Current de Apendicitis

Current Problems in Surgery 50 (2013) 5486
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Current Problems in Surgery

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Acute Appendicitis: Controversies in Diagnosis and 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 for appendicitis in the United States per year.1 Although the clinical scenario of periumbilical pain migrating to the right lower quadrant is classically associated with acute appendicitis, the presentation is rarely typical and the diagnosis cannot always be based on history and physical examination alone. Diagnostic errors are common, with over-diagnosis leading to negative appendectomies and with delays in diagnosis leading to perforations. The misdiagnosis of appendicitis has signicant economic ramications; in a nationwide study of administrative data over 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 patients with suspected appendicitis should all start with a thorough history and physical examination. The Surgical Infection Society (SIS) and Infectious Diseases Society of America (IDSA) published guidelines that recommend the establishment of local pathways for the diagnosis and management of acute appendicitis.3 The guidelines note that the combination of clinical and laboratory ndings of characteristic abdominal pain, localized tenderness, and laboratory evidence of inammation will identify most patients with suspected appendicitis.3 Other diagnostic strategies may include radiologic imaging or the use of scoring systems with or without computer support. Ultimately, the gold standard for a positive diagnosis is the histopathologic conrmation of appendicitis, although standard criteria are lacking.4 A negative diagnosis may be conrmed by intra-operative ndings or clinical follow-up or both. There are different measures for evaluating a diagnostic test or strategy (Table 1). Sensitivity refers to the proportion of true positive tests among all patients who have the disease (A/[A C]). Specicity refers to the proportion of true negatives among all patients who do not have the disease (D/[B D]). Highly sensitive tests rule disease out, whereas highly specic tests rule disease in. Accuracy refers to the proportion of true positives and negatives among all patients tested ([A D]/ [A B C D]). The positive predictive value of a test refers to the proportion of true positives among all patients who test positive (A/[A B]), whereas the negative predictive value refers to the proportion of true negatives among all patients who test negative (D/[C D]). The predictive values of a test should be applied with caution to local patients as they depend upon the incidence
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C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486
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TABLE 1 2 2 Table for calculating sensitivity, specicity, predictive values, and likelihood ratios Disease positive Test positive Test negative True positives (A) False positives (C) A C Disease negative False negatives (B) True negatives (D) B D A B C D A B C D
TABLE 2 Named clinical signs associated with acute appendicitis Name Dunphys sign Obturator sign Psoas sign Rovsings sign Description Increased right lower quadrant pain with coughing Increased pain with exion and internal rotation of the hip Increased pain with passive extension of the right hip (can be elicited with the patient lying on the left side) Increased right lower quadrant pain during palpation in the left lower quadrant
(frequency of new cases) or prevalence (frequency of all cases) of the disease in the population tested. Clinicians order diagnostic tests because the results may change the management of the patient. In the setting of abdominal pain, if the test suggests a high probability of acute appendicitis, then the clinician may choose to perform an appendectomy. If the test suggests a low probability of acute appendicitis, then the clinician may choose to discharge the patient. Likelihood ratios (LRs), which are calculated from sensitivity and specicity, assist the clinician in calculating these post-test probabilities. LR refers to the ratio of the chance that the test would be positive in patients with the disease vs the chance that the test would be positive in patients without the disease. LR similarly refers to the ratio of the chance that the test would be negative in patients with the disease vs the chance that the test would be negative in patients without the disease. A test with an LR of 1 does not offer any new information.5 A disease is strongly ruled in if the LR is greater than 10 and strongly ruled out if the LR is less than 0.1. LRs unlike predictive values are not affected by disease prevalence, and they can be applied to individual patients to inform clinical decision-making.
History and Physical Examination Despite advances in diagnostic tests, appendicitis remains a clinical diagnosis. Clinical symptoms elicited by the history may include fever, nausea, vomiting, anorexia, migration of pain to the right lower quadrant, and aggravation of pain by movement. Physical examination may reveal signs of peritoneal irritation in the right lower quadrant or diffusely. Rectal examination may reveal tenderness. Furthermore, there are a variety of named signs that may be associated with appendicitis depending upon the location of the inamed appendix (Table 2) (ie, pain caused by passive extension of the hip caused by a retrocecal appendix irritating the iliopsoas muscle or the psoas sign). The signs and symptoms described above are common and nonspecic; each individual sign and symptom is only weakly predictive of appendicitis (Table 3).4 Furthermore, the differential diagnosis for right lower quadrant abdominal pain is wide and varies with age and gender. When signs and symptoms were compared between children and adults, they were similarly predictive of appendicitis, with the exception of right lower quadrant pain which had a much higher LR in adults than in children.6,7 Another limitation of relying on clinical ndings alone is that elicitation of physical signs is subjective; multiple studies have demonstrated poor inter-rater reliability between
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TABLE 3 Sensitivities, specicities, and likelihood ratios for common clinical symptoms, signs, laboratory values, and radiologic tests (95% condence intervals provided in parentheses if available) Sensitivity History (symptoms) Fever4 Fever6 (children) Anorexia4 Anorexia (children)6 Vomiting4 Vomiting (children)6 Right lower quadrant pain (adults)7 Right lower quadrant pain (children)6 Pain migration4 Pain migration (children)16 Physical examination (signs) Rebound tenderness4 Rebound tenderness (children)6 Guarding or rigidity4 Psoas sign4 Laboratory values WBC ( 109/L) Z 104 WBC 4 14.9 or 4 10 (children)6 WBC ( 109/L) Z 154 WBC 4 14.9 or 4 15 (children)6 Proportion of polymorphonuclear cells (%) 4 75% CRP level (mg/L) 4 10 CRP level (mg/L) 4 20 Radiologic tests Ultrasound (adults)25 Ultrasound (children)25 CT (adults)25 CT (children)25 Scoring systems Alvarado ( Z 7)6 Pediatric Appendicitis Score ( Z 6)42 Ruptured appendicitis scoring system (in children, Z 4)35 Ruptured appendicitis scoring system (in children, Z 7)35 83% 88% 94% 94% (78%-87%) (86%-90%) (92%-95%) (92%-97%) 93% 94% 94% 95% (90%-96%) (92%-95%) (94%-96%) (94%-97%) Specicity LR LR
0.81
0.53
1.64 (0.89-3.01) 1.2 (1.1-1.4) 1.27 (1.14-1.41) 1.4 (1.2-1.6) 1.63 (1.45-1.84) 1.4 (1.3-1.6) 7.31-8.46 1.2 (1.0-1.5) 2.06 (1.63-2.60) 1.9 (1.4-2.5) 1.99 3.0 2.36 2.31 2.47 2.0 3.47 1.7 2.44 1.97 2.39 12 15 16 19 4.0 (3.2-4.9) 2.4 (2.0-2.8) 4.9 11.3 (1.61-2.45) (2.3-3.9) (1.76-3.15) (1.36-3.91) (2.06-2.95) (1.3-2.9) (1.55-7.77) (0.83-3.4) (1.60-3.74) (1.58-2.45) (1.67-3.41)
0.61 (0.49-0.77) 0.53 (0.29-0.97) 0.59 (0.45-0.77) 0.57 (0.44-0.73) 0.75 (0.69-0.80) 0.57 (0.47-0.69) 0-0.28 0.56 (0.43-0.73) 0.52 (0.40-0.69) 0.72 (0.62-0.85) 0.39 0.28 0.70 0.85 0.26 0.22 0.81 0.77 0.24 0.32 0.47 0.2 0.1 0.06 0.06 0.20 (0.09-0.41) 0.27 (0.20-0.37) 0.1 0.33 (0,32-0.48) (0.14-0.55) (0.61-0.80) (0.76-0.95) (0.18-0.36) (0.17-0.30) (0.69-0.95) (0.52-1.1) (0.11-0.50) (0.20-0.51) (0.28-0.81)
82% 92% 68%
65% 81% 94%
trainees and attending physicians, as well as between subspecialists.8,9 For example, Yen and colleagues reported that the inter-rater reliability for several common clinical ndings such as rebound tenderness and clinical diagnosis of peritonitis was poor to moderate between pediatric emergency medicine physicians and senior surgical residents.8 However, when used in combination with laboratory values, the diagnostic utility of the clinical ndings increases signicantly.
Laboratory Values Laboratory values that have been associated with acute appendicitis include: leukocytosis, left shift, and elevated markers of inammation such as C-reactive protein (CRP) and erythrocyte sedimentation rate (Table 3).4,6 As with the clinical symptoms and signs, each individual laboratory test value is only weakly discriminatory and predictive of acute appendicitis.4 However, combinations of clinical ndings and laboratory values or combinations of multiple laboratory values are more discriminatory and predictive.4 For example, the presence of guarding or rebound and a white blood cell (WBC) count of greater than or equal to 10 109/L has an LR of 11.34 (95% condence interval
