Distinguishing Acute from Ruptured Appendicitis Preoperatively in the Pediatric Patient

Advances in Surgery 44 (2010) 73–85

ADVANCES IN SURGERY Distinguishing Acute from Ruptured Appendicitis Preoperatively in the Pediatric Patient Ankush Gosain, MD, PhD, Regan F. Williams, MD, Martin L. Blakely, MD, MS* Division of Pediatric Surgery, Department of Surgery, University of Tennessee Health Sciences Center, 777 Washington Avenue, Suite P220, Memphis, TN 38105, USA

A

ppendicitis is the most common intra-abdominal condition requiring urgent operation in pediatric patients. Annually, more than 100,000 children are treated for appendicitis in the United States [1]. The spectrum of presentation ranges from acute nonruptured appendicitis to ruptured appendicitis (RA) with abscess formation. Although the management of acute appendicitis (AA) is rarely debated, the optimal treatment for ruptured appendicitis remains controversial. It is clear from the literature that patients with ruptured appendicitis undergo more diagnostic studies and invasive procedures and these patients have longer hospitalizations than those with nonruptured appendicitis. For these reasons, preoperatively diagnosing ruptured appendicitis may allow for triage of limited resources and informed discussions of expected clinical course. The distinction between nonruptured and ruptured appendicitis is also important because the optimal treatment of each condition may differ. Additionally, the design of prospective studies to compare early versus interval appendectomy for ruptured appendicitis will rely on the accurate preoperative diagnosis of ruptured appendicitis. DIAGNOSIS OF APPENDICITIS VERSUS NONAPPENDICITIS CAUSES OF ABDOMINAL PAIN Historically, there has been a great deal of focus in the primary care, emergency medicine, and surgical literature on the preoperative diagnosis of appendicitis in patients presenting with abdominal pain [2]. These studies have been motivated by the desire to accurately make the diagnosis of appendicitis while avoiding or reducing the incidence of negative appendectomy (appendectomy for a histologically normal appendix). Traditionally, a false-positive rate as high as 25% has been accepted to avoid high perforation rates [3,4]. However, an

*Corresponding author. E-mail address: [email protected]. 0065-3411/10/$ – see front matter doi:10.1016/j.yasu.2010.05.021

ª 2010 Elsevier Inc. All rights reserved.

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improved understanding of the morbidity associated with a negative appendectomy, including abscess formation, wound infection, and bowel obstruction, has lowered the acceptance level of negative appendectomies [5]. Because infants and children will often present with atypical symptoms, clinical scoring systems focusing on differentiating appendicitis from nonappendicitis conditions in adults and children are plentiful in the literature [6–9]. The Alvarado and Samuel scoring systems have received the most attention [8,10]. These systems have been based on elements of the history, physical examination, and laboratory findings. The MANTRELS score, described by Alvarado, includes migration of pain, anorexia, nausea/vomiting, tenderness in the right lower quadrant, rebound tenderness, elevation of temperature, leukocytosis, and shift to the left on the cell count differential. Since its publication, the MANTRELS score has been prospectively evaluated and shown to have a sensitivity of 76% to 90% and specificity of 50% to 81% [11]. The reported accuracy of these scoring systems has varied, depending on the study cohort involved [12]. Additionally, various groups have evaluated the value of imaging modalities, namely ultrasound or CT, for the diagnosis of appendicitis. Broadly speaking, ultrasound appears to be most helpful in nonobese patients and may provide alternative diagnoses to appendicitis [13,14]. Additionally, ultrasound has the benefit of avoiding exposing children to ionizing radiation [15]. Limitations of ultrasound include its operator-dependant nature, lack of sensitivity in early appendicitis when only a portion of the appendix is involved, and inability to visualize the appendix in obese individuals. Because of these limitations, the reported sensitivity varies from 78% to 94% and specificity from 89% to 98% in the pediatric literature [16–19]. CT is not subject to the limitations of operator dependence and is useful for identifying alternative diagnoses or sequelae of ruptured appendicitis. Additionally, CT is able to demonstrate a normal appendix in 66% to 100% of cases [20]. CT is highly sensitive for acute appendicitis, with most studies reporting 95% to 99%, and specificity widely reported as greater than 95% [21,22]. Limitations of CT in the diagnosis of appendicitis include the inability to evaluate the compressibility of the appendix and the administration of ionizing radiation and the subsequent risk of malignancy [2,23]. Additionally, the specific protocols for CT scan vary from institution to institution, with debate over the superiority of noncontrast enhanced studies versus intravenous contrast alone versus rectal contrast in addition to intravenous contrast [24,25]. Although imaging for possible appendicitis has become routine in many centers, there continue to be those that advocate a diagnostic strategy based on the clinical acumen of an experienced surgeon [26]. In their study, Kosloske and colleagues demonstrated 99% sensitivity, 93% specificity, and 97% diagnostic accuracy for appendicitis by surgeon-directed history and physical examination followed by diagnostic imaging. In their series, one-third of subjects had undergone ultrasound or CT imaging before surgical consultation, with another 17% of the subjects receiving imaging after evaluation by the surgeon.

