute appendicitis can be effectively accomplished using the laparoscope.
Appendiceal Rupture
Immediate appendectomy has long been the recommended treatment for acute appendicitis because of the presumed risk of progression to rupture. The overall rate of perforated appendicitis is 25.8%. Children <5 years of age and patients >65 years of age have the highest rates of perforation (45 and 51%, respectively) (Fig. 30-6).14,15,51 It has been suggested that delays in presentation are responsible for the majority of perforated appendices. There is no accurate way of determining when and if an appendix will rupture before resolution of the inflammatory process. Recent studies suggest that, in selected patients, observation and antibiotic therapy alone may be an appropriate treatment for acute appendicitis
Appendiceal rupture occurs most frequently distal to the point of luminal obstruction along the antimesenteric border of the appendix. Rupture should be suspected in the presence of fever with a temperature of >39°C (102°F) and a white blood cell count of >18,000 cells/mm3. In the majority of cases, rupture is contained and patients display localized rebound tenderness. Generalized peritonitis will be present if the walling-off process is ineffective in containing the rupture.
In 2 to 6% of cases, an ill-defined 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 at least 5 to 7 days. Distinguishing acute, uncomplicated appendicitis from acute appendicitis with perforation on the basis of clinical findings is often difficult, but it is important to make the distinction because their treatment differs. CT scan may be beneficial in guiding therapy. Phlegmons and small abscesses can be treated conservatively with IV antibiotics; well-localized abscesses can be managed with percutaneous drainage; complex abscesses should be considered for surgical drainage. If operative drainage is required, it should be performed using an extraperitoneal approach, with appendectomy reserved for cases in which the appendix is easily accessible. Interval appendectomy performed at least 6 weeks after the acute event has classically been recommended for all patients treated either nonoperatively or with simple drainage of an abscess.53,54
Differential Diagnosis
The differential diagnosis of acute appendicitis is essentially the diagnosis of the acute abdomen (see Chap. 35). This is because clinical manifestations are not specific for a given disease but are specific for disturbance of a given physiologic function or functions. Thus, an essentially identical clinical picture can result from a wide variety of acute processes within the peritoneal cavity that produce the same alterations of function as does acute appendicitis.
The accuracy of preoperative diagnosis should be approximately 85%. If it is consistently less, it is likely that some unnecessary operations are being performed, and a more rigorous preoperative differential diagnosis is in order. A diagnostic accuracy rate that is consistently >90% should also cause concern, because this may mean that some patients with atypical, but bona fide, cases of acute appendicitis are being "observed" when they should receive prompt surgical intervention. The Haller group, however, has shown that this is not invariably true.55 Before that group's study, the perforation rate at the hospital at which the study took place was 26.7%, and acute appendicitis was found in 80% of the patients undergoing operation. By implementing a policy of intensive inhospital observation when the diagnosis of appendicitis was unclear, the group raised the rate of acute appendicitis found at operation to 94%, but the perforation rate remained unchanged at 27.5%.55 The rate of false-negative appendectomies is highest in young adult females. A normal appendix is found in 32 to 45% of appendectomies performed in women 15 to 45 years of age.14
A common error is to make a preoperative diagnosis of acute appendicitis only to find some other condition (or nothing) at operation. Much less frequently, acute appendicitis is found after a preoperative diagnosis of another condition. The most common erroneous preoperative diagnoses—together accounting for >75% of cases—are, in descending order of frequency, acute mesenteric lymphadenitis, 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 (i.e., simple or ruptured); the patient's age; and the patient's sex.56–60
Acute Mesenteric Adenitis
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 in order if the diagnosis of mesenteric adenitis seems likely, because it is a self-limited disease. However, if the differentiation remains in doubt, immediate exploration is the safest course of action.
Human infection with Yersinia enterocolitica or Yersinia pseudotuberculosis, transmitted through food contaminated by feces or urine, causes mesenteric adenitis as well as ileitis, colitis, and acute appendicitis. Many of the infections are mild and self limited, but they may lead to systemic disease with a high fatality rate if untreated. The organisms are usually sensitive to tetracyclines, streptomycin, ampicillin, and kanamycin. A preoperative suspicion of the diagnosis should not delay operative intervention, because appendicitis caused by Yersinia cannot be clinically distinguished from appendicitis due to other causes. Approximately 6% of cases of mesenteric adenitis are caused by Yersinia infection.