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[CI] 6.65-19.56), whereas the absence of both of these variables has an LR D of 0.14 (95% CI 0.080.24).4 A meta-analysis by Anderson revealed that the greatest discriminators and predictors of acute appendicitis included a history of migration of pain, clinical ndings of peritoneal irritation, and laboratory values reecting an inammatory response (ie, CRP).4 There have been numerous studies evaluating other potential serum and urinary markers of appendicitis, including but not limited to inammatory cytokines such as serum interleukin-6, interleukin-8, and tumor necrosis factor alpha10,11; serum neutrophil proteins such as lactoferrin and 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 acute appendicitis 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 diagnostic strategies 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 acute appendicitis. Alvarado published his scoring system in 1986, also referred to as MANTRELS based on the mnemonic for remembering the combination of 8 signs and symptoms (Table 4).14 The score ranges from 0-10; a patient with a score of 5 or 6 is typically observed, whereas a patient with a score of 7 or greater should undergo operation.14 Since then, there have been several studies evaluating the diagnostic accuracy of the Alvarado score, modied versions of the Alvarado score such 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 symptoms or signs alone. However, these scoring systems do not have sufcient discriminatory or predictive ability to routinely be used alone to diagnose appendicitis. They have been used to determine the need 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 acute appendicitis has increased over time.22 On one hand, imaging may be helpful in the evaluation of patients with abdominal pain for ruling in or out other diagnoses or for preventing unnecessary operations.23 On the other hand, imaging could potentially delay operative intervention, and in the case of computed tomography (CT), radiologic imaging exposes patients to the risks of ionizing radiation.24 Ultrasonography (US) does not expose patients to ionizing radiation but is more operator dependent. In a meta-analysis of US and CT in children and adults, both US and CT were highly specic (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 4 Alvarado or MANTRELS scoring system14 Variable Symptoms Migration Anorexia Nausea-vomiting Tenderness in right lower quadrant Rebound of pain Elevation of temperature ( Z 37.31C) Leukocytosis (White blood cell count 4 10,000/mL) Shift to the left ( 4 75% neutrophils) Value 1 1 1 2 1 1 2 1 10
Signs
Laboratory Total score
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of intravenous (IV) but not oral or rectal contrast,3 although a recent meta-analysis suggested that noncontrast enhanced CT scan in adults had reasonably high sensitivity and specicity for clinical decision-making (93% and 96%, respectively).26 The Surgical Infection Society and Infectious Disease Society of America guidelines recommend helical CT with IV contrast as the test of choice when imaging is indicated in patients with suspected appendicitis, with moderate supporting evidence from 1 or more well-designed but nonrandomized trials.3,27 A recent meta-analysis evaluated the effect of CT on negative appendectomies, rates of perforation, and time to surgery in patients with acute right lower quadrant pain.28 The meta-analysis concluded that preoperative CT resulted in a reduced rate of negative appendectomies but an increase in time to surgery, although there was no increase in rate of perforation.28 However, of the 28 studies included in the analysis, only 2 were randomized, and most were retrospective cohort studies which can be subject to multiple sources of bias. There have been only a few randomized trials evaluating different strategies incorporating radiologic imaging on clinical outcomes. Only 1 trial identied a difference in accuracy. Lee and colleagues compared a strategy of mandatory vs selective CT scanning in patients with suspected appendicitis and less than 72 hours of symptoms. There were fewer negative appendectomies (2.6% vs 13.9%, P 0.07) and perforations (10.3% vs 18.4%, P 0.24) in the group undergoing mandatory scans.29 Another trial reported that CT scanning changed management in 26% of patients.30 Walker and colleagues compared CT scanning to standard management in patients with suspected appendicitis who clinically warranted either observation or operation. Standard management included observation with serial examinations, ultrasound, CT, or operation. Two additional trials of CT scanning vs clinical assessment in patients with suspected appendicitis, 1 in women only, identied no differences in diagnostic accuracy, length of stay, perforation rate, or costs or charges.31,32 However, these trials were small, single-center trials and underpowered to identify a small 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 a signicant increase in the use of US and CT, but no change in the rate of ruptured or negative appendectomies.22,33 A more recent follow-up study from the Washington state Surgical Care and Outcomes Assessment Program showed wide variability in the use of radiologic imaging across the 15 participating hospitals, ranging from 56%-97%.34 There was also a signicant difference in the rate of negative appendectomies, which was correlated to the accuracy of the radiologic studies.34 This study demonstrates that although the reported accuracy of radiologic imaging tests is high in the published literature, it is important to their diagnostic accuracy within each institution to evaluate their real-world utility.
Perforated vs Nonperforated Appendicitis Distinguishing whether or not a patient is likely to have perforated vs nonperforated appendicitis preoperatively 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 identied 4 studies that presented data for perforated appendicitis. Based on these studies, high values of laboratory markers of inammation such as a WBC and granulocyte 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 5 variables, including components of history, physical examination, laboratory values, and CT ndings.35 When the scoring system was applied to the study patient population, it increased the specicity of the pediatric surgeons preoperative assessment from 83%-98%.35 This was a singlecenter study that has not been validated in other centers or in adult patients. However, it demonstrates how a combination of clinical ndings and test results can improve the diagnostic accuracy for perforated appendicitis.
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Future Directions The above list of diagnostic tests and strategies is by no means comprehensive. Research is ongoing to identify accurate, efcient, and cost-effective methods of diagnosis. Advances have included using molecular techniques for proling gene and protein expression to identify novel markers for appendicitis.13,36,37 Imaging alternatives to CT scans such as bedside surgeon-performed ultrasound,38 magnetic resonance imaging,39 or low radiation CT scanning40 are being investigated in terms of their diagnostic accuracy and their potential to reduce exposure to radiation. Another avenue of investigation is the use of machine learning and advanced statistical models for informing decision-making.41 As advances in technology and diagnostic strategies are made, any improvements in accuracy must be balanced against the costs and potential harms. Conclusions Acute appendicitis is a common problem that continues to pose diagnostic dilemmas for clinicians. Although clinical ndings alone may not be sufcient for establishing a diagnosis of appendicitis, the importance of a thorough history and physical examination should not be underestimated. If additional tests are warranted, their risks and benets should be considered along with the likelihood that such tests will change the management. Advances in molecular methods, imaging technology, and computer decision support hold promise for the future, but further investigation is necessary to ensure the accuracy, efciency, and cost-effectiveness of novel diagnostic strategies for acute appendicitis.
Antibiotics vs Appendectomy for Acute Uncomplicated Appendicitis Appendectomy for acute appendicitis is one of the most common surgical procedures performed worldwide. In the United States, appendectomy incurs considerable indirect costs resulting from time lost from work, school, or usual activities after the procedure.42 The individual lifetime risk of appendicitis is 8.6% for men and 6.7% for women.43 Uncomplicated acute appendicitis is considered almost universally to be an indication for an appendectomy. In 1889, open appendectomy was accepted as the treatment standard, because it saved lives, and since that time, the dictum that surgical removal of the appendix is necessary has been largely unchallenged.44 Almost all surgeons regard acute appendicitis as an invariably progressive inammatory condition that over time will eventually lead to perforation. Thus, early surgical exploration and appendectomy is advocated for source control. However, appendectomy for nonperforated appendicitis is not without associated harm. The long-term risk of small bowel obstruction is estimated at 1.3% at 30 years 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 for various intra-abdominal infections such as uncomplicated diverticulitis, salpingitis, and neonatal enterocolitis.49 It is surprising that nonoperative management of uncomplicated acute appendicitis remains largely unexplored despite evidence that it often resolves, either spontaneously or with antibiotic therapy, and has been shown by limited studies to have outcomes equivalent to those of appendectomy.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 signicant increase in the number of studies performed annually.52 This has led to several interesting observations regarding the possibility of spontaneous resolution of appendicitis from several centers. Inclusion of a CT scan result in the Alvarado score has been shown to increase the rate of
