Current de Apendicitis

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Current Problems in Surgery

Current Problems in Surgery 50 (2013) 54–86

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Acute Appendicitis: Controversies in Diagnosisand Management

Curtis J. Wray, MD, Lillian S. Kao, MD, MS, Stefanos G. Millas, MD,Kuojen Tsao, MD, Tien C. Ko, MD

Challenges in the Diagnosis of Acute Appendicitis

Appendicitis is a common problem; there are more than 300,000 hospital discharges forappendicitis in the United States per year.1 Although the clinical scenario of periumbilical painmigrating to the right lower quadrant is classically associated with acute appendicitis, thepresentation is rarely typical and the diagnosis cannot always be based on history and physicalexamination alone. Diagnostic errors are common, with over-diagnosis leading to negativeappendectomies and with delays in diagnosis leading to perforations. The misdiagnosis ofappendicitis has significant economic ramifications; in a nationwide study of administrative dataover a 1-year period in the late 1990s, a negative appendectomy rate of 15% resulted in more than$740 million in hospital charges.2

Diagnostic strategies for evaluating patients with abdominal pain and for identifying patientswith suspected appendicitis should all start with a thorough history and physical examination. TheSurgical Infection Society (SIS) and Infectious Diseases Society of America (IDSA) publishedguidelines that recommend the establishment of local pathways for the diagnosis and managementof acute appendicitis.3 The guidelines note that the combination of clinical and laboratory findings ofcharacteristic abdominal pain, localized tenderness, and laboratory evidence of inflammation willidentify most patients with suspected appendicitis.3 Other diagnostic strategies may includeradiologic imaging or the use of scoring systems with or without computer support. Ultimately, the‘‘gold standard’’ for a positive diagnosis is the histopathologic confirmation of appendicitis, althoughstandard criteria are lacking.4 A negative diagnosis may be confirmed by intra-operative findings orclinical follow-up or both.

There are different measures for evaluating a diagnostic test or strategy (Table 1). Sensitivityrefers to the proportion of true positive tests among all patients who have the disease (A/[AþC]).Specificity refers to the proportion of true negatives among all patients who do not have the disease(D/[BþD]). Highly sensitive tests rule disease out, whereas highly specific tests rule disease in.Accuracy refers to the proportion of true positives and negatives among all patients tested ([AþD]/[AþBþCþD]). The positive predictive value of a test refers to the proportion of true positives amongall patients who test positive (A/[AþB]), whereas the negative predictive value refers to theproportion of true negatives among all patients who test negative (D/[CþD]). The predictive valuesof a test should be applied with caution to local patients as they depend upon the incidence

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TABLE 12 � 2 Table for calculating sensitivity, specificity, predictive values, and likelihood ratios

Disease positive Disease negative

Test positive True positives (A) False negatives (B) A þ B

Test negative False positives (C) True negatives (D) C þ D

A þ C B þ D A þ B þ C þ D

TABLE 2Named clinical signs associated with acute appendicitis

Name Description

Dunphy’s sign Increased right lower quadrant pain with coughing

Obturator sign Increased pain with flexion and internal rotation of the hip

Psoas sign Increased pain with passive extension of the right hip (can be elicited with the

patient lying on the left side)

Rovsing’s sign Increased right lower quadrant pain during palpation in the left lower quadrant

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 54–86 55

(frequency of new cases) or prevalence (frequency of all cases) of the disease in the populationtested.

Clinicians order diagnostic tests because the results may change the management of thepatient. In the setting of abdominal pain, if the test suggests a high probability of acuteappendicitis, then the clinician may choose to perform an appendectomy. If the test suggests a lowprobability of acute appendicitis, then the clinician may choose to discharge the patient.Likelihood ratios (LRs), which are calculated from sensitivity and specificity, assist the clinician incalculating these post-test probabilities. LRþ refers to the ratio of the chance that the test wouldbe positive in patients with the disease vs the chance that the test would be positive in patientswithout the disease. LR� similarly refers to the ratio of the chance that the test would be negativein patients with the disease vs the chance that the test would be negative in patients without thedisease. A test with an LR of 1 does not offer any new information.5 A disease is strongly ruled in ifthe LRþ is greater than 10 and strongly ruled out if the LR� is less than 0.1. LRs unlike predictivevalues are not affected by disease prevalence, and they can be applied to individual patients toinform clinical decision-making.

History and Physical Examination

Despite advances in diagnostic tests, appendicitis remains a clinical diagnosis. Clinical symptomselicited by the history may include fever, nausea, vomiting, anorexia, migration of pain to the rightlower quadrant, and aggravation of pain by movement. Physical examination may reveal signs ofperitoneal irritation in the right lower quadrant or diffusely. Rectal examination may revealtenderness. Furthermore, there are a variety of named signs that may be associated withappendicitis depending upon the location of the inflamed appendix (Table 2) (ie, pain caused bypassive extension of the hip caused by a retrocecal appendix irritating the iliopsoas muscle or thepsoas sign).

The signs and symptoms described above are common and nonspecific; each individual sign andsymptom is only weakly predictive of appendicitis (Table 3).4 Furthermore, the differential diagnosisfor right lower quadrant abdominal pain is wide and varies with age and gender. When signs andsymptoms were compared between children and adults, they were similarly predictive ofappendicitis, with the exception of right lower quadrant pain which had a much higher LRþ inadults than in children.6,7 Another limitation of relying on clinical findings alone is that elicitation ofphysical signs is subjective; multiple studies have demonstrated poor inter-rater reliability between

TABLE 3Sensitivities, specificities, and likelihood ratios for common clinical symptoms, signs, laboratory values, and radiologic tests

(95% confidence intervals provided in parentheses if available)

Sensitivity Specificity LRþ LR�

History (symptoms)

Fever4 1.64 (0.89-3.01) 0.61 (0.49-0.77)

Fever6 (children) 1.2 (1.1-1.4) 0.53 (0.29-0.97)

Anorexia4 1.27 (1.14-1.41) 0.59 (0.45-0.77)

Anorexia (children)6 1.4 (1.2-1.6) 0.57 (0.44-0.73)

Vomiting4 1.63 (1.45-1.84) 0.75 (0.69-0.80)

Vomiting (children)6 1.4 (1.3-1.6) 0.57 (0.47-0.69)

Right lower quadrant pain (adults)7 0.81 0.53 7.31-8.46 0-0.28

Right lower quadrant pain (children)6 1.2 (1.0-1.5) 0.56 (0.43-0.73)

Pain migration4 2.06 (1.63-2.60) 0.52 (0.40-0.69)

Pain migration (children)16 1.9 (1.4-2.5) 0.72 (0.62-0.85)

Physical examination (signs)

Rebound tenderness4 1.99 (1.61-2.45) 0.39 (0,32-0.48)

Rebound tenderness (children)6 3.0 (2.3-3.9) 0.28 (0.14-0.55)

Guarding or rigidity4 2.36 (1.76-3.15) 0.70 (0.61-0.80)

Psoas sign4 2.31 (1.36-3.91) 0.85 (0.76-0.95)

Laboratory values

WBC (�109/L) Z 104 2.47 (2.06-2.95) 0.26 (0.18-0.36)

WBC 4 14.9 or 4 10 (children)6 2.0 (1.3-2.9) 0.22 (0.17-0.30)

WBC (�109/L) Z 154 3.47 (1.55-7.77) 0.81 (0.69-0.95)

WBC 4 14.9 or 4 15 (children)6 1.7 (0.83-3.4) 0.77 (0.52-1.1)

Proportion of polymorphonuclear cells (%) 4 75% 2.44 (1.60-3.74) 0.24 (0.11-0.50)

CRP level (mg/L) 4 10 1.97 (1.58-2.45) 0.32 (0.20-0.51)

CRP level (mg/L) 4 20 2.39 (1.67-3.41) 0.47 (0.28-0.81)

Radiologic tests

Ultrasound (adults)25 83% (78%-87%) 93% (90%-96%) 12 0.2

Ultrasound (children)25 88% (86%-90%) 94% (92%-95%) 15 0.1

CT (adults)25 94% (92%-95%) 94% (94%-96%) 16 0.06

CT (children)25 94% (92%-97%) 95% (94%-97%) 19 0.06

Scoring systems

Alvarado (Z7)6 4.0 (3.2-4.9) 0.20 (0.09-0.41)

Pediatric Appendicitis Score (Z6)42 82% 65% 2.4 (2.0-2.8) 0.27 (0.20-0.37)

Ruptured appendicitis scoring system (in

children, Z4)35

92% 81% 4.9 0.1

Ruptured appendicitis scoring system (in

children, Z7)35

68% 94% 11.3 0.33

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 54–8656

trainees and attending physicians, as well as between subspecialists.8,9 For example, Yen andcolleagues reported that the inter-rater reliability for several common clinical findings such asrebound tenderness and clinical diagnosis of peritonitis was poor to moderate between pediatricemergency medicine physicians and senior surgical residents.8 However, when used in combinationwith laboratory values, the diagnostic utility of the clinical findings increases significantly.

Laboratory Values

Laboratory values that have been associated with acute appendicitis include: leukocytosis, leftshift, and elevated markers of inflammation such as C-reactive protein (CRP) and erythrocytesedimentation rate (Table 3).4,6 As with the clinical symptoms and signs, each individual laboratorytest value is only weakly discriminatory and predictive of acute appendicitis.4 However, combinationsof clinical findings and laboratory values or combinations of multiple laboratory values are morediscriminatory and predictive.4 For example, the presence of guarding or rebound and a white bloodcell (WBC) count of greater than or equal to 10 � 109/L has an LRþ of 11.34 (95% confidence interval


[CI] 6.65-19.56), whereas the absence of both of these variables has an LR�D of 0.14 (95% CI 0.08-0.24).4 A meta-analysis by Anderson revealed that the greatest discriminators and predictors of acuteappendicitis included a history of migration of pain, clinical findings of peritoneal irritation, andlaboratory values reflecting an inflammatory response (ie, CRP).4

There have been numerous studies evaluating other potential serum and urinary markers ofappendicitis, including but not limited to inflammatory cytokines such as serum interleukin-6,interleukin-8, and tumor necrosis factor alpha10,11; serum neutrophil proteins such as lactoferrinand calprotectin12; and urinary markers such as leucine-rich a-2-glycoprotein.13 However, at best,these studies may demonstrate that elevated levels distinguish patients with and without acuteappendicitis among those suspected of having the disease. Although these markers are promising,none have been evaluated in a prospective trial comparing their use to conventional diagnosticstrategies and evaluating the effect of their use on clinical outcomes and costs.

