Johan F. Lange

Controlled clinical trial of selective decontamination for the treatment of severe acute pancreatitis

ObjectiveA randomized, controlled, multicenter trial was undertaken in 102 patients with objective evidence of severe acute pancreatitis to evaluate whether selective decontamination reduces mortality. Summary Background DataSecondary pancreatic infection is the major cause of death in patients with acute necrotizing pancreatitis. Controlled clinical trials to study the effect of selective decontamination in such patients are not available. MethodsBetween April 22, 1990 and April 19, 1993, 102 patients with severe acute pancreatitis were admitted to 16 participating hospitals. Patients were entered into the study if severe acute pancreatitis was indicated, on admission, by multiple laboratory criteria (Imrie score ≥ 3) and/or computed tomography criteria (Balthazar grade D or E). Patents were randomly assigned to receive standard treatment (control group) or standard treatment plus selective decontamination (norfloxacin, colistin, amphotericin; selective decontamination group). All patients received full supportive treatment, and surveillance cultures were taken in both groups. ResultsFifty patients were assigned to the selective decontamination group and 52 were assigned to the control group. There were 18 deaths in the control group (35%), compared with 11 deaths (22%) in the selective decontamination group. (adjusted for Imrie score and Balthazar grade: p = 0.048). This difference was mainly caused by a reduction of late mortality (> 2 weeks) due to significant reduction of gram-negative pancreatic infection (p = 0.003). The average number of laparotomies per patient was reduced in patients treated with selective decontamination (p < 0.05). Failure of selective decontamination to prevent secondary gram-negative pancreatic infection with subsequent death was seen in only three patients (6%) and transient gram-negative pancreatic infection was seen in one (2%). In both groups of patients, all gram-negative aerobic pancreatic infection was preceded by colonization of the digestive tract by the same bacteria.

Human memory B cells originate from three distinct germinal center-dependent and -independent maturation pathways

Multiple distinct memory B-cell subsets have been identified in humans, but it remains unclear how their phenotypic diversity corresponds to the type of responses from which they originate. Especially, the contribution of germinal center-independent responses in humans remains controversial. We defined 6 memory B-cell subsets based on their antigen-experienced phenotype and differential expression of CD27 and IgH isotypes. Molecular characterization of their replication history, Ig somatic hypermutation, and class-switch profiles demonstrated their origin from 3 different pathways. CD27⁻IgG⁺ and CD27⁺IgM⁺ B cells are derived from primary germinal center reactions, and CD27⁺IgA⁺ and CD27⁺IgG⁺ B cells are from consecutive germinal center responses (pathway 1). In contrast, natural effector and CD27⁻IgA⁺ memory B cells have limited proliferation and are also present in CD40L-deficient patients, reflecting a germinal center-independent origin. Natural effector cells at least in part originate from systemic responses in the splenic marginal zone (pathway 2). CD27⁻IgA⁺ cells share low replication history and dominant Igλ and IgA2 use with gut lamina propria IgA+ B cells, suggesting their common origin from local germinal center-independent responses (pathway 3). Our findings shed light on human germinal center-dependent and -independent B-cell memory formation and provide new opportunities to study these processes in immunologic diseases.

Total Extraperitoneal Inguinal Hernia Repair Compared With Lichtenstein (the Level-trial): A Randomized Controlled Trial

