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Appendicitis

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A randomized clinical trial evaluating the efficacy of quality of life of antibiotic-only treatment of acute uncomplicated appendicitis: Results of the COMMA trial.
O'Leary DP, Walsh SM, Bolger J, Baban C, Humphreys H, O'Grady S, Hegarty A, Lee AM, Sheehan M, Alderson J, Dunne R, Morrin MM, Lee MJ, Power C, McNamara D, McCawley N, Robb W, Burke J, Sorensen J, Hill AD.
Ann Surg. 2021 Aug 1;274(2):240-247.

Rationale for inclusion: Patients with acute, uncomplicated appendicitis treated with antibiotics only experienced higher recurrence rates and an inferior quality of life compared to those treated with laparoscopic appendectomy.

CAVEAT: Single center study.

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Multicenter study of the treatment of appendicitis in America: Acute, Perforated and Gangrenous (MUSTANG), an EAST multicenter study
Yeh D, Eid AI, Young KA, Wild J, Kaafarani HM, Ray-Zach M, Kana'an T, Lawless R, Cralley AL, Crandall M. EAST Appendicitis Study Group.
Ann Surg. 2021 Mar 1;273(3):548-556.

Rationale for inclusion: Large multicenter prospective observational study of patients with appendicitis in America. Of the patients treated with antibiotic therapy alone, 16% required appendectomy during index hospitalization and 5% underwent appendectomy within 30 days with a cumulative failure rate of 21%. 

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Managing acute uncomplicated appendicitis in frail geriatric patients: A second hit may be too much.
Chehab M, Ditillo M, Khurrum M, Gries L, Asmar S, Douglas M, Bible L, Kulvatunyou N, Joseph B.
J Trauma Acute Care Surg. 2021 Mar 1;90(3):501-506.

Rationale for inclusion: Retrospective propensity-score matched review of the Nationwide Readmissions Database of frail geriatric patients. 1 in 6 patients failed antibiotic treatment alone, with resultant more complications and higher mortality.


CAVEAT: Inclusion criteria was age >65 years and frailty was assessed using a five-factor modified frailty index.

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Effect of oral moxifloxacin vs intravenous ertapenem plus oral levofloxacin for treatment of uncomplicated acute appendicitis: The APPAC II randomized clinical trial.
Sippola S, Haijanen J, Grönroos J, Rautio T, Norström P, Rantanen T, Pinta T, Ilves I, Mattila A, Rintala J, Löyttyniemi E, Hurme S, Tammilehto V, Marttila H, Meriläinen S, Laukkarinen J, Sävelä E, Savolainen H, Sippola T, Aarnio M, Paajanen H, Salminen P.
JAMA. 2021 Jan 26;325(4):353-362.

Rationale for inclusion: Multicenter randomized clinical trial evaluated patients with uncomplicated acute appendicitis treated with either 7 days of oral antibiotics or 2 days of IV antibiotics followed by 5 days of oral antibiotics. Results showed that oral antibiotics alone resulted in treatment success rates greater than 65%, but failed to demonstrate noninferiority comparted to IV antibiotics.

CAVEAT: Predefined noninferiority margin for clinical importance in the sample size calculations were set arbitrarily.

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Appendectomy versus conservative treatment with antibiotics for patients with uncomplicated acute appendicitis: a propensity score-matched analysis of patient-centered outcomes (the ACTUAA prospective trial).
Podda M, Poillucci G, Pacella D, Mortola L, Canfora A, Aresu S, Pisano M, Erdas E, Pisanu A, Cillara N. ACTUAA Study Collaborative Working Group.
Int J Colorectal Dis. 2021 Mar;36(3):589-598.

Rationale for inclusion: Prospective multicenter study to comparing antibiotic therapy to appendectomy showed a statistically significant higher complication-free treatment success in the appendectomy group. 65% of patients treated with antibiotics were symptom-free at 1 year without increased risk of adverse evets, had less pain and shorter period of absence from work compared to the appendectomy group.


CAVEAT: 
Smaller sample size.

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A randomized trial comparing antibiotics with appendectomy for appendicitis.
CODA Collaborative; Flum DR, Davidson GH, Monsell SE, Shapiro NI, Odom SR, Sanchez SE, Drake FT, Fischkoff K, Johnson J, Patton JH, Evans H, Cuschieri J, Sabbatini AK, Faine BA, Skeete DA, Liang MK, Sohn V, McGrane K, Kutcher ME, Chung B, Carter DW, Ayoung-Chee P, Chiang W, Rushing A, Steinberg S, Foster CS, Schaetzel SM, Price TP, Mandell KA, Ferrigno L, Salzberg M, DeUgarte DA, Kaji AH, Moran GJ, Saltzman D, Alam HB, Park PK, Kao LS, Thompson CM, Self WH, Yu JT, Wiebush A, Winchell RJ, Clark S, Krishnadasan A, Fannon E, Lavallee DC, Comstock BA, Bizzel B, Heagerty PJ, Kessler LG, Talan DA.
N Engl J Med. 2020 Nov 12;383(20):1907-1919.

