Partially randomised patient preference trials as an alternative design to randomised controlled trials: systematic review and meta-analyses

OBJECTIVE: Randomised controlled trials (RCT) are the gold standard to provide unbiased data. However, when patients have a treatment preference, randomisation may influence participation and outcomes (eg, external and internal validity). The aim of this study was to assess the influence of patients' preference in RCTs by analysing partially randomised patient preference trials (RPPT); an RCT and preference cohort combined. DESIGN: Systematic review and meta-analyses. DATA SOURCES: MEDLINE, Embase, PsycINFO and the Cochrane Library. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: RPPTs published between January 2005 and October 2018 reporting on allocation of patients to randomised and preference cohorts were included. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data. The main outcomes were the difference in external validity (participation and baseline characteristics) and internal validity (lost to follow-up, crossover and the primary outcome) between the randomised and the preference cohort within each RPPT, compared in a meta-regression using a Wald test. Risk of bias was not assessed, as no quality assessment for RPPTs has yet been developed. RESULTS: In total, 117 of 3734 identified articles met screening criteria and 44 were eligible (24 873 patients). The participation rate in RPPTs was >95% in 14 trials (range: 48%-100%) and the randomisation refusal rate was >50% in 26 trials (range: 19%-99%). Higher education, female, older age, race and prior experience with one treatment arm were characteristics of patients declining randomisation. The lost to follow-up and cross-over rate were significantly higher in the randomised cohort compared with the preference cohort. Following the meta-analysis, the reported primary outcomes were comparable between both cohorts of the RPPTs, mean difference 0.093 (95% CI -0.178 to 0.364, p=0.502). CONCLUSIONS: Patients' preference led to a substantial proportion of a specific patient group refusing randomisation, while it did not influence the primary outcome within an RPPT. Therefore, RPPTs could increase external validity without compromising the internal validity compared with RCTs. PROSPERO REGISTRATION NUMBER: CRD42019094438

Transanal Ileal Pouch-Anal Anastomosis for Ulcerative Colitis has Comparable Long-Term Functional Outcomes to Transabdominal Approach: A Multicentre Comparative Study

BACKGROUND: The transanal approach to ileal pouch-anal anastomosis [Ta-IPAA] provides better access to the lower pelvis with lower short-term morbidity in ulcerative colitis [UC]. The aim of this study was to assess the long-term functional outcomes after Ta-IPAA vs transabdominal IPAA [Abd-IPAA] in UC. METHODS: A multicentre cohort analysis was performed between March 2002 and September 2017. Patient characteristics, surgical details and postoperative outcomes were compared. CGQL [Cleveland global quality of life] score at 12 months with a functioning pouch was considered the primary end point. RESULTS: A total of 374 patients [100 Ta-IPAA vs 274 Abd-IPAA] were included. Ta-IPAA demonstrated a comparable overall quality of life [CGQL score] to Abd-IPAA [0.75 ± 0.11 vs 0.71 ± 0.14; respectively, p = 0.1]. Quality of life [7.71 ± 1.17 vs 7.30 ± 1.46; p = 0.04] and energy-level items [7.16 ± 1.52 vs 6.66 ± 1.68; p = 0.03] were significantly better after Ta-IPAA, while the quality of health item was comparable [7.68 ± 1.26 vs 7.64 ± 1.44; p = 0.96]. Analysis excluding anastomotic leaks did not change the overall CGQL scores. Stool frequencies [>10/24 h: 22% vs 21%; p = 1.0] and the rate of a single episode of major incontinence during the following 12-month period [27% vs 26%; p = 0.89] were similar. The differences in 30-day morbidity rates [33% vs 41%; p = 0.2] and anastomotic leak rates were not significant [6% vs 13%; p = 0.09]. CONCLUSIONS: This study provides evidence of comparable long-term functional outcome and quality of life after Ta-IPAA and Abd-IPAA for UC

Ileal pouch-anal anastomosis complications and pouch failure: A systematic review and meta-analysis

Objective: This systematic review aims to assess the incidence of pouch failure and the correlation between ileal pouch-anal anastomosis (IPAA)-related complications and pouch failure. Background: Previous studies demonstrated wide variation in postoperative complication rates following IPAA. Methods: A systematic review was performed by searching the MEDLINE, EMBASE, and Cochrane Library databases for studies reporting on pouch failure published from January 1, 2010, to May 6, 2020. A meta-analysis was performed using a random-effects model, and the relationship between pouch-related complications and pouch failure was assessed using Spearman's correlations. Results: Thirty studies comprising 22,978 patients were included. Included studies contained heterogenic patient populations, different procedural stages, varying definitions for IPAA-related complications, and different follow-up periods. The pooled pouch failure rate was 7.7% (95% confidence intervals: 5.56-10.59) and 10.3% (95% confidence intervals: 7.24-14.30) for studies with a median follow-up of ≥5 and ≥10 years, respectively. Observed IPAA-related complications were anastomotic leakage (1-17%), pelvic sepsis (2-18%), fistula (1-30%), stricture (1-34%), pouchitis (11-61%), and Crohn's disease of the pouch (0-18%). Pelvic sepsis (r = 0.51, P < 0.05) and fistula (r = 0.63, P < 0.01) were correlated with pouch failure. A sensitivity analysis including studies with a median follow-up of ≥5 years indicated that only fistula was significantly correlated with pouch failure (r = 0.77, P < 0.01). Conclusions: The single long-term determinant of pouch failure was pouch fistula, which is a manifestation of a chronic leak. Therefore, all effort should be taken to prevent an acute leak from becoming a chronic leak by early diagnosis and proactive management of the leak