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There was no difference in the diagnostic accuracy for those subjects that received imaging before pediatric surgical evaluation as compared with those that received it postreferral. Additionally, the negative appendectomy rate of 5% in their series compares favorably to other published series. Recently, the authors have demonstrated that pediatric surgeons are quite good at differentiating appendicitis and nonappendicitis causes of abdominal pain, and have focused our attention on the distinction between acute nonruptured and ruptured appendicitis [27]. DEFINITION OF RUPTURED APPENDICITIS The pathogenesis of appendicitis is well established [28,29]. The initiating event is luminal obstruction, typically caused by lymphoid hyperplasia or an obstructing fecalith. Additional etiologies of luminal obstruction have been described and include foreign bodies, malignancy, and parasitic infections. Luminal obstruction results in bacterial stasis and overgrowth, with resultant distention of the blind-ending appendix (acute appendicitis). With sufficient luminal distention, the intraluminal pressure of the appendix exceeds that of its arterial inflow, resulting in ischemia of the wall (gangrenous appendicitis). Finally, perforation occurs at the site of ischemia, resulting in free spillage of pus (ruptured appendicitis). Numerous investigators have postulated that perforation is more likely at the site of, and in the presence of, an obstructing fecalith [30]. Abscess formation may ensue as part of the normal host response to perforation. Intraoperatively, the distinction between gangrenous and ruptured appendicitis may be difficult to make. Accordingly, the incidence of RA in children varies greatly in multiple large series, from 20% to 76% [31]. Recently, multiple groups have advocated a strict definition of ruptured appendicitis to include the intraoperative or pathologic identification of either a hole in the appendix or the presence of a fecalith in the abdomen [32]. St Peter and colleagues argue that by adopting a strict definition of perforation, cases of suppurative and gangrenous appendicitis that may have been included in the ruptured category in prior studies will be eliminated from analysis and thereby reduce some of the variability in results that are reported in the literature and allow for direct comparisons between studies. IMPORTANCE OF DISTINGUISHING ACUTE AND RUPTURED APPENDICITIS Ruptured appendicitis comprises a larger percentage of appendicitis in children than in adults, ranging from 30% to 74% depending on the study population [33]. Although the optimal treatment for AA is rarely debated, the approach to RA varies greatly between pediatric surgeons and medical centers [31,34,35]. Some surgeons advocate early appendectomy, preceded by a brief period of antibiotic administration and fluid resuscitation. Others advocate for interval appendectomy, with antibiotic administration until the child has been afebrile for a variable period of time (typically 24–48 hours). These patients return 6 to 8 weeks after their initial presentation for elective removal of their appendix, often as an outpatient