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appendectomy. When classied as having a low likelihood of appendicitis (Alvarado score r 4), patients who underwent a CT scan had an appendectomy rate of 48%.52 In contrast, those with an Alvarado score r 4 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 with nonspecic abdominal pain.53 The investigators used diagnostic laparoscopy instead of CT scan in the management of patients with nonspecic abdominal pain. Patients were randomized to either (1) diagnostic laparoscopy or (2) nonoperative management (with operative intervention if peritonitis developed). The appendectomy rate was 39% for those randomized to diagnostic laparoscopy 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 of appendicitis.54 This meta-analysis included more than 50,000 patients from 15 geographic areas who had undergone appendectomy for acute appendicitis. In this study, the incidence of perforated appendicitis was equivalent regardless of geographic area, time, and gender. However, the incidence of acute nonuncomplicated appendicitis differed signicantly and correlated strongly to the incidence of removal of a normal appendix and was inversely related to diagnostic accuracy. This led the authors to conclude that the observed incidence of uncomplicated appendicitis was inuenced by the willingness to perform appendectomy in cases of suspected appendicitis. A high rate of appendectomy in suspected cases increases the proportion of conrmed cases presumably by adding instances of self-limited inammation that otherwise would escape detection.55 These indirect ndings and evidence are suggestive 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 nonoperative management of acute, uncomplicated appendicitis (Fig 1).56-59 The trial that has received the most attention was conducted in Sweden. All patients older than 18 years with presumed appendicitis were 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 allocated to 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 to treat was abandoned owing to criteria dened in the protocol. Patients allocated to antibiotic treatment could have surgery without any predetermined specication if the surgeon in charge deemed 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 this time patients received IV uids with no oral intake. Patients whose clinical status had improved the following morning were discharged to continue with per os antibiotics (ciprooxacin 500 mg twice per day and metronidazole 400 mg 3 times per day) for a total of 10 days. In patients whose clinical condition had not improved, IV treatment was prolonged. This study was conducted from May 2006-September 2007 and included 369 eligible consecutive patients. There were 202 patients in the study group (antibiotics) and 167 patients in the control group (appendectomy). In the study group, 106 (52.5%) completed the intended antibiotic treatment, and 154 (92.2%) in the control group underwent an appendectomy. Reasons for nonfulllment of scheduled treatment included patient preference for the other treatment (33 patients; 30.3%), the surgeon deciding that surgery was necessary based on clinical evaluation (19 patients; 17.4%), and surgery being deemed necessary without any further specication (45 patients; 41.3%). Of 108 patients who initially improved without surgery, 15 (13.9%) had recurrent appendicitis at a median follow-up time of 1 year. One third of recurrences appeared within 10 days following discharge from the hospital. Of the 15 patients with recurrence, 12 had surgery (4 patients had gangrenous or perforated appendicitis and 1 patient underwent ileocecal resection) and 3 had a second round of antibiotic treatment with success. Appendectomy was performed according to the authors usual practice: single-dose antibiotic prophylaxis, open or laparoscopic technique, and postoperative antibiotic treatment when the appendix was gangrenous or perforated.
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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.)
Efcacy 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 clinical progression. The preoperative characteristics of these patients were similar to those of the patients who fullled the antibiotic treatment. Of 250 surgically explored patients, 223 (89.2%) had appendicitis. Primary treatment efcacy was 90.8% for antibiotic therapy compared to 89.2% for surgical exploration analyzed per protocol. Major complications and total hospital cost for the primary admission were both lower in the antibiotic treatment group. One of the largest retrospective series reporting nonoperative management of appendicitis comes from Japan.60 In this retrospective study, Shindoh and colleagues reviewed their institutional experience with nonoperative management of appendicitis. In this report, 367 patients met inclusion criteria (right lower quadrant pain, WBC 4 9000 or CRP 4 1.0 mg/dL). The authors describe the following 3 study groups: (1) initial operation or appendectomy, (2) nonoperative group, 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 or laboratory parameters worsened, surgical management was considered. In this cohort, 143 (39%) underwent initial operation (group 1), whereas 224 (61%) were managed with initial antibiotic therapy. In the initial nonoperative group, 91 patients did not respond to antibiotics and underwent appendectomy. 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 recurrence of appendicitis was observed in 4.7% of patients initially managed nonoperatively.
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FIG 2. Consort diagram. (Reprinted with permission from Hansson et al.59)
Conclusions The data and available evidence regarding nonoperative management of acute appendicitis is provocative. At this time, however, level I data to suggest this is an alternative treatment option are not universally accepted. Despite the fact that appendectomy has been regarded as standard treatment for appendicitis for more than 100 years, there have been reports of patients being managed successfully without an operation. To date, there have been few randomized studies of nonoperative vs operative therapy for acute appendicitis, and none have been conducted in the United States. Yet there is some suggestion that a select group of patients may be managed nonoperatively. At best, we should consider the available data as hypothesis generating and not hypothesis conrming. One of the inherent difculties and biases in conducting a well-planned randomized clinical trial centers on pathologic conrmation of appendicitis. On one hand, for those patients with suspected appendicitis who receive antibiotics only, treatment successes may cause one to consider the underlying diagnosis (Is it really appendicitis?). On the other hand, the number of patients who undergo a negative appendectomy is not zero and exposure of these patients to surgical risks and complications is a valid concern. The report by Hansson and colleagues demonstrated a 3-fold increased rate of complications in the appendectomy group when compared to the nonoperative, antibiotic only group. The data presented herein are suggestive that in selected patients with acute, uncomplicated appendicitis, antibiotic treatment seems to be an appropriate alternative to conventional appendectomy. Multivariate analysis of patient characteristics failed to demonstrate any logistic model for inclusion or rejection of patients for the specied treatments. Furthermore, it conrmed that
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FIG 3. Intraoperative image of simple acute appenditis. (Photo Courtesy Kuojen Tsao, MD.)
CRP is not a signicant predictor in the assessment of the phlegmonous and gangrenous appendix, unlike total blood leucocyte count. Therefore most patients older than 18 years without obvious signs of intra-abdominal perforation can be offered antibiotic treatment as rst-line therapy. Clinical progression and surgical judgment may then determine whether there is a real need for surgical exploration in an expected subgroup of 5%-10% of all patients appearing with suspected or established appendicitis. The benet would be a signicantly reduced frequency of major complications related to surgery. 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; major complications following unnecessary surgery seem a more pertinent risk to patients. Another inherent problem with deciphering the issue of antibiotic therapy is the fact that getting clinicians to agree upon a consensus denition for acute, uncomplicated appendicitis remains problematic. In all likelihood, there is an arbitrary cut-off or threshold by which certain patients probably have a milder form of the disease (Fig 3) and would likely respond to systemic antibiotics alone. Above this arbitrary threshold, antibiotic therapy is unlikely to be effective in eradicating the infection (Fig 4). To resolve this dilemma, a few of these studies have completed multivariate analyses and found that presence of the fecaliths is predictive of failure. Further studies are needed to create informed multivariate models that adjust for all of the important clinical covariates. This effort may accurately predict which patients may or may not respond to systemic antibiotic therapy alone for the treatment of appendicitis.
