title: The NOTA study: non-operative treatment for acute appendicitis: prospective study on the efficacy and safety of antibiotic treatment (amoxicillin and clavulanic acid) in patients with right sided lower abdominal pain Laparoscopic Versus Open Appendectomy: Outcomes Comparison Based on a Large Administrative Database Appendectomy versus Antibiotic Treatment in Acute Appendicitis. A Prospective Multicenter Randomized Controlled Trial Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The APPAC Randomized Clinical Trial. Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, non-inferiority, randomised controlled trial Comparison of operative and non operative management of acute appendicitis. Long-term outcomes of patients with nonsurgically managed uncomplicated appendicitis.
abstract: Background Case control studies that r and omly assign patients with diagnosis of acute appendicitis to either surgical or non-surgical treatment yield a relapse rate of approximately 14 % at one year . It would be useful to know the relapse rate of patients who have , instead , been selected for a given treatment based on a thorough clinical evaluation , including physical examination and laboratory results ( Alvarado Score ) as well as radiological exams if needed or deemed helpful . If this clinical evaluation is useful , the investigators would expect patient selection to be better than chance , and relapse rate to be lower than 14 % . Once the investigators have established the utility of this evaluation , the investigators can begin to identify those components that have predictive value ( such as blood analysis , or US/CT findings ) . This is the first step toward developing an accurate diagnostic-therapeutic algorithm which will avoid risks and costs of needless surgery . Methods / design This will be a single-cohort prospect i ve observational study . It will not interfere with the usual pathway , consisting of clinical examination in the Emergency Department ( ED ) and execution of the following exams at the physician 's discretion : full blood count with differential , C reactive protein , abdominal ultrasound , abdominal CT .  Patients admitted to an ED with lower abdominal pain and suspicion of acute appendicitis and not needing immediate surgery , are requested by informed consent to undergo observation and non operative treatment with antibiotic therapy ( Amoxicillin and Clavulanic Acid ) . The patients by protocol should not have received any previous antibiotic treatment during the same clinical episode . Patients not undergoing surgery will be physically examined 5 days later . Further follow-up will be conducted at 7 , 15 days , 6 months and 12 months . The study will conform to clinical practice guidelines and will follow the recommendations of the Declaration of Helsinki . The protocol was approved on November 2009 by Maggiore Hospital Ethical Review Board ( ID CE09079 ) . Trial Registration Clinical Trials.gov identifier : NCT01096927 Objective : To compare length of hospital stay , in-hospital complications , in-hospital mortality , and rate of routine discharge between  laparoscopic and open appendectomy  based on a representative , nationwide data base . Summary Background Data : Numerous single-institutional r and omized clinical trials have assessed the efficacy of laparoscopic and open appendectomy . The results , however , are conflicting , and a consensus concerning the relative advantages of each procedure has not yet been reached . Methods : Patients with primary ICD-9 procedure codes for laparoscopic and open appendectomy were selected from the 1997 Nationwide Inpatient Sample , a data base that approximates 20 % of all US community hospital discharges .  Multiple linear and logistic regression analyses were used to assess the risk-adjusted endpoints . Results : Discharge abstract s of 43,757 patients were used for our analyses . 7618 patients ( 17.4 % ) underwent laparoscopic and 36,139 patients ( 82.6 % ) open appendectomy . Patients had an average age of 30.7 years and were predominantly white ( 58.1 % ) and male ( 58.6 % ) . After adjusting for other covariates , laparoscopic appendectomy was associated with shorter median hospital stay  ( laparoscopic appendectomy : 2.06 days , open appendectomy : 2.88 days , P < 0.0001 ) , lower rate of infections ( odds ratio [ OR ] = 0.5 [ 0.38 , 0.66 ] , P < 0.0001 ) , decreased gastrointestinal complications ( OR = 0.8 [ 0.68 , 0.96 ] , P = 0.02 ) , lower overall complications ( OR = 0.84 [ 0.75 , 0.94 ] , P = 0.002 ) , and higher rate of routine discharge ( OR = 3.22 [ 2.47 , 4.46 ] , P < 0.0001 ) . Conclusions : Laparoscopic appendectomy has significant advantages over open appendectomy with respect to length of hospital stay , rate of routine discharge , and postoperative in-hospital morbidity Background Appendectomy has been the treatment for acute appendicitis for over 120 years . Antibiotic treatment has occasionally been used in small uncontrolled studies , instead of operation , but this alternative has never before been tried in a multicenter r and