Huib A. Cense

Laparoscopy in combination with fast track multimodal management is the best perioperative strategy in patients undergoing colonic surgery: a randomized clinical trial (LAFA-study).

Objective:To investigate which perioperative treatment, ie, laparoscopic or open surgery combined with fast track (FT) or standard care, is the optimal approach for patients undergoing segmental resection for colon cancer. Summary Background Data:Important developments in elective colorectal surgery are the introduction of laparoscopy and implementation of FT care, both focusing on faster recovery. Methods:In a 9-center trial, patients eligible for segmental colectomy were randomized to laparoscopic or open colectomy, and to FT or standard care, resulting in 4 treatment groups. Primary outcome was total postoperative hospital stay (THS). Secondary outcomes were postoperative hospital stay (PHS), morbidity, reoperation rate, readmission rate, in-hospital mortality, quality of life at 2 and 4 weeks, patient satisfaction and in-hospital costs. Four hundred patients were required to find a minimum difference of 1 day in hospital stay. Results:Median THS in the laparoscopic/FT group was 5 (interquar-tile range: 4–8) days; open/FT 7 (5–11) days; laparoscopic/standard 6 (4.5–9.5) days, and open/standard 7 (6–13) days (P < 0.001). Median PHS in the laparoscopic/FT group was 5 (4–7) days; open/FT 6 (4.5–10) days; laparoscopic/standard 6 (4–8.5) days and open/standard 7 (6–10.5) days (P < 0.001). Secondary outcomes did not differ significantly among the groups. Regression analysis showed that laparoscopy was the only independent predictive factor to reduce hospital stay and morbidity. Conclusions:Optimal perioperative treatment for patients requiring segmental colectomy for colon cancer is laparoscopic resection embedded in a FT program. If open surgery is applied, it is preferentially done in FT care. This study was registered under NTR222 (www.trialregister.nl).

Small bites versus large bites for closure of abdominal midline incisions (STITCH): A double-blind, multicentre, randomised controlled trial

BACKGROUNDnIncisional hernia is a frequent complication of midline laparotomy and is associated with high morbidity, decreased quality of life, and high costs. We aimed to compare the large bites suture technique with the small bites technique for fascial closure of midline laparotomy incisions.nnnMETHODSnWe did this prospective, multicentre, double-blind, randomised controlled trial at surgical and gynaecological departments in ten hospitals in the Netherlands. Patients aged 18 years or older who were scheduled to undergo elective abdominal surgery with midline laparotomy were randomly assigned (1:1), via a computer-generated randomisation sequence, to receive small tissue bites of 5 mm every 5 mm or large bites of 1 cm every 1 cm. Randomisation was stratified by centre and between surgeons and residents with a minimisation procedure to ensure balanced allocation. Patients and study investigators were masked to group allocation. The primary outcome was the occurrence of incisional hernia; we postulated a reduced incidence in the small bites group. We analysed patients by intention to treat. This trial is registered at Clinicaltrials.gov, number NCT01132209 and with the Nederlands Trial Register, number NTR2052.nnnFINDINGSnBetween Oct 20, 2009, and March 12, 2012, we randomly assigned 560 patients to the large bites group (n=284) or the small bites group (n=276). Follow-up ended on Aug 30, 2013; 545 (97%) patients completed follow-up and were included in the primary outcome analysis. Patients in the small bites group had fascial closures sutured with more stitches than those in the large bites group (mean number of stitches 45 [SD 12] vs 25 [10]; p<0·0001), a higher ratio of suture length to wound length (5·0 [1·5] vs 4·3 [1·4]; p<0·0001) and a longer closure time (14 [6] vs 10 [4] min; p<0·0001). At 1 year follow-up, 57 (21%) of 277 patients in the large bites group and 35 (13%) of 268 patients in the small bites group had incisional hernia (p=0·0220, covariate adjusted odds ratio 0·52, 95% CI 0·31-0·87; p=0·0131). Rates of adverse events did not differ significantly between groups.nnnINTERPRETATIONnOur findings show that the small bites suture technique is more effective than the traditional large bites technique for prevention of incisional hernia in midline incisions and is not associated with a higher rate of adverse events. The small bites technique should become the standard closure technique for midline incisions.nnnFUNDINGnErasmus University Medical Center and Ethicon.

The ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitisA and Hartmann's procedure or resection with primary anastomosis for purulent or faecal peritonitisB in perforated diverticulitis (NTR2037)

BackgroundRecently, excellent results are reported on laparoscopic lavage in patients with purulent perforated diverticulitis as an alternative for sigmoidectomy and ostomy.The objective of this study is to determine whether LaparOscopic LAvage and drainage is a safe and effective treatment for patients with purulent peritonitis (LOLA-arm) and to determine the optimal resectional strategy in patients with a purulent or faecal peritonitis (DIVA-arm: perforated DIVerticulitis: sigmoidresection with or without Anastomosis).Methods/DesignIn this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmanns procedure or sigmoidectomy with primary anastomosis in a ratio of 2:1:1 (LOLA-arm). Patients with faecal peritonitis will be randomised 1:1 between Hartmanns procedure and resection with primary anastomosis (DIVA-arm). The primary combined endpoint of the LOLA-arm is major morbidity and mortality. A sample size of 132:66:66 patients will be able to detect a difference in the primary endpoint from 25% in resectional groups compared to 10% in the laparoscopic lavage group (two sided alpha = 5%, power = 90%). Endpoint of the DIVA-arm is stoma free survival one year after initial surgery. In this arm 212 patients are needed to significantly demonstrate a difference of 30% (log rank test two sided alpha = 5% and power = 90%) in favour of the patients with resection with primary anastomosis. Secondary endpoints for both arms are the number of days alive and outside the hospital, health related quality of life, health care utilisation and associated costs.DiscussionThe Ladies trial is a nationwide multicentre randomised trial on perforated diverticulitis that will provide evidence on the merits of laparoscopic lavage and drainage for purulent generalised peritonitis and on the optimal resectional strategy for both purulent and faecal generalised peritonitis.Trial registrationNederlands Trial Register NTR2037

A multicenter randomized clinical trial investigating the cost-effectiveness of treatment strategies with or without antibiotics for uncomplicated acute diverticulitis (DIABOLO trial)

BackgroundConservative treatment of uncomplicated or mild diverticulitis usually includes antibiotic therapy. It is, however, uncertain whether patients with acute diverticulitis indeed benefit from antibiotics. In most guidelines issued by professional organizations antibiotics are considered mandatory in the treatment of mild diverticulitis. This advice lacks evidence and is merely based on experts opinion. Adverse effects of the use of antibiotics are well known, including allergic reactions, development of bacterial resistance to antibiotics and other side-effects.MethodsA randomized multicenter pragmatic clinical trial comparing two treatment strategies for uncomplicated acute diverticulitis. I) A conservative strategy with antibiotics: hospital admission, supportive measures and at least 48 hours of intravenous antibiotics which subsequently are switched to oral, if tolerated (for a total duration of antibiotic treatment of 10 days). II) A liberal strategy without antibiotics: admission only if needed on clinical grounds, supportive measures only. Patients are eligible for inclusion if they have a diagnosis of acute uncomplicated diverticulitis as demonstrated by radiological imaging. Only patients with stages 1a and 1b according to Hincheys classification or mild diverticulitis according to the Ambrosetti criteria are included. The primary endpoint is time-to-full recovery within a 6-month follow-up period. Full recovery is defined as being discharged from the hospital, with a return to pre-illness activities, and VAS score below 4 without the use of daily pain medication. Secondary endpoints are proportion of patients who develop complicated diverticulitis requiring surgery or non-surgical intervention, morbidity, costs, health-related quality of life, readmission rate and acute diverticulitis recurrence rate. In a non-inferiority design 264 patients are needed in each study arm to detect a difference in time-to-full recovery of 5 days or more with a power of 85% and a confidence level of 95%. With an estimated one percent of patients lost to follow up, a total of 533 patients will be included.ConclusionA clinically relevant difference of more than 5 days in time-to-full recovery between the two treatment strategies is not expected. The liberal strategy without antibiotics and without the strict requirement for hospital admission is anticipated to be more a more cost-effective approach.Trial registrationTrial registration number: NCT01111253

Small bowel obstruction, incisional hernia and survival after laparoscopic and open colonic resection (LAFA study).

Short‐term advantages to laparoscopic surgery are well described. This study compared medium‐ to long‐term outcomes of a randomized clinical trial comparing laparoscopic and open colonic resection for cancer.