Salmonella typhimurium infection causes mesenteric adenitis and paralytic ileus with symptoms similar to those of appendicitis. The diagnosis can be established by serologic testing. Campylobacter jejuni causes diarrhea and pain that mimics that of appendicitis. The organism can be cultured from stool.
Gynecologic Disorders
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.
Pelvic Inflammatory Disease
In pelvic inflammatory disease the infection usually is 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%.
Ruptured Graafian Follicle
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 are rather diffuse. Leukocytosis and fever are minimal or absent. Because this pain occurs at the midpoint of the menstrual cycle, it is often called mittelschmerz.
Twisted Ovarian Cyst
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. If the mass is palpable on physical examination, the diagnosis can be made easily. Both transvaginal ultrasonography and CT scanning can be diagnostic if a mass is not palpable.
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. Leakage of ovarian cysts resolves spontaneously, however, and is best treated nonoperatively.24,56–61
Ruptured Ectopic Pregnancy
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 chorionic gonadotropin are characteristic. Although the leukocyte count rises slightly (to approximately 14,000 cells/mm3), 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.
Acute Gastroenteritis
Acute gastroenteritis is common but usually can be easily distinguished from acute appendicitis. Gastroenteritis is characterized by profuse diarrhea, nausea, and vomiting. Hyperperistaltic abdominal cramps precede the watery stools. The abdomen is relaxed between cramps, and there are no localizing signs. Laboratory values vary with the specific cause.
Other Intestinal Disorders
Meckel's Diverticulitis
Meckel's diverticulitis gives rise to a clinical picture similar to that of acute appendicitis. Meckel's diverticulum is located within the distal 2 ft of the ileum. Meckel's diverticulitis is associated with the same complications as appendicitis and requires the same treatment—prompt surgical intervention. Resection of the segment of ileum bearing the diverticulum with end-to-end anastomosis can nearly always be done through a McBurney incision, extended if necessary, or laparoscopically.
Crohn's Enteritis
The manifestations of acute regional enteritis—fever, right lower quadrant pain and tenderness, and leukocytosis—often simulate acute appendicitis. The presence of diarrhea and the absence of anorexia, nausea, and vomiting favor a diagnosis of enteritis, but this is not sufficient to exclude acute appendicitis. In an appreciable percentage of patients with chronic regional enteritis, the diagnosis is first made at the time of operation for presumed acute appendicitis. In cases of an acutely inflamed distal ileum with no cecal involvement and a normal appendix, appendectomy is indicated. Progression to chronic Crohn's ileitis is uncommon.
Colonic Lesions
Diverticulitis or perforating carcinoma of the cecum, or of that portion of the sigmoid that lies in the right side, may be impossible to distinguish from appendicitis. These entities should be considered in older patients. CT scanning is often helpful in making a diagnosis in older patients with right lower quadrant pain and atypical clinical presentations.
Epiploic appendagitis probably results from infarction of the colonic appendage(s) secondary to torsion. Symptoms may be minimal, or there may be continuous abdominal pain in an area corresponding to the contour of the colon, lasting several days. Pain shift is unusual, and there is no diagnostic sequence of symptoms. The patient does not look ill, nausea and vomiting are unusual, and appetite generally is unaffected. Localized tenderness over the site is usual and often is associated with rebound without rigidity. In 25% of reported cases, pain persists or recurs until the infarcted epiploic appendage is removed.

Despite the advent of more sophisticated diagnostic modalities, the importance of early operative intervention should not be minimized. Once the decision to operate for presumed acute appendicitis has been made, the patient should be prepared for the operating room. Adequate hydration should be ensured, electrolyte abnormalities should be corrected, and pre-existing cardiac, pulmonary, and renal conditions should be addressed. A large meta-analysis has demonstrated the efficacy of preoperative antibiotics in lowering the infectious complications in appendicitis. Most surgeons routinely administer antibiotics to all patients with suspected appendicitis. If simple acute appendicitis is encountered, there is no benefit in extending antibiotic coverage beyond 24 hours. If perforated or gangrenous appendicitis is found, antibiotics are continued until the patient is afebrile and has a normal white blood cell count. For intra-abdominal infections of GI tract origin that are of mild to moderate severity, the Surgical Infection Society has recommended single-agent therapy with cefoxitin, cefotetan, or ticarcillin-clavulanic acid. For more severe infections, single-agent therapy with carbapenems or combination therapy with a third-generation cephalosporin, monobactam, or aminoglycoside plus anaerobic coverage with clindamycin or metronidazole is indicated. The recommendations are similar for children.