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procedure [36]. Finally, there are those that advocate for total nonoperative treatment, with antibiotic therapy and no appendectomy [37]. There exists little consensus among pediatric surgeons as to the optimal treatment of ruptured appendicitis [38]. Initial nonoperative management of appendicitis presenting as appendiceal abscess or phlegmon has been shown to be safe and effective [39–41]. Following nonoperative management, interval appendectomy is employed to avoid a 5% to 37% risk of recurrent appendicitis [39,42,43]. Recently, a few groups have argued against this paradigm, citing low rates of recurrent appendicitis in patients treated nonoperatively. However, the follow-up period in these series is short, and there is some evidence that recurrent appendicitis results in larger resections (eg, cecectomy or hemicolectomy) than would otherwise have been necessary [37]. Retrospective reviews have demonstrated that those patients with a longer duration of symptoms tend to be the ones chosen for nonoperative management [44,45]. Additionally, these studies demonstrate that the patient subset undergoing immediate appendectomy has a higher incidence of complications [46,47], although this is possibly because sicker patients are chosen to undergo immediate appendectomy. The goals of therapy in the treatment of ruptured appendicitis are minimizing morbidity, costs, hospital length of stay, and readmissions. Following appendectomy, patients with ruptured appendicitis are at higher risk for development of intra-abdominal abscess. A recent trial used a case-control methodology to identify risk factors for abscess formation in patients undergoing appendectomy for ruptured appendicitis [48]. In this study, several demographic and perioperative factors that had previously been identified in the literature as predictive of abscess formation were studied in three-quarters of the subject population and a model to predict abscess formation was developed and tested in the remaining quarter of subjects. The investigators noted that diarrhea at the time of presentation substantially increased the odds of developing an intra-abdominal abscess or other infectious complications postoperatively. However, the predictive model generated based on their data set did not fit their remaining subjects well, decreasing the utility of their findings. One group has evaluated the incidence of abscess formation in their subject cohort before and after the application of a strict definition of ruptured appendicitis [32]. They have observed an increased incidence of intra-abdominal abscess in the ruptured subject cohort and a decreased incidence in the nonruptured cohort, reinforcing the concept that the risk of postoperative complications increases as one progresses further along the spectrum from acute to ruptured appendicitis. WHY DO PATIENTS FAIL NONOPERATIVE TREATMENT? The failure rate for nonoperative management varies in the literature from 9% to 40% [44–46,49]. Bufo and colleagues [50] reviewed 87 cases of ruptured appendicitis of which 41 were treated nonoperatively. In their cohort, 7 subjects

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(17%) failed nonoperative management almost exclusively because of the presence of bowel obstruction. Although the nonoperative group had a decreased hospital stay and fewer complications than the operative group, this benefit was not seen when the subjects were analyzed in an intent-to-treat fashion. Other groups have published data indicating that failure of nonoperative management results from persistent or increasing abdominal pain, increasing fevers, and worsening abdominal tenderness [51,52]. Additionally, multiple groups have also reported a higher incidence of complications in those patients that fail nonoperative management [44,53]. These complications include wound infections and abscess formation, resulting in longer hospital stay [54]. PREOPERATIVE DIAGNOSIS OF RUPTURED APPENDICITIS If treatment recommendations for ruptured and acute appendicitis differ and clinical trials are to be conducted in patients with ruptured appendicitis, it becomes critically important to distinguish between the two preoperatively [27]. In a recent study, the authors proposed to determine the accuracy of pediatric surgeons’ preoperative diagnosis of acute and ruptured appendicitis, to prospectively identify and rank patient characteristics that increase the likelihood of having ruptured appendicitis, and to investigate potential methods of improving our ability to distinguish acute from ruptured appendicitis preoperatively. Data were prospectively collected over a period of 9 months on all subjects younger than 18 years of age referred for surgical consultation for abdominal pain at a regional children’s hospital. Subject demographics, elements of the history and physical examination, laboratory values, and diagnostic imaging reports were collected. The pediatric surgical team, including an attending pediatric surgeon, a fellow in pediatric surgery, and a general surgery resident, recorded an agreed initial (preoperative) diagnosis using all data available. Establishing the preoperative diagnosis was a dedicated part of this study and typically involved repeated history and physical examinations by multiple team members (over a brief period, usually in the emergency department), independent reviews of the available data, and consultation with pediatric radiologists when needed for detailed review of the imaging studies. The use of advanced imaging (CT or ultrasonography) was decided by emergency department physicians, referral physicians, or pediatric surgeons. When there was disagreement between team members about the initial diagnosis, the attending pediatric surgeon made the final decision. Final diagnosis was determined using operative findings, pathology reports, or discharge diagnosis in those not undergoing operation. A total of 247 subjects were evaluated over a 9-month study period. Ninetyeight had AA, 53 had RA, and 96 did not have appendicitis. The median age was 10 years (range 1 to 17 years), 39% were girls, and the median duration of symptoms at the time of surgery consultation was 2.8 days. The majority of the subjects were Caucasian (52%); smaller percentages were African American (34%) or Hispanic (9%). Fifty-five percent of the subjects had