Rationale for inclusion: Randomized clinical trial comparing 10-day course of antibiotic therapy to appendectomy for treatment of appendicitis. Antibiotics were noninferior to appendectomy based on 30-day health status survey, however 30% of participants underwent appendectomy within 90 days in the antibiotic group. 

CAVEAT: Data only includes 90-day follow up and likely underrepresents recurrence and long-term complications.

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Quality of life and patient satisfaction at 7-year follow-up of antibiotic therapy vs appendectomy for uncomplicated acute appendicitis: A secondary analysis of a randomized clinical trial.
Sippola S, Haijanen J, Viinikainen L, Grönroos J, Paajanen H, Rautio T, Norström P, Aarnio M, Rantanen T, Hurme S, Mecklin J, Sand J, Jartti A, Salminen P.
JAMA Surg. 2020 Apr 1;155(4):283-289.

Rationale for inclusion: Observational long-term follow-up of the APPAC multicenter RCT comparing appendectomy with antibiotics. Quality of life metrics between appendectomy and antibiotic patients were similar in both groups, but patient satisfaction was higher in the appendectomy group.

CAVEAT: Limitations of original APPAC trial including open appendectomy approach and longer duration of antibiotic treatment. 

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Laparoscopic versus open approach for diffuse peritonitis from appendicitis ethiology: A subgroup analysis from the Physiologic parameters for Prognosis in Abdominal Sepsis (PIPAS) study.
Gomes CA, Sartelli M, Podda M, Di Saverio S, Coccolini F, Segovia-Lohse HA, De Simone B, Catena F.
Updates Surg. 2020 Mar;72(1):185-191.

Rationale for inclusion:  Prospective multicenter trial of patients with diffuse peritonitis from perforated appendicitis. There was no statistically significant difference between laparoscopic and open techniques in terms of intra-abdominal abscess, postoperative peritonitis, rate of reoperation and mortality.

 

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Risk of Appendiceal Neoplasm in Periappendicular Abscess in Patients Treated With Interval Appendectomy vs Follow-up With Magnetic Resonance Imaging: 1-year Outcomes of the Peri-Appendicitis Acuta Randomized Clinical Trial.
Mällinen J, Rautio T, Grönroos J, Rantanen T, Nordström P, Savolainen H, Ohtonen P, Hurme S, Salminen P.
JAMA Surg. 2018 Nov 28.

Rationale for inclusion: Informs decision with respect to interval appendectomy for patients with complicated appendicitis underging non-operative management.

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Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial
Salminen P, Tuominen R, Paajanen H, Rautio T, Nordström P, Aarnio M, Rantanen T, Hurme S, Mecklin JP, Sand J, Virtanen J, Jartti A, Grönroos JM.
JAMA. 2018;320(12):1259-1265.

Rationale for inclusion: Long follow up of one of the most prominent studies comparing appendectomy and antibiotics for acute appendicitis.

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Randomized clinical trial of antibiotic therapy for uncomplicated appendicitis.
Park HC, Kim MJ, Lee BH.
Br J Surg. 2017 Dec;104(13):1785-1790.

Rationale for inclusion: Largest trial of antibiotics versus placebo for uncomplicated appendicitis.

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Risky business? Investigating outcomes of patients undergoing urgent laparoscopic appendectomy on antithrombotic therapy.
Pearcy C, Almahmoud K, Jackson T, Hartline C, Cahill A, Spence L, Kim D, Olatubosun O, Todd SR, Campion EM, Burlew CC, Regner J, Frazee R, Michaels D, Dissanaike S, Stewart C, Foley N, Nelson P, Agrawal V, Truitt MS.
Am J Surg. 2017 Dec;214(6):1012-1015

Rationale for inclusion: large retrospective study within a multi-center trial suggests that irreversible antithrombotic therapy (aspirin and Plavix) is not associated with worse outcomes in urgent or emergent laparoscopic appendectomy.

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Laparoscopic appendectomy vs antibiotic therapy for acute appendicitis: a propensity score-matched analysis from a multicenter cohort study.
Poillucci G, Mortola L, Podda M, Di Saverio S, Casula L, Gerardi C, Cillara N, Presenti L.
Updates Surg. 2017 Dec;69(4):531-540.

