title: Feasibility of a nonoperative management strategy for uncomplicated acute appendicitis in children. Economic evaluation of antibiotic therapy versus appendicectomy for the treatment of uncomplicated acute appendicitis from the APPAC randomized clinical trial A prospective randomized controlled multicenter trial comparing antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis (APPAC trial) Randomized controlled trial of appendicectomy versus antibiotic therapy for acute appendicitis Antibiotics‐First Versus Surgery for Appendicitis: A US Pilot Randomized Controlled Trial Allowing Outpatient Antibiotic Management Non-operative management of early, acute appendicitis in children: is it safe and effective? Comparison of operative and non operative management of acute appendicitis. Initial antibiotic treatment for acute simple appendicitis in children is safe: Short-term results from a multicenter, prospective cohort study. Treatment of appendiceal mass: prospective, randomized clinical trial. Risk Factors for Adverse Outcomes After the Surgical Treatment of Appendicitis in Adults Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial
abstract: BACKGROUND For decades , urgent operation has been considered the only appropriate management of acute appendicitis in children . The purpose of this study was to investigate the feasibility of nonoperative management of uncomplicated acute appendicitis in children . STUDY DESIGN A prospect i ve nonr and omized clinical trial of children with uncomplicated acute appendicitis comparing nonoperative management with urgent appendectomy  was performed . The primary result was 30-day success rate of nonoperative management . Secondary outcomes included comparisons of disability days , missed school days , hospital length of stay , and measures of quality of life and health care satisfaction . RESULTS Seventy-seven patients were enrolled during October 2012 to October 2013 ; 30 chose nonoperative management and 47 chose surgery . There were no significant differences in demographic or clinical characteristics . The immediate and 30-day success rates of nonoperative management were 93 % ( 28 of 30 ) and 90 % ( 27 of 30 ) . There was no evidence of progression of appendicitis to rupture at the time of surgery in the 3 patients for whom nonoperative management failed . Compared with the surgery group , the nonoperative group had fewer disability days ( 3 vs 17 days ; p < 0.0001 ) , returned to school more quickly ( 3 vs 5 days ; p = 0.008 ) , and exhibited higher quality of life scores in both the child ( 93 vs 88 ; p = 0.01 ) and the parent ( 96 vs 90 ; p = 0.03 ) , but incurred a longer length of stay ( 38 vs 20 hours ; p < 0.0001 ) . CONCLUSIONS Nonoperative management of uncomplicated acute appendicitis in children is feasible , with a high 30-day success rate and short-term benefits that include quicker recovery and improved quality of life scores . Additional follow-up will allow for determination of longer-term success rate , safety , and cost effectiveness An increasing amount of evidence supports antibiotic therapy for treating uncomplicated acute appendicitis . The objective of this study was to compare the costs of antibiotics alone  versus  appendicectomy  in treating uncomplicated acute appendicitis within the r and omized controlled APPAC ( APPendicitis ACuta ) trial Background Although the st and ard treatment of acute appendicitis ( AA ) consists of an early appendectomy , there has recently been both an interest and an increase in the use of antibiotic therapy as the primary treatment for uncomplicated AA . However , the use of antibiotic therapy in the treatment of uncomplicated AA is still controversial . Methods / design The APPAC trial is a r and omized prospect i ve controlled , open label , non-inferiority multicenter trial design ed to compare antibiotic therapy ( ertapenem ) with emergency appendectomy in the treatment of uncomplicated AA . The primary endpoint of the study is the success of the r and omized treatment . In the antibiotic treatment arm successful treatment is defined as being discharged from the hospital without the need for surgical intervention and no recurrent appendicitis during a minimum follow-up of one-year ( treatment efficacy ) . Treatment efficacy in the operative treatment arm is defined as successful appendectomy evaluated to be 100 % . Secondary endpoints are post-intervention complications , overall morbidity