A multicenter randomized controlled trial evaluating the effect of small stitches on the incidence of incisional hernia in midline incisions

BackgroundThe median laparotomy is frequently used by abdominal surgeons to gain rapid and wide access to the abdominal cavity with minimal damage to nerves, vascular structures and muscles of the abdominal wall. However, incisional hernia remains the most common complication after median laparotomy, with reported incidences varying between 2-20%. Recent clinical and experimental data showed a continuous suture technique with many small tissue bites in the aponeurosis only, is possibly more effective in the prevention of incisional hernia when compared to the common used large bite technique or mass closure.Methods/DesignThe STITCH trial is a double-blinded multicenter randomized controlled trial designed to compare a standardized large bite technique with a standardized small bites technique. The main objective is to compare both suture techniques for incidence of incisional hernia after one year. Secondary outcomes will include postoperative complications, direct costs, indirect costs and quality of life.A total of 576 patients will be randomized between a standardized small bites or large bites technique. At least 10 departments of general surgery and two departments of oncological gynaecology will participate in this trial. Both techniques have a standardized amount of stitches per cm wound length and suture length wound length ratios are calculated in each patient. Follow up will be at 1 month for wound infection and 1 year for incisional hernia. Ultrasound examinations will be performed at both time points to measure the distance between the rectus muscles (at 3 points) and to objectify presence or absence of incisional hernia. Patients, investigators and radiologists will be blinded during follow up, although the surgeon can not be blinded during the surgical procedure.ConclusionThe STITCH trial will provide level 1b evidence to support the preference for either a continuous suture technique with many small tissue bites in the aponeurosis only or for the commonly used large bites technique.Trial registrationClinicaltrials.gov NCT01132209

Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial)

BackgroundWith the availability of infliximab, nowadays recurrent Crohns disease, defined as disease refractory to immunomodulatory agents that has been treated with steroids, is generally treated with infliximab. Infliximab is an effective but expensive treatment and once started it is unclear when therapy can be discontinued. Surgical resection has been the golden standard in recurrent Crohns disease. Laparoscopic ileocolic resection proved to be safe and is characterized by a quick symptom reduction.The objective of this study is to compare infliximab treatment with laparoscopic ileocolic resection in patients with recurrent Crohns disease of the distal ileum with respect to quality of life and costs.Methods/designThe study is designed as a multicenter randomized clinical trial including patients with Crohns disease located in the terminal ileum that require infliximab treatment following recent consensus statements on inflammatory bowel disease treatment: moderate to severe disease activity in patients that fail to respond to steroid therapy or immunomodulatory therapy. Patients will be randomized to receive either infliximab or undergo a laparoscopic ileocolic resection. Primary outcomes are quality of life and costs. Secondary outcomes are hospital stay, early and late morbidity, sick leave and surgical recurrence. In order to detect an effect size of 0.5 on the Inflammatory Bowel Disease Questionnaire at a 5% two sided significance level with a power of 80%, a sample size of 65 patients per treatment group can be calculated. An economic evaluation will be performed by assessing the marginal direct medical, non-medical and time costs and the costs per Quality Adjusted Life Year (QALY) will be calculated. For both treatment strategies a cost-utility ratio will be calculated. Patients will be included from December 2007.DiscussionThe LIR!C-trial is a randomized multicenter trial that will provide evidence whether infliximab treatment or surgery is the best treatment for recurrent distal ileitis in Crohns disease.Trial registrationNederlands Trial Register NTR1150

DIRECT trial. Diverticulitis recurrences or continuing symptoms: Operative versus conservative Treatment. A MULTICENTER RANDOMISED CLINICAL TRIAL

BackgroundPersisting abdominal complaints are common after an episode of diverticulitis treated conservatively. Furthermore, some patients develop frequent recurrences. These two groups of patients suffer greatly from their disease, as shown by impaired health related quality of life and increased costs due to multiple specialist consultations, pain medication and productivity losses.Both conservative and operative management of patients with persisting abdominal complaints after an episode of diverticulitis and/or frequently recurring diverticulitis are applied. However, direct comparison by a randomised controlled trial is necessary to determine which is superior in relieving symptoms, optimising health related quality of life, minimising costs and preventing diverticulitis recurrences against acceptable morbidity and mortality associated with surgery or the occurrence of a complicated recurrence after conservative management.We, therefore, constructed a randomised clinical trial comparing these two treatment strategies.Methods/designThe DIRECT trial is a multicenter randomised clinical trial. Patients (18-75 years) presenting themselves with persisting abdominal complaints after an episode of diverticulitis and/or three or more recurrences within 2 years will be included and randomised. Patients randomised for conservative treatment are treated according to the current daily practice (antibiotics, analgetics and/or expectant management). Patients randomised for elective resection will undergo an elective resection of the affected colon segment. Preferably, a laparoscopic approach is used.The primary outcome is health related quality of life measured by the Gastro-intestinal Quality of Life Index, Short-Form 36, EQ-5D and a visual analogue scale for pain quantification. Secondary endpoints are morbidity, mortality and total costs. The total follow-up will be three years.DiscussionConsidering the high incidence and the multicenter design of this study, it may be assumed that the number of patients needed for this study (n = 214), may be gathered within one and a half year.Depending on the expertise and available equipment, we prefer to perform a laparoscopic resection on patients randomised for elective surgery. Should this be impossible, an open technique may be used as this also reflects the current situation.Trial Registration(Trial register number: NTR1478)