Rationale for inclusion: A propensity score-matched analysis was performed in a multi-center European study aiming to assess safety and feasibility of both nonoperative management with antibiotics and appendectomy for patients with acute appendicitis.  Patients treated with antibiotics had both an initial treatment failure and recurrence rate at 1-year followup of 20%.  Due to low complication rates and the high efficacy of surgical therapy, laparoscopic appendectomy still represents the most effective treatment for patients with appendicitis.

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Operation versus antibiotics--The "appendicitis conundrum" continues: A meta-analysis.
Sakran JV, Mylonas KS, Gryparis A, Stawicki SP, Burns CJ, Matar MM, Economopoulos KP.
J Trauma Acute Care Surg. 2017 Jun;82(6):1129-1137.

Rationale for inclusion: recent metaanalysis synthesizes evidence from five RCTs comparing nonoperative versus surgical management of uncomplicated acute appendicitis in 1,430 adult patients. Treatment efficacy at 1-year follow-up was significantly lower (63.8%) for antibiotics compared with the surgery group (93%).

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Laparoscopic or open appendicectomy for suspected appendicitis in pregnancy and evaluation of foetal outcome in Australia.
Winter NN, Guest GD, Bozin M, Thomson BN, Mann GB, Tan SBM, Clark DA, Daruwalla J, Muralidharan V, Najan N, Pitcher ME, Vilhelm K, Cox MR, Lane SE, Watters DA.
ANZ J Surg. 2017 May;87(5):334-338.

Rationale for inclusion: Largest study comparing laparoscopic and open appendectomy in pregnancy.

CAVEAT: Used statistical methods to account for differnences in gestational age.

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The introduction of adult appendicitis score reduced negative appendectomy rate.
Sammalkorpi HE, Mentula P, Savolainen H, Leppäniemi A.
Scand J Surg. 2017 Sep;106(3):196-201.

Rationale for inclusion: Prospective study validating the adult appendicitis score (AAS) as a fast, accurate, and easily applicable method for straifying patients according to risk of appendiciits.  Additionally, AAS can be used to help reduce negative appendectomy rates without mandatory imaging in those patients suspected of having acute appendicitis.

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Evidence for an antibiotics-first strategy for uncomplicated appendicitis in adults: a systematic review and gap analysis.
Ehlers AP, Talan DA, Moran GJ, Flum DR, Davidson GH.
J Am Coll Surg. 2016 Mar;222(3):309-14.

Rationale for inclusion: This is an excellent review paper which discusses the limitations and methodological flaws (selection bias, diagnostic criteria, treatment strategy, outcome selection) of recently published randomized trials.

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Laparoscopic surgery or conservative treatment for appendiceal abscess in adults? A randomized controlled trial.
Mentula P, Sammalkorpi H, Leppäniemi A.
Ann Surg. 2015 Aug;262(2):237-42.

Rationale for inclusion: this study challenges the practice of percutaneous treatment for appendiceal abscess.

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Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis: the APPAC randomized clinical trial.
Salminen P, Paajanen H, Rautio T, Nordström P, Aarnio M, Rantanen T, Tuominen R, Hurme S, Virtanen J, Mecklin JP, Sand J, Jartti A, Rinta-Kiikka I, Grönroos JM.
JAMA. 2015 Jun 16;313(23):2340-8.

Rationale for inclusion: this European study concludes that antibiotic therapy is non-inferior to appendectomy for acute appendicitis.

CAVEAT: When trying to decide whether or not this study may be applicable to American practice, it is important to consider that the average hospital length of stay for the surgical group was 3 days and that only 5.5% of appendectomies were performed laparoscopically.  While the overall complication rate was significantly higher in the surgical group (20.5% vs. 2.8%), this was predominantly driven by superficial surgical site infections and incisional pain; this may be related to the overwhelming use of open appendectomy technique. There was a 16% negative appendectomy rate, which seems high in the modern era.  There was a 1.5% incidence to tumors in the surgical group.

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Trial of short-course antimicrobial therapy for intraabdominal infection.
Sawyer RG, Claridge JA, Nathens AB, Rotstein OD, Duane TM, Evans HL, Cook CH, O'Neill PJ, Mazuski JE, Askari R, Wilson MA, Napolitano LM, Namias N, Miller PR, Dellinger EP, Watson CM, Coimbra R, Dent DL, Lowry SF, Cocanour CS, West MA, Banton KL, Cheadle WG, Lipsett PA, Guidry CA, Popovsky K.
N Engl J Med. 2015 May 21;372(21):1996-2005.