The Impact of Rectal Stump Inflammation after Subtotal Colectomy on Pouch Outcomes in Ulcerative Colitis Patients

Background and Aims: Proctitis after subtotal colectomy with ileostomy for ulcerative colitis [UC] is common, but its impact on short- and long-term outcome after pouch surgery is unknown. The aim of this study was to determine the incidence of proctitis after subtotal colectomy and its impact on postoperative morbidity and pouchitis. Methods: The distal margin of the rectal stump of all consecutive patients undergoing completion proctectomy and pouch procedure for UC, between 1999 and 2017, was revised and scored for active inflammation according to the validated Geboes score, and for diversion proctitis. Pathological findings were correlated to complications after pouch surgery and pouchitis [including therapy-refractory] using multivariate analyses. Results: Out of 204 included patients, 167 [82%] had active inflammation in the rectal stump and diversion colitis was found in 170 specimens [83%]. Overall postoperative complications and anastomotic leakage rates were not significantly different between patients with and without active inflammation in the rectal stump [34.7% vs 32.4%, p = 0.79, and 10.2% vs 5.4%, p = 0.54, respectively]. Active inflammation of the rectal stump was significantly associated with the development of pouchitis [54.3% vs 25.5%, plog = 0.02], as well as with therapy refractory pouchitis [14% vs 0%, plog = 0.05]. Following multivariate analysis, active inflammation was an independent predictor for the development of pouchitis. Diversion proctitis showed no association with these outcome parameters. Conclusions: Active inflammation in the rectal stump after subtotal colectomy occurs in 80% of UC patients and is a predictor for the development of pouchitis and therapy-refractory pouchitis

Postoperative abdominal infections after resection of T4 colon cancer increase the risk of intra-abdominal recurrence

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Endo-sponge Assisted Early Surgical Closure of Ileal Pouch-anal Anastomotic Leakage Preserves Long-term Function: A Cohort Study

BACKGROUND AND AIMS: Endo-sponge [Braun Medical] assisted early surgical closure [ESC] is an effective treatment to control pelvic sepsis after ileal pouch-anal anastomosis [IPAA] leakage, and became standard treatment in our centre from 2010 onwards. The aim of this cohort study was to assess the long-term pouch function of ulcerative colitis [UC] patients treated with ESC or conventional management [CM] for anastomotic leakage after IPAA. METHODS: Consecutive patients who underwent an IPAA for UC between 2002 and 2017 were included. Patients treated with ESC [2010-2017] or CM [2002-2009] for anastomotic leakage were compared with control patients without anastomotic leakage of the corresponding time period. Main endpoints were long-term pouch function on a 3-point scale and pouch failure, as measured with the validated pouch dysfunction score questionnaire. RESULTS: Some 280 of 334 patients [84%] returned the pouch dysfunction questionnaire, of whom 18 were treated with ESC and 22 with CM for anastomotic leakage. Control cohorts included 133 [2010-2017] and 107 patients [2002-2009]. Between ESC-treated patients and control patients, pouch function [p = 0.647] and pouch failure rates [0/18 versus 5/133, p >0.99] were similar. CM resulted in worse pouch function [p = 0.016] and a higher pouch failure rate [5/22 versus 5/107, p = 0.013] compared with control patients. CONCLUSIONS: ESC, in contrast to CM, for IPAA leakage in UC patients is associated with preservation of pouch function and preclusion of pouch failure, probably due to early and effective treatment of pelvic sepsis

Laparoscopic surgery facilitates administration of adjuvant chemotherapy in locally advanced colon cancer: propensity score analyses

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Endoscopic Recurrence or Anastomotic Wound Healing Phenomenon after Ileocolic Resection for Crohn's Disease: The Challenges of Accurate Endoscopic Scoring.