and mortality , the length of hospital stay and sick leave , treatment costs and pain scores ( VAS , visual analoque scale ) . A maximum of 610 adult patients ( aged 18–60 years ) with a CT scan confirmed uncomplicated AA will be enrolled from six hospitals and r and omized by a closed envelope method in a 1:1 ratio either to undergo emergency appendectomy or to receive ertapenem ( 1 g per day ) for three days continued by oral levofloxacin ( 500 mg per day ) plus metronidazole ( 1.5 g per day ) for seven days . Follow-up by a telephone interview will be at 1 week , 2 months and 1 , 3 , 5 and 10 years ; the primary and secondary endpoints of the trial will be evaluated at each time point . Discussion The APPAC trial aims to provide level I evidence to support the hypothesis that approximately 75–85 % of patients with uncomplicated AA can be treated with effective antibiotic  therapy avoiding unnecessary appendectomies and the related operative morbidity , also result ing in major cost savings . Trial registration Clinical In a prospect i ve controlled study the effect of antibiotics as the only treatment in acute appendicitis was evaluated . Of 40 patients admitted with a duration of abdominal pain of less than 72 h , 20 received antibiotics intravenously for 2 days followed by oral treatment for 8 days and 20 considered as controls were r and omized to surgery . All patients treated conservatively were discharged within 2 days , except one who required surgery after 12 h because of peritonitis secondary to perforated appendicitis . Seven patients were readmitted within 1 year as a result of recurrent appendicitis and underwent surgery , when appendicitis was confirmed . The diagnostic accuracy within the operated group was 85 per cent . One patient had perforated appendicitis at operation .  Antibiotic treatment  in patients with  acute appendicitis was as effective as surgery . The patients had less pain and required less analgesia , but the recurrence rate was high Study objective R and omized trials suggest that nonoperative treatment of uncomplicated appendicitis with antibiotics‐first is safe . No trial has evaluated outpatient treatment and no US r and omized trial has been conducted , to our knowledge . This pilot study assessed feasibility of a multicenter US study comparing antibiotics‐first , including outpatient management , with appendectomy . Methods Patients aged 5 years or older with uncomplicated appendicitis at 1 US hospital were r and omized to appendectomy or intravenous ertapenem greater than or equal to 48 hours and oral cefdinir and metronidazole . Stable antibiotics‐first‐treated participants older than 13 years could be discharged after greater than or equal to 6‐hour emergency department ( ED ) observation with next‐day follow‐up . Outcomes included 1‐month major complication rate ( primary ) and hospital duration , pain , disability , quality of life , and hospital charges , and antibiotics‐first appendectomy rate . Results Of 48 eligible patients , 30 ( 62.5 % ) consented , of whom 16 ( 53.3 % ) were r and omized to antibiotics‐first  and 14 ( 46.7 % ) to appendectomy . Median age was 33 years ( range 9 to 73 years ) , median WBC count was 15,000/&mgr;L ( range 6,200 to 23,100/&mgr;L ) , and median computed tomography appendiceal diameter was 10 mm ( range 7 to 18 mm ) . Of 15 antibiotic‐treated adults , 14 ( 93.3 % ) were discharged from the ED and all had symptom resolution . At 1 month , major complications occurred in 2 appendectomy participants ( 14.3 % ; 95 % confidence interval [ CI ] 1.8 % to 42.8 % ) and 1 antibiotics‐first participant ( 6.3 % ; 95 % CI 0.2 % to 30.2 % ) . Antibiotics‐first participants had less total hospital time than appendectomy participants , 16.2 versus 42.1 hours , respectively . Antibiotics‐first‐treated participants had less pain and disability . During median 12‐month follow‐up , 2 of 15 antibiotics‐first‐treated participants ( 13.3 % ; 95 % CI 3.7 % to 37.9 % ) developed appendicitis and 1 was treated successfully with antibiotics ; 1 had appendectomy . No more major complications occurred in either group . Conclusion A multicenter US trial comparing antibiotics‐first to appendectomy , including outpatient management , is feasible to evaluate efficacy and safety PURPOSE The purpose of this study was to determine if early , acute appendicitis in children can be safely and effectively managed with antibiotics alone . METHODS A retrospective