Use of antibiotics alone for treatment of uncomplicated acute appendicitis: A systematic review and meta-analysis

2412 Cost effectiveness analysis of operative Versus antibiotic management for uncomplicated appendicitis

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 randomized clinical trial was conducted from November 2009 until June 2012 in Finland. The trial enrolled 530 patients aged 18 to 60 years with uncomplicated acute appendicitis confirmed by a CT scan. Patients were randomly assigned to early appendectomy or antibiotic treatment with a 1-year follow-up period. Interventions Patients randomized 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 randomized to the surgical treatment group were assigned to undergo standard 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, resulting 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 randomized 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 randomized 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 randomized 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 clinicaltrials.gov Identifier:NCT01022567

An increasing amount of evidence supports the use of antibiotics instead of surgery for treating patients with uncomplicated acute appendicitis. To compare antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis confirmed by computed tomography (CT). The Appendicitis Acuta (APPAC) multicenter, open-label, noninferiority randomized clinical trial was conducted from November 2009 until June 2012 in Finland. The trial enrolled 530 patients aged 18 to 60 years with uncomplicated acute appendicitis confirmed by a CT scan. Patients were randomly assigned to early appendectomy or antibiotic treatment with a 1-year follow-up period. Patients randomized 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 randomized to the surgical treatment group were assigned to undergo standard open appendectomy. 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. 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, resulting 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 randomized 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 randomized to antibiotic treatment. Among patients with CT-proven, uncomplicated appendicitis, antibiotic treatment did not meet the prespecified criterion for noninferiority compared with appendectomy. Most patients randomized 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. clinicaltrials.gov Identifier: NCT01022567.

Background Acute appendicitis remains the common surgical condition and appendicectomy remains the mainstay of treatment for over 130 years. Possibility of non-surgical treatment has been proposed since the middle of the 20th century. An increasing amount of evidence supports the use of antibiotics as conservative treatment instead of surgery for treating patients with uncomplicated acute appendicitis. Objectives To compare conservative treatmentwith appendicectomy in the management of uncomplicated acute appendicitis in adult confirmed by clinical findings and investigations. Methods Ahospital based prospective type of comparative observational study was conducted over a period of three years from 1st January 2020 to31st December 2022 in the Department of Surgery, Dhaka National Medical College Hospital. Total 224 patients of acute appendicitisdiagnosed with history taking, clinical examination, laboratory profile, ultrasonography proven in surgery department of Dhaka National Medical College Hospital were included. Total study population were divided into two groups randomly, one was surgically treated and another one was treated conservatively.Patient treated with conservative treatment received intravenous Ceftriaxone (1 gm/12 hourly) and Metronidazole (500mg/ 8 hourly) for 3 days followed by 7 days of oral Cefixime (400 mg twice daily) and oral metronidazole (500 mg 3 times per day) for 2 days. Patients randomized to the surgical treatment group were assigned to undergo standard open appendicectomy by grid iron incision. The primary end point for the surgical intervention was the successful completion of an appendicectomy and the primary end point for conservative treatment group was discharge from the hospital without the need for surgery. Results In this study, the maximum number of patients 80 (35.71%) was between18-25year age group.Out of 224 cases 126 (56.23%) cases were male and 96 (42.85%) were female. Male and female ratio was 1.3:1. Large numbers of respondents 99 (44.19%) werestudents followed by housewife 48 (21.42%). Leukocyte count (Mean±SD) in surgically treated groupwas 12.7× 109/L and conservative treatment group was12.3× 109/L. Alvarado score was 6-7, which was same in bothgroups. Per-operatively, no collection was seen in right iliac fossa in 86 (76.78%) and serous and purulent collection found in 15 (13.39%) and 11 (9.82%) cases respectively. Only 15 (13.39%) patients had greater omentum present around the appendix, rest 97 (86.60%) patients don’t have greater omentum around the appendix. During operation, 81 (72.32%) appendixes found severely inflamed, 3 (2.67%) were gangrenous and 2 (1.78%) were perforated. Although 8 (6.77%) patients had macroscopically normal appendix. Per-operatively, we found appendiceal lumen was obstructed in only 26 (23.21%) patients. Outcome of the acute appendicitis patient were, median hospitalstay more in conservative treatment group 4.1 days in comparison to surgically treated group 3.4 days. Treatment failed 31 (27.67%) patients were treated by appendicectomy.Among 31 patients, appendix of all 31 (100%) patients were severely inflamed and 25 (80.64%) patients lumen found obstructed with fecalith. Greater omentum found fixed with appendix in 26 (83.87%) patients and serous and purulent collection found in 20 (64.51%) and 11 (35.48%) patients respectively. Readmission required due to recurrent appendicitis occurred in 9 (8.03%) patients in conservative treatment group, who was then treated by appendicectomy, where surgically treated group required no readmission. One third of recurrences appeared within 30 days and two-thirds between 3 and 6 months after hospital discharge. Surgical site infection occurred in 29 (25.89%) patients. Treatment efficacy was 72.32% for conservative treatment. Conclusions The current evidence does not support the routine use of antibiotics as the mainstay of treatment of uncomplicated acute appendicitis because of recurrence and appendicectomy remains the current gold standard. J. Dhaka National Med. Coll. Hos. 2024; 30 (02): 07-14