BACKGROUND AND AIMS: Adequate endoscopic scoring in Crohn's disease [CD] is crucial, as it dictates the need for initiating postoperative medical therapy and is utilized as an outcome parameter in clinical trials. Here we aimed to observe anastomotic wound healing in relation to endoscopic scoring of both inverted and everted stapled lines in side-to-side anastomoses. METHODS: Two prospective patient cohorts were included: ileocolic resection [ICR] for CD, and right-sided colon resection for colorectal cancer [CRC]. Videos taken during colonoscopy 6 months postoperatively were evaluated. The Simplified Endoscopic Activity Score for Crohn's Disease and modified Rutgeerts score were determined. The primary outcome was the presence of ulcerations in CD patients on both the inverted and the everted stapled lines. Secondary outcomes were the presence of anastomotic ulcerations in CRC patients and the number of cases having ulcerations exclusively at the inverted stapled line. RESULTS: Of the 82 patients included in the CD cohort, ulcerations were present in 63/82 [76.8%] at the inverted- vs 1/71 [1.4%] at the everted stapled line. Likewise in the CRC cohort, ulcerations were present in 4/6 [67.7%] at the inverted vs 0/6 [0%] at the everted stapled line. In total, 27% of the 63 patients in the CD cohort had ulcerations exclusively on the inverted stapled line. CONCLUSION: Inverted stapled lines heal with ulcerations, whereas everted stapled lines heal without any ulcerations, in both CD and non-CD patients. The abnormalities at the inverted stapled line might interfere with endoscopic scoring of recurrence, with potentially an impact on patients' quality of life and on healthcare costs if postoperative treatment is initiated incorrectly

Ileal Pouch-anal Anastomosis Complications and Pouch Failure

Objective:. This systematic review aims to assess the incidence of pouch failure and the correlation between ileal pouch-anal anastomosis (IPAA)-related complications and pouch failure. Background:. Previous studies demonstrated wide variation in postoperative complication rates following IPAA. Methods:. A systematic review was performed by searching the MEDLINE, EMBASE, and Cochrane Library databases for studies reporting on pouch failure published from January 1, 2010, to May 6, 2020. A meta-analysis was performed using a random-effects model, and the relationship between pouch-related complications and pouch failure was assessed using Spearman’s correlations. Results:. Thirty studies comprising 22,978 patients were included. Included studies contained heterogenic patient populations, different procedural stages, varying definitions for IPAA-related complications, and different follow-up periods. The pooled pouch failure rate was 7.7% (95% confidence intervals: 5.56–10.59) and 10.3% (95% confidence intervals: 7.24–14.30) for studies with a median follow-up of ≥5 and ≥10 years, respectively. Observed IPAA-related complications were anastomotic leakage (1–17%), pelvic sepsis (2–18%), fistula (1–30%), stricture (1–34%), pouchitis (11–61%), and Crohn’s disease of the pouch (0–18%). Pelvic sepsis (r = 0.51, P < 0.05) and fistula (r = 0.63, P < 0.01) were correlated with pouch failure. A sensitivity analysis including studies with a median follow-up of ≥5 years indicated that only fistula was significantly correlated with pouch failure (r = 0.77, P < 0.01). Conclusions:. The single long-term determinant of pouch failure was pouch fistula, which is a manifestation of a chronic leak. Therefore, all effort should be taken to prevent an acute leak from becoming a chronic leak by early diagnosis and proactive management of the leak. Mini abstract:. This systematic review aims to assess the incidence of pouch failure and the correlation between IPAA-related complications and pouch failure. Long-term pouch failure was correlated with fistula, suggesting that early septic complications may result in fistula formation during long-term follow-up, leading to an increased risk of pouch failure

Subclassification of Multivisceral Resections for T4b Colon Cancer with Relevance for Postoperative Complications and Oncological Risks

BACKGROUND: Multivisceral resection for T4b colon cancer constitutes a heterogeneous group of surgical procedures. The purpose of this study was to explore clinically distinct categories of multivisceral resection, with subsequent correlation to postoperative complications and oncological outcomes. METHODS: In this multicenter cohort study, all consecutive patients without metastases who underwent multivisceral resection for pT4bN0-2M0 colon cancer between 2000 and 2014 were included. Multivisceral resection was divided into four categories: (i) gastrointestinal (including the stomach), (ii) urologic ((partial) bladder and ureter), (iii) solid organ (spleen, kidney, liver, pancreas, and uterus), and (iv) abdominal wall/omentum/ovaries. The primary outcome was surgical complications and secondary outcomes were 5-year intra-abdominal recurrence, disease-free survival, and overall survival. RESULTS: In total, 130 patients who underwent curative intent resection of pT4 colon cancer were included. Patients who underwent multivisceral resection within multiple categories were assigned to one of the categories based on hierarchy of clinical impact after exploratory analysis. For the primary endpoint, 55 patients were assigned to gastrointestinal, 14 to urologic, 14 to solid organ, and 47 to abdominal wall/omentum/ovaries multivisceral resection. Gastrointestinal multivisceral resection was independently associated with surgical complications (HR 3.9, 95% CI 1.4-10.6). Abdominal wall/omentum/ovaries multivisceral resection was significantly related with intra-abdominal recurrence (HR 7.8, 95% CI 1.0-57.8). The 5-year disease-free survival and overall survival showed no significant differences per multivisceral resection category. CONCLUSIONS: Multivisceral resections for T4b colon cancer are heterogeneous procedures considering risk profiles. The proposed multivisceral resection subclassification needs validation, but might improve comparability between studies and hospitals (auditing).status: publishe