Scoring Systems

There are several clinical scoring systems that have been used in the diagnosis of acuteappendicitis. Alvarado published his scoring system in 1986, also referred to as MANTRELS based onthe mnemonic for remembering the combination of 8 signs and symptoms (Table 4).14 The scoreranges from 0-10; a patient with a score of 5 or 6 is typically observed, whereas a patient with ascore of 7 or greater should undergo operation.14 Since then, there have been several studiesevaluating the diagnostic accuracy of the Alvarado score, modified versions of the Alvarado scoresuch as the Pediatric Appendicitis Score,15 and other scores such as the Kharbanda16 and Lintula17-19

scores (Table 3). In general, these clinical scoring systems have better LRs than individual symptomsor signs alone. However, these scoring systems do not have sufficient discriminatory or predictiveability to routinely be used alone to diagnose appendicitis. They have been used to determine theneed for further radiologic studies20 or as a guide for dictating clinical management.21

Radiologic Imaging

The use of radiologic imaging in the evaluation of abdominal pain and in the diagnosis of acuteappendicitis has increased over time.22 On one hand, imaging may be helpful in the evaluation ofpatients with abdominal pain for ruling in or out other diagnoses or for preventing unnecessaryoperations.23 On the other hand, imaging could potentially delay operative intervention, and in thecase of computed tomography (CT), radiologic imaging exposes patients to the risks of ionizingradiation.24 Ultrasonography (US) does not expose patients to ionizing radiation but is moreoperator dependent. In a meta-analysis of US and CT in children and adults, both US and CT werehighly specific (93%-95%) in children and adults, whereas CT was more sensitive than US25 (Table 2).The Surgical Infection Society and Infectious Disease Society of America guidelines recommend use

TABLE 4Alvarado or MANTRELS scoring system14

Variable Value

Symptoms Migration 1

Anorexia 1

Nausea-vomiting 1

Signs Tenderness in right lower quadrant 2

Rebound of pain 1

Elevation of temperature (Z37.31C) 1

Laboratory Leukocytosis (White blood cell count 410,000/mL) 2

Shift to the left (475% neutrophils) 1

Total score 10


of intravenous (IV) but not oral or rectal contrast,3 although a recent meta-analysis suggested thatnoncontrast enhanced CT scan in adults had reasonably high sensitivity and specificity for clinicaldecision-making (93% and 96%, respectively).26

The Surgical Infection Society and Infectious Disease Society of America guidelines recommendhelical CT with IV contrast as the test of choice when imaging is indicated in patients with suspectedappendicitis, with moderate supporting evidence from 1 or more well-designed but nonrandomizedtrials.3,27 A recent meta-analysis evaluated the effect of CT on negative appendectomies, rates ofperforation, and time to surgery in patients with acute right lower quadrant pain.28 The meta-analysisconcluded that preoperative CT resulted in a reduced rate of negative appendectomies but an increasein time to surgery, although there was no increase in rate of perforation.28 However, of the 28 studiesincluded in the analysis, only 2 were randomized, and most were retrospective cohort studies whichcan be subject to multiple sources of bias.

There have been only a few randomized trials evaluating different strategies incorporatingradiologic imaging on clinical outcomes. Only 1 trial identified a difference in accuracy. Lee andcolleagues compared a strategy of mandatory vs selective CT scanning in patients with suspectedappendicitis and less than 72 hours of symptoms. There were fewer negative appendectomies (2.6%vs 13.9%, P ¼ 0.07) and perforations (10.3% vs 18.4%, P ¼ 0.24) in the group undergoing mandatoryscans.29 Another trial reported that CT scanning changed management in 26% of patients.30 Walkerand colleagues compared CT scanning to standard management in patients with suspectedappendicitis who clinically warranted either observation or operation. Standard managementincluded observation with serial examinations, ultrasound, CT, or operation. Two additional trials ofCT scanning vs clinical assessment in patients with suspected appendicitis, 1 in women only,identified no differences in diagnostic accuracy, length of stay, perforation rate, or costs orcharges.31,32 However, these trials were small, single-center trials and underpowered to identify asmall difference in clinical outcome.

The use of radiologic imaging in the diagnosis of acute appendicitis has increased over time.Population-based analyses of regional administrative data in the 1980s and 1990s demonstrated asignificant increase in the use of US and CT, but no change in the rate of ruptured or negativeappendectomies.22,33 A more recent follow-up study from the Washington state Surgical Care andOutcomes Assessment Program showed wide variability in the use of radiologic imaging across the15 participating hospitals, ranging from 56%-97%.34 There was also a significant difference in the rateof negative appendectomies, which was correlated to the accuracy of the radiologic studies.34 Thisstudy demonstrates that although the reported accuracy of radiologic imaging tests is high in thepublished literature, it is important to their diagnostic accuracy within each institution to evaluatetheir ‘‘real-world’’ utility.

Perforated vs Nonperforated Appendicitis

Distinguishing whether or not a patient is likely to have perforated vs nonperforated appendicitispreoperatively may be helpful in terms of counseling the patient about alternatives for management(ie, early vs delayed appendectomy), risk for complications, and the expected postoperative course.The Anderson meta-analysis identified 4 studies that presented data for perforated appendicitis.Based on these studies, high values of laboratory markers of inflammation such as a WBC andgranulocyte count and the CRP level were relatively strong predictors of perforated appendicitis,whereas low values were relatively strong predictors of not having perforated appendicitis.4

Williams and colleagues developed a ruptured appendicitis scoring system for children based on 5variables, including components of history, physical examination, laboratory values, and CTfindings.35 When the scoring system was applied to the study patient population, it increased thespecificity of the pediatric surgeon’s preoperative assessment from 83%-98%.35 This was a single-center study that has not been validated in other centers or in adult patients. However, itdemonstrates how a combination of clinical findings and test results can improve the diagnosticaccuracy for perforated appendicitis.


Future Directions

The above list of diagnostic tests and strategies is by no means comprehensive. Research isongoing to identify accurate, efficient, and cost-effective methods of diagnosis. Advances haveincluded using molecular techniques for profiling gene and protein expression to identify novelmarkers for appendicitis.13,36,37 Imaging alternatives to CT scans such as bedside surgeon-performedultrasound,38 magnetic resonance imaging,39 or low radiation CT scanning40 are being investigatedin terms of their diagnostic accuracy and their potential to reduce exposure to radiation. Anotheravenue of investigation is the use of machine learning and advanced statistical models for informingdecision-making.41 As advances in technology and diagnostic strategies are made, any improve-ments in accuracy must be balanced against the costs and potential harms.

Conclusions

Acute appendicitis is a common problem that continues to pose diagnostic dilemmas forclinicians. Although clinical findings alone may not be sufficient for establishing a diagnosis ofappendicitis, the importance of a thorough history and physical examination should not beunderestimated. If additional tests are warranted, their risks and benefits should be consideredalong with the likelihood that such tests will change the management. Advances in molecularmethods, imaging technology, and computer decision support hold promise for the future, butfurther investigation is necessary to ensure the accuracy, efficiency, and cost-effectiveness of noveldiagnostic strategies for acute appendicitis.

Antibiotics vs Appendectomy for Acute Uncomplicated Appendicitis

Appendectomy for acute appendicitis is one of the most common surgical procedures performedworldwide. In the United States, appendectomy incurs considerable indirect costs resulting fromtime lost from work, school, or usual activities after the procedure.42 The individual lifetime risk ofappendicitis is 8.6% for men and 6.7% for women.43 Uncomplicated acute appendicitis is consideredalmost universally to be an indication for an appendectomy. In 1889, open appendectomy wasaccepted as the treatment standard, because it saved lives, and since that time, the dictum thatsurgical removal of the appendix is necessary has been largely unchallenged.44 Almost all surgeonsregard acute appendicitis as an invariably progressive inflammatory condition that over timewill eventually lead to perforation. Thus, early surgical exploration and appendectomy isadvocated for source control. However, appendectomy for nonperforated appendicitis is notwithout associated harm. The long-term risk of small bowel obstruction is estimated at 1.3% at 30years after appendectomy.45 In addition, the ‘‘negative’’ appendectomy rate ranges from 10%-20%despite the widespread use of CT scans.46-48

Meanwhile, nonoperative management with antibiotics has been established as the treatment forvarious intra-abdominal infections such as uncomplicated diverticulitis, salpingitis, and neonatalenterocolitis.49 It is surprising that nonoperative management of uncomplicated acute appendicitisremains largely unexplored despite evidence that it often resolves, either spontaneously or withantibiotic therapy, and has been shown by limited studies to have outcomes equivalent to those ofappendectomy.50,51 Accordingly, it may be reasonable to call into question the assumptions and‘‘evidence’’ that have supported appendectomy for this condition.

Evidence for Spontaneous Resolution of Appendicitis

Widespread CT scan utilization for the diagnosis of appendicitis has resulted in a significantincrease in the number of studies performed annually.52 This has led to several interestingobservations regarding the possibility of spontaneous resolution of appendicitis from severalcenters. Inclusion of a CT scan result in the Alvarado score has been shown to increase the rate of


appendectomy. When classified as having a low likelihood of appendicitis (Alvarado score r4),patients who underwent a CT scan had an appendectomy rate of 48%.52 In contrast, those with anAlvarado score r4 who did not undergo a CT scan had an appendectomy rate of only 12%.