ABSTRACTBACKGROUND:This study aims to compare medical treatment and appendectomy in patients diagnosed with uncomplicated acute appendicitis during the COVID-19 pandemic.METHODS:Retrospectively analyzed were the data of 80 patients who received medical or surgical treatment for uncomplicated acute appendicitis between March 15, 2020, and August 31, 2020. The demographic characteristics of the patients, length of hospital stay, physical examination and radiology findings, laboratory results, and any complications were recorded. Patients were divided into two groups depending on the mode of treatment, as surgical and non-surgical.RESULTS:Forty patients were given medical treatment and 40 patients were directly operated on for appendicitis. Of the 40 patients who received medical treatment, 8 (20%) ended up requiring an operation due to recurrence. The mean duration of hospitalization was 2 days (range: 1–3), and the mean follow-up duration was 285.35±65.66 days (range: 101–379). The white blood cell count was significantly higher in the surgical group (p=0.004), and the length of hospital stay was longer in the non-surgical group (p<0.001). The prevalence of post-operative complications was similar for patients who underwent appendectomy directly on admission or after recurrence (p=1.000). Among the patients who received medical treatment, the most important predictors of requiring surgery were the red cell distribution width and increased appendix diameter in computed tomography (p<0.05).CONCLUSION:Medical treatment is an effective alternative in patients with uncomplicated appendicitis. Even in the case of a recurrence in follow-up, surgery due to a potential recurrence is not associated with an increased rate of complication compared to direct surgery.

Antibiotics are safe and efficient for CT-diagnosed uncomplicated acute appendicitis. Identifying predictive factors of primary non-responsiveness or recurrence would further improve antibiotic treatment success and safety. All patients treated with antibiotics in two large RCTs (APPAC and APPAC II) were included. The primary non-responsiveness analysis compared patients operated on within 30 days after randomization for complicated appendicitis with either patients presenting with uncomplicated appendicitis at surgery within 30 days or patients with successful antibiotic treatment during 3-year follow-up. Prognostic factors for appendicitis recurrence were assessed by comparing patients with successful antibiotic treatment with patients with acute appendicitis operated on after 30 days of initial antibiotics. Of 856 patients randomized to antibiotics (mean(s.d.) age of 36(12) years; 365 (42.6%) were women), 832 were eligible for non-responsiveness analysis and 732 for appendicitis recurrence analysis. Findings associated with primary non-responsiveness on admission included an appendiceal diameter ≥15 mm (adjusted risk ratio (RR) 4.00 (95% c.i. 2.00 to 7.92) (P < 0.001)) and a body temperature >38°C (adjusted RR 2.76 (95% c.i. 1.27 to 6.03) (P = 0.011)). During the first 6-30 h after admission, C-reactive protein (CRP) ≥100 mg/l (negative predictive value of 99%) and leucocyte count ≥9 × 109/l were associated with primary non-responsiveness (adjusted RR 8.29 (95% c.i. 3.69 to 18.63) (P < 0.001) and adjusted RR 4.44 (95% c.i. 1.79 to 11.05) (P = 0.001) respectively). No prognostic findings for appendicitis recurrence were identified. Patients with an appendiceal diameter ≥15 mm and a body temperature >38°C may not be optimal candidates for non-operative treatment for uncomplicated acute appendicitis. Patients with CRP <100 mg/l at 24 h of antibiotic treatment for uncomplicated acute appendicitis have a 99% likelihood of successful antibiotic therapy. NCT03236961 and NCT01022567 (http://www.clinicaltrials.gov).

