Willem A. Bemelman

Colonic stenting versus emergency surgery for acute left-sided malignant colonic obstruction: a multicentre randomised trial

BACKGROUND Colonic stenting as a bridge to elective surgery is an alternative for emergency surgery in patients with acute malignant colonic obstruction, but its benefits are uncertain. We aimed to establish whether colonic stenting has better health outcomes than does emergency surgery. METHODS Patients with acute obstructive left-sided colorectal cancer were enrolled from 25 hospitals in the Netherlands and randomly assigned (1:1 ratio) to receive colonic stenting as a bridge to elective surgery or emergency surgery. The randomisation sequence was computer generated with permuted blocks and was stratified by centre; treatment allocation was concealed by use of a web-based application. Investigators and patients were unmasked to treatment assignment. The primary outcome was mean global health status during a 6-month follow-up, which was assessed with the QL2 subscale of the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (EORTC QLQ-C30). Analysis was by intention to treat. This study is registered, number ISRCTN46462267. FINDINGS Between March 9, 2007, and Aug 27, 2009, 98 patients were assigned to receive colonic stenting (n=47 patients) or emergency surgery (n=51). Two successive interim analyses showed increased 30-day morbidity in the colonic stenting group, with an absolute risk increase of 0.19 (95% CI -0.06 to 0.41) in analysis of the first 60 patients (14 of 28 patients receiving colonic stenting vs 10 of 32 receiving emergency surgery), and an absolute risk increase of 0.19 (-0.01 to 0.37) in analysis of the first 90 patients (23 of 47 patients vs 13 of 43). In accordance with the advice of the data safety monitoring committee, the study was suspended on Sept 18, 2009, and ended on March 12, 2010. At the final analysis of 98 patients, mean global health status during follow-up was 63.0 (SD 23.8) in the colonic stenting group and 61.4 (SD 21.9) in the emergency surgery group; after adjustment for baseline values, mean global health status did not differ between treatment groups (-4.7, 95% CI -14.8 to 5.5, p=0.36). No difference was recorded between treatment groups in 30-day mortality (absolute risk difference -0.01, 95% CI -0.14 to 0.12, p=0.89), overall mortality (-0.02, -0.17 to 0.14, p=0.84), morbidity (-0.08, -0.27 to 0.11, p=0.43), and stoma rates at latest follow-up (0.09, -0.10 to 0.27, p=0.35). However, the emergency surgery group had an increased stoma rate directly after initial intervention (0.23, 0.04 to 0.40, p=0.016) and a reduced frequency of stoma-related problems (between-group difference -12.0, -23.7 to -0.2, p=0.046). The most common serious adverse events were abscess (three in the colonic stenting group vs four in the emergency surgery group), perforations (six vs none), and anastomotic leakage (five vs one), and the most common adverse events were pneumonia (three vs one) and wound infection (one vs three). INTERPRETATION Colonic stenting has no decisive clinical advantages to emergency surgery. It could be used as an alternative treatment in as yet undefined subsets of patients, although with caution because of concerns about tumour spread caused by perforations. FUNDING None.

Interleukin-12 and -23 Control Plasticity of CD127+ Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria

Human group 1 ILCs consist of at least three phenotypically distinct subsets, including NK cells, CD127(+) ILC1, and intraepithelial CD103(+) ILC1. In inflamed intestinal tissues from Crohns disease patients, numbers of CD127(+) ILC1 increased at the cost of ILC3. Here we found that differentiation of ILC3 to CD127(+) ILC1 is reversible in vitro and in vivo. CD127(+) ILC1 differentiated to ILC3 in the presence of interleukin-2 (IL-2), IL-23, and IL-1β dependent on the transcription factor RORγt, and this process was enhanced in the presence of retinoic acid. Furthermore, we observed in resection specimen from Crohns disease patients a higher proportion of CD14(+) dendritic cells (DC), which in vitro promoted polarization from ILC3 to CD127(+) ILC1. In contrast, CD14(-) DCs promoted differentiation from CD127(+) ILC1 toward ILC3. These observations suggest that environmental cues determine the composition, function, and phenotype of CD127(+) ILC1 and ILC3 in the gut.

Esophageal sphincter device for gastroesophageal reflux disease.