Open Appendectomy
For open appendectomy most surgeons use either a McBurney (oblique) or Rocky-Davis (transverse) right lower quadrant muscle-splitting incision in patients with suspected appendicitis. The incision should be centered over either the point of maximal tenderness or a palpable mass. If an abscess is suspected, a laterally placed incision is imperative to allow retroperitoneal drainage and to avoid generalized contamination of the peritoneal cavity. If the diagnosis is in doubt, a lower midline incision is recommended to allow a more extensive examination of the peritoneal cavity. This is especially relevant in older patients with possible malignancy or diverticulitis.
Several techniques can be used to locate the appendix. Because the cecum usually is visible within the incision, the convergence of the taeniae can be followed to the base of the appendix. A sweeping lateral to medial motion can aid in delivering the appendiceal tip into the operative field. Occasionally, limited mobilization of the cecum is needed to aid in adequate visualization. Once identified, the appendix is mobilized by dividing the mesoappendix, with care taken to ligate the appendiceal artery securely.
The appendiceal stump can be managed by simple ligation or by ligation and inversion with either a purse-string or Z stitch. As long as the stump is clearly viable and the base of the cecum is not involved with the inflammatory process, the stump can be safely ligated with a nonabsorbable suture. The mucosa is frequently obliterated to avoid the development of mucocele. The peritoneal cavity is irrigated and the wound closed in layers. If perforation or gangrene is found in adults, the skin and subcutaneous tissue should be left open and allowed to heal by secondary intent or closed in 4 to 5 days as a delayed primary closure. In children, who generally have little subcutaneous fat, primary wound closure has not led to an increased incidence of wound infection.
If appendicitis is not found, a methodical search must be made for an alternative diagnosis. The cecum and mesentery should first be inspected. Next, the small bowel should be examined in a retrograde fashion beginning at the ileocecal valve and extending at least 2 ft. In females, special attention should be paid to the pelvic organs. An attempt also should be made to examine the upper abdominal contents. Peritoneal fluid should be sent for Gram's staining and culture. If purulent fluid is encountered, it is imperative that the source be identified. A medial extension of the incision (Fowler-Weir), with division of the anterior and posterior rectus sheath, is acceptable if further evaluation of the lower abdomen is indicated. If upper abdominal pathology is encountered, the right lower quadrant incision is closed and an appropriate upper midline incision is made
Laparoscopic Appendectomy
Semm first reported successful laparoscopic appendectomy several years before the first laparoscopic cholecystectomy.10 However, the laparoscopic approach to appendectomy did not come into widespread use until after the success of laparoscopic cholecystectomy. This may be due to the fact that appendectomy, by virtue of its small incision, is already a form of minimal-access surgery.
Laparoscopic appendectomy is performed under general anesthesia. A nasogastric tube and a urinary catheter are placed before obtaining a pneumoperitoneum. Laparoscopic appendectomy usually requires the use of three ports. Four ports may occasionally be necessary to mobilize a retrocecal appendix. The surgeon usually stands to the patient's left. One assistant is required to operate the camera. One trocar is placed in the umbilicus (10 mm), and a second trocar is placed in the suprapubic position. Some surgeons place this second port in the left lower quadrant. The suprapubic trocar is either 10 or 12 mm, depending on whether or not a linear stapler will be used. The placement of the third trocar (5 mm) is variable and usually is either in the left lower quadrant, epigastrium, or right upper quadrant. Placement is based on location of the appendix and surgeon preference. Initially, the abdomen is thoroughly explored to exclude other pathology. The appendix is identified by following the anterior taeniae to its base. Dissection at the base of the appendix enables the surgeon to create a window between the mesentery and the base of the appendix. The mesentery and base of the appendix are then secured and divided separately. When the mesoappendix is involved with the inflammatory process, it is often best to divide the appendix first with a linear stapler and then to divide the mesoappendix immediately adjacent to the appendix with clips, electrocautery, Harmonic Scalpel, or staples. The base of the appendix is not inverted. The appendix is removed from the abdominal cavity through a trocar site or within a retrieval bag. The base of the appendix and the mesoappendix should be evaluated for hemostasis. The right lower quadrant should be irrigated. Trocars are removed under direct vision.