Decadt and colleagues made a comparable observation for those patients who presented withnonspecific abdominal pain.53 The investigators used diagnostic laparoscopy instead of CT scan inthe management of patients with nonspecific abdominal pain. Patients were randomized to either(1) diagnostic laparoscopy or (2) nonoperative management (with operative intervention ifperitonitis developed). The appendectomy rate was 39% for those randomized to diagnosticlaparoscopy and 13% for those managed nonoperatively.

There are also modest epidemiologic data for spontaneous resolution of acute appendicitis.Andersson and colleagues performed a meta-analysis of studies examining the epidemiology ofappendicitis.54 This meta-analysis included more than 50,000 patients from 15 geographic areas whohad undergone appendectomy for acute appendicitis. In this study, the incidence of perforatedappendicitis was equivalent regardless of geographic area, time, and gender. However, the incidence ofacute nonuncomplicated appendicitis differed significantly and correlated strongly to the incidence ofremoval of a normal appendix and was inversely related to diagnostic accuracy. This led the authors toconclude that the observed incidence of uncomplicated appendicitis was influenced by the willingnessto perform appendectomy in cases of suspected appendicitis. A high rate of appendectomy in suspectedcases increases the proportion of confirmed cases presumably by adding instances of self-limitedinflammation that otherwise would escape detection.55 These indirect findings and evidence aresuggestive that uncomplicated, acute appendicitis may be initially managed nonoperatively.

Nonoperative Management of Acute Appendicitis

Several reports have appeared in the literature over the last half-decade describing nonoperativemanagement of acute, uncomplicated appendicitis (Fig 1).56-59 The trial that has received the mostattention was conducted in Sweden. All patients older than 18 years with presumed appendicitiswere eligible for inclusion. Appendicitis was diagnosed by the physician based on clinical history,laboratory tests, US, CT, and physical examination. A total of 369 consecutive patients were allocatedto antibiotic treatment or surgery (Fig 2); allocation was determined by odd or even date of birth.All included patients remained in their allocated groups during follow-up, even when intention totreat was abandoned owing to criteria defined in the protocol. Patients allocated to antibiotictreatment could have surgery without any predetermined specification if the surgeon in chargedeemed it necessary or if the patient preferred initial operation. Study patients received intravenous(IV) antibiotics (cefotaxime 1 g twice and metronidazole 1.5 g once) for at least 24 hours. During thistime patients received IV fluids with no oral intake. Patients whose clinical status had improved thefollowing morning were discharged to continue with per os antibiotics (ciprofloxacin 500 mg twiceper day and metronidazole 400 mg 3 times per day) for a total of 10 days. In patients whose clinicalcondition had not improved, IV treatment was prolonged.

This study was conducted from May 2006-September 2007 and included 369 eligible consecutivepatients. There were 202 patients in the study group (antibiotics) and 167 patients in the controlgroup (appendectomy). In the study group, 106 (52.5%) completed the intended antibiotictreatment, and 154 (92.2%) in the control group underwent an appendectomy. Reasons fornonfulfillment of scheduled treatment included patient preference for the other treatment (33patients; 30.3%), the surgeon deciding that surgery was necessary based on clinical evaluation (19patients; 17.4%), and surgery being deemed necessary without any further specification (45patients; 41.3%). Of 108 patients who initially improved without surgery, 15 (13.9%) had recurrentappendicitis at a median follow-up time of 1 year. One third of recurrences appeared within 10 daysfollowing discharge from the hospital. Of the 15 patients with recurrence, 12 had surgery (4 patientshad gangrenous or perforated appendicitis and 1 patient underwent ileocecal resection) and 3 hada second round of antibiotic treatment with success. Appendectomy was performed according to theauthors’ usual practice: single-dose antibiotic prophylaxis, open or laparoscopic technique, andpostoperative antibiotic treatment when the appendix was gangrenous or perforated.

FIG 1. Randomized trials of appendectomy vs antibiotics alone for the treatment of acute appendicitis. (Reprinted with

permission from Fitzmaurice GJ, McWilliams B, Hurreiz H, Epanomeritakis E. Antibiotics versus appendectomy in the

management of acute appendicitis. Can J Surg. 2011;54:43-53.)


Efficacy in the study group according to intention to treat was 48.0% (97 of 202). Eleven of 119(9.2%) patients who primarily received antibiotics had an appendectomy owing to clinicalprogression. The preoperative characteristics of these patients were similar to those of the patientswho fulfilled the antibiotic treatment. Of 250 surgically explored patients, 223 (89.2%) hadappendicitis. Primary treatment efficacy was 90.8% for antibiotic therapy compared to 89.2% forsurgical exploration analyzed per protocol. Major complications and total hospital cost for theprimary admission were both lower in the antibiotic treatment group.

One of the largest retrospective series reporting nonoperative management of appendicitis comesfrom Japan.60 In this retrospective study, Shindoh and colleagues reviewed their institutionalexperience with nonoperative management of appendicitis. In this report, 367 patients metinclusion criteria (right lower quadrant pain, WBC 4 9000 or CRP 4 1.0 mg/dL). The authorsdescribe the following 3 study groups: (1) initial operation or appendectomy, (2) nonoperativegroup, and (3) initial nonoperative group converted to surgery (failure). In the nonoperative groups,patients received antibiotics and were evaluated 24 hours later. If the physical examination orlaboratory parameters worsened, surgical management was considered. In this cohort, 143 (39%)underwent initial operation (group 1), whereas 224 (61%) were managed with initial antibiotictherapy. In the initial nonoperative group, 91 patients did not respond to antibiotics and underwentappendectomy. Factors predictive of failure included CRP (odds ratio [OR] 5.5, 95% CI: 1.94-17.29)and the presence of an appendicolith (OR 4.7, 95% CI: 1.15-24.46). Of note, in this study recurrenceof appendicitis was observed in 4.7% of patients initially managed nonoperatively.

FIG 2. Consort diagram. (Reprinted with permission from Hansson et al.59)


Conclusions

The data and available evidence regarding nonoperative management of acute appendicitis isprovocative. At this time, however, level I data to suggest this is an alternative treatment option arenot universally accepted. Despite the fact that appendectomy has been regarded as standardtreatment for appendicitis for more than 100 years, there have been reports of patients being managedsuccessfully without an operation. To date, there have been few randomized studies of nonoperativevs operative therapy for acute appendicitis, and none have been conducted in the United States. Yetthere is some suggestion that a select group of patients may be managed nonoperatively. At best, weshould consider the available data as hypothesis generating and not hypothesis confirming.

One of the inherent difficulties and biases in conducting a well-planned randomized clinical trialcenters on pathologic confirmation of appendicitis. On one hand, for those patients with ‘‘suspected’’appendicitis who receive antibiotics only, treatment successes may cause one to consider the underlyingdiagnosis (‘‘Is it really appendicitis?’’). On the other hand, the number of patients who undergo anegative appendectomy is not zero and exposure of these patients to surgical risks and complications isa valid concern. The report by Hansson and colleagues demonstrated a 3-fold increased rate ofcomplications in the appendectomy group when compared to the nonoperative, antibiotic only group.

The data presented herein are suggestive that in selected patients with acute, uncomplicatedappendicitis, antibiotic treatment seems to be an appropriate alternative to conventionalappendectomy. Multivariate analysis of patient characteristics failed to demonstrate any logisticmodel for inclusion or rejection of patients for the specified treatments. Furthermore, it confirmed that

FIG 3. Intraoperative image of simple acute appenditis. (Photo Courtesy Kuojen Tsao, MD.)


CRP is not a significant predictor in the assessment of the phlegmonous and gangrenous appendix,unlike total blood leucocyte count. Therefore most patients older than 18 years without obvious signsof intra-abdominal perforation can be offered antibiotic treatment as first-line therapy. Clinicalprogression and surgical judgment may then determine whether there is a real need for surgicalexploration in an expected subgroup of 5%-10% of all patients appearing with suspected or establishedappendicitis. The benefit would be a significantly reduced frequency of major complications related tosurgery. The possible drawbacks to treating acute appendicitis with antibiotics do not appear relevant,despite the well-recognized risk of increased environmental burden and antibiotic resistance; majorcomplications following unnecessary surgery seem a more pertinent risk to patients.

Another inherent problem with deciphering the issue of antibiotic therapy is the fact that gettingclinicians to agree upon a consensus definition for acute, uncomplicated appendicitis remainsproblematic. In all likelihood, there is an arbitrary cut-off or threshold by which certain patientsprobably have a milder form of the disease (Fig 3) and would likely respond to systemic antibioticsalone. Above this arbitrary threshold, antibiotic therapy is unlikely to be effective in eradicating theinfection (Fig 4). To resolve this dilemma, a few of these studies have completed multivariateanalyses and found that presence of the fecaliths is predictive of failure. Further studies are neededto create informed multivariate models that adjust for all of the important clinical covariates. Thiseffort may accurately predict which patients may or may not respond to systemic antibiotic therapyalone for the treatment of appendicitis.

Management of Complicated Appendicitis

In the United States, approximately 11 of 10,000 people will develop acute appendicitis over theirlifetime, with the typical age of onset between the ages of 11 and 19 years.61 Of these, an estimated2%-6% of patients will present with an appendiceal mass, either in the form of an inflammatoryphlegmon or abscess.62 The optimal management of acute appendicitis complicated by aninflammatory phlegmon or abscess remains controversial. There is no consensus in the surgicalliterature on whether to proceed immediately with appendectomy or initial nonoperativemanagement in this setting of complicated appendicitis. Another dilemma in the management ofappendicitis initially managed conservatively with antibiotics is whether or not to perform anappendectomy at a later date (interval appendectomy). The data are disparate regarding actualrecurrence rates of appendicitis following nonoperative management, but they are commonly

FIG 4. Intraoperative image of appendicitis with perforation and gangrenous tip. (Photo Courtesy Kuojen Tsao, MD.)