Management of Complicated Appendicitis In the United States, approximately 11 of 10,000 people will develop acute appendicitis over their lifetime, with the typical age of onset between the ages of 11 and 19 years.61 Of these, an estimated 2%-6% of patients will present with an appendiceal mass, either in the form of an inammatory phlegmon or abscess.62 The optimal management of acute appendicitis complicated by an inammatory phlegmon or abscess remains controversial. There is no consensus in the surgical literature on whether to proceed immediately with appendectomy or initial nonoperative management in this setting of complicated appendicitis. Another dilemma in the management of appendicitis initially managed conservatively with antibiotics is whether or not to perform an appendectomy at a later date (interval appendectomy). The data are disparate regarding actual recurrence rates of appendicitis following nonoperative management, but they are commonly
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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-uid levels.
reported between 5% and 20%.63-65 In addition to recurrent appendicitis, a clinical concern in older patients who present with a cecal phlegmon is malignancy. In these cases, interval appendectomy allows the correct pathologic diagnosis to be made.66 The effect of these management decisions on duration of hospital stay, number of interventions, healthcare costs, and overall patient satisfaction must be considered.
Appendiceal Abscess Appendiceal abscess is commonly associated with delay in presentation, fever, leukocytosis, and a palpable mass in the right lower quadrant (Figs 5 and 6). The diagnosis is conrmed with CT or US. Management of these patients remains controversial with the traditional nonsurgical approach of percutaneous drainage and IV antibiotics with or without interval appendectomy vs immediate appendectomy and surgical drainage of the abscess. The evidence supporting both approaches is
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FIG 6. CT scan demonstrating appendiceal abscess with rim-enhancing wall.
weak, as most studies are retrospective and often combine patients with appendiceal abscess and phlegmon into a single cohort called appendiceal mass. Several meta-analyses have been performed to try to identify differences between the 2 treatment strategies. Andersson and Petzold performed a meta-analysis on 19 retrospective studies from 1969-2005. The limitation of this study is the lack of uniform denition of appendiceal abscess vs phlegmon. Nevertheless, the meta-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 ndings, the authors recommend nonsurgical management of patients with appendiceal abscess.67 Similar conclusions were reached by Simillis and colleagues who performed a meta-analysis of 16 retrospective studies and 1 nonrandomized prospective study from 1969-2007 comparing immediate appendectomy (725 patients) vs nonsurgical treatment (847 patients).68 Immediate appendectomy is associated with greater incidence of ileus or bowel obstruction, abdominal or pelvic abscess, and wound infection compared to nonsurgical treatment. There was no difference in the overall duration of hospitalization, but the immediate appendectomy group required more reoperations. The higher rate of complications associated with immediate appendectomy has been attributed to greater inammatory response to surgery in the setting of infection, as well as the technical difculty with inamed tissue. Most of the studies analyzed in these meta-analyses utilized open appendectomy techniques. The potential disadvantages of early operation may be mitigated by the laparoscopic techniques. Laparoscopic appendectomy results in less local inammation due to better visualization and instrumentation.69 St. Peter and colleagues conducted a prospective randomized trial comparing immediate laparoscopic appendectomy to nonsurgical treatment in 40 pediatric patients presenting with appendiceal abscess.70 Immediate laparoscopic appendectomy tends toward longer operative time (61 minutes vs 42 minutes) compared with interval laparoscopic appendectomy performed at 10 weeks from initial presentation (Fig 7). The immediate appendectomy group had fewer health care visits and few CT scans. However, there was no difference in recurrent abscess rate, total length of hospitalization, or total charges. They conclude that immediate laparoscopic appendectomy is as safe as nonsurgical management. The safety of immediate laparoscopic appendectomy for appendiceal abscess is supported by several other retrospective or uncontrolled studies.71-74 The infectious complications of immediate appendectomy can be reduced by improved laparoscopic techniques, such as use of extraction bag, endostaplers rather than endoloops, and limited irrigation to avoid bacterial contamination.75,76 Appendiceal Phlegmon The management of acute appendicitis complicated by an appendiceal phlegmon typically involves 1 of 3 treatment strategies. The rst, and most commonly accepted, is initial treatment with
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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 uids until the acute inammation subsides; appendectomy is then performed on an interval basis. Another strategy involves appendectomy upon initial presentation. Lastly, following resolution of the acute inammation with broad spectrum antibiotics, the patient is managed expectantly without interval appendectomy. Prospective data comparing these 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. A recently published survey of a group of general surgeons in England found that 75% still favor interval appendectomy following resolution of symptoms.77 Proponents for interval appendectomy state that removing the appendix is a technically easier operation once the acute inammation subsides, potentially avoiding inadvertent injury to adjacent loops of involved bowel, as well as extended resection of the cecum or ascending colon.66 Although the risk of recurrent appendicitis remains small after successful nonoperative treatment of an appendiceal phlegmon, proponents of interval appendectomy state that the risk of interval appendectomy is also small and eliminates the possibility of recurrent appendicitis.63 In a recent systematic review published by Hall and colleagues, 127 children were managed without planned interval appendectomy.78 The incidence of recurrent appendicitis ranged from 0%-42% in the 3 studies included in the review, with an overall risk of 20.5% (95% CI 14.328.4) (Fig 8). The complication rates following interval appendectomy were also published in this review, with an overall incidence of 3.4% (95% CI, 2.2-5.1) (Fig 9). The authors conclude that the likelihood of recurrent appendicitis as well as the risk of complication after interval appendectomy are both sufciently low that the decision to proceed with interval appendectomy is typically based on clinical criteria. Unfortunately, these data are from retrospective studies; prospective data from a randomized trial comparing these 2 approaches will help further guide surgical management. Interval Appendectomy Interval appendectomy provides a tissue diagnosis when diagnostic uncertainty exists. This is particularly important in adults because the differential diagnosis of an inammatory mass in the right lower quadrant can be quite extensive, with neoplastic etiologies of particular concern. In a systematic review and meta-analysis by Andersson and colleagues, 2771 included patients were initially treated nonoperatively for an appendiceal phlegmon or abscess.65 On follow-up, 31 patients were found to have a malignant diagnosis. In patients younger than 40 years with an appendiceal mass, only 4 were found to have a malignant diagnosis on follow-up: 2 children had carcinoid of the appendix, a 26 year old woman presented with an ovarian malignancy, and a 25 year old man presented with metastatic gastric cancer. The overall estimate of a malignant diagnosis was 1.2% (95% CI 0.6%-1.7%), with an incidence of 0.2% (95% CI 0.0%-0.05%) in children. Inammatory bowel disease was established as a diagnosis during follow-up in 0.7% of patients (95% CI 0.2%-11.9%), with a higher incidence again seen in adults. Although primarily retrospective, these data underscore the need for follow-up, either with CT scan or colonoscopy, after successful treatment of an appendiceal phlegmon in adults.65
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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 special mention because its presence has been used as a guide to proceed with interval appendectomy following successful nonoperative management. A retrospective cohort study published by Ein and colleagues reviewed the outcomes of 96 pediatric patients with appendicitis who presented with either an inammatory mass or phlegmon and were initially managed nonoperatively by the staff surgeon.79 Six patients who failed initial nonoperative management underwent appendectomy and were excluded. Forty-one patients were scheduled for elective appendectomy by their surgeon and were also excluded from analysis. The remaining patients were included in the study and their outcomes 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, the recurrence rate was 72% compared to 26% in patients without an appendicolith (relative risk of 2.8 in patients with an appendicolith) (Table 5). The authors conclude that the presence of an appendicolith predicts failure of nonoperative management of peri-appendiceal phlegmon or abscess. It is important to note that the overall recurrence rate of appendicitis in this study is higher than what is typically reported elsewhere in the literature, and this may inuence the true effect of an appendicolith on failure of nonoperative management. Unfortunately, there are no data from a randomized, prospective trial evaluating whether or not the presence of an appendicolith is predictive of failure of initial nonoperative management of ruptured appendicitis with phlegmon or abscess. As such, any conclusions from this study should be viewed as hypothesis-generating for a future randomized controlled trial. In deciding whether or not to proceed with routine interval appendectomy following successful nonoperative management of an appendiceal phlegmon or abscess, the effect of cost must also be considered. A cost analysis of interval appendectomy following successful nonoperative management of periappendiceal phlegmon or abscess was conducted by Raval and colleagues80 In this study, a decision tree analysis was created with outcome probabilities obtained from literature review and cost estimates from the Healthcare Cost and Utilization Project Kids Inpatient Database.81 It should be noted that the Kids Inpatient Database provides a conversion factor for translating total charges into costs. With an estimated probability of successful observation set at 0.85, the cost of observation was calculated to be $3080.78 as opposed to $5034.58 seen in the interval appendectomy arm. Using one-way sensitivity analysis, cost savings were observed up to a