Rationale for inclusion: this high-quality randomized trial demonstrated that for complicated intra-abdominal infections (including perforated appendicitis) with adequate surgical source control, four days of post-operative antibiotics is non-inferior to a longer (median eight days) course of antibiotics.

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The NOTA study (non operative treatment for acute appendicitis): prospective study on the efficacy and safety of antibiotics (amoxicillin and clavulanic acid) for treating patients with right lower quadrant abdominal pain and long-term follow-up of conservatively treated suspected appendicitis.
Di Saverio S, Sibilio A, Giorgini E, Biscardi A, Villani S, Coccolini F, Smerieri N, Pisano M, Ansaloni L, Sartelli M, Catena F, Tugnoli G.
Ann Surg. 2014 Jul;260(1):109-17.

Rationale for inclusion: this observational study of 159 patients treated non-operatively for suspected acute appendicitis demonstrated 83% long-term efficacy at 2 years.

CAVEAT: this study included patients suspected of having acute appendicitis by clinical exam, Alvarado and/or Appendicitis Inflammatory Response (AIR) scores, but only 73% underwent ultrasound assessment and only 17% underwent CT scan to confirm the diagnosis.

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Comparison of outcomes of laparoscopic and open appendectomy in management of uncomplicated and complicated appendicitis.
Tiwari MM, Reynoso JF, Tsang AW, Oleynikov D.
Ann Surg. 2011 Dec;254(6):927-32.

Rationale for inclusion: this analysis of the University HealthSystem Consortium database concludes that laparoscopic appendectomy is superior to open appendectomy.

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Appendectomy versus antibiotic treatment for acute appendicitis.
Wilms IM, de Hoog DE, de Visser DC, Janzing HM.
Cochrane Database Syst Rev. 2011 Nov 9;(11):CD008359.

Rationale for inclusion: this Cochrane review concludes that appendectomy remains the standard treatment for acute appendicitis because of the low quality of available evidence.

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Laparoscopic versus open appendectomy: an analysis of outcomes in 17,199 patients using ACS/NSQIP.
Page AJ, Pollock JD, Perez S, Davis SS, Lin E, Sweeney JF.
J Gastrointest Surg. 2010 Dec;14(12):1955-62.

Rationale for inclusion: this very large NSQIP study confirms that laparoscopic appendectomy has better outcomes compared to open appendectomy.

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Laparoscopic versus open surgery for suspected appendicitis.
Sauerland S, Jaschinski T, Neugebauer EA.
Cochrane Database Syst Rev. 2010 Oct 6;(10):CD001546.

Rationale for inclusion: this Cochrane meta-analysis concludes that laparoscopic appendectomy has advantages over open appendectomy.

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Comparison of outcomes after laparoscopic versus open appendectomy for acute appendicitis at 222 ACS NSQIP hospitals.
Ingraham AM, Cohen ME, Bilimoria KY, Pritts TA, Ko CY, Esposito TJ.
Surgery. 2010 Oct;148(4):625-35; discussion 635-7.

Rationale for inclusion: this analysis of the NSQIP database concludes that laparoscopic appendectomy (compared to open appendectomy) is associated with lower overall morbidity, but may result in higher rates of organ space infection in patients with complicated appendicitis.

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An acute care surgery model improves outcomes in patients with appendicitis.
Earley AS, Pryor JP, Kim PK, Hedrick JH, Kurichi JE, Minogue AC, Sonnad SS, Reilly PM, Schwab CW.
Ann Surg. 2006 Oct;244(4):498-504.

Rationale for inclusion: this parallel-cohort study demonstrates that an acute care surgery (ACS) model, compared to the traditional home-call model, was associated with decreased time to operation, decreased complications, and shorter hospital length of stay.

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Laparoscopic versus open appendectomy: outcomes comparison based on a large administrative database.
Guller U, Hervey S, Purves H, Muhlbaier LH, Peterson ED, Eubanks S, Pietrobon R.
Ann Surg. 2004 Jan;239(1):43-52.

Rationale for inclusion: this analysis of the Nationwide Inpatient Sample (NIS) concludes that laparoscopic appendectomy is superior to open appendectomy with regards to hospital length of stay and post-operative in-hospital morbidity.

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A practical score for the early diagnosis of acute appendicitis.
Alvarado A.
Ann Emerg Med. 1986 May;15(5):557-64.

Rationale for inclusion: this widely cited paper describes the “Alvarado score”, a clinical scoring system which can help clinicians decide whether or not to order CT imaging for suspected acute appendicitis.

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