review was performed of children ( < 18 yrs ) treated non-operatively ( NOM ) for early , acute appendicitis since May 2012 . These were compared to patients treated with appendectomy between January 2011 and October 2011 ( OM ) . Inclusion criteria included : ( a ) symptoms < 48 h , ( b ) localized peritonitis , and ( c ) ultrasound findings consistent with early , acute appendicitis . RESULTS Twelve patients ( 66 % female , mean age 12.2,SD=4.2 yrs ) were treated non-operatively , while 12 ( 50 % female , mean age 12.5,SD=3.2 yrs ) were treated operatively . Two NOM children ( 16.7 % ) required initial appendectomy . One patient developed recurrent appendicitis requiring appendectomy 7 months post-discharge . Four other NOM patients returned with symptoms but did not require admission or surgery . Two OM patients ( 8.3 % ) had hospital visits and admissions related to surgical site infections . Mean length of stay ( LOS ) for the first visit was 1.5 days ( SD=1.0d ) ( NOM ) vs. 1.3 days ( SD=0.5d ) ( OM ) ( p=0.61 ) . Including first and subsequent admissions , mean LOS was 1.8 days ( SD=1.1d ) ( NOM ) vs. 1.7 days ( SD=1.5d ) ( OM ) ( p=0.97 ) . CONCLUSION Early acute appendicitis in appropriately selected children can be successfully treated non-operatively . R and omized trials with longer follow-up are required BACKGROUND In this prospect i ve study , operative and nonoperative management of acute appendicitis were evaluated regarding their safety and cost effectiveness . METHODS Two hundred ninety patients presenting to our Emergency Department between March 2005 and March 2006 with acute appendicitis were included in this prospect i ve study . Nonoperative medical therapy was performed in 107 patients ( Group 1 ) , and 183 patients were treated surgically ( Group 2 ) . Routine follow-up controls were done on the 10th day , at the 3rd and 6th months and at the first year after discharge in Group 1 . Both groups were compared regarding age , gender , mean hospital stay , modified Alvarado score , morbidity , mortality , and cost effectiveness . RESULTS The male/female ratio of Groups 1 and 2 were 65/42 ( mean age : 30.98+/-1.30 ) and 125/58 ( mean age : 26.25+/-0.79 ) , respectively . In Group 1 , 19 patients were operated . Operation indications were resistance to therapy , patient 's request , and operation in another hospital . Although the mean hospital stay of Group 1 was statistically significantly longer than Group 2 , the mean cost of the therapy was $ 559 in Group 2 and $ 433 in Group 1 . Morbidity rates were similar , with no mortality in either group . CONCLUSION With its high success rate and cost effectiveness , medical treatment seems to be a good alternative to the gold st and ard therapy of surgery in management of acute appendicitis BACKGROUND Initial antibiotic treatment for acute appendicitis has been shown to be safe in adults ; so far , not much is known about the safety and efficacy of this treatment in children . The aims of this study were to investigate the feasibility of a r and omized controlled trial ( RCT ) evaluating initial antibiotic treatment for acute appendectomy in children with acute simple appendicitis and to evaluate the safety of this approach . METHODS In a multicenter , prospect i ve cohort study patients aged 7 - 17 years with a radiologically confirmed simple appendicitis were eligible .  Intravenous antibiotics ( amoxicillin/clavulanic acid 250/25 mg/kg 4 times daily ; maximum 6,000/600 mg/d and gentamicin 7 mg/kg once daily ) were administered for 48 - 72 hours . Clinical reevaluation every 6 hours , daily blood sample s , and  ultrasound follow-up  after 48 hours was performed . In case of improvement after 48 hours , oral antibiotics were given for a total of 7 days . At any time , in case of clinical deterioration or non-improvement after 72 hours , an appendectomy could be performed . Follow-up continued until 8 weeks after discharge . Adverse events were defined as major complications of antibiotic treatment , such as allergic reactions , perforated appendicitis , and recurrent appendicitis . RESULTS Of 44 eligible patients , 25 participated ( inclusion rate , 57 % ; 95 % CI , 42%-70 % ) . Delayed appendectomy was performed in 2 , and the other 23 were without symptoms at the 8 weeks follow-up . Minor complications occurred in three patients . None of the patients suffered from an adverse event or a recurrent appendicitis . CONCLUSION Our study