Florian Herrle

Randomized controlled trial: comparison of two surgical techniques for closing the wound following ileostomy closure: purse string vs direct suture

Surgical site infection (SSI) is a common complication following ileostomy closure with a frequency of up to 40%. This prospective randomized controlled trial was initiated to compare two surgical techniques – direct suture (DS) and purse‐string suture (PSS) – used to close the wound following ileostomy closure. The primary end‐point was the SSI rate. Secondary end‐points were cosmetic outcome [using two validated scales: the Patient and Observer Scar Assessment Scale (POSAS) and the Body Image Questionnaire (BIQ)] and the influence of other factors on the SSI rate.

DeloRes trial: study protocol for a randomized trial comparing two standardized surgical approaches in rectal prolapse - Delorme’s procedure versus resection rectopexy

BackgroundMore than 100 surgical approaches to treat rectal prolapse have been described. These can be done through the perineum or transabdominally. Delorme’s procedure is the most frequently used perineal, resection rectopexy the most commonly used abdominal procedure. Recurrences seem more common after perineal compared to abdominal techniques, but the latter may carry a higher risk of peri- and postoperative morbidity and mortality.Methods/DesignDeloRes is a randomized, controlled, observer-blinded multicenter trial with two parallel groups. Patients with a full-thickness rectal prolapse (third degree prolapse), considered eligible for both operative methods are included. The primary outcome is time to recurrence of full-thickness rectal prolapse during the 24 months following primary surgery. Secondary endpoints are time to and incidence of recurrence of full-thickness rectal prolapse during the 5-year follow-up, duration of surgery, morbidity, hospital stay, quality of life, constipation, and fecal incontinence. A meta-analysis was done on the basis of the available data on recurrence rates from 17 publications comprising 1,140 patients. Based on the results of a meta-analysis it is assumed that the recurrence rate after 2 years is 20% for Delorme’s procedure and 5% for resection rectopexy. Considering a rate of lost to follow-up without recurrence of 30% a total of 130 patients (2 x 65 patients) was calculated as an adequate sample size to assure a power of 80% for the confirmatory analysis.DiscussionThe DeloRes Trial will clarify which procedure results in a smaller recurrence rate but also give information on how morbidity and functional results compare.Trial registrationGerman Clinical Trial Number DRKS00000482

Scientific value of systematic reviews: survey of editors of core clinical journals.

Background Synthesizing research evidence using systematic and rigorous methods has become a key feature of evidence-based medicine and knowledge translation. Systematic reviews (SRs) may or may not include a meta-analysis depending on the suitability of available data. They are often being criticised as ‘secondary research’ and denied the status of original research. Scientific journals play an important role in the publication process. How they appraise a given type of research influences the status of that research in the scientific community. We investigated the attitudes of editors of core clinical journals towards SRs and their value for publication. Methods We identified the 118 journals labelled as “core clinical journals” by the National Library of Medicine, USA in April 2009. The journals’ editors were surveyed by email in 2009 and asked whether they considered SRs as original research projects; whether they published SRs; and for which section of the journal they would consider a SR manuscript. Results The editors of 65 journals (55%) responded. Most respondents considered SRs to be original research (71%) and almost all journals (93%) published SRs. Several editors regarded the use of Cochrane methodology or a meta-analysis as quality criteria; for some respondents these criteria were premises for the consideration of SRs as original research. Journals placed SRs in various sections such as “Review” or “Feature article”. Characterization of non-responding journals showed that about two thirds do publish systematic reviews. Discussion Currently, the editors of most core clinical journals consider SRs original research. Our findings are limited by a non-responder rate of 45%. Individual comments suggest that this is a grey area and attitudes differ widely. A debate about the definition of ‘original research’ in the context of SRs is warranted.

Quality of Life and Timing of Stoma Closure in Patients With Rectal Cancer Undergoing Low Anterior Resection With Diverting Stoma: A Multicenter Longitudinal Observational Study.

