Intervju: akademik Jakša Barbić

Over the past 20 years evidence has accumulated confirming the immunomodulatory role of the appendix in ulcerative colitis (UC). This led to the idea that appendectomy might alter the clinical course of established UC. The objective of this body of research is to evaluate the short-term and medium-term efficacy of appendectomy to maintain remission in patients with UC, and to establish the acceptability and cost-effectiveness of the intervention compared to standard treatment. These paired phase III multicenter prospective randomised studies will include patients over 18 years of age with an established diagnosis of ulcerative colitis and a disease relapse within 12 months prior to randomisation. Patients need to have been medically treated until complete clinical (Mayo score <3) and endoscopic (Mayo score 0 or 1) remission. Patients will then be randomised 1:1 to a control group (maintenance 5-ASA treatment, no appendectomy) or elective laparoscopic appendectomy plus maintenance treatment. The primary outcome measure is the one year cumulative UC relapse rate - defined both clinically and endoscopically as a total Mayo-score ≥5 with endoscopic subscore of 2 or 3. Secondary outcomes that will be assessed include the number of relapses per patient at 12 months, the time to first relapse, health related quality of life and treatment costs, and number of colectomies in each arm. The ACCURE and ACCURE-UK trials will provide evidence on the role and acceptability of appendectomy in the treatment of ulcerative colitis and the effects of appendectomy on the disease course. NTR2883 ; ISRCTN5652301

Single-port versus multiport laparoscopic ileocecal resection for Crohn's disease

Several case series have demonstrated the feasibility of single-port laparoscopic ileocecal resection in Crohn's disease. However, only a few studies compared the single-port with a multiport laparoscopic ileocecal approach. The aim of this study was to compare short term surgical outcome parameters between single-port and multiport laparoscopic ileocecal resections for Crohn's disease. Twenty-one patients who underwent single-port laparoscopic ileocecal resection between March 2010 and September 2012 were prospectively registered. A matched comparison on a 1:2 basis was performed with patients who underwent multiport laparoscopic ileocecal resection from January 1999 to March 2010. Matching parameters were BMI, length of diseased bowel resected and the presence of fistulas. Endpoints were the length of postoperative hospital stay, operative time, conversions, complications, postoperative pain scores and postoperative analgesia consumption. Twenty-one patients undergoing single-port resection were matched to 42 patients undergoing multiport resection. The postoperative stay (4 days, iqr 4-5 vs. 5 days, iqr 4-6; p=0.033), operative time (103 min, iqr 94.0-121.0 vs. 123.5 min, iqr 100.0-157.0; p=0.036) and morphine use on the first postoperative day (12.5 mg, iqr 5.0-33.3 vs. 28 mg, 15.0-50.0; p=0.012) differed significantly. Postoperative pain scores and complications were similar in both groups. This study was limited by potential selection bias. Single-port laparoscopic ileocecal resection is safe and feasible in Crohn's disease and is associated with less need for pain medication postoperatively as opposed to multiport laparoscopic ileocecal resectio

Health-related quality of life and disability in patients with ulcerative colitis and proctocolectomy with ileoanal pouch versus treatment with anti-TNF agents

We compared health-related quality of life (HRQL) and disability in ulcerative colitis (UC) patients in remission with anti-tumor necrosis factor agents (TNF) or after restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA). Two patient cohorts were studied. The first group consisted of patients in remission after RPC with IPAA (surgery group). The second group consisted of patients in remission with infliximab or adalimumab (medical group). For inclusion in the surgery group the pouch had to be functional for ≥1year and patients were excluded in case of postoperative complications. In the medical group, patients had to be on maintenance therapy with anti-TNF agents for ≥1year and in clinical remission. HRQL and disability outcomes were assessed using SF-36, COREFO, WPAI:UC and EORTC questionnaires. 60 patients were included, 30 patients in both groups. 58 out of 60 patients (97%) returned the completed questionnaires: 29 patients in the surgery group (median age 42 years [22-67]; 48% female) and 29 patients in the medical group (median age 45 years [19-68]; 65% female). Patient characteristics were comparable between the two groups. There were no significant differences in SF-36, WPAI:UC and EORTC questionnaires between both groups, except for the medication and stool frequency scale (COREFO questionnaire) that was significantly higher in the surgery vs. the medical group (p=0.004 and p <0.001, respectively). HRQL and disability were not different among the medical and surgical group, except for stool frequency and anti-diarrhea medication use that was significantly higher in surgically treated patient