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localized right lower quadrant pain and 9% presented with generalized peritonitis. Most subjects underwent some form of diagnostic imaging, with 79% of subjects having a CT scan, 21% receiving an abdominal ultrasound, and 15% undergoing both. The perforation rate among all subjects with appendicitis was 35%. The 98 children with a discharge diagnosis of AA based on intraoperative findings were older and had a shorter duration of symptoms than subjects with ruptured or no appendicitis. These children had a median duration of symptoms of 24 hours, with 73% presenting with emesis and 75% complaining of anorexia. Ninety-one percent of subjects with AA had localized right lower quadrant pain and only 30% had rebound tenderness. The median white blood cell (WBC) count was lower in subjects with AA, although there was no difference in the percentage of bands among the 3 diagnostic groups. Seventy-two percent of these subjects had a CT scan performed and 10% underwent abdominal ultrasonography. All subjects with a preoperative diagnosis of AA underwent an operation, with a negative appendectomy rate of 4.4%. The RA group consisted of 53 subjects, with a median age of 9.2 years; 34% were girls. Subjects with RA had symptoms for a median of 86.7 hours, similar to the not appendicitis (NA) group, and had a higher WBC count (median 17,900 cells/lL). The majority of subjects with RA had diffuse abdominal pain (62%) and CT scans performed (94%). Of the 53 subjects, 35 underwent immediate appendectomy, 17 had an interval appendectomy 7 to 21 weeks after initial presentation with RA, and 1 subject was managed with intravenous antibiotics but did not return for interval appendectomy. Ninety-six subjects in the study cohort did not have appendicitis. These subjects were similar to subjects in the RA group in age and duration of symptoms. But the NA group had a larger percentage of girls and a lower median WBC count than the AA or RA groups. There were 8 subjects with diagnoses other than appendicitis that underwent exploratory laparotomy. Two of these subjects had RA identified at the time of exploration. Follow-up was conducted on all subjects who did not undergo an operation (11 to 20 months after discharge) either by telephone follow-up questionnaire (76%), review of the hospital medical record system, or both. No subject reported a subsequent diagnosis of appendicitis during this follow-up period. Pediatric surgeons at the authors’ institution diagnosed acute, ruptured, and not appendicitis with an accuracy of 93.5%, 93.5%, and 96.8%, respectively. Although pediatric surgeons were able to diagnose AA with high sensitivity (92.6%) and specificity (94.9%), these figures for the diagnosis of RA were mixed. RA was correctly diagnosed preoperatively with a sensitivity of 96.4% and a specificity of 83%. Appendicitis was excluded with high sensitivity (98.7%) and specificity (93.8%). Although the overall surgeon’s preoperative diagnostic accuracy was 92%, there was variability among the 5 attending pediatric surgeons participating in the study. Accuracy rates varied from 97% (36 subjects) to 83% (30 subjects) among the pediatric surgeons, for an absolute difference of approximately 14%.

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Univariate analysis was also performed on all preoperative variables comparing subjects with a discharge diagnosis of RA to those with AA (Table 1). Continuous variables were converted to categorical variables by using a cut point that maximized the Youden’s index. The Youden’s index is the value that maximizes the sensitivity and specificity of any continuous variable, helping to choose an appropriate cut point for dichotomization. No single variable accurately predicted the final diagnosis. Decreased age and African American race were significantly more common in subjects with RA. Gender had no association with final diagnosis. Elements of the history significantly associated with RA included anorexia, emesis, and duration of symptoms greater than 48 hours. Signs of ruptured appendicitis included fever (temperature >38 C), right lower quadrant tenderness to palpation, diffuse abdominal tenderness, generalized peritonitis, and high white blood cell count (WBC >19,400 cells/lL), although the presence of diffuse abdominal pain and generalized peritonitis was positively correlated with each other and negatively correlated with right lower quadrant tenderness to palpation. Extra-luminal air, fecalith and abscess on CT scan were also associated with RA. All variables from the univariate analysis with a P value less than or equal to .2 were placed into the multivariable analysis. Table 1 Univariate analysis for ruptured appendicitis Variable Patient demographics Age >6 y Female gender African American Hispanic Symptoms Anorexia Diarrhea Emesis Duration >48 h Signs Temperature >38 C Localized RLQ ttp Rebound RLQ ttp Diffuse ttp Generalized peritonitis WBC >19,400 cells/lL CT findings Extraluminal air Fecalith Free fluid Abscess Dilated appendix

Odds ratio

95% CI

P value

0.848 0.945 2.357 1.8

0.386–1.864 0.465–1.919 1.109–5.007 0.580–5.58

.6812 .8748 .0258 .3088

3.810 1.583 3.268 11.511

1.243–11.676 0.754–3.323 1.176–9.082 4.991–26.547

.0192 .2244 .0231 <.0001

4.514 0.078 0.725 12.912 18.364 4.049

2.205–9.241 0.034–0.176 0.335–1.567 5.647–29.526 5.086–66.303 1.926–8.509

<.0001 <.0001 .4131 <.0001 <.0001 .0002

8.654 4.070 1.703 14.194 0.767

1.782–42.025 1.893–8.752 0.822–3.528 4.464–45.131 0.372–1.579

.0074 .0003 .1520 <.0001 .4710

Abbreviations: CI, confidence interval; RLQ, right lower quadrant.