The utility of laparoscopic appendectomy in the management of acute appendicitis remains controversial. Surgeons may be hesitant to implement a new technique because the conventional open approach already has proved to be simple and effective. A number of articles in peer-reviewed journals have compared laparoscopic and open appendectomy, including >20 randomized, controlled trials and 6 meta-analyses.The overall quality of these randomized, controlled trials has been limited by the failure to blind patients and providers as to the treatment modality used. Furthermore, investigators have failed to perform prestudy sample size analysis for the outcomes studied. The largest meta-analysis comparing open to laparoscopic appendectomy included 47 studies, 39 of which were studies of adult patients. This analysis demonstrated that the duration of surgery and costs of operation were higher for laparoscopic appendectomy than for open appendectomy. Wound infections were approximately half as likely after laparoscopic appendectomy as after open appendectomy. However, the rate of intra-abdominal abscess was three times higher after laparoscopic appendectomy than after open appendectomy.
A principal proposed benefit of laparoscopic appendectomy has been decreased postoperative pain. Patient-reported pain on the first postoperative day is significantly less after laparoscopic appendectomy. However, the difference has been calculated to be only 8 points on a 100-point visual analogue scale. This difference is below the level of pain that an average patient is able to perceive. Hospital length of stay also is statistically significantly less after laparoscopic appendectomy. However, in most studies this difference is <1 day. It appears that a more important determinant of length of stay after appendectomy is the pathology found at operation—specifically, whether a patient has perforated or nonperforated appendicitis. In nearly all studies, laparoscopic appendectomy is associated with a shorter period before return to normal activity, return to work, and return to sports. However, treatment and subject bias may have a significant impact on the data. Although the majority of studies have been performed in adults, similar data have been obtained in children.
There appears to be little benefit to laparoscopic appendectomy over open appendectomy in thin males between the ages of 15 and 45 years. In these patients, the diagnosis usually is straightforward. Open appendectomy has been associated with outstanding results for several decades. Laparoscopic appendectomy should be considered an option in these patients, based on surgeon and patient preference. Laparoscopic appendectomy may be beneficial in obese patients, in whom it may be difficult to gain adequate access through a small right lower quadrant incision. In a retrospective study of 116 patients with a mean body mass index of 35, postoperative length of stay was significantly shorter in the group undergoing laparoscopic appendectomy, and there were fewer open wounds. In all obese patients in whom the procedure was completed laparoscopically the incisions closed primarily, whereas the wounds closed primarily in only 58% of obese patients who underwent open appendectomy. There was no difference in rates of wound infection; intra-abdominal abscess rates were not reported.
Diagnostic laparoscopy has been advocated as a potential tool to decrease the number of negative appendectomies performed. However, the morbidity associated with laparoscopy and general anesthesia is acceptable only if pathology requiring surgical treatment is present and is amenable to treatment using laparoscopic techniques. The question of leaving a normal appendix in situ is a controversial one. Seventeen to 26% of appendices that appear normal at exploration are found to have pathologic features on histologic analysis. The availability of diagnostic laparoscopy may actually lower the threshold for exploration and thus adversely impact the negative appendectomy rate. Fertile women with presumed appendicitis constitute the group of patients most likely to benefit from diagnostic laparoscopy. Up to one third of these patients do not have appendicitis at exploration. In most of the patients without appendicitis, gynecologic pathology is identified. A large meta-analysis demonstrated that in fertile women in whom appendectomy was deemed necessary, diagnostic laparoscopy reduced the number of unnecessary appendectomies. In addition, the number of women without a final diagnosis was smaller. It appears that leaving a normal-appearing appendix in fertile women with identifiable gynecologic pathology is safe.
In summary, it has not been resolved whether laparoscopic appendectomy is more effective in treating acute appendicitis than the time-proven method of open appendectomy. It does appear that laparoscopic appendectomy is effective in the management of acute appendicitis. Laparoscopic appendectomy should be considered part of the surgical armamentarium available to treat acute appendicitis. The decision on how to treat a specific patient with appendicitis should be based on surgical skill, patient characteristics, clinical scenario, and patient preference. Additional well-controlled, prospective, blinded studies are needed to determine which subsets of patients may benefit from any given approach to the treatment of appendicitis.
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. The first case of transvaginal removal of a normal appendix has recently been reported. Much work remains to determine if NOTES provides any additional advantages over the laparoscopic approach to appendectomy.