The effect of appendectomy on the course of ulcerative colitis: a systematic review

Aim Previous studies have shown significantly lower appendectomy rates in ulcerative colitis (UC) patients compared with healthy controls. Evidence indicating that the appendix has an immunomodulatory role in UC has been accumulating. To examine the latest evidence on the effect of appendectomy on the disease course of UC. Method PubMed, The Cochrane Library and EMBASE were searched. Primary end-points were number of relapses, use of steroids, number of hospital admissions and number of colectomies. Results The search resulted in six observational studies (five case-control studies and one cohort study) totalling 2532 patients. Owing to clinical heterogeneity, no metaanalysis could be conducted. One study found lower relapse rates in patients appendectomized before the onset of UC [ absolute risk reduction (ARR) = 21.5%; 95% CI: 1.71-45.92%]. Another two studies found a reduced requirement for immunosuppression in appendectomized patients (ARR = 20.2%; 95% CI: 9.6730.46% in the first study and ARR = 21.4%; 95% CI: 10.32-32.97% in the second study). In addition, one study found lower colectomy rates in nonappendectomized patients (ARR = 8.7%; 95% CI: 1.29-18.66%) and two studies found lower colectomy rates in appendectomized patients (ARR = 21.4%; 95% CI: 13.17-28.79% in the first study and ARR = 18.7%; 95% CI: 7.5029.97% in the second study). Conclusion There are limited and conflicting data available regarding the effect of appendectomy on the disease course of UC. Most studies suggest a beneficial effect and the minority find no, or a negative, effec

The association between intensified medical treatment, time to surgery and ileocolic specimen length in Crohn's disease

Aim During the last decade, treatment protocols have changed for patients with ileocolic Crohn's disease. Anti-tumour necrosis factor (anti-TNF) has become part of standard medical treatment, usually in a step-up approach. The aim was to analyse if improved medical treatment has resulted in more limited ileocolic resections and a longer interval between diagnosis and surgery. Method Patients undergoing ileocolic resection for Crohn's disease were included (1999-2014). Patient characteristics were compared to the results of a population-based study (between 2004 and 2010) previously performed in the catchment area of the present tertiary referral centre. Time trends were analysed using the Cochrane-Armitage trend, Spearman's correlation coefficient and linear regression. Results In total, 195 patients undergoing ileocolic resection were included. Patient characteristics were not significantly different from the background cohort, confirming a representative study group. Sixty-three patients were men (32.3%, median age at surgery 30.0years, interquartile range 23.0-40.0). Anti-TNF and immunomodulator use prior to surgery increased significantly during the study period (chi(2)=49.1, P <0.001). Over the years, a significant increase in time from diagnosis to operation was found (median 39.0 months, interquartile range 12.0-86.0, rho 0.175, P = 0.014). The length of the resected ileum did not change significantly (median 20.0cm, interquartile range 12.0-30.0, rho -0.107, P = 0.143). The number of fistulas or postoperative complications that needed re-intervention was not significantly different between the groups with or without anti-TNF. Conclusion This study demonstrated that over time patients with ileocolic Crohn's disease who eventually underwent ileocolic resection have been treated more intensively medically; however, this did not result in reduced specimen siz

Prolonged preoperative hospital stay is a risk factor for complications after emergency colectomy for severe colitis

Risk factors for postoperative complications in patients undergoing emergency colectomy for severe colitis in inflammatory bowel disease have hardly been studied. Therefore, this study aimed to define predictors of a complicated postoperative course in these patients. A retrospective review was performed of 71 consecutive patients who underwent emergency colectomy for severe colitis between 1999 and 2012 at a tertiary referral centre. Complications were graded according to the Clavien-Dindo classification. Patients with a complication Grade II or higher were compared with those with no complications or a Grade I complication. Nineteen patients (26.7%) had at least one postoperative complication classified as Clavien-Dindo Grade II or higher. In the group with postoperative complications, patients had a higher age (mean 45 vs 35 years, P = 0.020) and a higher body mass index (BMI) (mean 25.9 vs 21.0 kg/m(2), P = 0.006). Length of preoperative hospital stay (median 15 vs 6 days, P = 0.032) was longer in the group with postoperative complications. During the study period, the preoperative hospital stay decreased by 0.8 days per study year (95% CI 0.2-1.5 days, P < 0.001). This did not influence the complication rate over time, however. Factors increasing the risk of complications after emergency colectomy for severe colitis were a higher age, a higher BMI and a longer preoperative hospital sta