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Table 2 Multivariate analysis for ruptured appendicitis and scoring system Variable

Odds ratio

95% CI

P value

Beta coefficient

Score

Generalized tenderness Abscess on CT Duration >48 h WBC >19,400 cells/lL Fecalith on CT

7.4 6.7 6.4 5.6 4.5

2.2–24.5 1.6–27.1 1.9–21.7 1.6–19.6 1.4–14.7

<.01 <.01 <.01 <.01 .01

2.00 1.90 1.86 1.75 1.51

4 3 3 2 1

Abbreviation: CI, confidence interval.

The final multivariable model of RA was completed in a manual, backward, stepwise fashion to determine preoperative variables independently associated with RA (Table 2). Based on this analysis, 5 preoperative variables were independently associated with the diagnosis of RA: duration of symptoms greater than 48 hours, pain not localized to the right lower quadrant, WBC greater than 19,400 cells/lL, and fecalith and abscess on CT scan. Using the predictors identified with multivariable analysis, a scoring system was constructed to evaluate whether an objective score based on available data might improve the ability to accurately diagnose RA (see Table 2). Points were assigned to each preoperative variable based on the beta coefficients from the multivariable final model. Pain not localized to the right lower quadrant had a beta coefficient of 2.00 and was assigned 4 points. Abscess on CT scan and duration of symptoms greater than 48 hours had similar coefficients (1.90 and 1.86, respectively) and were assigned 3 points each. WBC count greater than 19,400 cells/lL had a beta coefficient of 1.75 and was assigned 2 points, and fecalith on CT scan had the lowest significant correlation with ruptured appendicitis, with a beta coefficient of 1.51 (1 point). The subject’s Table 3 Accuracy of ruptured appendicitis scoring system Score

Sensitivity

Specificity

PDLR

NDLR

1 2 3 4 5 6 7 8 9 10 11 12 13

98 96 92 92 82 78 68 62 47 35 18 7 6

46 56 65 81 90 92 94 97 98 99 1 1 1

1.8 2.1 2.6 4.9 7.9 9.1 11.3 24.3 27.0 41.0 — — —

0.04 0.07 0.12 0.1 0.19 0.24 0.33 0.38 0.53 0.65 0.82 0.92 0.94

Abbreviations: NDLR, negative diagnostic likelihood ratio; PDLR, positive diagnostic likelihood ratio.

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score was calculated by adding the appropriate points based on the number of significant preoperative variables present. Positive and negative likelihood ratios (LR) were calculated for the pediatric surgeon’s preoperative diagnosis and the score according to the scoring system (Table 3). SUMMARY There have been several retrospective studies addressing which patient characteristics are associated with an increased risk for RA rather than AA. The most common variables reported to increase the risk of RA from these studies include longer duration of symptoms (>2 to 3 days), signs of diffuse peritoneal irritation on abdominal examination, age younger than 8 to 9 years, higher temperature elevation, and multiple CT findings [55–60]. Laboratory data reported to be associated with ruptured appendicitis include elevated C-reactive protein, erythrocyte sedimentation rate greater than 25 mm/h, increased band neutrophils, and increased total white blood cell count [55,58–60]. The authors’ data provide a ranking of variables that are routinely available preoperatively in patients referred for surgical consultation to rule out appendicitis in order of strength of association with a final diagnosis of RA. The most important preoperative risk factors identified in the authors’ study cohort, in rank order, were duration of symptoms greater than 48 hours, diffuse abdominal pain, WBC greater than 19,400 cells/lL, abscess identified on CT, and fecalith identified on CT. Age was not an independent significant risk factor for RA. The derivation of a novel scoring system, based on the variables found to be significant in the multivariable regression analyses, is an attempt to improve the diagnostic accuracy of RA in the future. As mentioned earlier, the pediatric surgeon’s preoperative diagnosis was somewhat variable between the 5 attending surgeons participating in this study. Because the distinction between AA and RA was a major part of this prospective study, it is possible that this distinction in routine clinical practice could be somewhat lower. Also, the accuracy of other pediatric surgeon groups and other medical centers is largely unknown. An objective scoring system, if validated, could decrease the variability of this diagnostic process and potentially improve overall distinction between AA and RA. Depending on the cut point chosen, the sensitivity and specificity of the scoring system vary considerably. The authors propose that a cut point that achieves a high specificity (at the expense of sensitivity) would potentially be most valuable. The authors’ data indicate that the pediatric surgeons accurately distinguish appendicitis from nonappendicitis abdominal pain with high sensitivity, specificity, and accuracy. Distinguishing AA from RA is more difficult. Once a diagnosis of appendicitis has been made, the scoring system might be used to assist in distinguishing the acute from the ruptured form. Deciding where the cut point should be in this scoring system significantly influences its performance. As the cut-point value increases, specificity and the positive likelihood ratio increase, and the sensitivity decreases markedly. Using a cut point of 9, the scoring system outperforms the surgeon’s preoperative diagnosis in terms of positive LR and specificity by a degree that, if reproducible, would