omized trial . Patients and Methods Male patients , 18–50 years of age , admitted to six different hospitals in Sweden between 1996 and 1999 were enrolled in the study . No women were enrolled by decision of the local ethics committee . If appendectomy was planned , patients were asked to participate , and those who agreed were r and omized either to surgery or to antibiotic therapy . Patients r and omized to surgery were operated on with open surgery or laparoscopically . Those r and omized to antibiotic therapy were treated intravenously for 2 days , followed by oral treatment for 10 days . If symptoms did not resolve within 24 hours , an appendectomy was performed . Participants were monitored at the end of 1 week , 6 weeks , and 1 year . Results During the study period 252 men participated , 124 in the surgery group and 128 in the antibiotic group .  The frequency of appendicitis was 97 % in the surgery group and 5 % had a perforated appendix . The complication rate was 14 % in the surgery group . In the antibiotic group 86 % improved without surgery ; 18 patients were operated on within 24 hours , and the diagnosis of acute appendicitis was confirmed in all but one patient , and he was suffering from terminal ileitis . There were seven patients ( 5 % ) with a perforated appendix in this group . The rate of recurrence of symptoms of appendicitis among the 111 patients treated with antibiotics was 14 % during the 1-year follow-up . Conclusions Acute nonperforated appendicitis can be treated successfully with antibiotics . However , there is a risk of recurrence in cases of acute appendicitis , and this risk should be compared with the risk of complications after appendectomy IMPORTANCE An increasing amount of evidence supports the use of antibiotics instead of surgery for treating patients with uncomplicated acute appendicitis . OBJECTIVE To compare antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis confirmed by computed tomography ( CT ) . DESIGN , SETTING , AND PARTICIPANTS The Appendicitis Acuta ( APPAC ) multicenter , open-label , noninferiority r and omized clinical trial was conducted from November 2009 until June 2012 in Finl and . The trial enrolled 530 patients aged 18 to 60 years with uncomplicated acute appendicitis confirmed by a CT scan . Patients were r and omly assigned to early appendectomy or antibiotic treatment with a 1-year follow-up period . INTERVENTIONS Patients r and omized to antibiotic therapy received intravenous ertapenem ( 1 g/d ) for 3 days followed by 7 days of oral levofloxacin ( 500 mg once daily ) and metronidazole ( 500 mg 3 times per day ) . Patients r and omized to the surgical treatment group were assigned to undergo st and ard open appendectomy . MAIN OUTCOMES AND MEASURES The primary end point for the surgical intervention was the successful completion of an appendectomy . The primary end point for antibiotic-treated patients was discharge from the hospital without the need for surgery and no recurrent appendicitis during a 1-year follow-up period . RESULTS There were 273 patients in the surgical group and 257 in the antibiotic group . Of 273 patients in the surgical group , all but 1 underwent successful appendectomy , result ing in a success rate of 99.6 % ( 95 % CI , 98.0 % to 100.0 % ) . In the antibiotic group , 70 patients ( 27.3 % ; 95 % CI , 22.0 % to 33.2 % ) underwent appendectomy within 1 year of initial presentation for appendicitis . Of the 256 patients available for follow-up in the antibiotic group , 186 ( 72.7 % ; 95 % CI , 66.8 % to 78.0 % ) did not require surgery . The intention-to-treat analysis yielded a difference in treatment efficacy between groups of -27.0 % ( 95 % CI , -31.6 % to ∞ ) ( P = .89 ) . Given the prespecified noninferiority margin of 24 % , we were unable to demonstrate noninferiority of antibiotic treatment relative to surgery . Of the 70 patients r and omized to antibiotic treatment who subsequently underwent appendectomy , 58 ( 82.9 % ; 95 % CI , 72.0 % to 90.8 % ) had uncomplicated appendicitis , 7 ( 10.0 % ; 95 % CI , 4.1 % to 19.5 % ) had complicated acute appendicitis , and 5 ( 7.1 % ; 95 % CI , 2.4 % to 15.9 % ) did not have appendicitis but received appendectomy for suspected recurrence . There were no intra-abdominal abscesses or other major complications associated with delayed appendectomy in patients r and omized to antibiotic treatment . CONCLUSIONS AND RELEVANCE Among patients with CT-proven , uncomplicated appendicitis , antibiotic treatment did not meet the prespecified criterion for noninferiority compared with appendectomy . Most patients r and omized to antibiotic treatment for uncomplicated appendicitis did not require appendectomy during the 1-year follow-up period , and those who required appendectomy did not experience significant complications . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01022567 BACKGROUND Research ers have suggested that antibiotics could cure acute appendicitis . We assessed the efficacy of amoxicillin plus clavulanic acid by comparison with emergency appendicectomy for treatment of patients with uncomplicated acute appendicitis . METHODS In this open-label , non-inferiority , r and omised trial , adult patients ( aged 18 - 68 years ) with uncomplicated acute appendicitis , as assessed by CT scan , were enrolled at six university hospitals in France . A computer-generated r and omisation sequence was used to allocate patients r and omly in a 1:1 ratio to receive amoxicillin plus clavulanic acid ( 3 g per day ) for 8 - 15 days or emergency appendicectomy . The primary endpoint was occurrence of postintervention peritonitis within 30 days of treatment initiation . Non-inferiority was shown if the upper limit of the two-sided 95 % CI for the difference in rates was lower than 10 percentage points . Both intention-to-treat and per- protocol analyses were done . This trial is registered with Clinical Trials.gov , number NCT00135603 . FINDINGS Of 243 patients r and omised , 123 were allocated to the antibiotic group and 120 to the appendicectomy group . Four were excluded from analysis because of early dropout before receiving the intervention , leaving 239 ( antibiotic group , 120 ; appendicectomy group , 119 ) patients for intention-to-treat analysis . 30-day postintervention peritonitis was significantly more frequent in the antibiotic group ( 8 % , n=9 ) than in the appendicectomy group ( 2 % , n=2 ; treatment difference 5·8 ; 95 % CI 0·3 - 12·1 ) . In the appendicectomy group , despite CT-scan assessment , 21 ( 18 % ) of 119 patients were unexpectedly identified at surgery to have complicated appendicitis with peritonitis . In the antibiotic group , 14 ( 12 % [ 7·1 - 18·6 ] ) of 120 underwent an appendicectomy during the first 30 days and 30 ( 29 % [ 21·4 - 38·9 ] ) of 102 underwent appendicectomy between 1 month and 1 year , 26 of whom had acute appendicitis ( recurrence rate 26 % ; 18·0 - 34·7 ) . INTERPRETATION Amoxicillin plus clavulanic acid was not non-inferior to emergency appendicectomy for treatment of acute appendicitis . Identification of predictive markers on CT scans might enable improved targeting of antibiotic treatment .  FUNDING French Ministry of Health , Programme Hospitalier de Recherche Clinique 2002 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 Emerging literature has supported the safety of nonoperative management of uncomplicated appendicitis . STUDY DESIGN Patients with emergent , uncomplicated appendicitis were identified by appropriate ICD-9 diagnosis codes in the California Office of Statewide Health Planning and Development data base from 1997 to 2008 . Rates of treatment failure , recurrence , and perforation after nonsurgical management were calculated . Factors associated with treatment failure , recurrence , and perforation were identified using multivariable logistic regression . Mortality , length of stay , and total charges were compared between treatment cohorts using matched propensity score analysis . RESULTS Of 231,678 patients with uncomplicated appendicitis , the majority ( 98.5 % ) were managed operatively . Of the 3,236 nonsurgically managed patients who survived to discharge without an interval appendectomy , 5.9 % and 4.4 % experienced treatment failure or recurrence , respectively , during a median follow-up of more than 7 years . There were no mortalities associated with treatment failure or recurrence . The risk of perforation after discharge was approximately 3 % . Using multivariable analysis , race and age were significantly associated with the odds of treatment failure . Sex , age , and hospital teaching status were significantly associated with the odds of recurrence . Age and hospital teaching status were significantly associated with the odds of perforation . Matched propensity score analysis indicated that after risk adjustment , mortality rates ( 0.1 % vs 0.3 % ; p = 0.65 ) and total charges ( $ 23,243 vs $ 24,793 ; p = 0.70 ) were not statistically different between operative and nonoperative patients ; however , length of stay was significantly longer in the nonoperative treatment group ( 2.1 days vs 3.2 days ; p < 0.001 ) . CONCLUSIONS This study suggests that nonoperative management of uncomplicated appendicitis can be safe and prompts additional investigations . Comparative effectiveness research using prospect i ve r and omized studies can be particularly useful
target: Conclusion The paradigm remains unchanged , that appendectomy is the gold st and ard of treatment for uncomplicated appendicitis , given its higher efficacy rate when compared to NOM
background: Introduction Appendectomy has long been the mainstay of intervention for acute appendicitis , aim ing at preventing perforation , peritonitis , abscess formation and recurrence .
  With better underst and ing of the disease process , non-operative management ( NOM ) with antibiotics alone has been proved a feasible treatment for uncomplicated appendicitis .
  This article aim ed at systematic ally review ing the available literature s and discussing the question whether NOM should replace appendectomy as the st and ard first-line treatment for uncomplicated appendicitis .