BackgroundBased on epidemiological and clinical data acute appendicitis can present either as uncomplicated (70–80%) or complicated (20–30%) disease. Recent studies have shown that antibiotic therapy is both safe and cost-effective for a CT-scan confirmed uncomplicated acute appendicitis. However, based on the study protocols to ensure patient safety, these randomised studies used mainly broad-spectrum intravenous antibiotics requiring additional hospital resources and prolonged hospital stay. As we now know that antibiotic therapy for uncomplicated acute appendicitis is feasible and safe, further studies evaluating optimisation of the antibiotic treatment regarding both antibiotic spectrum and shorter hospital stay are needed to evaluate antibiotics as the first-line treatment for uncomplicated acute appendicitis.MethodsAPPAC II trial is a multicentre, open-label, non-inferiority randomised controlled trial comparing per oral (p.o.) antibiotic monotherapy with intravenous (i.v.) antibiotic therapy followed by p.o. antibiotics in the treatment of CT-scan confirmed uncomplicated acute appendicitis. Adult patients with CT-scan diagnosed uncomplicated acute appendicitis will be enrolled in nine Finnish hospitals. The intended sample size is 552 patients.Primary endpoint is the success of the randomised treatment, defined as resolution of acute appendicitis resulting in discharge from the hospital without the need for surgical intervention and no recurrent appendicitis during one-year follow-up. Secondary endpoints include post-intervention complications, late recurrence of acute appendicitis after one year, duration of hospital stay, pain, quality of life, sick leave and treatment costs. Primary endpoint will be evaluated in two stages: point estimates with 95% confidence interval (CI) will be calculated for both groups and proportion difference between groups with 95% CI will be calculated and evaluated based on 6 percentage point non-inferiority margin.DiscussionTo our knowledge, APPAC II trial is the first randomised controlled trial comparing per oral antibiotic monotherapy with intravenous antibiotic therapy continued by per oral antibiotics in the treatment of uncomplicated acute appendicitis. The APPAC II trial aims to add clinical evidence on the debated role of antibiotics as the first-line treatment for a CT-confirmed uncomplicated acute appendicitis as well as to optimise the non-operative treatment for uncomplicated acute appendicitis.Trial registrationClinicaltrials.gov, NCT03236961, retrospectively registered on the 2nd of August 2017.

Background: Acute appendicitis is one of the commonest cause of acute abdomen. For more than 100 years, surgeons have been successfully performing appendectomy to treat acute appendicitis. However, there is a recent trend to shift towards a more conservative approach. There has been a wide discussion and controversy on the surgical and non-surgical treatment of acute uncomplicated appendicitis. This work aimed to assess the effectiveness of non-operative conservative management in the treatment of acute uncomplicated appendicitis. Method: This was a single tertiary care level hospital based study done within the duration from 1st September 2016 to 31st January 2018. 180 patients with clinical and radiological features of acute appendicitis presenting within 48 hrs of onset of the symptoms were enrolled. The patients received a broad spectrum antibiotic and symptomatic treatment. The patients were followed up for 6 months. Results: Total 180 patients were enrolled. 108 (60%) of patients were female and 72 (40%) patients were males with mean age of 36 years. 144 (80%) patients successfully responded with the conservative treatment with antibiotics while 36 (20%) patients failed. No mortality was recorded in our study. Out of 36 patients who failed, 13 patients developed appendicular abscess, 12 patients had perforation of appendix while 11 patients had appendicular lump. Conclusions: Conservative management can be established as the first line of management for uncomplicated acute appendicitis patients having first attack successfully, but it should be followed with close monitoring of patients.

Is preoperative distinction between complicated and uncomplicated acute appendicitis feasible without imaging?