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likely help practicing pediatric surgeons make clinically relevant decisions. Confirmation of this scoring system in a different subject cohort will be necessary to validate its clinical utility. To this end, plans are underway to test this scoring system in a multicenter, prospective cohort study. FUTURE DIRECTIONS The diagnosis of appendicitis has shifted from one made purely on the basis of history and physical examination to a sophisticated evaluation of elements of the presentation and imaging. This evolution has resulted from an improved understanding of the differing natural history of acute and ruptured appendicitis and the ongoing debate as to optimal treatment of these conditions (eg, initial nonoperative vs immediate operation). Additionally, as imaging techniques improve, the diagnosis of appendicitis is more frequently being made before consultation with a surgeon. As more data are published about potential harmful effects of ionizing radiation from abdominal and pelvic CT scans, heavy reliance on these studies is problematic. Limitations of the authors’ recent study, and those of others, include single-center design, low numbers of subjects, and frequent use of advanced imaging (especially abdominal CT). Many scoring systems appear accurate when applied to the study populations from which they are derived, but then are less accurate when one attempts to validate them in other studies. It remains unknown how accurate pediatric surgeons’ preoperative diagnoses are across multiple centers or how the authors’ recently developed scoring system might perform in larger and more diverse study populations. References [1] Addiss DG, Shaffer N, Fowler BS, et al. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol 1990;132(5):910–25. [2] Brennan GD. Pediatric appendicitis: pathophysiology and appropriate use of diagnostic imaging. CJEM 2006;8(6):425–32. [3] Larsson PG, Henriksson G, Olsson M, et al. Laparoscopy reduces unnecessary appendectomies and improves diagnosis in fertile women. A randomized study. Surg Endosc 2001;15(2):200–2. [4] Wilson EB. Surgical evaluation of appendicitis in the new era of radiographic imaging. Semin Ultrasound CT MR 2003;24(2):65–8. [5] Colson M, Skinner KA, Dunnington G. High negative appendectomy rates are no longer acceptable. Am J Surg 1997;174(6):723–6 [discussion: 726–7]. [6] Bundy DG, Byerley JS, Liles EA, et al. Does this child have appendicitis? JAMA 2007;298(4):438–51. [7] Kharbanda AB, Taylor GA, Fishman SJ, et al. A clinical decision rule to identify children at low risk for appendicitis. Pediatrics 2005;116(3):709–16. [8] Alvarado A. A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med 1986;15(5):557–64. [9] Enochsson L, Gudbjartsson T, Hellberg A, et al. The Fenyo-Lindberg scoring system for appendicitis increases positive predictive value in fertile women–a prospective study in 455 patients randomized to either laparoscopic or open appendectomy. Surg Endosc 2004;18(10):1509–13. [10] Samuel M. Pediatric appendicitis score. J Pediatr Surg 2002;37(6):877–81.