BACKGROUND Patients with gastroesophageal reflux disease who have a partial response to proton-pump inhibitors often seek alternative therapy. We evaluated the safety and effectiveness of a new magnetic device to augment the lower esophageal sphincter. METHODS We prospectively assessed 100 patients with gastroesophageal reflux disease before and after sphincter augmentation. The study did not include a concurrent control group. The primary outcome measure was normalization of esophageal acid exposure or a 50% or greater reduction in exposure at 1 year. Secondary outcomes were 50% or greater improvement in quality of life related to gastroesophageal reflux disease and a 50% or greater reduction in the use of proton-pump inhibitors at 1 year. For each outcome, the prespecified definition of successful treatment was achievement of the outcome in at least 60% of the patients. The 3-year results of a 5-year study are reported. RESULTS The primary outcome was achieved in 64% of patients (95% confidence interval [CI], 54 to 73). For the secondary outcomes, a reduction of 50% or more in the use of proton-pump inhibitors occurred in 93% of patients, and there was improvement of 50% or more in quality-of-life scores in 92%, as compared with scores for patients assessed at baseline while they were not taking proton-pump inhibitors. The most frequent adverse event was dysphagia (in 68% of patients postoperatively, in 11% at 1 year, and in 4% at 3 years). Serious adverse events occurred in six patients, and in six patients the device was removed. CONCLUSIONS In this single-group evaluation of 100 patients before and after sphincter augmentation with a magnetic device, exposure to esophageal acid decreased, reflux symptoms improved, and use of proton-pump inhibitors decreased. Follow-up studies are needed to assess long-term safety. (Funded by Torax Medical; ClinicalTrials.gov number, NCT00776997.).

A global consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn's disease

Objective To develop a consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohns disease (pCD), based on best available evidence. Methods Based on a systematic literature review, statements were formed, discussed and approved in multiple rounds by the 20 working group participants. Consensus was defined as at least 80% agreement among voters. Evidence was assessed using the modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. Results Highest diagnostic accuracy can only be established if a combination of modalities is used. Drainage of sepsis is always first line therapy before initiating immunosuppressive treatment. Mucosal healing is the goal in the presence of proctitis. Whereas antibiotics and thiopurines have a role as adjunctive treatments in pCD, anti-tumour necrosis factor (anti-TNF) is the current gold standard. The efficacy of infliximab is best documented although adalimumab and certolizumab pegol are moderately effective. Oral tacrolimus could be used in patients failing anti-TNF therapy. Definite surgical repair is only of consideration in the absence of luminal inflammation. Conclusions Based on a multidisciplinary approach, items relevant for fistula management were identified and algorithms on diagnosis and treatment of pCD were developed.

Morbidity of Temporary Loop Ileostomies

Background/Aims: A temporary loop ileostomy is constructed to protect a distal colonic anastomosis. Closure is usually performed not earlier than 8–12 weeks after the primary operation. During this period, stoma-related complications can occur and enhance the adverse effect on quality of life. The aim of this study was to evaluate the length of time between ileostomy construction and closure, to quantify stoma-related morbidity and to examine the potential advantages of early ileostomy closure. Methods: Sixty-nine patients with a temporary, protective loop ileostomy (constructed between January 1996 and December 2000) were retrospectively analysed. The analysis was done by reviewing the medical records and the notes of the stoma care nurse. Results: Sixty ileostomies (87%) were closed after a median period of 24 weeks (range 2–124 weeks). Stoma-related complications occurred in 29 of the 69 patients (42%), and 11 patients (18%) had complications after ileostomy closure. Conclusion: The length of time between ileostomy construction and closure was substantially longer than initially planned. Earlier ileostomy closure (preferably even during the initial admission) could reduce the frequently occurring stoma-related morbidity in these patients and thus improve quality of life.

Anal Fistula Plug for Closure of Difficult Anorectal Fistula: A Prospective Study

PurposeComplex high and recurrent fistulas remain a surgical challenge. Simple division, i.e., fistulotomy, will likely result in fecal incontinence. Various surgical treatment options for these fistulas have shown disappointing results. Recently a biologic anal fistula plug was developed to treat these high transsphincteric fistulas. To assess the results of the anal fistula plug in patients with complex high perianal fistulas, a prospective, two-center, clinical study was undertaken.MethodsBetween April 2006 and October 2006, a consecutive series of patients with difficult therapy-resistant high fistulas were enrolled. During surgery, the internal fistula tract opening was identified. A conical shaped collagen plug was pulled through the fistula tract. Any remaining portion of the plug that was not implanted in the tract was removed. The plug was fixed at the internal opening with a deep 3/0 polydioxanone suture.ResultsSeventeen patients with a median age of 45 (range, 27–75) years were included. Of these patients, 71 percent (12/17) were male. At a median length of follow-up of 7 (range, 3–9) months, 7 of 17 fistulas had healed (41 percent). In ten patients, the fistula recurred.ConclusionsIn these small series of 17 patients with difficult high perianal fistulas, a success rate of 41 percent is noted. Larger series, preferably in trial setting, must be performed to establish the efficacy of the anal fistula plug in perianal fistula.

Fibrin glue and transanal rectal advancement flap for high transsphincteric perianal fistulas; is there any advantage?