FIG 5. CT scan demonstrating appendiceal abscess containing air-fluid levels.


reported between 5% and 20%.63-65 In addition to recurrent appendicitis, a clinical concern in olderpatients who present with a cecal phlegmon is malignancy. In these cases, interval appendectomyallows the correct pathologic diagnosis to be made.66 The effect of these management decisions onduration of hospital stay, number of interventions, healthcare costs, and overall patient satisfactionmust be considered.

Appendiceal Abscess

Appendiceal abscess is commonly associated with delay in presentation, fever, leukocytosis, anda palpable mass in the right lower quadrant (Figs 5 and 6). The diagnosis is confirmed with CT or US.Management of these patients remains controversial with the traditional nonsurgical approach ofpercutaneous drainage and IV antibiotics with or without interval appendectomy vs immediateappendectomy and surgical drainage of the abscess. The evidence supporting both approaches is

FIG 6. CT scan demonstrating appendiceal abscess with rim-enhancing wall.


weak, as most studies are retrospective and often combine patients with appendiceal abscess andphlegmon into a single cohort called ‘‘appendiceal mass.’’ Several meta-analyses have beenperformed to try to identify differences between the 2 treatment strategies. Andersson andPetzold performed a meta-analysis on 19 retrospective studies from 1969-2005. The limitation ofthis study is the lack of uniform definition of appendiceal abscess vs phlegmon. Nevertheless, themeta-analysis revealed that nonsurgical treatment failed in 7.6% of patients (CI 3.2-12.0).Immediate appendectomy is associated with a higher morbidity with an OR of 3.3 (CI: 1.9-5.6).Based on these findings, the authors recommend nonsurgical management of patients withappendiceal abscess.67 Similar conclusions were reached by Simillis and colleagues whoperformed a meta-analysis of 16 retrospective studies and 1 nonrandomized prospective studyfrom 1969-2007 comparing immediate appendectomy (725 patients) vs nonsurgical treatment(847 patients).68 Immediate appendectomy is associated with greater incidence of ileus or bowelobstruction, abdominal or pelvic abscess, and wound infection compared to nonsurgicaltreatment. There was no difference in the overall duration of hospitalization, but the immediateappendectomy group required more reoperations. The higher rate of complications associatedwith immediate appendectomy has been attributed to greater inflammatory response to surgeryin the setting of infection, as well as the technical difficulty with inflamed tissue. Most of thestudies analyzed in these meta-analyses utilized open appendectomy techniques. The potentialdisadvantages of early operation may be mitigated by the laparoscopic techniques. Laparo-scopic appendectomy results in less local inflammation due to better visualization andinstrumentation.69

St. Peter and colleagues conducted a prospective randomized trial comparing immediatelaparoscopic appendectomy to nonsurgical treatment in 40 pediatric patients presenting withappendiceal abscess.70 Immediate laparoscopic appendectomy tends toward longer operative time(61 minutes vs 42 minutes) compared with interval laparoscopic appendectomy performed at 10weeks from initial presentation (Fig 7). The immediate appendectomy group had fewer health carevisits and few CT scans. However, there was no difference in recurrent abscess rate, total length ofhospitalization, or total charges. They conclude that immediate laparoscopic appendectomy is assafe as nonsurgical management. The safety of immediate laparoscopic appendectomy forappendiceal abscess is supported by several other retrospective or uncontrolled studies.71-74 Theinfectious complications of immediate appendectomy can be reduced by improved laparoscopictechniques, such as use of extraction bag, endostaplers rather than endoloops, and limited irrigationto avoid bacterial contamination.75,76

Appendiceal Phlegmon

The management of acute appendicitis complicated by an appendiceal phlegmon typicallyinvolves 1 of 3 treatment strategies. The first, and most commonly accepted, is initial treatment with

FIG 7. Results from pilot trial of appendectomy for perforated appendicitis with abscess. (Reprinted with permission from St

Peter et al.70)


broad spectrum antibiotics and IV fluids until the acute inflammation subsides; appendectomy isthen performed on an interval basis. Another strategy involves appendectomy upon initialpresentation. Lastly, following resolution of the acute inflammation with broad spectrum antibiotics,the patient is managed expectantly without interval appendectomy. Prospective data comparingthese strategies are sparse, with most systematic reviews drawing heavily upon retrospective data.

At present, there is no agreed upon approach for the management of an appendiceal phlegmon. Arecently published survey of a group of general surgeons in England found that 75% still favor intervalappendectomy following resolution of symptoms.77 Proponents for interval appendectomy state thatremoving the appendix is a technically easier operation once the acute inflammation subsides,potentially avoiding inadvertent injury to adjacent loops of involved bowel, as well as extendedresection of the cecum or ascending colon.66 Although the risk of recurrent appendicitis remains smallafter successful nonoperative treatment of an appendiceal phlegmon, proponents of intervalappendectomy state that the risk of interval appendectomy is also small and eliminates the possibilityof recurrent appendicitis.63 In a recent systematic review published by Hall and colleagues, 127 childrenwere managed without planned interval appendectomy.78 The incidence of recurrent appendicitisranged from 0%-42% in the 3 studies included in the review, with an overall risk of 20.5% (95% CI 14.3-28.4) (Fig 8). The complication rates following interval appendectomy were also published in thisreview, with an overall incidence of 3.4% (95% CI, 2.2-5.1) (Fig 9). The authors conclude that thelikelihood of recurrent appendicitis as well as the risk of complication after interval appendectomy areboth sufficiently low that the decision to proceed with interval appendectomy is typically based onclinical criteria. Unfortunately, these data are from retrospective studies; prospective data from arandomized trial comparing these 2 approaches will help further guide surgical management.

Interval Appendectomy

Interval appendectomy provides a tissue diagnosis when diagnostic uncertainty exists. This isparticularly important in adults because the differential diagnosis of an inflammatory mass in the rightlower quadrant can be quite extensive, with neoplastic etiologies of particular concern. In a systematicreview and meta-analysis by Andersson and colleagues, 2771 included patients were initially treatednonoperatively for an appendiceal phlegmon or abscess.65 On follow-up, 31 patients were found tohave a malignant diagnosis. In patients younger than 40 years with an appendiceal mass, only 4 werefound to have a malignant diagnosis on follow-up: 2 children had carcinoid of the appendix, a 26 yearold woman presented with an ovarian malignancy, and a 25 year old man presented with metastaticgastric cancer. The overall estimate of a malignant diagnosis was 1.2% (95% CI 0.6%-1.7%), with anincidence of 0.2% (95% CI 0.0%-0.05%) in children. Inflammatory bowel disease was established as adiagnosis during follow-up in 0.7% of patients (95% CI 0.2%-11.9%), with a higher incidence again seenin adults. Although primarily retrospective, these data underscore the need for follow-up, either withCT scan or colonoscopy, after successful treatment of an appendiceal phlegmon in adults.65

FIG 8. Incidence of recurrent appendicitis in individual studies included in this systematic review. Overall incidence 20.5%

(95% CI, 14.3-28.4) was calculated using binomial multilevel regression model. (Reprinted with permission from Hall et al.78)


The presence of an appendicolith associated with an appendiceal phlegmon deserves specialmention because its presence has been used as a guide to proceed with interval appendectomyfollowing successful nonoperative management. A retrospective cohort study published by Ein andcolleagues reviewed the outcomes of 96 pediatric patients with appendicitis who presented witheither an inflammatory mass or phlegmon and were initially managed nonoperatively by the staffsurgeon.79 Six patients who failed initial nonoperative management underwent appendectomy andwere excluded. Forty-one patients were scheduled for elective appendectomy by their surgeon andwere also excluded from analysis. The remaining patients were included in the study and theiroutcomes over a 2-year period were reported. Of these, 37% had an appendicolith and 63% did not.The overall recurrence rate for appendicitis was 42%; in patients with an appendicolith, therecurrence rate was 72% compared to 26% in patients without an appendicolith (relative risk of 2.8 inpatients with an appendicolith) (Table 5). The authors conclude that the presence of anappendicolith predicts failure of nonoperative management of peri-appendiceal phlegmon orabscess. It is important to note that the overall recurrence rate of appendicitis in this study is higherthan what is typically reported elsewhere in the literature, and this may influence the true effect ofan appendicolith on failure of nonoperative management. Unfortunately, there are no data from arandomized, prospective trial evaluating whether or not the presence of an appendicolith ispredictive of failure of initial nonoperative management of ruptured appendicitis with phlegmon orabscess. As such, any conclusions from this study should be viewed as hypothesis-generating for afuture randomized controlled trial.

In deciding whether or not to proceed with routine interval appendectomy following successfulnonoperative management of an appendiceal phlegmon or abscess, the effect of cost must also beconsidered. A cost analysis of interval appendectomy following successful nonoperative manage-ment of periappendiceal phlegmon or abscess was conducted by Raval and colleagues80 In thisstudy, a decision tree analysis was created with outcome probabilities obtained from literaturereview and cost estimates from the Healthcare Cost and Utilization Project Kids’ InpatientDatabase.81 It should be noted that the Kids’ Inpatient Database provides a conversion factor fortranslating total charges into costs. With an estimated probability of successful observation set at0.85, the cost of observation was calculated to be $3080.78 as opposed to $5034.58 seen in theinterval appendectomy arm. Using one-way sensitivity analysis, cost savings were observed up to a

FIG 9. Incidence of complications after interval appendectomy. Overall incidence 3.4% (95% CI 2.2-5.1). (Reprinted with

permission from Hall et al.78)

TABLE 5Effect of presence of appendicolith on recurrence

No. of patients Recurrence

No appendicolith 31 (63) 8 (26)

Appendicolith 18 (37) 13 (72)*

Total 49 21 (43)

Recurrence, values are presented as n (%).n P o 0.004.