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[11] Kwok MY, Kim MK, Gorelick MH. Evidence-based approach to the diagnosis of appendicitis in children. Pediatr Emerg Care 2004;20(10):690–8 [quiz: 699–701]. [12] Schneider C, Kharbanda A, Bachur R. Evaluating appendicitis scoring systems using a prospective pediatric cohort. Ann Emerg Med 2007;49(6):778–84, 784, e771. [13] Blebea JS, Meilstrup JW, Wise SW. Appendiceal imaging: which test is best? Semin Ultrasound CT MR 2003;24(2):91–5. [14] Even-Bendahan G, Lazar I, Erez I, et al. Role of imaging in the diagnosis of acute appendicitis in children. Clin Pediatr (Phila) 2003;42(1):23–7. [15] Taylor GA. Suspected appendicitis in children: in search of the single best diagnostic test. Radiology 2004;231(2):293–5. [16] Hayden CK Jr, Kuchelmeister J, Lipscomb TS. Sonography of acute appendicitis in childhood: perforation versus nonperforation. J Ultrasound Med 1992;11(5):209–16. [17] Rubin SZ, Martin DJ. Ultrasonography in the management of possible appendicitis in childhood. J Pediatr Surg 1990;25(7):737–40. [18] Sivit CJ, Newman KD, Boenning DA, et al. Appendicitis: usefulness of US in diagnosis in a pediatric population. Radiology 1992;185(2):549–52. [19] Vignault F, Filiatrault D, Brandt ML, et al. Acute appendicitis in children: evaluation with US. Radiology 1990;176(2):501–4. [20] Sivit CJ, Applegate KE. Imaging of acute appendicitis in children. Semin Ultrasound CT MR 2003;24(2):74–82. [21] Rao PM, Rhea JT, Rattner DW, et al. Introduction of appendiceal CT: impact on negative appendectomy and appendiceal perforation rates. Ann Surg 1999;229(3):344–9. [22] Stroman DL, Bayouth CV, Kuhn JA, et al. The role of computed tomography in the diagnosis of acute appendicitis. Am J Surg 1999;178(6):485–9. [23] Hall EJ. Lessons we have learned from our children: cancer risks from diagnostic radiology. Pediatr Radiol 2002;32(10):700–6. [24] Kaiser S, Finnbogason T, Jorulf HK, et al. Suspected appendicitis in children: diagnosis with contrast-enhanced versus nonenhanced Helical CT. Radiology 2004;231(2):427–33. [25] Kharbanda AB, Taylor GA, Bachur RG. Suspected appendicitis in children: rectal and intravenous contrast-enhanced versus intravenous contrast-enhanced CT. Radiology 2007;243(2):520–6. [26] Kosloske AM, Love CL, Rohrer JE, et al. The diagnosis of appendicitis in children: outcomes of a strategy based on pediatric surgical evaluation. Pediatrics 2004;113(1 Pt 1):29–34. [27] Williams RF, Blakely ML, Fischer PE, et al. Diagnosing ruptured appendicitis preoperatively in pediatric patients. J Am Coll Surg 2009;208(5):819–25 [discussion: 826–8]. [28] Fitz R. Perforating inflammation of the vermiform appendix with special reference to its early diagnosis and treatment. Trans Assoc Am Physicians 1886;1:107–44. [29] Wangensteen OH, Dennis C. Experimental proof of the obstructive origin of appendicitis in man. Ann Surg 1939;110(4):629–47. [30] Ein SH, Langer JC, Daneman A. Nonoperative management of pediatric ruptured appendix with inflammatory mass or abscess: presence of an appendicolith predicts recurrent appendicitis. J Pediatr Surg 2005;40(10):1612–5. [31] Newman K, Ponsky T, Kittle K, et al. Appendicitis 2000: variability in practice, outcomes, and resource utilization at thirty pediatric hospitals. J Pediatr Surg 2003;38(3):372–9 [discussion: 372–9]. [32] St Peter SD, Sharp SW, Holcomb GW 3rd, et al. An evidence-based definition for perforated appendicitis derived from a prospective randomized trial. J Pediatr Surg 2008;43(12):2242–5. [33] Ponsky TA, Huang ZJ, Kittle K, et al. Hospital- and patient-level characteristics and the risk of appendiceal rupture and negative appendectomy in children. JAMA 2004;292(16): 1977–82. [34] Morrow SE, Newman KD. Current management of appendicitis. Semin Pediatr Surg 2007;16(1):34–40.