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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 5 Effect of presence of appendicolith on recurrence No. of patients No appendicolith Appendicolith Total 31 (63) 18 (37) 49 Recurrence 8 (26) 13 (72)* 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 a 0.4 probability of recurrent appendicitis following observation, which is similar to the recurrence rate published by Ein and colleagues79 Thus, even in a patient population with a relatively high likelihood of recurrent appendicitis, the cost analysis does not recommend proceeding with elective interval appendectomy. Although prospective data on the management of periappendiceal phlegmon or abscess are limited, 2 recently published randomized trials in children address the question of whether or not to
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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 note that these trials include interval appendectomy as a treatment arm; foregoing appendectomy altogether was not specically investigated. In the study published by St. Peter and colleagues, 40 children with appendicitis complicated by phlegmon or abscess were randomized to either immediate appendectomy or initial nonoperative management followed by scheduled interval appendectomy in 6 weeks.83 Of note, this is a pilot study in which an outcome variable was not dened or used in a sample size calculation. The number of patients chosen to be enrolled into the study was based on the anticipated clinical volume over a study period of 2 years. Patients who were offered initial appendectomy had a longer operative time (20 minutes), fewer CT scans, and fewer total healthcare visits. Otherwise, the total length of hospital stay, hospital charges, and recurrent intra-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 patients enrolled: 64 receiving initial appendectomy and 67 assigned to interval appendectomy.82 This study was powered to detect a 5-day difference in return to normal activity and intention-to-treat analyses were performed. The primary outcome of time to return to normal activity was chosen as it is readily measured and functions as a composite of many objective and subjective measures. In the primary appendectomy group, time to normal activity was 13.8 [7.5] days (mean [standard deviation]) vs 19.4 (8.7) days in the interval appendectomy group (P o 0.001). Of note, the relative risk of any adverse effect associated with interval appendectomy was 1.86 (95% CI 1.21-2.87);
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specic outcomes measured included intra-abdominal abscess, small bowel obstruction, unplanned readmission, and recurrent appendicitis, and these were all seen with higher frequency in the interval appendectomy group. The authors conclude that early appendectomy signicantly reduced the time away from normal activity and showed a signicantly lower adverse event rate. Future Directions The optimal management strategy of an appendiceal phlegmon or abscess remains elusive as most recommendations are based on retrospective data, but recent randomized trials in children indicate that early appendectomy results in faster return to normal activity with favorable complication rates when compared to interval appendectomy.82 Performing an interval appendectomy following successful nonoperative management with antibiotics and percutaneous drainage, as needed, has yet to be evaluated in a randomized trial. The clinical decision to perform an interval appendectomy in the setting of an appendicolith is based on a retrospective cohort study published by Ein and colleagues79 As stated previously, the incidence of recurrent appendicitis in this cohort was higher than that seen in other series, and thus inuences the recommendation to proceed with interval appendectomy. Higher-quality evidence from prospective, randomized trials will help surgeons decide 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 remained relatively unchanged since its introduction. In 1983, Semm described a laparoscopic approach for removing the appendix, advocating the advantages of laparoscopic surgery for one of the most frequently performed surgical procedures.84 Because open appendectomy typically involves a small incision, 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 many randomized control trials comparing open vs laparoscopic appendectomy have been performed, many contain methodological aws, including inadequate allocation concealment, lack of reporting of randomization method, failure of adequate blinding, lack of analysis by intention-to-treat, and incomplete follow-up data.85 That being said, these randomized trials, as well as systematic reviews and meta-analyses of these studies, have provided a great deal of insight into the specic benets and drawbacks of each approach. In deciding between a laparoscopic and open approach, specic issues 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 vs open appendectomy in 222 hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) was conducted by Ingraham and colleagues86 Over the course of 3 years (2005-2008), 32,683 patients in the database underwent appendectomy at these institutions, with 24,969 performed laparoscopically (76.4%) and 7,714 (23.6%) performed using an open technique. 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 ASA class, and more likely to have a variety of comorbidities; these are summarized in (Table 6). The analysis of 30-day outcomes following laparoscopic vs open appendectomy showed overall morbidity, serious morbidity, surgical site infection, and serious morbidity or mortality (Table 7) to be higher in patients undergoing open appendectomy, although these complications were generally low in both groups.
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TABLE 6 Distribution of patient risk factors associated with 32,683 appendectomies performed at 222 NSQIP hospitals Risk factor Open (n 7,714; Laparoscopic (n 23.6%) 24,969; 76.4%) Total (n 32,683) P value
Postoperative diagnosis Peritonitis or abscess No perforation or peritonitis or abscess or rupture Age (mean 7 SD) Gender Female Male Race White Black Other Body mass index Normal Overweight Obese Underweight Unknown ASA class 1No disturbance 2Mild disturbance 3Severe disturbance 4Life threatening Functional status Independent Partially dependent Diabetes Renal failure (dialysis or acute renal failure) Dyspnea Ascites Alcohol use Current smoker within 1 y Chronic obstructive pulmonary disease Pneumonia Steroid use for chronic condition Bleeding disorder Congestive heart failure Hypertension requiring medication Coronary artery disease* Peripheral vascular diseasey Disseminated cancer Weight loss ( 4 10% loss in last 6 mo) Chemotherapy for malignancy within 30 d preoperatively Radiotherapy for malignancy in last 90 d
o 0.0001 2,704 (26.89) 5,640 (73.11) 40.2 7 17.2 3,260 (42.26) 4,454 (57.74) 4,809 (62.34) 445 (5.77) 2,460 (31.89) 2,577 2,266 1,603 159 1,109 2,850 3,890 878 96 (33.41) (29.38) (20.78) (2.06) (14.38) (36.95) (50.43) (11.38) (1.24) 3,331 (13.34) 21,638 (86.66) 37.3 7 15.8 11,808 (47.29) 13,161 (52.71) 16,527 (66.19) 1,479 (5.92) 6,963 (27.89) 8,079 7,372 5,827 470 3,221 9,541 13,146 2,128 154 (32.36) (29.52) (23.34) (1.88) (12.90) (38.21) (52.65) (8.52) (0.62) 5,405 (16.54) 27,278 (83.46) 38.0 7 16.2 15,068 (46.10) 17,615 (53.90) o 0.0001 21,336 (65.28) 1,924 (5.89) 9,423 (28.83) 0.0001 10,656 9,638 7,430 629 4,330 12,391 17,036 3,006 250 (32.60) (29.49) (22.73) (1.92) (13.25) o 0.0001 (37.91) (52.12) (9.20) (0.76) o 0.0001 7,532 (97.64) 182 (2.36) 339 (4.39) 26 (0.34) 163 (2.11) 96 (1.24) 213 (2.76) 1,627 (21.09) 106 (1.37) 12 (0.16) 81 (1.05) 199 (2.58) 13 (0.17) 1,369 (17.75) 275 (3.56) 39 (0.51) 15 (0.19) 8 (0.10) 22 (0.29) 8 (0.10) 24,620 (98.60) 349 (1.40) 953 (3.82) 39 (0.16) 315 (1.26) 279 (1.12) 510 (2.04) 5,418 (21.70) 181 (0.72) 18 (0.07) 175 (0.70) 451 (1.81) 14 (0.06) 3,561 (14.26) 586 (2.35) 44 (0.18) 44 (0.18) 43 (0.17) 54 (0.22) 14 (0.06) 32,152 (98.38) 531 (1.62) 1,292 (3.95) 65 (0.20) 478 (1.46) 375 (1.15) 723 (2.21) 7,045 (21.56) 287 (0.88) 30 (0.09) 256 (0.78) 650 (1.99) 27 (0.08) 4,930 (15.08) 861 (2.63) 83 (0.25) 59 (0.18) 51 (0.16) 76 (0.23) 22 (0.07) 0.02 0.002 o 0.0001 0.36 0.0002 0.26 o 0.0001 0.03 0.002 o 0.0001 0.003 o 0.0001 o 0.0001 o 0.0001 0.74 0.18 0.27 0.16 o 0.0001 o 0.0001
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TABLE 6 (continued ) Risk factor Open (n 7,714; Laparoscopic (n 23.6%) 24,969; 76.4%) 134 (1.74) 3 (0.04) 2,955 (38.31) 299 (1.20) 1 (0.00) 8,795 (35.22) Total (n 32,683) 433 (1.32) 4 (0.01) 11,750 (35.95) P value
Neurologic disorderz Transfusion99,y Preoperative sepsisz
