Two versus five days of antibiotics after appendectomy for complex acute appendicitis (APPIC): Study protocol for a randomized controlled trial

Background: Acute appendicitis is one of the most common indications for emergency surgery. In patients with a complex appendicitis, prolonged antibiotic prophylaxis is recommended after appendectomy. There is no consensus regarding the optimum duration of antibiotics. Guidelines propose 3 to 7 days of treatment, but shorter courses may be as effective in the prevention of infectious complications. At the same time, the global issue of increasing antimicrobial resistance urges for optimization of antibiotic strategies. The aim of this study is to determine whether a short course (48 h) of postoperative antibiotics is non-inferior to current standard practice of 5 days. Methods: Patients of 8 years and older undergoing appendectomy for acute complex appendicitis - defined as a gangrenous and/or perforated appendicitis or appendicitis in presence of an abscess - are eligible for inclusion. Immunocompromised or pregnant patients are excluded, as well as patients with a contraindication to the study antibiotics. In total, 1066 patients will be randomly allocated in a 1:1 ratio to the experimental treatment arm (48 h of postoperative intravenously administered (IV) antibiotics) or the control arm (5 days of postoperative IV antibiotics). After discharge from the hospital, patients participate in a productivity-cost-questionnaire at 4 weeks and a standardized telephone follow-up at 90 days after appendectomy. The primary outcome is a composite endpoint of infectious complications, including intra-abdominal abscess (IAA) and surgical site infection (SSI), and mortality within 90 days after appendectomy. Secondary outcomes include IAA, SSI, restart of antibiotics, length of hospital stay (LOS), reoperation, percutaneous drainage, readmission rate, and cost-effectiveness. The non-inferiority margin for the difference in the primary endpoint rate is set at 7.5% (one-sided test at α 0.025). Both per-protocol and intention-to-treat analyses will be performed. Discussion: This trial will provide evidence on whether 48 h of postoperative antibiotics is non-inferior to a standard course of 5 days of antibiotics. If non-inferiority is established, longer intravenous administration following appendectomy for complex appendicitis can be abandoned, and guidelines need to be adjusted accordingly

Long-term follow-up of functional outcome in patients with a cloacal malformation: A systematic review

Background Reconstructive surgery is performed in patients with cloacal malformations to achieve anorectal, urological, and gynecological function. The aim of this study was to evaluate the functional outcome of cloacal malformation repair as reported in literature. Methods A systematic literature search was conducted according to PRISMA guidelines using PubMed, EMbase, and Web-of-Science. Records were assessed for the reporting of functional outcomes, which was divided into anorectal, urological, or gynecological function. Studies were used in qualitative (Rangel score) and quantitative syntheses. Results Twelve publications were eligible for inclusion. Voluntary bowel movements were reported in 108 of 188 (57%), soiling in 146 of 205 (71%), and constipation in 31 of 61 patients (51%). Spontaneous voiding was reported for 138 of 299 patients (46%). 141 of 332 patients (42%) used intermittent catheterization, and 53 of 237 patients (22%) had a urinary diversion. Normal menstruations were reported for 25 of 71 patients (35%). Centers with limited experience reported similar outcome compared to centers with more experience (≥ 1 patients/year). Conclusion In this review we present functional outcome of the largest pooled cohort of patients with cloacal malformations as reported from 1993 to 2012. Functional disturbances are frequently encountered in anorectal, urological, as well as gynecological systems. Reporting of functional outcome in these patients should improve to increase knowledge about long-term results in patients with this rare malformation and to reach higher study quality. Especially, sacral and spinal anomalies should always be reported given their impact on functional outcome. Specialized care centers may be of great importance for patients with rare and complex conditions. © 2013 Elsevier Inc.All rights reserved

Reconsidering Diagnosis, Treatment, and Postoperative Care in Children with Cloacal Malformations

Cloacal malformations are among the most complex types of anorectal malformation and are characterized by the urological, genital, and intestinal tracts opening through a single common channel in the perineum. Long-term outcome is affected by multiple factors, which include anatomical variants of the malformation itself, associated anomalies, and the surgical approach. Reconsidering these variables and their influence on “patient important” function might lead to strategies that are more outcome-driven than focused on the creation of normal anatomy. Key outcomes reflect function in each of the involved tracts and the follow-up needed should therefore not only include the classical fields of colorectal surgery and urology but also focus on items such as gynecology, sexuality, family-building, and quality of life as well as other psychological aspects. Involving patients and families in determining optimal treatment strategies and outcome measures could lead to improved outcomes for the individual patient. A strategy to support delivery of personalized care for patients with cloacal malformations by aiming to define the best functional outcomes achievable for any individual, then select the treatment pathway most likely deliver that, with the minimum morbidity and cost, would be attractive. Combining the current therapies with ongoing technological advances such as tissue expansion might be a way to achieve this