Reprinted with permission from Ein SH, Langer et al.79


0.60 probability of successful observation (Fig 10). Stated another way, this represents a0.4 probability of recurrent appendicitis following observation, which is similar to the recurrencerate published by Ein and colleagues79 Thus, even in a patient population with a relatively highlikelihood of recurrent appendicitis, the cost analysis does not recommend proceeding with electiveinterval appendectomy.

Although prospective data on the management of periappendiceal phlegmon or abscess arelimited, 2 recently published randomized trials in children address the question of whether or not to

FIG 10. One-way sensitivity analysis of the probability of successful observation demonstrating a threshold of 0.60.

(Reprinted with permission Raval et al.80)


offer an appendectomy on initial presentation vs interval appendectomy82,83. It is important to notethat these trials include interval appendectomy as a treatment arm; foregoing appendectomyaltogether was not specifically investigated. In the study published by St. Peter and colleagues, 40children with appendicitis complicated by phlegmon or abscess were randomized to eitherimmediate appendectomy or initial nonoperative management followed by scheduled intervalappendectomy in 6 weeks.83 Of note, this is a pilot study in which an outcome variable was notdefined or used in a sample size calculation. The number of patients chosen to be enrolled into thestudy was based on the anticipated clinical volume over a study period of 2 years. Patients who wereoffered initial appendectomy had a longer operative time (20 minutes), fewer CT scans, and fewertotal healthcare visits. Otherwise, the total length of hospital stay, hospital charges, and recurrentintra-abdominal abscess rates were similar between the 2 groups.

Randomized Trial of Interval Appendectomy

A more robust randomized trial was conducted by Blakely and colleagues with 131 total patientsenrolled: 64 receiving initial appendectomy and 67 assigned to interval appendectomy.82 This studywas powered to detect a 5-day difference in return to normal activity and intention-to-treatanalyses were performed. The primary outcome of time to return to normal activity was chosen as itis readily measured and functions as a composite of many objective and subjective measures. In theprimary appendectomy group, time to normal activity was 13.8 [7.5] days (mean [standarddeviation]) vs 19.4 (8.7) days in the interval appendectomy group (P o 0.001). Of note, the relativerisk of any adverse effect associated with interval appendectomy was 1.86 (95% CI 1.21-2.87);


specific outcomes measured included intra-abdominal abscess, small bowel obstruction, unplannedreadmission, and recurrent appendicitis, and these were all seen with higher frequency in theinterval appendectomy group. The authors conclude that early appendectomy significantly reducedthe time away from normal activity and showed a significantly lower adverse event rate.

Future Directions

The optimal management strategy of an appendiceal phlegmon or abscess remains elusive as mostrecommendations are based on retrospective data, but recent randomized trials in children indicatethat early appendectomy results in faster return to normal activity with favorable complication rateswhen compared to interval appendectomy.82 Performing an interval appendectomy followingsuccessful nonoperative management with antibiotics and percutaneous drainage, as needed, has yetto be evaluated in a randomized trial. The clinical decision to perform an interval appendectomy inthe setting of an appendicolith is based on a retrospective cohort study published by Ein andcolleagues79 As stated previously, the incidence of recurrent appendicitis in this cohort was higherthan that seen in other series, and thus influences the recommendation to proceed with intervalappendectomy. Higher-quality evidence from prospective, randomized trials will help surgeonsdecide whether or not interval appendectomy in the setting of an appendicolith is appropriate.

Surgical Options for Acute Appendicitis

Laparoscopic vs Open Appendectomy

The open appendectomy was initially described by McBurney in 1894, and has remainedrelatively unchanged since its introduction. In 1983, Semm described a laparoscopic approach forremoving the appendix, advocating the advantages of laparoscopic surgery for one of the mostfrequently performed surgical procedures.84 Because open appendectomy typically involves a smallincision, short hospital stay, rapid return to normal activity, and low postoperative morbidity,demonstrating clear superiority of 1 approach over the other has been elusive. Although manyrandomized control trials comparing open vs laparoscopic appendectomy have been performed,many contain methodological flaws, including inadequate allocation concealment, lack of reportingof randomization method, failure of adequate blinding, lack of analysis by intention-to-treat, andincomplete follow-up data.85 That being said, these randomized trials, as well as systematic reviewsand meta-analyses of these studies, have provided a great deal of insight into the specific benefitsand drawbacks of each approach. In deciding between a laparoscopic and open approach, specificissues that must be considered include learning curve, operative time, associated morbidity, cost,pain, cosmesis, hospital length of stay, and time to return to normal activity. Unfortunately,measures vary across studies and conclusions have been inconsistent.

Predictors of Surgical Choice

A large retrospective review of prospectively acquired data comparing outcomes of laparoscopic vsopen appendectomy in 222 hospitals participating in the American College of Surgeons National SurgicalQuality Improvement Program (ACS NSQIP) was conducted by Ingraham and colleagues86 Over thecourse of 3 years (2005-2008), 32,683 patients in the database underwent appendectomy at theseinstitutions, with 24,969 performed laparoscopically (76.4%) and 7,714 (23.6%) performed using an opentechnique. Risk factors among patients undergoing laparoscopic vs open appendectomy were evaluated.Patients undergoing open appendectomy were more likely to be older, of normal weight, higher ASAclass, and more likely to have a variety of comorbidities; these are summarized in (Table 6). The analysisof 30-day outcomes following laparoscopic vs open appendectomy showed overall morbidity, seriousmorbidity, surgical site infection, and serious morbidity or mortality (Table 7) to be higher in patientsundergoing open appendectomy, although these complications were generally low in both groups.

TABLE 6Distribution of patient risk factors associated with 32,683 appendectomies performed at 222 NSQIP hospitals

Risk factor Open (n ¼ 7,714;23.6%)

Laparoscopic (n ¼24,969; 76.4%)

Total (n ¼32,683)

P value

Postoperative diagnosis o0.0001

Peritonitis or abscess 2,704 (26.89) 3,331 (13.34) 5,405 (16.54)

No perforation or peritonitis or abscess or

rupture

5,640 (73.11) 21,638 (86.66) 27,278 (83.46)

Age (mean 7 SD) 40.2 7 17.2 37.3 7 15.8 38.0 7 16.2 o0.0001

Gender o0.0001

Female 3,260 (42.26) 11,808 (47.29) 15,068 (46.10)

Male 4,454 (57.74) 13,161 (52.71) 17,615 (53.90)

Race o0.0001

White 4,809 (62.34) 16,527 (66.19) 21,336 (65.28)

Black 445 (5.77) 1,479 (5.92) 1,924 (5.89)

Other 2,460 (31.89) 6,963 (27.89) 9,423 (28.83)

Body mass index 0.0001

Normal 2,577 (33.41) 8,079 (32.36) 10,656 (32.60)

Overweight 2,266 (29.38) 7,372 (29.52) 9,638 (29.49)

Obese 1,603 (20.78) 5,827 (23.34) 7,430 (22.73)

Underweight 159 (2.06) 470 (1.88) 629 (1.92)

Unknown 1,109 (14.38) 3,221 (12.90) 4,330 (13.25)

ASA class o0.0001

1—No disturbance 2,850 (36.95) 9,541 (38.21) 12,391 (37.91)

2—Mild disturbance 3,890 (50.43) 13,146 (52.65) 17,036 (52.12)

3—Severe disturbance 878 (11.38) 2,128 (8.52) 3,006 (9.20)

4—Life threatening 96 (1.24) 154 (0.62) 250 (0.76)

Functional status o0.0001

Independent 7,532 (97.64) 24,620 (98.60) 32,152 (98.38)

Partially dependent 182 (2.36) 349 (1.40) 531 (1.62)

Diabetes 339 (4.39) 953 (3.82) 1,292 (3.95) 0.02

Renal failure (dialysis or acute renal failure) 26 (0.34) 39 (0.16) 65 (0.20) 0.002

Dyspnea 163 (2.11) 315 (1.26) 478 (1.46) o0.0001

Ascites 96 (1.24) 279 (1.12) 375 (1.15) 0.36

Alcohol use 213 (2.76) 510 (2.04) 723 (2.21) 0.0002

Current smoker within 1 y 1,627 (21.09) 5,418 (21.70) 7,045 (21.56) 0.26

Chronic obstructive pulmonary disease 106 (1.37) 181 (0.72) 287 (0.88) o0.0001

Pneumonia 12 (0.16) 18 (0.07) 30 (0.09) 0.03

Steroid use for chronic condition 81 (1.05) 175 (0.70) 256 (0.78) 0.002

Bleeding disorder 199 (2.58) 451 (1.81) 650 (1.99) o0.0001

Congestive heart failure 13 (0.17) 14 (0.06) 27 (0.08) 0.003

Hypertension requiring medication 1,369 (17.75) 3,561 (14.26) 4,930 (15.08) o0.0001

Coronary artery disease* 275 (3.56) 586 (2.35) 861 (2.63) o0.0001

Peripheral vascular diseasey 39 (0.51) 44 (0.18) 83 (0.25) o0.0001

Disseminated cancer 15 (0.19) 44 (0.18) 59 (0.18) 0.74

Weight loss (410% loss in last 6 mo) 8 (0.10) 43 (0.17) 51 (0.16) 0.18

Chemotherapy for malignancy within 30 d

preoperatively

22 (0.29) 54 (0.22) 76 (0.23) 0.27

Radiotherapy for malignancy in last 90 d 8 (0.10) 14 (0.06) 22 (0.07) 0.16


TABLE 6 (continued )

Risk factor Open (n ¼ 7,714;23.6%)

Laparoscopic (n ¼24,969; 76.4%)

Total (n ¼32,683)

P value

Neurologic disorderz 134 (1.74) 299 (1.20) 433 (1.32) 0.0003

Transfusion99,y 3 (0.04) 1 (0.00) 4 (0.01) 0.02

Preoperative sepsisz 2,955 (38.31) 8,795 (35.22) 11,750 (35.95) o0.0001

ASA, American Society of Anesthesiology; CVA, cerebrovascular accident; SD, standard deviation.n History of angina in the month prior to the index operation, history of myocardial infarction 6 mo before the index

operation, previous percutaneous cardiac intervention, or previous cardiac surgery.y History of revascularization or amputation for peripheral vascular disease and rest pain or gangrene.z CVA or stroke with or without neurologic deficit, history of transient ischemic attacks (TIA), hemiplegia, paraplegia,

impaired sensorium, quadriplegia.99 Transfusion 44 U packed red blood cells 72 h before surgery.y Significance calculated via Fisher’s exact test owing to small sample sizes.z Preoperative systemic inflammatory response syndrome or sepsis.