Early reconstruction of the leaking ileal pouch-anal anastomosis: a novel solution to an old problem

The study aimed to determine the effectiveness and direct medical costs of early surgical closure of the anastomotic defect after a short course of Endo-sponge® therapy of the presacral cavity, compared with conventional treatment in patients with anastomotic leakage after ileal pouch-anal anastomosis (IPAA). Patients with anastomotic leakage after IPAA undergoing early surgical closure of the anastomotic defect after a short Endo-sponge® treatment were prospectively followed and compared with a consecutive cohort of patients with an anastomotic leak treated by creation of a loop ileostomy and occasional drainage of the presacral cavity. A total of 15 patients were treated with early surgical closure and 29 were treated conventionally. In the early surgical closure group, the Endo-sponge® treatment was continued for a median of 12 days [interquartile range (IQR) 7-15 days] with a median of 3 (IQR 2-4) Endo-sponge® changes. Secondary anastomotic healing was achieved in all patients (n = 15) in the early surgical closure group compared with 52% (n = 16) in the conventional treatment group (P = 0.003). Closure of the anastomotic defect was achieved after a median of 48 (25-103) days in the early surgical closure group compared with 70 (IQR 49-175) days in the conventional treatment group (P = 0.013). A functional pouch was seen in 93% and 86% of the patients in each group. There was no significant difference in direct medical cost. Early surgical closure after a short period of Endo-sponge® treatment is highly effective in treating anastomotic leakage after IPAA without increasing cos

Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease:retrospective long-term follow-up of the LIR!C trial

BACKGROUND: The LIR!C trial showed that laparoscopic ileocaecal resection is a cost-effective treatment that has similar quality-of-life outcomes to treatment with infliximab, an anti-tumour necrosis factor (TNF) drug. We aimed to compare long-term outcomes of both interventions and identify baseline factors associated with the duration of treatment effect in each group. METHODS: In this retrospective follow-up study, we collected data from patients who participated in the LIR!C trial, a multicentre randomised controlled trial that compared quality of life after surgical resection versus infliximab in adult patients with non-stricturing and immunomodulator-refractory ileocaecal Crohn's disease. From Jan 1 to May 1, 2018, we collected follow-up data from the time from enrolment in the LIR!C trial until the last visit at either the gastrointestinal surgeon or gastroenterologist. In this study, outcomes of interest were need for surgery or repeat surgery or anti-TNF therapy, duration of treatment effect, and identification of factors associated with the duration of treatment effect. Duration of treatment effect was defined as the time without need for additional Crohn's disease-related treatment (corticosteroids, immunomodulators, biologics, or surgery). FINDINGS: We collected long-term follow-up data for 134 (94%) of 143 patients included in the LIR!C trial, of whom 69 were in the resection group and 65 were in the infliximab group. Median follow-up was 63·5 months (IQR 39·0-94·5). In the resection group, 18 (26%) of 69 patients started anti-TNF therapy and none required a second resection. 29 (42%) patients in the resection group did not require additional Crohn's disease-related medication, although 14 (48%) of these patients were given prophylactic immunomodulator therapy. In the infliximab group, 31 (48%) of 65 patients had a Crohn's disease-related resection, and the remaining 34 patients maintained, switched, or escalated their anti-TNF therapy. Duration of treatment effect was similar in both groups, with a median time without additional Crohn's disease-related treatment of 33·0 months (95% CI 15·1-50·9) in the resection group and 34·0 months (0·0-69·3) in the infliximab group (log-rank p=0·52). In both groups, therapy with an immunomodulator, in addition to the allocated treatment, was associated with duration of treatment effect (hazard ratio for resection group 0·34 [95% CI 0·16-0·69] and for infliximab group 0·49 [0·26-0·93]). INTERPRETATION: These findings further support laparoscopic ileocaecal resection as a treatment option in patients with Crohn's disease with limited (affected segment ≤40 cm) and predominantly inflammatory terminal ileitis for whom conventional treatment is not successful. FUNDING: None