0.0003 0.02 o 0.0001
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 decit, history of transient ischemic attacks (TIA), hemiplegia, paraplegia, impaired sensorium, quadriplegia. 99 Transfusion 4 4 U packed red blood cells 72 h before surgery. y Signicance calculated via Fishers exact test owing to small sample sizes. z Preoperative systemic inammatory response syndrome or sepsis. Reprinted with permission from Ingraham et al.86
TABLE 7 Comparison of 30-day outcomes after laparoscopic vs open appendectomy at 222 NSQIP hospitals (20052008) Outcomes Open (n 7,714; 23.6%) 682 (8.84) 326 (4.23) 513 (6.65) 329 (4.26) 10 (0.13) 300 76 133 35 33 30 6 24 10 28 1 7 5 1 9 167 (3.89) (0.99) (1.72) (0.45) (0.43) (0.39) (0.08) (0.31) (0.13) (0.36) (0.01) (0.09) (0.06) (0.01) (0.12) (2.16) Laparoscopic (n 24,969; 76.4%) 1,114 (4.46) 644 (2.58) 814 (3.26) 649 (2.60) 18 (0.07) 314 60 448 15 61 36 21 26 21 92 8 8 3 9 11 288 (1.26) (0.24) (1.79) (0.06) (0.24) (0.14) (0.08) (0.10) (0.08) (0.37) (0.03) (0.03) (0.01) (0.04) (0.04) (1.15) Total (n 32,683) 1,796 (5.50) 970 (2.97) 1,327 (4.06) 978 (2.99) 28 (0.09) 614 136 581 50 94 66 27 50 31 120 9 15 8 10 20 455 (1.88) (0.42) (1.78) (0.15) (0.29) (0.20) (0.08) (0.15) (0.09) (0.37) (0.03) (0.05) (0.02) (0.03) (0.06) (1.39) P value
Overall morbidity Serious morbidity SSI Serious morbidity or mortality Mortality Individual morbities Supercial SSI Deep incisional SSI Organ space SSI Wound disruption Pneumonia Unplanned intubation Pulmonary embolism Failure to wean (on ventilator 4 48 h) Renal failure Urinary tract infection Neurologic event Cardiac arrest requiring CPR Myocardial infarction Bleeding DVT Sepsis or septic shock
o 0.0001 o 0.0001 o 0.0001 o 0.0001 0.13 o 0.0001 o 0.0001 0.68 o 0.0001 0.01 o 0.0001 0.87 o 0.0001 0.26 0.94 0.70* 0.03* 0.02* 0.47* 0.03* o 0.0001
CPR, cardiopulmonary resuscitation; DVT, deep vein thrombosis; NSQIP, National Surgical Quality Improvement Program; SSI, surgical site infection. n Utilizing Fishers exact test. Reprinted with permission from Ingraham et al.86
Patients with complicated appendicitis had a signicantly lower likelihood of developing a supercial or deep 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
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group. In uncomplicated appendicitis, the risk of both supercial and deep surgical site infection was lower in the laparoscopic group. Although this study evaluates a large number of patients across multiple hospital systems, the data are limited in that retrospective reviews cannot account for specic clinical reasons 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 acknowledged by the authors include generalizability of the results to non-NSQIP centers and data being limited to those that are collected in the NSQIP database. That being said, the authors conclude that the available evidence from the American College of Surgeons NSQIP database indicates that a laparoscopic approach is associated with fewer complications when compared to an open procedure. A Cochrane review of 67 trials comparing laparoscopic and open appendectomy was updated in 2010.87 Of these studies, the vast majority (56) were conducted in adults. The interventions used in the included trials were fairly similar; in laparoscopic cases, 3 trocars were typically used and the appendiceal stump was secured primarily with looped sutures, although 3 trials did use an endoscopic stapler. Antibiotic usage was stated as being the same in both groups for each included trial. Specic 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 that although all participants in the included trials were randomized to either laparoscopic or open appendectomy, the quality of these trials was judged to be moderate to poor, with many of the included studies having similar aws. Specically, only 42 trials took adequate measures to ensure that the process of randomization was adequately concealed. Furthermore, protocol violations were seen 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, due to inconsistencies in the denition and reporting of these complications, the authors only examined 2 specic complications in their analysis: wound infection and intra-abdominal abscess. Following laparoscopic appendectomy, wound infections were approximately one half as likely when compared to open appendectomy (OR 0.43; 95% CI 0.34-0.54). This is a highly signicant difference based on nearly 6000 appendectomies. Conversely, laparoscopic appendectomy was associated with a nearly 3-fold increase in the likelihood of intra-abdominal abscess when compared to an open technique (OR 1.77; 95% CI 1.14-2.76). These results are similar to the ndings published in the NSQIP analysis by Ingraham and colleagues86 Operative time was 10 minutes longer for laparoscopic appendectomy (95% CI 6-15 minutes), but this difference has been getting smaller with more recently published trials. Laparoscopic appendectomy was also associated with lower postoperative pain, 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 results are strongly heterogeneous. The authors conclude that laparoscopic appendectomy confers many benets over open appendectomy, and should be strongly considered as the preferred approach where 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 laparoscopic technique has been inherently difcult to answer because both approaches offer similar advantages, namely, a small incision, low incidence of complications, a short hospital stay, and rapid return to normal activity. Although multiple randomized trials and meta-analyses of these trials have been conducted and published, the data indicate that the choice of surgical approach ultimately remains up to the surgeon. As stated in the Cochrane review, is avoiding 3 supercial surgical site infections for 1 intra-abdominal abscess a reasonable choice? As experience with laparoscopic appendectomy increases and the equipment becomes more ubiquitous, the estimated complication proles of both operations will become more accurate and precise, and this question can be suitably answered.
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Pediatric Appendectomy Acute appendicitis is one of the most common surgical diagnoses in pediatrics, with an estimated incidence of 59,000-70,000 children per year in the United States.88,89 Appendicitis occurs in all age groups, but is rare in younger children. Although the highest incidence is in older children, with 25 cases per 10,000 pediatric patients per year between the ages of 10 and 17 years, there is a reported rate of 1-2 cases per 10,000 in children younger than 4 years of age. In most cases in the United States, 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 is 0.1%-1% with the highest proportion in younger children.88,92 Death in infants and neonates is mostly likely due to (1) failure to recognize disease due to its clinical presentation, which is similar to other common conditions in this age group; and (2) the inability of the younger patient to communicate abdominal pain or to manifest systemic symptoms, such as fever. However, there remains signicant morbidity 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 as 80%-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 different compared to adult therapies. Appendectomy is indicated based on the diagnosis of acute appendicitis which, in most cases, can be made clinically. Utilizing history from the patient or caretaker or both, as well as physical signs of localized peritonitis in the right lower quadrant of the abdomen, acute appendicitis should be strongly considered. In equivocal cases, adjunctive imaging such as US or computerized tomography (CT) has proven to be effective.94 With increased utilization of routine imaging studies, the negative 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 pediatric patients. Key issues regarding diagnosis,35,39 surgical technique,96,97 and antibiotic therapy98,99 remain unanswered for all patient populations. These specic issues related to the treatment of acute appendicitis are addressed elsewhere in this issue. However, there are specic considerations for pediatric appendectomy that remain controversial. These include the increasing adoption of single-incision or single-port laparoscopic appendectomy (SILS) and the initial nonoperative management of acute appendicitis with or without subsequent interval appendectomy. The surgical treatment of acute appendicitis has evolved over the last 2 decades. Since McBurneys rst description in 1894,100 the transverse or oblique right lower quadrant incision for appendectomy is the incision of choice for the open approach in children. The abdominal muscles are split with the mesoappendix divided prior to excision of the appendix at the base. The appendiceal 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 McBurney is 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 to improve patient outcome in multiple reports.101-106 Some authors have suggested that the minimally invasive technique is the preferred approach among pediatric surgeons,107 whereas others have demonstrated heterogeneity in surgical approaches.108 Although there remains a paucity of high-level clinical evidence to support this superior efcacy,87,109 it is indisputable that laparoscopic appendectomy is widely utilized and, at times, expected by patients and their families in the surgical treatment of acute appendicitis in children. Laparoscopic Appendectomy The rst case of laparoscopic appendectomy was described by Semm in 1983, and was carried out as an incidental procedure during a pelvic exploration.84 In the last 30 years, controlled studies and