Reprinted with permission from Ingraham et al.86

TABLE 7Comparison of 30-day outcomes after laparoscopic vs open appendectomy at 222 NSQIP hospitals (2005–2008)

Outcomes Open (n ¼ 7,714;23.6%)

Laparoscopic (n ¼ 24,969;76.4%)

Total (n ¼32,683)

P value

Overall morbidity 682 (8.84) 1,114 (4.46) 1,796 (5.50) o0.0001

Serious morbidity 326 (4.23) 644 (2.58) 970 (2.97) o0.0001

SSI 513 (6.65) 814 (3.26) 1,327 (4.06) o0.0001

Serious morbidity or mortality 329 (4.26) 649 (2.60) 978 (2.99) o0.0001

Mortality 10 (0.13) 18 (0.07) 28 (0.09) 0.13

Individual morbities

Superficial SSI 300 (3.89) 314 (1.26) 614 (1.88) o0.0001

Deep incisional SSI 76 (0.99) 60 (0.24) 136 (0.42) o0.0001

Organ space SSI 133 (1.72) 448 (1.79) 581 (1.78) 0.68

Wound disruption 35 (0.45) 15 (0.06) 50 (0.15) o0.0001

Pneumonia 33 (0.43) 61 (0.24) 94 (0.29) 0.01

Unplanned intubation 30 (0.39) 36 (0.14) 66 (0.20) o0.0001

Pulmonary embolism 6 (0.08) 21 (0.08) 27 (0.08) 0.87

Failure to wean (on ventilator

448 h)

24 (0.31) 26 (0.10) 50 (0.15) o0.0001

Renal failure 10 (0.13) 21 (0.08) 31 (0.09) 0.26

Urinary tract infection 28 (0.36) 92 (0.37) 120 (0.37) 0.94

Neurologic event 1 (0.01) 8 (0.03) 9 (0.03) 0.70*

Cardiac arrest requiring CPR 7 (0.09) 8 (0.03) 15 (0.05) 0.03*

Myocardial infarction 5 (0.06) 3 (0.01) 8 (0.02) 0.02*

Bleeding 1 (0.01) 9 (0.04) 10 (0.03) 0.47*

DVT 9 (0.12) 11 (0.04) 20 (0.06) 0.03*

Sepsis or septic shock 167 (2.16) 288 (1.15) 455 (1.39) o0.0001

CPR, cardiopulmonary resuscitation; DVT, deep vein thrombosis; NSQIP, National Surgical Quality Improvement Program; SSI,

surgical site infection.n Utilizing Fisher’s exact test.

Reprinted with permission from Ingraham et al.86


Patients with complicated appendicitis had a significantly lower likelihood of developing a superficial ordeep incisional surgical site infection after laparoscopic appendectomy compared to open appendectomy;the likelihood of developing a deep organ space surgical site infection was higher in the laparoscopic


group. In uncomplicated appendicitis, the risk of both superficial and deep surgical site infection waslower in the laparoscopic group. Although this study evaluates a large number of patients across multiplehospital systems, the data are limited in that retrospective reviews cannot account for specific clinicalreasons for why 1 treatment was chosen over another, in this case laparoscopic vs open appendectomy.As such, these clinical decisions function as an uncontrolled confounder. Other limitations acknowledgedby the authors include generalizability of the results to non-NSQIP centers and data being limited to thosethat are collected in the NSQIP database. That being said, the authors conclude that the available evidencefrom the American College of Surgeons NSQIP database indicates that a laparoscopic approach isassociated with fewer complications when compared to an open procedure.

A Cochrane review of 67 trials comparing laparoscopic and open appendectomy was updated in2010.87 Of these studies, the vast majority (56) were conducted in adults. The interventions used inthe included trials were fairly similar; in laparoscopic cases, 3 trocars were typically used and theappendiceal stump was secured primarily with looped sutures, although 3 trials did use anendoscopic stapler. Antibiotic usage was stated as being the same in both groups for each includedtrial. Specific outcomes assessed by the included trials most frequently included operating time,complication rates, hospital stay, pain, and return to normal activity. It is important to note thatalthough all participants in the included trials were randomized to either laparoscopic or openappendectomy, the quality of these trials was judged to be moderate to poor, with many of theincluded studies having similar flaws. Specifically, only 42 trials took adequate measures to ensurethat the process of randomization was adequately concealed. Furthermore, protocol violations wereseen in nearly all trials with inconsistent analysis on an intention-to-treat basis.

Surgical Complications

Although a variety of complications were evaluated among the 67 trials in the meta-analysis, dueto inconsistencies in the definition and reporting of these complications, the authors only examined2 specific complications in their analysis: wound infection and intra-abdominal abscess. Followinglaparoscopic appendectomy, wound infections were approximately one half as likely whencompared to open appendectomy (OR 0.43; 95% CI 0.34-0.54). This is a highly significant differencebased on nearly 6000 appendectomies. Conversely, laparoscopic appendectomy was associated witha nearly 3-fold increase in the likelihood of intra-abdominal abscess when compared to an opentechnique (OR 1.77; 95% CI 1.14-2.76). These results are similar to the findings published in theNSQIP analysis by Ingraham and colleagues86 Operative time was 10 minutes longer for laparoscopicappendectomy (95% CI 6-15 minutes), but this difference has been getting smaller with morerecently published trials. Laparoscopic appendectomy was also associated with lower postoperativepain, shorter hospital stay (1.1 days; 95% CI 0.7-1.5), and faster return to normal activity (5 days;95% CI 4-7), although these results are highly heterogeneous and further study is warranted.Hospital and operational costs are higher with laparoscopic appendectomy, but again, these resultsare strongly heterogeneous. The authors conclude that laparoscopic appendectomy confers manybenefits over open appendectomy, and should be strongly considered as the preferred approachwhere surgical expertise is appropriate and equipment is available and affordable.

Conclusions

The question of whether or not appendectomy should be performed via an open or laparoscopictechnique has been inherently difficult to answer because both approaches offer similar advantages,namely, a small incision, low incidence of complications, a short hospital stay, and rapid return tonormal activity. Although multiple randomized trials and meta-analyses of these trials have beenconducted and published, the data indicate that the choice of surgical approach ultimately remainsup to the surgeon. As stated in the Cochrane review, is avoiding 3 superficial surgical site infectionsfor 1 intra-abdominal abscess a reasonable choice? As experience with laparoscopic appendectomyincreases and the equipment becomes more ubiquitous, the estimated complication profiles of bothoperations will become more accurate and precise, and this question can be suitably answered.


Pediatric Appendectomy

Acute appendicitis is one of the most common surgical diagnoses in pediatrics, with an estimatedincidence of 59,000-70,000 children per year in the United States.88,89 Appendicitis occurs in all agegroups, but is rare in younger children. Although the highest incidence is in older children, with 25cases per 10,000 pediatric patients per year between the ages of 10 and 17 years, there is a reportedrate of 1-2 cases per 10,000 in children younger than 4 years of age. In most cases in the UnitedStates, this results in an appendectomy in an estimated 7%-8% of the general population.7,43,90,91

Subsequently, appendectomy is one of the most common operations performed in children.

Prognosis

In general the prognosis for pediatric appendicitis is excellent. The mortality rate for appendicitis is0.1%-1% with the highest proportion in younger children.88,92 Death in infants and neonates is mostlylikely due to (1) failure to recognize disease due to its clinical presentation, which is similar to othercommon conditions in this age group; and (2) the inability of the younger patient to communicateabdominal pain or to manifest systemic symptoms, such as fever. However, there remains significantmorbidity and at the time of diagnosis, the rate of perforated appendicitis has been estimated up to 30%.93

For the same reasons attributed to higher mortality, the rate of perforation has been reported as high as80%-100% for children younger than 3 years, compared with 10%-20% in children 10-17 years of age.88,92

In general, the diagnosis and treatment strategies for pediatric acute appendicitis are not much differentcompared to adult therapies. Appendectomy is indicated based on the diagnosis of acute appendicitiswhich, in most cases, can be made clinically. Utilizing history from the patient or caretaker or both, as wellas physical signs of localized peritonitis in the right lower quadrant of the abdomen, acute appendicitisshould be strongly considered. In equivocal cases, adjunctive imaging such as US or computerizedtomography (CT) has proven to be effective.94 With increased utilization of routine imaging studies, thenegative appendectomy rate has decreased to 2%-3% without increasing the perforation rate.93,95

Challenges in the treatment of acute appendicitis are generally the same in adult and pediatricpatients. Key issues regarding diagnosis,35,39 surgical technique,96,97 and antibiotic therapy98,99

remain unanswered for all patient populations. These specific issues related to the treatment ofacute appendicitis are addressed elsewhere in this issue. However, there are specific considerationsfor pediatric appendectomy that remain controversial. These include the increasing adoption ofsingle-incision or single-port laparoscopic appendectomy (SILS) and the initial nonoperativemanagement of acute appendicitis with or without subsequent interval appendectomy.