Antibiotics as Definitive Therapy
Traditional management of acute appendicitis has emphasized emergent surgical management. This approach has been based on the theory that, over time, simple appendicitis will progress to perforation, with resulting increases in morbidity and mortality. As a result, a relatively high negative appendectomy rate has been accepted to avoid the possibility of progression to perforation. Recent data suggest that acute appendicitis and acute appendicitis with perforation may be separate disease entities with distinct pathophysiology. A time series analysis performed on a 25-year data set did not find a significant negative relationship between the rates of negative appendectomy and perforation.17 A study analyzing time to surgery and perforation demonstrated that risk of rupture is minimal within 36 hours of symptom onset. Beyond this point, there is about a 5% risk of rupture in each ensuing 12-hour period. However, in many patients the disease will have an indolent course. In one study 10 of the 18 patients who did not undergo operation for ≥6 days after their symptoms began did not experience rupture.89
Many acute abdominal conditions such as acute diverticulitis and acute cholecystitis are managed with urgent but not emergent surgery. Moreover, evidence from submarine personnel who develop appendicitis suggests that nonoperative management of appendicitis may be a viable treatment option. Sailors who develop appendicitis while stationed on submarines do not have access to prompt surgical care. They are successfully treated with antibiotics and fluids days to weeks after the initial attack until the ship can surface and they can be transferred to a hospital for care.90
A randomized study comparing antibiotic treatment with immediate appendectomy has been completed. Two hundred and fifty-two men 18 to 50 years of age with the presumptive diagnosis of appendicitis were enrolled in the study between March 1996 and June 1999. For patients randomly assigned to antibiotic therapy, if symptoms did not improve within the first 24 hours, an appendectomy was performed. Participants were evaluated after 1 week, 6 weeks, and 1 year. Acute appendicitis was found in 97% of the 124 patients randomly assigned to surgery. Six patients (5%) had perforated appendices. The complication rate in the surgery group was 14% (17 of 124). Of the 128 patients enrolled in the antibiotic group, 15 patients (12%) underwent operation within the first 24 hours due to lack of improvement in symptoms and apparent local peritonitis. At operation seven patients (5%) had perforation. The rate of recurrence within 1 year was 15% (16 patients) in the group treated with antibiotics. In five of these patients a perforated appendix was found at operation.52 Although it initially appears from these data that the use of antibiotics alone may be reasonable therapy for acute appendicitis, there are several issues to take into account. First, this study included only men between the ages of 18 and 50 and may not have broad applicability to all patients with appendicitis, especially those populations known to have higher perforation rates. Second, the incidence of perforation was 9% in the antibiotic group when patients requiring operation in both the acute and delayed settings are considered. This compares unfavorably with the perforation rate of 5% for those patients operated on immediately. In addition, the study follow-up was only 1 year, which suggests that patients receiving only antibiotic therapy may still be at risk for the development of appendicitis. Finally, when patients are treated with antibiotics alone it is possible that diagnoses of significant pathology such as carcinoid or carcinoma may be delayed. Because no laboratory test or clinical investigation can reliably distinguish patients whose appendicitis is potentially amenable to conservative treatment, surgery still remains the gold standard of care for patients with acute appendicitis.
Interval Appendectomy
The accepted approach for the treatment of appendicitis associated with a palpable or radiographically documented mass (abscess or phlegmon) is conservative therapy with interval appendectomy 6 to 10 weeks later. This technique has been quite successful and produces much lower morbidity and mortality rates than immediate appendectomy. Unfortunately, this treatment is associated with greater expense and longer hospitalization time (8 to 13 days vs. 3 to 5 days).
The initial treatment consists of IV antibiotics and bowel rest. Although this therapy is generally effective, there is a 9 to 15% failure rate, with operative intervention required at 3 to 5 days after presentation. Percutaneous or operative drainage of abscesses is not considered a failure of conservative therapy.
Although the second stage of this treatment plan, interval appendectomy, has usually been carried out, the need for subsequent operation has been questioned. The major argument against interval appendectomy is that approximately 50% of patients treated conservatively never develop manifestations of appendicitis, and those who do generally can be treated nonoperatively. In addition, pathologic examination of the resected appendix shows normal findings in 20 to 50% of cases.