BACKGROUND: After low anterior resection for rectal cancer, creation of a diverting stoma is recommended. Data on the impact of a diverting stoma on quality of life are conflicting. Optimal timing of stoma closure in the setting of adjuvant chemotherapy is unclear. OBJECTIVE: The purpose of this study was to investigate the impact of a diverting stoma on quality of life in patients undergoing rectal cancer resection before and after stoma closure. Furthermore, the study was conducted to look at the timing of stoma reversal and the potential influence of factors such as adjuvant chemotherapy. DESIGN: This was a longitudinal, observational, multicenter study. SETTINGS: The study was conducted at 17 German colorectal centers. PATIENTS: Patients with rectal cancer who planned for elective curative surgery with creation of temporary diverting stoma were included. MAIN OUTCOME MEASURES: This longitudinal observational study assessed quality of life at 3 occasions using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core Questionnaire/Colorectal Cancer Module before cancer resection, before stoma closure, and 6 months after stoma closure. Furthermore, the timing of stoma closure and continence were evaluated. RESULTS: A total of 120 patients (64% men; mean age, 63.2 ± 11.5 years) were analyzed. Longitudinal global quality of life was not influenced by the presence of a stoma. Several functional and GI symptom scales were markedly impaired after stoma creation. Physical, role functioning, and sexual interest recovered after stoma closure. Social functioning stayed impaired (p < 0.0001). Median time to stoma closure was 5 months (range, 17 days to 18 months). A total of 3.4% of patients had very early stoma closure (within 30 days). Adjuvant chemotherapy delayed stoma closure (median, 5.6 vs 3.4 months without chemotherapy; p = 0.0001). LIMITATIONS: The study was limited by its missing quality-of-life data for sexual function. CONCLUSIONS: The presence of a stoma had a negative impact on social functioning and GI symptoms. However, this had no clinically relevant influence on global quality of life. Time to stoma closure was nearly doubled when patients underwent adjuvant chemotherapy.

A pilot single-centre randomized trial assessing the safety and efficacy of lateral pararectus abdominis compared with transrectus abdominis muscle stoma placement in patients with temporary loop ileostomies: the PATRASTOM trial.

Transrectal stoma placement is considered the standard technique for positioning a stoma. A prospective series using a novel method of lateral pararectal stoma placement recently revealed a remarkably low stoma herniation rate. A randomized trial was conducted to compare the lateral pararectal with the transrectal stoma position with regard to parastomal herniation, stoma‐related morbidity and quality of life.

Effect on the tensile strength of human acellular dermis (Epiflex®) of in-vitro incubation simulating an open abdomen setting

BackgroundThe use of human acellular dermis (hAD) to close open abdomen in the treatment process of severe peritonitis might be an alternative to standard care. This paper describes an investigation of the effects of fluids simulating an open abdomen environment on the biomechanical properties of Epiflex® a cell-free human dermis transplant.MethodshAD was incubated in Ringers solution, blood, urine, upper gastrointestinal (upper GI) secretion and a peritonitis-like bacterial solution in-vitro for 3 weeks. At day 0, 7, 14 and 21 breaking strength was measured, tensile strength was calculated and standard fluorescence microscopy was performed.ResultshAD incubated in all five of the five fluids showed a decrease in mean breaking strength at day 21 when compared to day 0. However, upper GI secretion was the only incubation fluid that significantly reduced the mechanical strength of Epiflex after 21days of incubation when compared to incubation in Ringer’s solution.ConclusionhAD may be a suitable material for closure of the open abdomen in the absence of upper GI leakage and pancreatic fistulae.

Influence of complete administration of adjuvant chemotherapy cycles on overall and disease-free survival in locally advanced rectal cancer: post hoc analysis of a randomized, multicenter, non-inferiority, phase 3 trial

BackgroundA randomized trial demonstrated that capecitabine is at least as effective as fluorouracil in the adjuvant treatment of patients with locally advanced rectal cancer. However, not all patients receive all planned cycles of chemotherapy. Therefore it is of interest how complete or partial administration of chemotherapy influences oncological outcome.MethodsA post hoc analysis of a trial with 401 randomized patients, nine being excluded because of missing data, was performed. 392 patients (197 - capecitabine, 195 - fluorouracil) could be analyzed regarding the number of administered adjuvant chemotherapy cycles. In the subgroup of 361 patients with an overall survival of at least six months, five-year overall and disease-free survival were analyzed in respect to completion (complete vs. incomplete) of chemotherapy cycles. Survival rates and curves were calculated and compared using the log-rank test. The effect of completion of chemotherapy was adjusted for relevant confounding factors.ResultsTwo hundred fifty-one (64.0%) of analyzed patients received all postoperative scheduled cycles. Five-year overall survival was significantly better in these patients compared to the incomplete group (76.0 vs. 60.6%, p < 0.0001). Of 361 patients with an overall survival of at least six months, 251(69.5%) patients received all cycles. Five-year overall survival was also significantly better than in the incomplete group (76.0 vs. 66.4%, p = 0.0073). Five-year disease free survival was numerically better (64.9 vs. 58.7%, p = 0.0646; HR [not all cycles vs. all cycles] = 1.42 95% CI: [0.98, 2.07]). Cox regression models show a non-significant better OS (p = 0.061) and DFS (p = 0.083), if chemotherapy cycles were administered completely.ConclusionComplete administration of chemotherapy cycles was associated with improved five-year overall and disease-free survival in patients with locally advanced rectal cancer.