The INCH-Trial: a multicentre randomized controlled trial comparing the efficacy of conventional open surgery and laparoscopic surgery for incisional hernia repair

BackgroundAnnually approximately 100.000 patients undergo a laparotomy in the Netherlands. About 15,000 of these patients will develop an incisional hernia. Both open and laparoscopic surgical repair have been proven to be safe. However, the most effective treatment of incisional hernias remains unclear. This study, the ‘INCH-trial’, comparing cost-effectiveness of open and laparoscopic incisional hernia repair, is therefore needed.Methods/DesignA randomized multi-center clinical trial comparing cost-effectiveness of open and laparoscopic repair of incisional hernias. Patients with a symptomatic incisional hernia, eligible for laparoscopic and open incisional hernia repair. Only surgeons, experienced in both open and laparoscopic incisional hernia repair, will participate in the INCH trial. During incisional hernia repair, a mesh is placed under or on top of the fascia, with a minimal overlap of 5xa0cm. Primary endpoint is length of hospital stay after an incisional hernia repair. Secondary endpoints are time to full recovery within three months after index surgery, post-operative complications, recurrences, mortality and quality of life.Our hypothesis is that laparoscopic incisional hernia repair comes with a significant shorter hospital stay compared to open incisional hernia repair. A difference of two days is considered significant. One-hunderd-and-thirty-five patients are enrolled in each treatment arm. The economic evaluation will be performed from a societal perspective. Primary outcomes are costs per patient related to time-to-recovery and quality of life.The main goal of the trial is to establish whether laparoscopic incisional hernia repair is superior to conventional open incisional hernia repair in terms of cost-effectiveness. This is measured through length of hospital stay and quality of life. Secondary endpoints are re-operation rate due to post-operative complications or recurrences, mortality and quality of life.DiscussionThe difference in time to full recovery between the two treatment strategies is thought to be in favor of laparoscopic incisional hernia repair. Laparoscopic incisional hernia repair is therefore expected to be a more cost-effective approach.Trial registrationNetherlands Trial register: NTR2808

The Impact of Surgical Complications as a Main Risk Factor for Venous Thromboembolism: A Multicenter Study

BackgroundStudies suggest that postoperative complications are a risk factor for venous thromboembolism (VTE) after bariatric surgery. Knowledge of factors associated with a higher risk of VTE after bariatric surgery may be essential to select patients who may benefit from either prolonged or intensified thrombosis prophylaxis. The aim of this study is to determine the relationship between postoperative complications and VTE after bariatric surgery and other classical risk factors.MethodsA retrospective multicenter case-control study was performed in patients who had bariatric surgery between January 2008 and September 2011. VTE until 6xa0months after surgery was registered, and patients were contacted to ascertain the results. For every case of VTE after surgery, 6 control patients were selected who were matched for gender, age, participating center and type of surgery. Risk factors for VTE before and after surgery and postoperative complications were registered.ResultsA total of 2,064 surgeries were included. In 12 patients, VTE occurred within 6xa0months after bariatric surgery (incidence 0.58xa0%, 95xa0% confidence interval (CI)u2009=u20090.25–0.93). There was a strong association of complications after surgery (cases 91.7xa0%, controls 15.3xa0%, odds ratio (OR) 61.0; 95xa0% CIu2009=u20097.1–521.3) or intensive care admission (cases 50.0xa0%, controls 11.1xa0%, ORu2009=u20098.0; 95xa0% CIu2009=u20092.1–30.8) with VTE. The majority of postoperative complications were anastomotic leak, abdominal abscess, and infection. We could not detect an association between classical thrombosis risk factors and postoperative VTE.ConclusionsThe incidence of VTE is low after bariatric surgery using thrombosis prophylaxis. However, there is a strong association between postoperative complications and VTE. These patients may benefit from more intensive thrombosis prophylaxis.