The surgical treatment of acute appendicitis has evolved over the last 2 decades. SinceMcBurney’s first description in 1894,100 the transverse or oblique right lower quadrant incision forappendectomy is the incision of choice for the open approach in children. The abdominal musclesare split with the mesoappendix divided prior to excision of the appendix at the base. Theappendiceal stump can be closed with a simple ligation, ligation with inversion using a purse-string,or to inversion without ligature. The classic open appendectomy approach described by McBurneyis still widely utilized in children, especially in younger patients with thin body habitus.

In recent years, laparoscopic appendectomy has gained wide adoption and has been shown toimprove patient outcome in multiple reports.101-106 Some authors have suggested that theminimally invasive technique is the preferred approach among pediatric surgeons,107 whereasothers have demonstrated heterogeneity in surgical approaches.108 Although there remains apaucity of high-level clinical evidence to support this superior efficacy,87,109 it is indisputable thatlaparoscopic appendectomy is widely utilized and, at times, expected by patients and their familiesin the surgical treatment of acute appendicitis in children.

Laparoscopic Appendectomy

The first case of laparoscopic appendectomy was described by Semm in 1983, and was carried outas an incidental procedure during a pelvic exploration.84 In the last 30 years, controlled studies and


meta-analysis in adult patients have demonstrated advantages with laparoscopic appendectomy,including fewer wound infections, faster return to normal activity, and decreased length ofhospitalization.102,104 However, not until the 1990s was laparoscopic appendectomy established asa reasonable approach in the treatment of pediatric acute appendicitis.101,105 The reportedadvantages of laparoscopic appendectomy, compared to open surgery in children, are similar tothose in adults which include shorter hospitalization, fewer wound infections, earlier return tonormal activity, and better cosmesis.101,103,105,110-113

The standard approach to laparoscopic appendectomy in children usually involves a 3-trocartechnique. A 10- to 12-mm cannula is placed in the umbilicus to allow the passage of laparoscopicinstruments, the telescope, a ligation device such as a stapler, and the retrieval of the appendix. Two5 mm cannulae are then placed in the left lower quadrant and midline immediately over the pubis.Various methods, such as endoscopic clips, endoscopic staplers, or thermocoagulating devices,can be used for division of the mesoappendix.101,105,114 Similarly, the base of the appendix can beligated inside the abdomen with endoloops, endoscopic sutures, or staplers, or can be securedextracorporeally.105,114,115

Single-Incision or Single-Port Laparoscopic Appendectomy

In the evolving era of ‘‘scarless surgery,’’ SILS has been utilized for appendectomy. A single-incision laparoscopic-assisted appendectomy for acute appendicitis was first reported in adultspatients in 1992.116 Soon thereafter, this surgical approach began to be reported in children, withthe first reports utilizing a single umbilical incision with a laparoscopic-assisted appendectomy, inwhich the appendectomy was performed after exteriorization through the umbilical incision.117

Since then, several techniques under the auspices of SILS have been utilized including natural orificetransluminal endoscopic surgery and many variations of single-incision techniques.118-121

In general, there are various approaches to SILS for appendectomy ranging from single-port SILSwhich utilizes conventional or specialized instruments through a single skin incision, without regardto number of fascia incisions122-126 to a single-incision, laparoscopic-assisted operation in which theappendix is exteriorized and open techniques are utilized.122,124,127 The touted advantages of theSILS approach to appendectomy are similar to general laparoscopy compared to open operations,including less pain, faster recovery, and better cosmesis. However, critics countered these withconcerns about increased costs, longer operation times, and higher complication rates.124

Unfortunately, comparative evidence for SILS appendectomy in children has been limited despiteits widespread adoption into clinical practice. In adult studies comparing SILS with conventional3-port laparoscopic appendectomy, advantages in cosmetic outcomes were at the cost of longeroperation times and substantial early postoperative pain.123 Oltmann and colleagues128 reportedthat SILS with appendectomy is feasible and safe in the pediatric population. Although operatingtimes were longer than the conventional 3-port laparoscopic appendectomy, the authors suggestedthese should improve with better instrumentation and experience. St. Peter and colleagues127

reported on the only randomized control trial comparing SILS-assisted appendectomy toconventional 3-port laparoscopic appendectomy in 160 children with nonperforated acuteappendicitis. Utilizing an extracorporeal appendectomy, there was a nonsignificant differencein wound infection rates of 3.3% for SILS patients compared to 1.7% for conventional laparoscopy.Although there was a statistically significant difference in operative time between the 2 approaches,the SILS technique was only 5.4 minutes longer (29.8 7 11.6 vs 35.2 7 14.5 minutes).The investigators suggested that the difference was not clinically relevant and both techniqueshad comparable outcomes.

Clinical evidence that supports the laparoscopic approach for complicated (perforated or intra-abdominal abscess) appendicitis remains controversial. The concern over greater incidence of intra-abdominal abscess following the laparoscopic approach was reported in some studies129-131 but notsupported by others.110,113 Because of the increased morbidity associated with complicated disease,some surgeons have opted for an initial nonoperative approach.127,132,133 Using nonoperativetreatment for complicated appendicitis followed by interval appendectomy obviates the need to


manage the inflammatory environment in the acute stage. Such a strategy has been shown to besuccessful in treating most of the cases of complicated appendicitis with shorter hospitalization,lower charges, and lower morbidity.134,135

Pediatric Interval Appendectomy

Although early appendectomy remains the accepted conventional treatment for simple acuteappendicitis in adults and children, the treatment strategy for complicated disease, such asperforated appendicitis and appendiceal mass, is controversial.134-138 With early appendectomy,patients undergo an urgent appendectomy within the first 24 hours of hospitalization, and any intra-abdominal abscess is drained during the operation. Alternatively, with interval appendectomy, theappendectomy is planned for 6-8 weeks after the initial diagnosis, after the patient has beendischarged and is back to normal activity. Intra-abdominal abscesses are percutaneously drained,if possible. Several retrospective studies have reported that interval appendectomy has shownthe benefits of reducing major complications, fewer wound infections, and shortening thehospital stay, as well as decreasing the overall cost of treatment.68,134,135,139 The need and timingfor interval appendectomy at 2-3 months following initial medical management remainsunclear.132,134

Recent evidence has shown that acute appendicitis can be treated successfully nonoperatively inadults and children.58,140-142 Two meta-analyses have demonstrated that conservative treatmentwith antibiotics only is associated with a lower risk of complications without differences in length ofhospitalization.68,143 However, the success of initial nonoperative treatment of complicatedappendicitis has stimulated some surgeons to question the need for subsequent intervalappendectomy. Some have suggested that interval appendectomy is unnecessary.78,144,145 Otherssupport the need for interval appendectomy based on the risk of recurrent appendicitis.142,146

Conclusion

Appendectomy is one of the most common surgical procedures in children. Evolution of theclinical practice in the treatment of acute appendicitis in children has resulted in an extremely lowmortality rate. As such, clinical research has focused on reduction in morbidity. Despite thefrequency of acute appendicitis in children, there remains a paucity of evidence-based treatmentguidelines and lack of consensus on treatment strategies.

Management of the Unanticipated Appendiceal Neoplasm

An unanticipated appendiceal neoplasm may be encountered at any elective or emergencyabdominal operation. It is estimated that nearly 50% of cases manifest as appendicitis, but variablepresentations have also been reported.147 The pathology and behavior of appendiceal neoplasms arediverse, which only complicates the confusing classification and terminology.148 Increasingly, anappendiceal neoplasm may be suspected on radiological cross-sectional imaging for diagnosis orstaging of abdominal disease. In a number of cases, an appendiceal neoplasm is discovered onhistopathologic analysis of an appendectomy specimen. Unfortunately, these factors lead todiagnostic and therapeutic challenges, particularly for those surgeons who provide predominantlyemergency surgical services. The aim of this review is to summarize the incidence, classification,presentation, and management of the common appendiceal neoplasms. Algorithms to assisttherapeutic decisions and management of unexpected appendiceal neoplasms will be discussed.

Appendiceal Neoplasms

Embryologically, the appendix arises as a small diverticulum of the cecum, and any neoplasticpathology of the colon can occur in the appendix.149 Appendiceal neoplasms are thought to account

TABLE 8Classification of appendiceal neoplasms

Primary

Epithelial

Benign

Hyperplastic polyp and diffuse mucosal hyperplasia

Serrated adenoma

Colonic type adenomas

Malignant

Low-grade mucinous neoplasms

Adenocarcinoma or high-grade mucinous neoplasms

Nonepithelial

Carcinoid tumors

Classical carcinoid

Goblet cell carcinoids or adenocarcinoids

Mesenchymal tumors

GIST

Neuroma

Leiomyoma or sarcoma Kaposi’s sarcoma lymphoma

Secondary

Ovarian

Colonic

Rare, such as melanoma

GIST, gastrointestinal stromal tumor.

Reprinted with permission from Murphy et al.157


for 0.4%-1% of all gastrointestinal malignancies.150 Their clinical presentation is unpredictable, asmost manifest with appendicitis as a consequence of luminal obstruction. Some appendiceal lesionsare obvious at operation, but a number are found only on histopathologic analysis of appendectomyspecimens. In reports of several large series, appendiceal neoplasms were found in 0.7%-1.7%of specimens.151

The classification of appendiceal neoplasms has been controversial.152-154 Although severalclassifications have been suggested, lack of standard terminology for both benign and malignantlesions has hampered valid comparisons between studies.155 Several investigators have proposed asimple classification of epithelial appendiceal neoplasms.156,157 This classification schema includescarcinoid neoplasms, resulting in an inclusive classification system for appendiceal neoplasms(Table 8).