On the other hand, the data clearly support the need for interval appendectomy. In a prospective series, 19 of 48 patients (40%) who were successfully treated conservatively needed appendectomy at an earlier time (mean of 4.3 weeks) than the 10 weeks planned because of bouts of appendicitis.91 Overall, the rate of late failure as a consequence of acute disease averages 20%. An additional 14% of patients either continue to have, or redevelop, right lower quadrant pain. Although the appendix may occasionally be pathologically normal, persistent periappendiceal abscesses and adhesions are found in 80% of patients. In addition, almost 50% have histologic evidence of inflammation in the organ itself. Several neoplasms also have been detected in the resected appendices, even in those of children.
The timing of interval appendectomy is somewhat controversial. Appendectomy may be required as early as 3 weeks after conservative therapy. Two thirds of the cases of recurrent appendicitis occur within 2 years, and this is the outside limit. Interval appendectomy is associated with a morbidity rate of ≤3% and a hospitalization time of 1 to 3 days. The laparoscopic approach has been used and has been successful in 68% of procedures. In a more recent study in children, interval appendectomy was performed successfully using the laparoscopic approach in all 35 patients.
The mortality from appendicitis in the United States has steadily decreased from a rate of 9.9 per 100,000 in 1939 to 0.2 per 100,000 today. Among the factors responsible are advances in anesthesia, antibiotics, IV fluids, and blood products. Principal factors influencing mortality are whether rupture occurs before surgical treatment and the age of the patient. The overall mortality rate in acute appendicitis with rupture is approximately 1%. The mortality rate of appendicitis with rupture in the elderly is approximately 5%—a fivefold increase from the overall rate. Death is usually attributable to uncontrolled sepsis—peritonitis, intra-abdominal abscesses, or gram-negative septicemia. Pulmonary embolism continues to account for some deaths.
Morbidity rates parallel mortality rates and are significantly increased by rupture of the appendix and, to a lesser extent, by old age. In one report, complications occurred in 3% of patients with nonperforated appendicitis and in 47% of patients with perforations. Most of the serious early complications are septic and include abscess and wound infection. Wound infection is common but is nearly always confined to the subcutaneous tissues and responds promptly to wound drainage, which is accomplished by reopening the skin incision. Wound infection predisposes the patient to wound dehiscence. The type of incision is relevant; complete dehiscence rarely occurs in a McBurney incision.
The incidence of intra-abdominal abscess secondary to peritoneal contamination from gangrenous or perforated appendicitis has decreased markedly since the introduction of potent antibiotics. The sites of predilection for abscesses are the appendiceal fossa, pouch of Douglas, the subhepatic space, and between loops of intestine. In the latter site abscesses are usually multiple. Transrectal drainage is preferred for an abscess that bulges into the rectum.
Fecal fistula is an annoying, but not particularly dangerous, complication of appendectomy that may be caused by sloughing of the portion of the cecum inside a constricting purse-string suture; by slipping of the ligature off a tied, but not inverted, appendiceal stump; or by necrosis from an abscess encroaching on the cecum.
Intestinal obstruction, initially paralytic but sometimes progressing to mechanical obstruction, may occur with slowly resolving peritonitis with loculated abscesses and exuberant adhesion formation. Late complications are quite uncommon. Adhesive band intestinal obstruction after appendectomy does occur, but much less frequently than after pelvic surgical therapy. The incidence of inguinal hernia is three times higher in patients who have had an appendectomy. Incisional hernia is like wound dehiscence in that infection predisposes to it, it rarely occurs in a McBurney incision, and it is not uncommon in a lower right paramedian incision.
Chronic Appendicitis
Whether chronic appendicitis is a true clinical entity has been questioned for many years. However, clinical data document the existence of this uncommon disease. Histologic criteria have been established. Characteristically, the pain lasts longer and is less intense than that of acute appendicitis but is in the same location. There is a much lower incidence of vomiting, but anorexia and occasionally nausea, pain with motion, and malaise are characteristic. Leukocyte counts are predictably normal and CT scans are generally nondiagnostic.
At operation, surgeons can establish the diagnosis with 94% specificity and 78% sensitivity. There is an excellent correlation between clinical symptomatology, intraoperative findings, and histologic abnormalities. Laparoscopy can be used effectively in the management of this clinical entity. Appendectomy is curative. Symptoms resolve postoperatively in 82 to 93% of patients. Many of those whose symptoms are not cured or recur are ultimately diagnosed with Crohn's disease.

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