Introduction/Objective. Studies about possibilities of conservative, i.e., non-operative management of acute uncomplicated appendicitis in adult and pediatric population have been published lately, considering benefits of preserving appendix and potential complications related to appendectomy. Methods. In this retrospective study, medical data of 76 patients treated at the Institute for Child and Youth Health Care of Vojvodina in Novi Sad for acute uncomplicated appendicitis in 2015 and 2016 have been analyzed, comparing length of stay, antibiotic therapy use, complications occurrence, as well as the financial burden depending of the type of therapy applied. Results. During this period, 76 patients (55 operated on and 21 treated conservatively) were treated for acute uncomplicated appendicitis. Conservatively treated children spent statistically significantly shorter period of time at the hospital compared to the ones operated on (4.24 vs. 5.76 days; p &lt; 0.001). Early surgical complications occurred in 10.91% of those operated on and in 9.52% conservatively treated children, which was not a statistically significant difference (p = 0.863). The total cost of hospital stay was significantly lower in those who underwent non-operative management (10,340 RSD vs. 54,281 RSD; p &lt; 0.001). The difference was significant even when analyzing costs related to rehospitalization and operative treatment of children initially treated conservatively (p &lt; 0.001). Conclusion. Non-operative, i.e., conservative treatment of acute uncomplicated appendicitis in the pediatric population is safe and effective compared to the operative one, and it is not associated with more frequent occurrence of early surgical complications. Total costs for the non-operative treatment are significantly lower, even considering costs related to re-hospitalization of children initially treated conservatively.

Appendectomy has historically been the standard treatment of acute appendicitis, but lately, conservative treatment of uncomplicated acute appendicitis with antibiotics has successfully been used in selected patients. Complicated acute appendicitis is often treated conservatively initially, but may benefit from interval appendectomy due to the higher risk of appendiceal malignancy and recurrence. Recommendations for follow-up after conservatively treated appendicitis vary. Furthermore, the risk of underlying malignancy and the necessity of routine interval appendectomy are unclear. This study aims to evaluate follow-up status, recurrence, and underlying appendiceal malignancy in conservatively treated uncomplicated and complicated acute appendicitis. This study included patients with conservatively treated acute appendicitis at Skåne University Hospital, Sweden during 2012-2019. Information on patient demographics at index admission and data on follow-up, recurrence, number of appendectomies after initial conservative treatment, and underlying malignancy were retrieved from medical charts. The study cohort included 391 patients, 152 with uncomplicated and 239 with complicated acute appendicitis. Median time of study follow-up was 52 months. The recurrence risk was 23 (15.1%) after uncomplicated and 58 (24.3%) after complicated acute appendicitis (p = 0.030). During follow-up, 55 (23%) patients with complicated acute appendicitis underwent appendectomy. Appendiceal malignancies were found in 12 (5%) patients with previous complicated acute appendicitis versus no appendiceal malignancies after uncomplicated acute appendicitis (p = 0.002). The risk of appendiceal malignancy and recurrent appendicitis was significantly higher in patients with complicated acute appendicitis compared with uncomplicated acute appendicitis.

Uncomplicated acute appendicitis has been managed traditionally by early appendicectomy. However, recently, there has been increasing interest in the potential for primary treatment with antibiotics, with studies finding this to be associated with fewer complications than appendicectomy. The aim of this study was to compare outcomes of antibiotic therapy with appendicectomy for uncomplicated acute appendicitis. This meta-analysis of randomised controlled trials included adult patients presenting with uncomplicated acute appendicitis treated with antibiotics or appendicectomy. The primary outcome measure was complications. Secondary outcomes included treatment efficacy, hospital length of stay (LOS), readmission rate and incidence of complicated appendicitis. Five randomised controlled trials with a total of 1430 participants (727 undergoing antibiotic therapy and 703 undergoing appendicectomy) were included. There was a 39% risk reduction in overall complication rates in those treated with antibiotics compared with those undergoing appendicectomy (RR 0.61, 95% CI 0.44-0.83, p=0.002). There was no significant difference in hospital LOS (mean difference 0.25days, 95% CI -0.05 to 0.56, p=0.10). In the antibiotic cohort, 123 of 587 patients initially treatedsuccessfully with antibiotics were readmitted with symptoms suspicious of recurrent appendicitis. The incidence of complicated appendicitis was not increased in patients who underwent appendicectomy after "failed" antibiotic treatment (10.8%) versus those who underwent primary appendicectomy (17.9%). Increasing evidence supports the primary treatment of acute uncomplicated appendicitis with antibiotics, in terms of complications, hospital LOS and risk of complicated appendicitis. Antibiotics should be prescribed once a diagnosis of acute appendicitis is made or considered.