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meta-analysis in adult patients have demonstrated advantages with laparoscopic appendectomy, including fewer wound infections, faster return to normal activity, and decreased length of hospitalization.102,104 However, not until the 1990s was laparoscopic appendectomy established as a reasonable approach in the treatment of pediatric acute appendicitis.101,105 The reported advantages of laparoscopic appendectomy, compared to open surgery in children, are similar to those in adults which include shorter hospitalization, fewer wound infections, earlier return to normal activity, and better cosmesis.101,103,105,110-113 The standard approach to laparoscopic appendectomy in children usually involves a 3-trocar technique. A 10- to 12-mm cannula is placed in the umbilicus to allow the passage of laparoscopic instruments, the telescope, a ligation device such as a stapler, and the retrieval of the appendix. Two 5 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 be ligated inside the abdomen with endoloops, endoscopic sutures, or staplers, or can be secured extracorporeally.105,114,115
Single-Incision or Single-Port Laparoscopic Appendectomy In the evolving era of scarless surgery, SILS has been utilized for appendectomy. A singleincision laparoscopic-assisted appendectomy for acute appendicitis was rst reported in adults patients in 1992.116 Soon thereafter, this surgical approach began to be reported in children, with the rst reports utilizing a single umbilical incision with a laparoscopic-assisted appendectomy, in which 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 orice transluminal 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 SILS which utilizes conventional or specialized instruments through a single skin incision, without regard to number of fascia incisions122-126 to a single-incision, laparoscopic-assisted operation in which the appendix is exteriorized and open techniques are utilized.122,124,127 The touted advantages of the SILS approach to appendectomy are similar to general laparoscopy compared to open operations, including less pain, faster recovery, and better cosmesis. However, critics countered these with concerns about increased costs, longer operation times, and higher complication rates.124 Unfortunately, comparative evidence for SILS appendectomy in children has been limited despite its widespread adoption into clinical practice. In adult studies comparing SILS with conventional 3-port laparoscopic appendectomy, advantages in cosmetic outcomes were at the cost of longer operation times and substantial early postoperative pain.123 Oltmann and colleagues128 reported that SILS with appendectomy is feasible and safe in the pediatric population. Although operating times were longer than the conventional 3-port laparoscopic appendectomy, the authors suggested these should improve with better instrumentation and experience. St. Peter and colleagues127 reported on the only randomized control trial comparing SILS-assisted appendectomy to conventional 3-port laparoscopic appendectomy in 160 children with nonperforated acute appendicitis. Utilizing an extracorporeal appendectomy, there was a nonsignicant difference in wound infection rates of 3.3% for SILS patients compared to 1.7% for conventional laparoscopy. Although there was a statistically signicant 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 techniques had comparable outcomes. Clinical evidence that supports the laparoscopic approach for complicated (perforated or intraabdominal abscess) appendicitis remains controversial. The concern over greater incidence of intraabdominal abscess following the laparoscopic approach was reported in some studies129-131 but not supported 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 nonoperative treatment for complicated appendicitis followed by interval appendectomy obviates the need to
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manage the inammatory environment in the acute stage. Such a strategy has been shown to be successful 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 acute appendicitis in adults and children, the treatment strategy for complicated disease, such as perforated appendicitis and appendiceal mass, is controversial.134-138 With early appendectomy, patients undergo an urgent appendectomy within the rst 24 hours of hospitalization, and any intraabdominal abscess is drained during the operation. Alternatively, with interval appendectomy, the appendectomy is planned for 6-8 weeks after the initial diagnosis, after the patient has been discharged and is back to normal activity. Intra-abdominal abscesses are percutaneously drained, if possible. Several retrospective studies have reported that interval appendectomy has shown the benets of reducing major complications, fewer wound infections, and shortening the hospital stay, as well as decreasing the overall cost of treatment.68,134,135,139 The need and timing for interval appendectomy at 2-3 months following initial medical management remains unclear.132,134 Recent evidence has shown that acute appendicitis can be treated successfully nonoperatively in adults and children.58,140-142 Two meta-analyses have demonstrated that conservative treatment with antibiotics only is associated with a lower risk of complications without differences in length of hospitalization.68,143 However, the success of initial nonoperative treatment of complicated appendicitis has stimulated some surgeons to question the need for subsequent interval appendectomy. Some have suggested that interval appendectomy is unnecessary.78,144,145 Others support 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 the clinical practice in the treatment of acute appendicitis in children has resulted in an extremely low mortality rate. As such, clinical research has focused on reduction in morbidity. Despite the frequency of acute appendicitis in children, there remains a paucity of evidence-based treatment guidelines and lack of consensus on treatment strategies.
Management of the Unanticipated Appendiceal Neoplasm An unanticipated appendiceal neoplasm may be encountered at any elective or emergency abdominal operation. It is estimated that nearly 50% of cases manifest as appendicitis, but variable presentations have also been reported.147 The pathology and behavior of appendiceal neoplasms are diverse, which only complicates the confusing classication and terminology.148 Increasingly, an appendiceal neoplasm may be suspected on radiological cross-sectional imaging for diagnosis or staging of abdominal disease. In a number of cases, an appendiceal neoplasm is discovered on histopathologic analysis of an appendectomy specimen. Unfortunately, these factors lead to diagnostic and therapeutic challenges, particularly for those surgeons who provide predominantly emergency surgical services. The aim of this review is to summarize the incidence, classication, presentation, and management of the common appendiceal neoplasms. Algorithms to assist therapeutic 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 neoplastic pathology of the colon can occur in the appendix.149 Appendiceal neoplasms are thought to account
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TABLE 8 Classication 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 Kaposis 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, as most manifest with appendicitis as a consequence of luminal obstruction. Some appendiceal lesions are obvious at operation, but a number are found only on histopathologic analysis of appendectomy specimens. In reports of several large series, appendiceal neoplasms were found in 0.7%-1.7% of specimens.151 The classication of appendiceal neoplasms has been controversial.152-154 Although several classications have been suggested, lack of standard terminology for both benign and malignant lesions has hampered valid comparisons between studies.155 Several investigators have proposed a simple classication of epithelial appendiceal neoplasms.156,157 This classication schema includes carcinoid neoplasms, resulting in an inclusive classication 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 of neuroendocrine tumors of the appendix is 0.16 per 100,000, with a comparable frequency in men and women.160 Little is known about the epidemiology of these tumors and associated risk factors.161 Appendiceal carcinoids are detected in 0.3%-0.9% of appendectomy specimens, and commonly 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 or distal 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 may assist management decisions. Small carcinoids of the appendix rarely metastasize, unlike those in other locations in the gastrointestinal tract. Adverse prognostic features with an increased risk of metastasis include tumors greater than 2 cm and meso-appendiceal extension.165 Most carcinoids are small and can be