Backgrounds and aimIn recent decades, fibrin glue has appeared as an alternative treatment for high perianal fistulas. Early results seemed promising, with high success rates being reported. However, with increasing follow-up, the enthusiasm was tempered because of disappointing results. The aim of this retrospective study was to assess the additional value of fibrin glue in combination with transanal advancement flap, compared to advancement flap alone, for the treatment of high transsphincteric fistulas of cryptoglandular origin.Materials and methodsBetween January 1995 and January 2006, 127 patients were operated for high perianal fistulas with an advancement flap. After exclusion of patients with inflammatory bowel disease or HIV, 80 patients remained. A consecutive series of 26 patients had an advancement flap combined with obliteration of the fistula tract with fibrin glue. Patients were matched for prior fistula surgery, and the advancement was performed identically in all patients. In the fibrin glue group, glue was installed retrogradely in the fistula tract after the advancement was completed and the fistula tract had been curetted.ResultsMinimal follow-up after surgery was 13 months [median of 67 months (range, 13–127)]. The overall recurrence rate was 26% (n = 21). Recurrence rates for advancement flap alone vs the combination with glue were 13% vs 56% (p = 0.014) in the group without previous fistula surgery and 23% vs 41% (p = 0.216) in the group with previous fistula surgery.ConclusionObliterating the fistula tract with fibrin glue was associated with worse outcome after rectal advancement flap for high perianal fistulas.

Long-term Outcomes of Patients Receiving a Magnetic Sphincter Augmentation Device for Gastroesophageal Reflux

BACKGROUND & AIMS Based on results from year 2 of a 5-year trial, in 2012 the US Food and Drug Administration approved the use of a magnetic device to augment lower esophageal sphincter function in patients with gastroesophageal reflux disease (GERD). We report the final results of 5 years of follow-up evaluation of patients who received this device. METHODS We performed a prospective study of the safety and efficacy of a magnetic device in 100 adults with GERD for 6 months or more, who were partially responsive to daily proton pump inhibitors (PPIs) and had evidence of pathologic esophageal acid exposure, at 14 centers in the United States and The Netherlands. The magnetic device was placed using standard laparoscopic tools and techniques. Eighty-five subjects were followed up for 5 years to evaluate quality of life, reflux control, use of PPIs, and side effects. The GERD-health-related quality of life (GERD-HRQL) questionnaire was administered at baseline to patients on and off PPIs, and after placement of the device; patients served as their own controls. A partial response to PPIs was defined as a GERD-HRQL score of 10 or less on PPIs and a score of 15 or higher off PPIs, or a 6-point or more improvement when scores on vs off PPI were compared. RESULTS Over the follow-up period, no device erosions, migrations, or malfunctions occurred. At baseline, the median GERD-HRQL scores were 27 in patients not taking PPIs and 11 in patients on PPIs; 5 years after device placement this score decreased to 4. All patients used PPIs at baseline; this value decreased to 15.3% at 5 years. Moderate or severe regurgitation occurred in 57% of subjects at baseline, but only 1.2% at 5 years. All patients reported the ability to belch and vomit if needed. Bothersome dysphagia was present in 5% at baseline and in 6% at 5 years. Bothersome gas-bloat was present in 52% at baseline and decreased to 8.3% at 5 years. CONCLUSIONS Augmentation of the lower esophageal sphincter with a magnetic device provides significant and sustained control of reflux, with minimal side effects or complications. No new safety risks emerged over a 5-year follow-up period. These findings validate the long-term safety and efficacy of the magnetic sphincter augmentation device for patients with GERD. ClinicalTrials.gov no: NCT00776997.

Feasibility of early closure of loop ileostomies: a pilot study.

PurposeA loop ileostomy is constructed to protect a distal anastomosis, and closure is usually performed not earlier than after two to three months. Earlier closure might reduce stoma-related morbidity, improve quality of life, and still effectively protect the distal anastomosis. This pilot study was designed to investigate the feasibility of early closure of loop ileostomies, i.e., during the same hospital admission as the initial operation. METHODS: Twenty-seven consecutive patients with a protective loop ileostomy were included. If patient’s recovery was uneventful, water-soluble contrast enema examination was performed, preferably after seven to eight days. If no radiologie signs of leakage were detected, the ileostomy was closed during the same hospital admission. RESULTS: Twenty-seven patients (8 females; mean age, 60 years) were analyzed. Eighteen patients had early ileostomy closure on average 11 (range, 7-21) days after the initial procedure. In nine patients the procedure was postponed because of leakage of the anastomosis (n = 3), delayed recovery (n = 1), small bowel obstruction (n = 1), gastroparesis (n = 1), logistic reasons (n = 2), or irradical cancer resection followed by radiotherapy (n = 1). There was no mortality and four mild complications occurred after early closure: superficial wound infection (n = 2), intravenous-catheter sepsis (n = 1), small bowel obstruction (n = 1). CONCLUSION: Closure of a loop ileostomy early after the initial operation was feasible in 18 of 27 patients and was associated with low morbidity and no mortality.

Outcome of surgical treatment for fistula in ano in Crohn's disease.

Recurrence rates and long‐term functional outcome after surgical treatment of anal fistula in Crohns disease were assessed.