&lt;p dir="ltr"&gt;Acute appendicitis is a clinical term for inflammation of the vermiform appendix with a sudden onset. Symptoms depend both on the age of a patient and on the position of appendix intraabdominally. The aetiology remains unknown, although, there are multiple theories. The lifetime risk of acute appendicitis in Western countries has been established as 7-8%, with 8.6% for males and 6.7% for females. The standard treatment has been surgery for many decades, but non-operative treatment, in the form of antibiotics, has more recently come to light as a feasible alternative to appendectomies.&lt;/p&gt;&lt;p dir="ltr"&gt;Aims: The aim of this thesis was to assess intermediate and long-term outcomes of non- operative treatment in both children and adults. This included assessing safety and feasibility of non-operative treatment and its complications. An additional aim was to ascertain the failure rate of non-operative treatment and recurrence of acute uncomplicated appendicitis in children and try to establish the reasons for the treatment failure.&lt;/p&gt;&lt;p dir="ltr"&gt;Methods: Study I was a 5-year follow-up of all participants who underwent surgery or non- operative treatment with antibiotics in a previous randomised controlled pilot trial. Data was extracted from the hospital notes and telephone interviews.&lt;/p&gt;&lt;p dir="ltr"&gt;Study II was a long-term follow-up of adults with acute appendicitis who were involved in two randomised controlled trials, which compared non-operative treatment with appendectomy. The first trial consisted of 40 patients (13 female) and second trial was a multicentre study with 252 male patients. National registers were used to retrieve data at follow up, including the Swedish National Patient Register, the Cancer Register, the Cause of Death Register and Statistics Sweden.&lt;/p&gt;&lt;p dir="ltr"&gt;Study III was a systematic review that was registered in PROSPERO (CRD42024592607) and done according to PRISMA statement. We searched three databases (PubMed, Medline, Web of Science). Eligible studies were randomised controlled trials or prospective cohort studies with children aged &lt;18 years that received non-operative treatment for uncomplicated appendicitis and reporting at least 30 days follow-up. We carried out a meta- analysis.&lt;/p&gt;&lt;p dir="ltr"&gt;Results: In Study I, we followed up all 50 children (26 children in the appendectomy group, 24 children in the nonoperative group) for at least 5 years. The surgical group was without failures and in the nonoperative group there were 11 failures and recurrences. In the first year there were nine failures, two of them had an appendicitis on the histopathology. Another two recurrences, that were histopathologically confirmed appendicitis occurred one to five years after the initial trial. At the 5-year follow-up, 54% of children had been successfully treated nonoperatively with antibiotics alone.&lt;/p&gt;&lt;p dir="ltr"&gt;In Study II, in total, we were able to trace down 259 patients in the Patient Register, 137 patients in the non-operative group and 122 in the surgical group. At the end of follow-up, 82 (60%) patients had had successful non-operative treatment without an appendectomy. In the non-operative group there were 21 (15%) failures during the first admission. Thirty-four recurrences happened after discharge, all with a diagnostic code of acute appendicitis. After successful initial treatment, 82/116 (71%) remained without appendectomy.&lt;/p&gt;&lt;p dir="ltr"&gt;In Study III, through a systematic search we were able to identify 2343 abstracts. Thirty studies were eligible, 8 randomised controlled trials and 22 prospective cohort studies reporting 27 different patient cohorts. An early failure rate occurred in 10% (95% CI 7-14%) and the recurrence rate was 29% (95% CI 24-34%) at the end of follow-up. When analysing studies with faecalith, a failure rate was higher (17% versus 6.4%) with P-value &lt;0.0001.&lt;/p&gt;&lt;p dir="ltr"&gt;Conclusions: Studies I and II demonstrated intermediate- and long-term safety of non- operative treatment alone in children and adults. This treatment does not increase the risk of malignancy and other complications and patients avoid surgery. Study III demonstrated a low initial failure rate and the recurrence rate was 29%. Non-operative treatment was less successful in children with a faecalith, particularly during first admission. These results can be used for discussion about treatment options of uncomplicated appendicitis with child patients and their caregivers.&lt;/p&gt;&lt;h3&gt;List of scientific papers&lt;/h3&gt;&lt;p dir="ltr"&gt;I. &lt;b&gt;Patkova B&lt;/b&gt;, Svenningsson A, Almström M, Eaton S, Wester T, Svensson JF. Nonoperative Treatment Versus Appendectomy for Acute Nonperforated Appendicitis in Children: Five-year Follow Up of a Randomized Controlled Pilot Trial. Ann Surg. 2020 Jun;271(6):1030-1035. &lt;a href="https://doi.org/10.1097/SLA.0000000000003646"&gt;https://doi.org/10.1097/SLA.0000000000003646&lt;/a&gt;&lt;/p&gt;&lt;p dir="ltr"&gt;II. &lt;b&gt;Pátková B,&lt;/b&gt; Svenningsson A, Almström M, Svensson JF, Eriksson S, Wester T, Eaton S. Long-Term Outcome of Nonoperative Treatment of Appendicitis. JAMA Surg. 2023 Oct 1;158(10):1105-1106. &lt;a href="https://doi.org/10.1001/jamasurg.2023.2756"&gt;https://doi.org/10.1001/jamasurg.2023.2756&lt;/a&gt;&lt;/p&gt;&lt;p dir="ltr"&gt;III. &lt;b&gt;Patková B&lt;/b&gt;, Svenningsson A, Jumah S, Wester T, Eaton S. Failure and recurrence of non-operative treatment of uncomplicated appendicitis in children; a systematic review and meta-analysis. [Manuscript]&lt;/p&gt;