shows that an RCT comparing initial antibiotic treatment strategy with urgent appendectomy is feasible in children ; the intervention seems to be safe BACKGROUND Appendiceal mass may be treated in several ways . However , no r and omized trial has been conducted to find the best option . OBJECTIVE To compare the three most commonly used methods for treating appendiceal mass . METHODS Over a three-year period , 60 consecutive patients with appendiceal mass were r and omly allocated to three groups : Group A -- initial conservative treatment followed by interval appendectomy six weeks later ; Group B -- appendectomy as soon as appendiceal mass resolved using conservative means ; Group C -- conservative treatment alone . Short-term outcome measures included operative time , operative difficulty , postoperative complications , length of hospital stay , and duration of time away from work . Long-term outcome measures were : number of hospital visits made , presence of severe incisional pain , scar appearance , and patients with recurrent appendicitis . RESULTS Baseline characteristics were comparable in the three groups . In patients in Group A , operative time was less , adhesions were encountered less frequently , the incision had to be extended less often and post-operative complications were fewer , as compared to Group B. Patients in Group C had the shortest hospital stay and duration of work-days lost ; only 2 of 20 patients in this group developed recurrent appendicitis during a follow-up period of 24 - 52 ( median 33.5 ) months . CONCLUSION Of the three treatment modalities compared , conservative treatment without subsequent appendectomy appears to be the best Objective To define risk factors that predict adverse outcomes after the surgical treatment of appendicitis in Department of Veterans Affairs Medical Centers . Summary Background Data Risk factors for adverse outcomes after the surgical treatment of appendicitis in adults are poorly defined . Accurate presurgical assessment of the risk of perioperative complications and death is important in planning surgical therapy . Methods The VA National Surgical Quality Improvement Program contains prospect ively collected and extensively vali date d data on ∼1,000,000 major surgical operations . All patients undergoing surgical intervention for appendicitis from 1991 to 1999 registered in this data base were selected for study . Independent variables examined included 68 putative preoperative risk factors and 12 intraoperative process measures . Dependent variables were 21 specific adverse outcomes , including death . Stepwise logistic regression analysis was used to construct models predicting 30-day morbidity rate and the 30-day postoperative mortality rate . Results There were 4163 patients identified . The mean age was 50 years ; 96 % were male . Sixteen percent of patients had 1 or more complications after surgical intervention . Prolonged ileus , failure to wean from the ventilator , pneumonia , and both superficial and deep wound infection were the most frequently reported complications , accounting for the majority of the morbidity . The 30-day mortality rate was 1.8 % ( 74 deaths ) . For > 50 % of the complications reported , the 30-day mortality rates were significantly higher ( P < 0.01 ) for patients with complications than for those without . Thirty-day mortality rates for several complications exceeded 30 % , including cardiac arrest , coma > 24 hours , myocardial infa rct ion , acute renal failure , bleeding requiring > 4 units of red cells , and systemic sepsis . Four preoperative factors predicted a high risk of 30-day mortality in the logistic regression analysis : “ completely dependent ” functional status , bleeding disorder , steroid usage , and current pneumonia . “ Threat to life ” or “ moribund ” American Society of Anesthesiologists classification and more than a 10 % weight loss in the 6 months before surgery were associated with a high risk of complications . Conclusions Morbidity and mortality rates after the surgical treatment of appendicitis in VA hospitals are comparable with those reported in other large series . Most postsurgical complications are associated with an increased 30-day mortality rate . The models presented here are the most robust available in predicting 30-day morbidity and mortality for VA patients with appendicitis . Furthermore , they provide a starting point for the design of similar models to evaluate