Nonepithelial Tumors of the Appendix

Carcinoid Tumors

Carcinoid tumors can arise from the neuroendocrine cells of any part of the gastrointestinal tract,and are the most common primary neoplasm in the appendix.158,159 The annual incidence ofneuroendocrine tumors of the appendix is 0.16 per 100,000, with a comparable frequency in menand women.160 Little is known about the epidemiology of these tumors and associated riskfactors.161 Appendiceal carcinoids are detected in 0.3%-0.9% of appendectomy specimens, andcommonly present as appendicitis (50% of cases) or as an incidental lesion at appendectomy,laparotomy, or laparoscopy.162 A carcinoid of the appendix is most likely to be located in the tip ordistal third of the appendix, and is usually a small, round, well-demarcated, globular swelling.163,164

These features may help to identify an appendiceal tumor found at operation as a carcinoid and mayassist management decisions.

Small carcinoids of the appendix rarely metastasize, unlike those in other locations in thegastrointestinal tract. Adverse prognostic features with an increased risk of metastasis includetumors greater than 2 cm and meso-appendiceal extension.165 Most carcinoids are small and can be


treated by simple appendectomy.166 There is agreement, however, that a right hemicolectomyshould be performed if carcinoids are larger than 2 cm or when there is involvement of the base ofthe appendix or the mesoappendix.167 Data from the National Cancer Institute’s Surveillance,Epidemiology and End Results (SEER) database from 1973-2004 demonstrated the distribution oflocalized, regional, and distant disease to be 60%, 28%, and 12% respectively.160 However, data fromother sources have demonstrated higher 5-year survival rates (up to 94%) for those patients withlocalized disease.168

Surgical therapy remains the only potentially curative treatment for well-differentiated carcinoidtumors of the appendix. Small (o1 cm) carcinoid tumors confined to the tip of the appendix that arecompletely excised can be considered cured if there is no evidence of lymphovascular invasion.However, there are a few situations that require additional consideration. Approximately 10% ofpatients will be found to have the base of the appendix involved with tumor. Most appendicealcarcinoids are typically considered benign; however, deep invasion or regional metastases have beenreported among tumors 1-2 cm.167 Careful pathologic examination of the specimen is mandatory.

Epithelial Lesions of the Appendix

Malignant Epithelial Lesions

Malignant epithelial tumors of the appendix range from low-grade mucinous neoplasms toinvasive adenocarcinomas. This range incorporates a spectrum of disease, often difficult to classifyhistopathologically, with only the clinical behavior over time truly defining the biologic nature of thetumor. Ronnett and colleagues have classified appendiceal mucinous neoplasms into 3 groups:disseminated peritoneal adenomucinosis, peritoneal mucinous carcinomatosis, and an intermediategroup.169,170 Others have classified mucinous neoplasms into low-grade mucinous neoplasms andadenocarcinoma (high-grade neoplasms).171,172 In light of the difficulties regarding pathologicclassification and uncertain clinical behavior, it is recommended that all patients with anappendiceal neoplasm be discussed at a multidisciplinary gastrointestinal oncology conference.

Low-Grade Mucinous Neoplasms

A variety of terms have been used to describe appendiceal mucinous lesions that are not franklymalignant, including cystadenomas, mucinous tumor of unknown or uncertain potential,disseminated peritoneal adenomucinosis, malignant mucocele, and ‘‘borderline’’ appendicealtumors.150,160 These tumors may spread in the peritoneal cavity, producing mucinous intraper-itoneal ascites, resulting in pseudomyxoma peritonei (PMP).148,173 The precise etiology andpathophysiology of PMP is a matter of some debate. Some suggest that mucinous material outsidethe appendix, including mucin-producing cells, arises from a ruptured adenoma, and that onlyif there is histologic evidence of infiltrative invasion should the condition be categorized as‘‘adenocarcinoma.’’170,174,175 An alternate view considers any production of mucin by epitheliumoutside the appendix to indicate a mucinous carcinoma, which may vary from low-grade to high-grade mucinous adenocarcinoma.176

Many institutions use the term ‘‘low-grade mucinous neoplasm’’ to describe lesions with scantmucinous epithelium that demonstrate varying degrees of cellular atypia in conjunction withextracellular mucin accumulation.156 Some cases show evidence of extra-appendiceal mucin withor without obvious rupture of the appendix. These lesions often present with acute appendicitis or aright lower quadrant mass.177,178 Others present with abdominal swelling secondary to mucin, ormucin in a hernia sac.179,180 (Fig 11). Many cases are incidental findings at laparotomy, laparoscopy,or other radiologic imaging.181 The prognosis of these neoplasms is dependent upon whether theyhave perforated and whether mucin and epithelial cells are present outside the appendix.182,183

Perforated low-grade mucinous neoplasms with extra-appendiceal mucin almost inevitablyresult in PMP, although this phenomenon may take several years to manifest clinically. Such

RD: 380Tilt: 0mA: 487KVp: 120Acq no: 1

FFS

Z: 1C: 50

W: 400DFOV:38x38cm

RR LL

FIG 11. CT scan demonstrating mucocoele (identified by arrow) in right lower quadrant.


perforated tumors are best treated with macroscopic tumor removal (cytoreduction) combined withan intraperitoneal chemotherapy regimen.184-187 The rationale for this intensive treatment is basedon the likely pathophysiology of PMP. As an appendiceal adenoma enlarges and occludes theappendiceal lumen, it leads to distention with mucinous tumor cells and mucus. Eventually,perforation occurs as the primary lesion continues to grow slowly, but due to appendiceal ruptureepithelial cells within the peritoneal cavity also proliferate and produce large quantities of mucus.

Due to the rarity of mucoceles and mucinous appendiceal neoplasms, the epidemiology of PMP isnot well understood. A recent population-based study from The Netherlands examined 167,744appendectomy specimens.188 A mucocele or epithelial neoplasm was identified in 1482 patients(0.9%). A benign lesion (including mucocele) was found in 1 of every 150 appendices (0.7%) andmalignancy in 1 of every 460 appendices (0.2%). One of every 163 resected appendices (0.6%)contained an epithelial neoplasm: 56% mucinous and 44% nonmucinous. The mucinous epithelialneoplasms were benign in 73% and malignant in 27%, whereas this distribution was 53% vs 47% forthe nonmucinous epithelial neoplasms. One of 11 patients (9%) with a primary epithelialappendiceal lesion (including mucocele) developed PMP. The chance of developing PMP wassignificantly higher in patients with a mucinous epithelial neoplasm (20%) as compared withpatients with either a mucocele (2%) or a nonmucinous epithelial neoplasm (3%) (P o 0.001).

Appendiceal Adenocarcinoma

Appendiceal adenocarcinomas are rare, with reported incidences varying from 0.08%–0.1% of allappendectomies.189 These patients usually present with right lower quadrant pain or an abdomino-pelvic mass, and up to 88% may present with symptoms consistent with appendicitis.190 The extentof disease may be such that an appendiceal primary is impossible to confirm or exclude even atlaparotomy or autopsy, and extensive investigations are frequently inappropriate with suchadvanced disease. Reported series of appendiceal adenocarcinoma are difficult to compare, asterminology and classification of these lesions have not been consistent.191 Adenocarcinoma of theappendix has traditionally been treated by right hemicolectomy, with improved survival in patientsundergoing right hemicolectomy compared with appendectomy alone.192,193

Incidental Finding at Operation

An appendiceal tumor may be encountered during an operation for appendicitis or an abnormalappendix may be noted incidentally, during an open or laparoscopic procedure (see algorithm in

Tumor identified during operation

Evidence of perforation

Tumor<2cm

Base of appendix/meso-

appendix univolved

Evidence of peritoneal mucin/mucinousascites

If appendectomy not possible, tissue biopsy,

peritoneal lavage

Right hemicolectomy

Right hemicolectomy

Appendectomy+tissue biopsy

Appendectomy+tissue biopsy

No

No

No

No

Yes

Yes

Yes

Yes

Yes

FIG 12. Algorithm for the management of unanticipated appendiceal tumors.


Fig 12). Initial assessment of the appendiceal tumor should include noting its size and identifyingfeatures typical of one of the more common appendiceal neoplasms (solid vs cystic consistency).In addition, inspection and palpation of the appendiceal base and mesoappendix, as well asan assessment of whether or not the appendix is perforated, provides additional criticalinformation.

The operating surgeon should look carefully for evidence of extra-appendiceal disease, suchas mucin (which should always be sent for cytologic analysis), local lymphadenopathy, orobvious disseminated metastatic spread. Sites of possible primary disease (including the ovaries infemale patients) and synchronous colorectal malignancies should also be sought. Laparoscopyfacilitates an examination of the peritoneal cavity, although it lacks the tactile input achievable atlaparotomy.194

If the tumor is confined to the appendix, smaller than 2 cm, without evidence of meso-appendiceal involvement, and not involving the base of the appendix, appendectomy is appropriatetreatment.195 Rarely will definitive pathology require further surgical intervention. The evidenceexamining the role of laparoscopic appendectomy for the resection of these neoplasms is limited. Ifthere is concern at laparoscopy, particularly if an appendiceal neoplasm is greater than 2 cm, theprocedure should be converted to a standard laparotomy.196 Midline ports should be consideredbecause these locations facilitate a much easier excision should a secondary procedure be performedat a later date. Extreme care should be taken to ensure the mesoappendix is resected satisfactorilyand that there is an extensive washout of the peritoneal cavity and surgical wounds.

It is of critical importance that appendiceal neoplasms are removed intact. This can bechallenging with a large mucin-filled appendix, and may require a larger incision or conversion toan open operation. If the appendix has ruptured just before removal or during the operation,it is important to remove all free mucin and perform a thorough peritoneal lavage. Such patients,and those who present with a perforated mucinous neoplasm, without evidence of anyextra-appendiceal spread, are at risk of developing PMP and require careful postoperativesurveillance. An initial CT scan of the abdomen and pelvis as well as the following tumor markersprovides baseline measurements: carcinoembryonic antigen, cancer antigen CA-125, andCA-19-9.


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