Reply to 'Response to a pilot single centre randomized trial: the PATRASTOM trial' and 'Assessing the efficacy of lateral rectus abdominis positioned stoma (LRAPS) formation in the PATRASTOM trial'.

Dear Editor, We appreciate the constructive response of Mr Stephenson and the CIPHER study group to our PATRASTOM trial [1,2]. Some of the aspects need to be discussed and clarified. As suggested by the CIPHER group, we agree that patients should rather be randomized intra-operatively to prevent exclusion of randomized patients as this may result in bias. The PATRASTOM trial was designed accordingly. Patients were randomized intra-operatively and none of the 15 patients excluded intra-operatively had actually been randomized. In detail, 60 of 82 potentially eligible patients were randomized; 56 of these underwent the final analysis (see Methods section and Fig. 1, the CONSORT diagram) [3]. The second point refers to the method of detection of parastomal herniation, which was the primary end-point of the study. After our Cochrane Review had shown inconclusive evidence regarding our question whether the lateral pararectal approach lowers the rate of parastomal herniation compared to the transrectal standard [4], the PATRASTOM trial was designed as a pilot with the aim of assessing the incidence of the primary end-point in both intervention groups (lateral pararectal vs transrectal stoma placement). Obviously, there are several ways to diagnose parastomal hernia (PSH) but most are rather subjective and inaccurate, especially when the PSH is small. Moreover, CT scanning often suggested as the ‘gold standard’ involves application of radiation and is debatable in the setting of a benign disease within a prospective study. In contrast direct visualization of parastomal herniation during an ileostomy reversal procedure is obviously a very sensitive and simple method, which allows the detection of even subclinical hernia formation. A covering ileostomy is a commonly carried out procedure and, as most are closed within a short time after construction, this clinical model seemed ideal for a study to generate useful initial data for a later larger study. As correctly stated the rate of PSH in loop ileostomies does not necessarily correspond to the absolute rate in end stomas but it gives an impression of the magnitude of the potential difference of the two stoma techniques of lateral pararectal and transrectal stoma formation. In our study we therefore opted for the design presented in our paper as it allowed generation of randomized data in a clinically feasible setting. As Stephenson correctly points out [2], due to the short follow-up, the incidence of long-term PSH is bound to be much higher than the overall ‘subclinical’ rate of around 16% after 3 4 months as diagnosed by intra-operative visualization. As he suspects, the patients having undergone ileostomy closure after transrectal placement may possibly have a higher true herniation rate at the original stoma site for the reasons he states. We shall look into this aspect during the follow-up study. It is true that none of the quality of life questionnaires used was specifically validated for patients with a loop ileostomy, but as most of our patients were assumed to have had a rectal cancer it seemed reasonable to use health questionnaires validated for such patients. In fact two-thirds of patients did have rectal cancer. Moreover, when looking at other randomized clinical trials (RCTs) of PSH, to the best of our knowledge only one, the Scandinavian multicentre StomaConst RCT (NCT01694238) trial, actually used specifically validated questionnaires for quality of life assessment in PSH patients [5]. Other RCTs used generic health quality of life questionnaires, such as SF-36 or EQ-5D. The CIPHER (Cohort Study to Investigate the Prevention of Parastomal Herniation) study is referred to. This is a prospective cohort study on 4000 patients in the UK and will add to the already large bulk of non-randomized data on PSH. It is hoped that the study will contribute to designing a valid randomized controlled study for PSH in end stomas. This will be especially interesting in the wake of several upcoming RCTs comparing mesh reinforcement with standard stoma formation (Dutch PREVENT trial [6], the Swedish STOMAMESH trial (https://clinicaltrials.gov/ct2/ show/study/NCT00917995), the Pan-European SMART trial (http://www.isrctn.com/ISRCTN94943190) and the Stoma-Const trial (https://clinicaltrials.gov/ ct2/show/study/NCT01694238). In conclusion, the data are still conflicting on how best to prevent PSH. But well-designed studies are in