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treated by simple appendectomy.166 There is agreement, however, that a right hemicolectomy should be performed if carcinoids are larger than 2 cm or when there is involvement of the base of the appendix or the mesoappendix.167 Data from the National Cancer Institutes Surveillance, Epidemiology and End Results (SEER) database from 1973-2004 demonstrated the distribution of localized, regional, and distant disease to be 60%, 28%, and 12% respectively.160 However, data from other sources have demonstrated higher 5-year survival rates (up to 94%) for those patients with localized disease.168 Surgical therapy remains the only potentially curative treatment for well-differentiated carcinoid tumors of the appendix. Small ( o 1 cm) carcinoid tumors conned to the tip of the appendix that are completely 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% of patients will be found to have the base of the appendix involved with tumor. Most appendiceal carcinoids are typically considered benign; however, deep invasion or regional metastases have been reported 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 to invasive adenocarcinomas. This range incorporates a spectrum of disease, often difcult to classify histopathologically, with only the clinical behavior over time truly dening the biologic nature of the tumor. Ronnett and colleagues have classied appendiceal mucinous neoplasms into 3 groups: disseminated peritoneal adenomucinosis, peritoneal mucinous carcinomatosis, and an intermediate group.169,170 Others have classied mucinous neoplasms into low-grade mucinous neoplasms and adenocarcinoma (high-grade neoplasms).171,172 In light of the difculties regarding pathologic classication and uncertain clinical behavior, it is recommended that all patients with an appendiceal 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 frankly malignant, including cystadenomas, mucinous tumor of unknown or uncertain potential, disseminated peritoneal adenomucinosis, malignant mucocele, and borderline appendiceal tumors.150,160 These tumors may spread in the peritoneal cavity, producing mucinous intraperitoneal ascites, resulting in pseudomyxoma peritonei (PMP).148,173 The precise etiology and pathophysiology of PMP is a matter of some debate. Some suggest that mucinous material outside the appendix, including mucin-producing cells, arises from a ruptured adenoma, and that only if there is histologic evidence of inltrative invasion should the condition be categorized as adenocarcinoma.170,174,175 An alternate view considers any production of mucin by epithelium outside the appendix to indicate a mucinous carcinoma, which may vary from low-grade to highgrade mucinous adenocarcinoma.176 Many institutions use the term low-grade mucinous neoplasm to describe lesions with scant mucinous epithelium that demonstrate varying degrees of cellular atypia in conjunction with extracellular mucin accumulation.156 Some cases show evidence of extra-appendiceal mucin with or without obvious rupture of the appendix. These lesions often present with acute appendicitis or a right lower quadrant mass.177,178 Others present with abdominal swelling secondary to mucin, or mucin in a hernia sac.179,180 (Fig 11). Many cases are incidental ndings at laparotomy, laparoscopy, or other radiologic imaging.181 The prognosis of these neoplasms is dependent upon whether they have perforated and whether mucin and epithelial cells are present outside the appendix.182,183 Perforated low-grade mucinous neoplasms with extra-appendiceal mucin almost inevitably result in PMP, although this phenomenon may take several years to manifest clinically. Such
79
FFS
RD: 380 Tilt: 0 mA : 487 KVp: 120 A cq no: 1
Z: 1 C : 50 W: 400 DFO V :38x38cm
FIG 11. CT scan demonstrating mucocoele (identied by arrow) in right lower quadrant.
perforated tumors are best treated with macroscopic tumor removal (cytoreduction) combined with an intraperitoneal chemotherapy regimen.184-187 The rationale for this intensive treatment is based on the likely pathophysiology of PMP. As an appendiceal adenoma enlarges and occludes the appendiceal 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 rupture epithelial 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 is not well understood. A recent population-based study from The Netherlands examined 167,744 appendectomy specimens.188 A mucocele or epithelial neoplasm was identied in 1482 patients (0.9%). A benign lesion (including mucocele) was found in 1 of every 150 appendices (0.7%) and malignancy 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 epithelial neoplasms were benign in 73% and malignant in 27%, whereas this distribution was 53% vs 47% for the nonmucinous epithelial neoplasms. One of 11 patients (9%) with a primary epithelial appendiceal lesion (including mucocele) developed PMP. The chance of developing PMP was signicantly higher in patients with a mucinous epithelial neoplasm (20%) as compared with patients 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 all appendectomies.189 These patients usually present with right lower quadrant pain or an abdominopelvic mass, and up to 88% may present with symptoms consistent with appendicitis.190 The extent of disease may be such that an appendiceal primary is impossible to conrm or exclude even at laparotomy or autopsy, and extensive investigations are frequently inappropriate with such advanced disease. Reported series of appendiceal adenocarcinoma are difcult to compare, as terminology and classication of these lesions have not been consistent.191 Adenocarcinoma of the appendix has traditionally been treated by right hemicolectomy, with improved survival in patients undergoing 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 abnormal appendix may be noted incidentally, during an open or laparoscopic procedure (see algorithm in
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Tumor identified during operation Yes No Tumor<2cm Yes Base of appendix/mesoappendix univolved Yes Evidence of perforation Yes Evidence of peritoneal mucin/mucinous ascites Yes If appendectomy not possible, tissue biopsy, peritoneal lavage
FIG 12. Algorithm for the management of unanticipated appendiceal tumors.
Right hemicolectomy
No
Right hemicolectomy
No
Appendectomy+ tissue biopsy
No
Appendectomy+ tissue biopsy
Fig 12). Initial assessment of the appendiceal tumor should include noting its size and identifying features 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 as an assessment of whether or not the appendix is perforated, provides additional critical information. The operating surgeon should look carefully for evidence of extra-appendiceal disease, such as mucin (which should always be sent for cytologic analysis), local lymphadenopathy, or obvious disseminated metastatic spread. Sites of possible primary disease (including the ovaries in female patients) and synchronous colorectal malignancies should also be sought. Laparoscopy facilitates an examination of the peritoneal cavity, although it lacks the tactile input achievable at laparotomy.194 If the tumor is conned to the appendix, smaller than 2 cm, without evidence of mesoappendiceal involvement, and not involving the base of the appendix, appendectomy is appropriate treatment.195 Rarely will denitive pathology require further surgical intervention. The evidence examining the role of laparoscopic appendectomy for the resection of these neoplasms is limited. If there is concern at laparoscopy, particularly if an appendiceal neoplasm is greater than 2 cm, the procedure should be converted to a standard laparotomy.196 Midline ports should be considered because these locations facilitate a much easier excision should a secondary procedure be performed at a later date. Extreme care should be taken to ensure the mesoappendix is resected satisfactorily and 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 be challenging with a large mucin-lled appendix, and may require a larger incision or conversion to an 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 any extra-appendiceal spread, are at risk of developing PMP and require careful postoperative surveillance. An initial CT scan of the abdomen and pelvis as well as the following tumor markers provides baseline measurements: carcinoembryonic antigen, cancer antigen CA-125, and CA-19-9.
81
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106. Chung RS, Rowland DY. Meta-analyses of randomized controlled trials of laparoscopic vs conventional inguinal hernia repairs. Surg Endosc. 1999;13:689694. 107. Ostlie DJ. Single-site umbilical laparoscopic appendectomy. Semin Pediatr Surg. 2011;20:196200. 108. Muehlstedt SG, Pham TQ, Schmeling DJ. The management of pediatric appendicitis: a survey of North American Pediatric Surgeons. J Pediatr Surg. 2004;39:875879. [discussion-9]. 109. Sauerland S., Lefering R., Neugebauer E.A. Laparoscopic versus open surgery for suspected appendicitis. Cochrane Database Syst Rev. 2002:CD001546. 110. Meguerditchian AN, Prasil P, Cloutier R, Leclerc S, Peloquin J, Roy G. Laparoscopic appendectomy in children: a favorable alternative in simple and complicated appendicitis. J Pediatr Surg. 2002;37:695698. 111. Kokoska ER, Murayama KM, Silen ML, Miller TA, Dillon PA, Weber TR. A state-wide evaluation of appendectomy in children. Am J Surg. 1999;178:537540. 112. 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Current Problems in Surgery 50 (2013) 5486

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Current Problems in Surgery

Acute Appendicitis: Controversies in Diagnosis and Management

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

82% 92% 68%

65% 81% 94%

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

Laboratory Total score

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

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

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

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

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

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

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

Neurologic disorderz Transfusion99,y Preoperative sepsisz

0.0003 0.02 o 0.0001

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

RD: 380 Tilt: 0 mA : 487 KVp: 120 A cq no: 1

Z: 1 C : 50 W: 400 DFO V :38x38cm

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

Appendectomy+ tissue biopsy

Appendectomy+ tissue biopsy

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

C.J. Wray et al. / Current Problems in Surgery 50 (2013) 5486

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