Urogenital function after cloacal reconstruction, two techniques evaluated

Current surgical techniques for cloacal reconstruction are posterior sagittal anorecto vagino urethroplasty (PSARVUP) and posterior sagittal anorectoplasty (PSARP) with total urogenital mobilization (TUM). The aim of this study was to explore the results of reconstructive cloaca surgery in the Netherlands and evaluate urogenital function after PSARVUP and TUM. Medical records from five pediatric surgical departments in the Netherlands were studied for patients with cloacal malformations treated between 1985 and 2009. Forty-two patients were eligible, and patients with short common channels were categorized into PSARVUP and TUM groups. Groups were compared using Fisher's exact test. Median age at time of surgery was 9 months (range 1-121). In 24 patients (57%) a PSARVUP was done, in 18 patients (43%) TUM. Median follow-up was 142 months (range 15-289). At follow-up spontaneous voiding was seen in 29 patients (69%). Clean intermittent catheterization (CIC) was needed in 14 patients (33%); a urinary diversion was created in 10 patients (24%). In total 32 patients (76%) were dry with no involuntary loss of urine per urethra. Recurrent urinary tract infections were seen in 23 patients (55%). When comparing PSARVUP and TUM groups in our series of patients with short common channels, there were no differences in urological outcome. Normal menstruation was present in 11 of the 20 patients who reached puberty (55%). Urogenital functional outcome after reconstructive surgery for cloacal malformations was similar in PSARVUP and TUM groups in patients with short common channels. A thorough urological follow-up is needed to establish the long-term bladder function and urinary incontinence results to prevent long-term risks of recurrent UTI. Albeit without differences between PSARVUP and TUM groups, 45% of the patients present with abnormal or absent menstruations. Gynecological follow-up is mandatory in all patients with cloacal malformations 6 months after the first sign of pubert

Two versus five days of antibiotics after appendectomy for complex acute appendicitis (APPIC): study protocol for a randomized controlled trial

Abstract Background Acute appendicitis is one of the most common indications for emergency surgery. In patients with a complex appendicitis, prolonged antibiotic prophylaxis is recommended after appendectomy. There is no consensus regarding the optimum duration of antibiotics. Guidelines propose 3 to 7 days of treatment, but shorter courses may be as effective in the prevention of infectious complications. At the same time, the global issue of increasing antimicrobial resistance urges for optimization of antibiotic strategies. The aim of this study is to determine whether a short course (48 h) of postoperative antibiotics is non-inferior to current standard practice of 5 days. Methods Patients of 8 years and older undergoing appendectomy for acute complex appendicitis – defined as a gangrenous and/or perforated appendicitis or appendicitis in presence of an abscess – are eligible for inclusion. Immunocompromised or pregnant patients are excluded, as well as patients with a contraindication to the study antibiotics. In total, 1066 patients will be randomly allocated in a 1:1 ratio to the experimental treatment arm (48 h of postoperative intravenously administered (IV) antibiotics) or the control arm (5 days of postoperative IV antibiotics). After discharge from the hospital, patients participate in a productivity-cost-questionnaire at 4 weeks and a standardized telephone follow-up at 90 days after appendectomy. The primary outcome is a composite endpoint of infectious complications, including intra-abdominal abscess (IAA) and surgical site infection (SSI), and mortality within 90 days after appendectomy. Secondary outcomes include IAA, SSI, restart of antibiotics, length of hospital stay (LOS), reoperation, percutaneous drainage, readmission rate, and cost-effectiveness. The non-inferiority margin for the difference in the primary endpoint rate is set at 7.5% (one-sided test at ɑ 0.025). Both per-protocol and intention-to-treat analyses will be performed. Discussion This trial will provide evidence on whether 48 h of postoperative antibiotics is non-inferior to a standard course of 5 days of antibiotics. If non-inferiority is established, longer intravenous administration following appendectomy for complex appendicitis can be abandoned, and guidelines need to be adjusted accordingly. Trial registration Dutch Trial Register, NTR6128. Registered on 20 December 2016

2 days versus 5 days of postoperative antibiotics for complex appendicitis: a pragmatic, open-label, multicentre, non-inferiority randomised trial