&lt;p dir="ltr"&gt;Acute appendicitis is a clinical term for inflammation of the vermiform appendix with a sudden onset. Symptoms depend both on the age of a patient and on the position of appendix intraabdominally. The aetiology remains unknown, although, there are multiple theories. The lifetime risk of acute appendicitis in Western countries has been established as 7-8%, with 8.6% for males and 6.7% for females. The standard treatment has been surgery for many decades, but non-operative treatment, in the form of antibiotics, has more recently come to light as a feasible alternative to appendectomies.&lt;/p&gt;&lt;p dir="ltr"&gt;Aims: The aim of this thesis was to assess intermediate and long-term outcomes of non- operative treatment in both children and adults. This included assessing safety and feasibility of non-operative treatment and its complications. An additional aim was to ascertain the failure rate of non-operative treatment and recurrence of acute uncomplicated appendicitis in children and try to establish the reasons for the treatment failure.&lt;/p&gt;&lt;p dir="ltr"&gt;Methods: Study I was a 5-year follow-up of all participants who underwent surgery or non- operative treatment with antibiotics in a previous randomised controlled pilot trial. Data was extracted from the hospital notes and telephone interviews.&lt;/p&gt;&lt;p dir="ltr"&gt;Study II was a long-term follow-up of adults with acute appendicitis who were involved in two randomised controlled trials, which compared non-operative treatment with appendectomy. The first trial consisted of 40 patients (13 female) and second trial was a multicentre study with 252 male patients. National registers were used to retrieve data at follow up, including the Swedish National Patient Register, the Cancer Register, the Cause of Death Register and Statistics Sweden.&lt;/p&gt;&lt;p dir="ltr"&gt;Study III was a systematic review that was registered in PROSPERO (CRD42024592607) and done according to PRISMA statement. We searched three databases (PubMed, Medline, Web of Science). Eligible studies were randomised controlled trials or prospective cohort studies with children aged &lt;18 years that received non-operative treatment for uncomplicated appendicitis and reporting at least 30 days follow-up. We carried out a meta- analysis.&lt;/p&gt;&lt;p dir="ltr"&gt;Results: In Study I, we followed up all 50 children (26 children in the appendectomy group, 24 children in the nonoperative group) for at least 5 years. The surgical group was without failures and in the nonoperative group there were 11 failures and recurrences. In the first year there were nine failures, two of them had an appendicitis on the histopathology. Another two recurrences, that were histopathologically confirmed appendicitis occurred one to five years after the initial trial. At the 5-year follow-up, 54% of children had been successfully treated nonoperatively with antibiotics alone.&lt;/p&gt;&lt;p dir="ltr"&gt;In Study II, in total, we were able to trace down 259 patients in the Patient Register, 137 patients in the non-operative group and 122 in the surgical group. At the end of follow-up, 82 (60%) patients had had successful non-operative treatment without an appendectomy. In the non-operative group there were 21 (15%) failures during the first admission. Thirty-four recurrences happened after discharge, all with a diagnostic code of acute appendicitis. After successful initial treatment, 82/116 (71%) remained without appendectomy.&lt;/p&gt;&lt;p dir="ltr"&gt;In Study III, through a systematic search we were able to identify 2343 abstracts. Thirty studies were eligible, 8 randomised controlled trials and 22 prospective cohort studies reporting 27 different patient cohorts. An early failure rate occurred in 10% (95% CI 7-14%) and the recurrence rate was 29% (95% CI 24-34%) at the end of follow-up. When analysing studies with faecalith, a failure rate was higher (17% versus 6.4%) with P-value &lt;0.0001.&lt;/p&gt;&lt;p dir="ltr"&gt;Conclusions: Studies I and II demonstrated intermediate- and long-term safety of non- operative treatment alone in children and adults. This treatment does not increase the risk of malignancy and other complications and patients avoid surgery. Study III demonstrated a low initial failure rate and the recurrence rate was 29%. Non-operative treatment was less successful in children with a faecalith, particularly during first admission. These results can be used for discussion about treatment options of uncomplicated appendicitis with child patients and their caregivers.&lt;/p&gt;&lt;h3&gt;List of scientific papers&lt;/h3&gt;&lt;p dir="ltr"&gt;I. &lt;b&gt;Patkova B&lt;/b&gt;, Svenningsson A, Almström M, Eaton S, Wester T, Svensson JF. Nonoperative Treatment Versus Appendectomy for Acute Nonperforated Appendicitis in Children: Five-year Follow Up of a Randomized Controlled Pilot Trial. Ann Surg. 2020 Jun;271(6):1030-1035. &lt;a href="https://doi.org/10.1097/SLA.0000000000003646"&gt;https://doi.org/10.1097/SLA.0000000000003646&lt;/a&gt;&lt;/p&gt;&lt;p dir="ltr"&gt;II. &lt;b&gt;Pátková B,&lt;/b&gt; Svenningsson A, Almström M, Svensson JF, Eriksson S, Wester T, Eaton S. Long-Term Outcome of Nonoperative Treatment of Appendicitis. JAMA Surg. 2023 Oct 1;158(10):1105-1106. &lt;a href="https://doi.org/10.1001/jamasurg.2023.2756"&gt;https://doi.org/10.1001/jamasurg.2023.2756&lt;/a&gt;&lt;/p&gt;&lt;p dir="ltr"&gt;III. &lt;b&gt;Patková B&lt;/b&gt;, Svenningsson A, Jumah S, Wester T, Eaton S. Failure and recurrence of non-operative treatment of uncomplicated appendicitis in children; a systematic review and meta-analysis. [Manuscript]&lt;/p&gt;