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[35] Muehlstedt SG, Pham TQ, Schmeling DJ. The management of pediatric appendicitis: a survey of North American Pediatric Surgeons. J Pediatr Surg 2004;39(6):875–9 [discussion: 875–9]. [36] Whyte C, Tran E, Lopez ME, et al. Outpatient interval appendectomy after perforated appendicitis. J Pediatr Surg 2008;43(11):1970–2. [37] Kaminski A, Liu IL, Applebaum H, et al. Routine interval appendectomy is not justified after initial nonoperative treatment of acute appendicitis. Arch Surg 2005;140(9): 897–901. [38] Chen C, Botelho C, Cooper A, et al. Current practice patterns in the treatment of perforated appendicitis in children. J Am Coll Surg 2003;196(2):212–21. [39] Brown CV, Abrishami M, Muller M, et al. Appendiceal abscess: immediate operation or percutaneous drainage? Am Surg 2003;69(10):829–32. [40] Oliak D, Yamini D, Udani VM, et al. Initial nonoperative management for periappendiceal abscess. Dis Colon Rectum 2001;44(7):936–41. [41] Janik JS, Ein SH, Shandling B, et al. Nonsurgical management of appendiceal mass in late presenting children. J Pediatr Surg 1980;15(4):574–6. [42] Friedell ML, Perez-Izquierdo M. Is there a role for interval appendectomy in the management of acute appendicitis? Am Surg 2000;66(12):1158–62. [43] Yamini D, Vargas H, Bongard F, et al. Perforated appendicitis: is it truly a surgical urgency? Am Surg 1998;64(10):970–5. [44] Henry MC, Gollin G, Islam S, et al. Matched analysis of nonoperative management vs immediate appendectomy for perforated appendicitis. J Pediatr Surg 2007;42(1):19–23 [discussion: 23–4]. [45] Weber TR, Keller MA, Bower RJ, et al. Is delayed operative treatment worth the trouble with perforated appendicitis is children? Am J Surg 2003;186(6):685–8 [discussion: 688–9]. [46] Vane DW, Fernandez N. Role of interval appendectomy in the management of complicated appendicitis in children. World J Surg 2006;30(1):51–4. [47] Roach JP, Partrick DA, Bruny JL, et al. Complicated appendicitis in children: a clear role for drainage and delayed appendectomy. Am J Surg 2007;194(6):769–72 [discussion: 772–3]. [48] Henry MC, Walker A, Silverman BL, et al. Risk factors for the development of abdominal abscess following operation for perforated appendicitis in children: a multicenter casecontrol study. Arch Surg 2007;142(3):236–41 [discussion: 241]. [49] Samuel M, Hosie G, Holmes K. Prospective evaluation of nonsurgical versus surgical management of appendiceal mass. J Pediatr Surg 2002;37(6):882–6. [50] Bufo AJ, Shah RS, Li MH, et al. Interval appendectomy for perforated appendicitis in children. J Laparoendosc Adv Surg Tech A 1998;8(4):209–14. [51] Aprahamian CJ, Barnhart DC, Bledsoe SE, et al. Failure in the nonoperative management of pediatric ruptured appendicitis: predictors and consequences. J Pediatr Surg 2007;42(6): 934–8 [discussion: 938]. [52] Whyte C, Levin T, Harris BH. Early decisions in perforated appendicitis in children: lessons from a study of nonoperative management. J Pediatr Surg 2008;43(8):1459–63. [53] Kogut KA, Blakely ML, Schropp KP, et al. The association of elevated percent bands on admission with failure and complications of interval appendectomy. J Pediatr Surg 2001;36(1):165–8. [54] Gillick J, Mohanan N, Das L, et al. Laparoscopic appendectomy after conservative management of appendix mass. Pediatr Surg Int 2008;24(3):299–301. [55] Beltran MA, Almonacid J, Vicencio A, et al. Predictive value of white blood cell count and C-reactive protein in children with appendicitis. J Pediatr Surg 2007;42(7):1208–14. [56] Bickell NA, Aufses AH Jr, Rojas M, et al. How time affects the risk of rupture in appendicitis. J Am Coll Surg 2006;202(3):401–6. [57] Brender JD, Marcuse EK, Koepsell TD, et al. Childhood appendicitis: factors associated with perforation. Pediatrics 1985;76(2):301–6.

RUPTURED APPENDICITIS

85

[58] Lin CJ, Chen JD, Tiu CM, et al. Can ruptured appendicitis be detected preoperatively in the ED? Am J Emerg Med 2005;23(1):60–6. [59] Nelson DS, Bateman B, Bolte RG. Appendiceal perforation in children diagnosed in a pediatric emergency department. Pediatr Emerg Care 2000;16(4):233–7. [60] Peng YS, Lee HC, Yeung CY, et al. Clinical criteria for diagnosing perforated appendix in pediatric patients. Pediatr Emerg Care 2006;22(7):475–9.