Background: The appropriate duration of postoperative antibiotics for complex appendicitis is unclear. The increasing global threat of antimicrobial resistance warrants restrictive antibiotic use, which could also reduce side-effects, length of hospital stay, and costs. Methods: In this pragmatic, open-label, non-inferiority trial in 15 hospitals in the Netherlands, patients with complex appendicitis (aged ≥8 years) were randomly assigned (1:1) to receive 2 days or 5 days of intravenous antibiotics after appendicectomy. Randomisation was stratified by centre, and treating physicians and patients were not masked to treatment allocation. The primary endpoint was a composite endpoint of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference (95% CI) in the primary endpoint, adjusted for age and severity of appendicitis, with a non-inferiority margin of 7·5%. Outcome assessment was based on electronic patient records and a telephone consultation 90 days after appendicectomy. Efficacy was analysed in the intention-to-treat and per-protocol populations. Safety outcomes were analysed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register, NL5946. Findings: Between April 12, 2017, and June 3, 2021, 13 267 patients were screened and 1066 were randomly assigned, 533 to each group. 31 were excluded from intention-to-treat analysis of the 2-day group and 30 from the 5-day group owing to errors in recruitment or consent. Appendicectomy was done laparoscopically in 955 (95%) of 1005 patients. The telephone follow-up was completed in 664 (66%) of 1005 patients. The primary endpoint occurred in 51 (10%) of 502 patients analysed in the 2-day group and 41 (8%) of 503 patients analysed in the 5-day group (adjusted absolute risk difference 2·0%, 95% CI −1·6 to 5·6). Rates of complications and re-interventions were similar between trial groups. Fewer patients had adverse effects of antibiotics in the 2-day group (45 [9%] of 502 patients) than in the 5-day group (112 [22%] of 503 patients; odds ratio [OR] 0·344, 95% CI 0·237 to 0·498). Re-admission to hospital was more frequent in the 2-day group (58 [12%] of 502 patients) than in the 5-day group (29 [6%] of 503 patients; OR 2·135, 1·342 to 3·396). There were no treatment-related deaths. Interpretation: 2 days of postoperative intravenous antibiotics for complex appendicitis is non-inferior to 5 days in terms of infectious complications and mortality within 90 days, based on a non-inferiority margin of 7·5%. These findings apply to laparoscopic appendicectomy conducted in a well resourced health-care setting. Adopting this strategy will reduce adverse effects of antibiotics and length of hospital stay. Funding: The Netherlands Organization for Health Research and Development

Two versus five days of antibiotics after appendectomy for complex acute appendicitis (APPIC): study protocol for a randomized controlled trial

Abstract Background Acute appendicitis is one of the most common indications for emergency surgery. In patients with a complex appendicitis, prolonged antibiotic prophylaxis is recommended after appendectomy. There is no consensus regarding the optimum duration of antibiotics. Guidelines propose 3 to 7 days of treatment, but shorter courses may be as effective in the prevention of infectious complications. At the same time, the global issue of increasing antimicrobial resistance urges for optimization of antibiotic strategies. The aim of this study is to determine whether a short course (48 h) of postoperative antibiotics is non-inferior to current standard practice of 5 days. Methods Patients of 8 years and older undergoing appendectomy for acute complex appendicitis – defined as a gangrenous and/or perforated appendicitis or appendicitis in presence of an abscess – are eligible for inclusion. Immunocompromised or pregnant patients are excluded, as well as patients with a contraindication to the study antibiotics. In total, 1066 patients will be randomly allocated in a 1:1 ratio to the experimental treatment arm (48 h of postoperative intravenously administered (IV) antibiotics) or the control arm (5 days of postoperative IV antibiotics). After discharge from the hospital, patients participate in a productivity-cost-questionnaire at 4 weeks and a standardized telephone follow-up at 90 days after appendectomy. The primary outcome is a composite endpoint of infectious complications, including intra-abdominal abscess (IAA) and surgical site infection (SSI), and mortality within 90 days after appendectomy. Secondary outcomes include IAA, SSI, restart of antibiotics, length of hospital stay (LOS), reoperation, percutaneous drainage, readmission rate, and cost-effectiveness. The non-inferiority margin for the difference in the primary endpoint rate is set at 7.5% (one-sided test at ɑ 0.025). Both per-protocol and intention-to-treat analyses will be performed. Discussion This trial will provide evidence on whether 48 h of postoperative antibiotics is non-inferior to a standard course of 5 days of antibiotics. If non-inferiority is established, longer intravenous administration following appendectomy for complex appendicitis can be abandoned, and guidelines need to be adjusted accordingly. Trial registration Dutch Trial Register, NTR6128 . Registered on 20 December 2016