non-VA patients with appendicitis using the data the National Surgical Quality Improvement Program is currently gathering from private hospitals Importance Short-term results support antibiotics as an alternative to surgery for treating uncomplicated acute appendicitis , but long-term outcomes are not known . Objective To determine the late recurrence rate of appendicitis after antibiotic therapy for the treatment of uncomplicated acute appendicitis . Design , Setting , and Participants Five-year observational follow-up of patients in the Appendicitis Acuta ( APPAC ) multicenter r and omized clinical trial comparing appendectomy with antibiotic therapy , in which 530 patients aged 18 to 60 years with computed tomography – confirmed uncomplicated acute appendicitis were r and omized to undergo an appendectomy ( n = 273 ) or receive antibiotic therapy ( n = 257 ) . The initial trial was conducted from November 2009 to June 2012 in Finl and ; last follow-up was September 6 , 2017 . This current analysis focused on assessing the 5-year outcomes for the group of patients treated with antibiotics alone . Interventions Open appendectomy vs antibiotic therapy with intravenous ertapenem for 3 days followed by 7 days of oral levofloxacin and metronidazole . Main Outcomes and Measures In this analysis , prespecified secondary end points reported at 5-year follow-up included late ( after 1 year ) appendicitis recurrence after antibiotic treatment , complications , length of hospital stay , and sick leave . Results Of the 530 patients ( 201 women ; 329 men ) enrolled in the trial , 273 patients ( median age , 35 years [ IQR , 27 - 46 ] ) were r and omized to undergo appendectomy , and 257 ( median age , 33 years , [ IQR , 26 - 47 ] ) were r and omized to receive antibiotic therapy . In addition to 70 patients who initially received antibiotics but underwent appendectomy within the first year ( 27.3 % [ 95 % CI , 22.0%-33.2 % ] ; 70/256 ) , 30 additional antibiotic-treated patients ( 16.1 % [ 95 % CI , 11.2%-22.2 % ] ; 30/186 ) underwent appendectomy between 1 and 5 years . The cumulative incidence of appendicitis recurrence was 34.0 % ( 95 % CI , 28.2%-40.1 % ; 87/256 ) at 2 years , 35.2 % ( 95 % CI , 29.3%-41.4 % ; 90/256 ) at 3 years , 37.1 % ( 95 % CI , 31.2%-43.3 % ; 95/256 ) at 4 years , and 39.1 % ( 95 % CI , 33.1%-45.3 % ; 100/256 ) at 5 years . Of the 85 patients in the antibiotic group who subsequently underwent appendectomy for recurrent appendicitis , 76 had uncomplicated appendicitis , 2 had complicated appendicitis , and 7 did not have appendicitis . At 5 years , the overall complication rate ( surgical site infections , incisional hernias , abdominal pain , and obstructive symptoms ) was 24.4 % ( 95 % CI , 19.2%-30.3 % ) ( n = 60/246 ) in the appendectomy group and 6.5 % ( 95 % CI , 3.8%-10.4 % ) ( n = 16/246 ) in antibiotic group ( P < .001 ) , which calculates to 17.9 percentage points ( 95 % CI , 11.7 - 24.1 ) higher after surgery . There was no difference between groups for length of hospital stay , but there was a significant difference in sick leave ( 11 days more for the appendectomy group ) . Conclusions and Relevance Among patients who were initially treated with antibiotics for uncomplicated acute appendicitis , the likelihood of late recurrence within 5 years was 39.1 % . This long-term follow-up supports the feasibility of antibiotic treatment alone as an alternative to surgery for uncomplicated acute appendicitis . Trial Registration Clinical Trials.gov Identifier :
target: The major primary outcomes show a high recurrence rate and failed treatment associated with the conservative management of appendicitis .
  The other outcomes obtained show that there is an increased incidence of complications associated with operative management .
  Economic implication s and cost-effectiveness analysis show that conservative treatment may be preferred .
  The length of hospital stay was significantly higher in conservative approach to management ; however , shorter time off activities was observed .
background: Appendicectomy has been accepted as the gold st and ard for the management of appendicitis over the years , but there has been an increasing evidence and trend toward the conservative approach to the management of appendicitis .
  The aim of this review is to search existing literature and to evaluate and compare the conservative and operative approaches to the management of appendicitis .