Antibiotic therapy is currently considered a safe and effective treatment alternative for computed tomography (CT)-confirmed uncomplicated acute appendicitis with recent studies reporting good results on both oral antibiotics only and outpatient management. Furthermore, there are promising pilot results on uncomplicated acute appendicitis management with symptomatic treatment (placebo). This trial aims to assess whether both antibiotics and hospitalization can be safely omitted from the treatment of uncomplicated acute appendicitis. The APPAC IV (APPendicitis Acuta IV) trial is a randomized, double-blind, multicenter noninferiority clinical trial comparing oral moxifloxacin with oral placebo in an outpatient setting with a discharge directly from the emergency room (ER). Adult patients (18-60 years) with CT-confirmed uncomplicated acute appendicitis (absence of appendicolith, abscess, perforation, tumor, appendiceal diameter ⩾15 mm on CT, or body temperature >38 °C) will be enrolled in nine Finnish hospitals. Primary outcome is treatment success at 30 days, that is, the resolution of acute appendicitis resulting in discharge from the hospital without appendectomy during the 30-day follow-up evaluated using a noninferiority design with a noninferiority margin of 6 percentage points. Noninferiority will be evaluated using one-sided 95% confidence interval of proportion difference between groups. Secondary endpoints include postintervention complications, recurrent appendicitis after the 30-day follow-up, duration of hospital stay, admission to hospital and reason for admission, readmissions to emergency department or hospitalization, VAS pain scores, quality of life, sick leave, and treatment costs. The follow-up after discharge from the ER includes a phone call at day 1, and at 3-4 days, 30 days, and 1, 3, 5, 10, and 20 years. Those eligible patients, who decline to undergo randomization, will be invited to participate in a concurrent observational cohort study with follow-up at 30 days, and 1 and 5 years. To our knowledge, APPAC IV trial is the first large randomized, double-blind, noninferiority multicenter clinical trial aiming to compare oral antibiotics and placebo for CT-diagnosed uncomplicated acute appendicitis in an outpatient setting. The study aims to bridge the major knowledge gap on whether antibiotics and hospitalization or both can be omitted in the treatment of uncomplicated acute appendicitis. The study protocol has been approved by the Clinical Trials Information System (CTIS) of the European Medicines Agency (EMA), study number: 2023-506213-21-00 and the trial has been registered in ClinicalTrials.gov, NCT06210269.