Background:This randomized controlled trial was designed to compare the most common technique for open mesh repair (Lichtenstein) with the currently preferred minimally invasive technique (total extra peritoneal, TEP) for the surgical correction of inguinal hernia. Methods:A total of 660 patients were randomized to Lichtenstein or TEP procedure. Primary outcomes were postoperative pain, length of hospital stay, period until complete recovery, and quality of life (QOL). Recurrences, operating time, complications, chronic pain, and costs were secondary endpoints. This study was registered at www.clinicaltrials.gov and carries the ID: NCT00788554. Results:About 336 patients were randomized to TEP, and 324 to Lichtenstein repair. TEP was associated with less postoperative pain until 6 weeks postoperatively (P = 0.01). Chronic pain was comparable (25% vs. 29%). Less impairment of inguinal sensibility was seen after TEP (7% vs. 30%, P = 0.01). Mean operating time for a unilateral hernia with TEP was longer (54 vs. 49 minutes, P = 0.03) but comparable for bilateral hernias. Incidence of adverse events during surgery was higher with TEP (5.8% vs. 1.6%, P < 0.004), but postoperative complications (33% vs. 33%), hospital stay and QOL were similar. After TEP, patients had a faster recovery of daily activities (ADL) and less absence from work (P = 0.01). After a mean follow-up of 49 months, recurrences (3.8% vs. 3.0%, P = 0.64) and total costs (&U20AC;3.096 vs. &U20AC;3.198) were similar. Conclusion:TEP procedure was associated with more adverse events during surgery but less postoperative pain, faster recovery of daily activities, quicker return to work, and less impairment of sensibility after 1 year. Recurrence rates and chronic pain were comparable. TEP is recommended in experienced hands.

Laparoscopic peritoneal lavage or sigmoidectomy for perforated diverticulitis with purulent peritonitis : a multicentre, parallel-group, randomised, open-label trial

BACKGROUND Case series suggest that laparoscopic peritoneal lavage might be a promising alternative to sigmoidectomy in patients with perforated diverticulitis. We aimed to assess the superiority of laparoscopic lavage compared with sigmoidectomy in patients with purulent perforated diverticulitis, with respect to overall long-term morbidity and mortality. METHODS We did a multicentre, parallel-group, randomised, open-label trial in 34 teaching hospitals and eight academic hospitals in Belgium, Italy, and the Netherlands (the Ladies trial). The Ladies trial is split into two groups: the LOLA group comparing laparoscopic lavage with sigmoidectomy and the DIVA group comparing Hartmanns procedure with sigmoidectomy plus primary anastomosis. The DIVA section of this trial is still underway but here we report the results of the LOLA section. Patients with purulent perforated diverticulitis were enrolled for LOLA, excluding patients with faecal peritonitis, aged older than 85 years, with high-dose steroid use (≥20 mg daily), and haemodynamic instability. Patients were randomly assigned (2:1:1; stratified by age [<60 years vs ≥60 years]) using secure online computer randomisation to laparoscopic lavage, Hartmanns procedure, or primary anastomosis in a parallel design after diagnostic laparoscopy. Patients were analysed according to a modified intention-to-treat principle and were followed up after the index operation at least once in the outpatient setting and after sigmoidoscopy and stoma reversal, according to local protocols. The primary endpoint was a composite endpoint of major morbidity and mortality within 12 months. This trial is registered with ClinicalTrials.gov, number NCT01317485. FINDINGS Between July 1, 2010, and Feb 22, 2013, 90 patients were randomly assigned in the LOLA section of the Ladies trial when the study was terminated by the data and safety monitoring board because of an increased event rate in the lavage group. Two patients were excluded for protocol violations. The primary endpoint occurred in 30 (67%) of 45 patients in the lavage group and 25 (60%) of 42 patients in the sigmoidectomy group (odds ratio 1·28, 95% CI 0·54-3·03, p=0·58). By 12 months, four patients had died after lavage and six patients had died after sigmoidectomy (p=0·43). INTERPRETATION Laparoscopic lavage is not superior to sigmoidectomy for the treatment of purulent perforated diverticulitis. FUNDING Netherlands Organisation for Health Research and Development.

Laparoscopic vs open appendectomy : A randomized clinical trial

AbstractBackground: A randomized clinical trial was performed to compare open appendectomy (OA) and laparoscopic appendectomy (LA). Methods: 201 patients with similar characteristics of appendicitis were randomized to either OA or LA. Operative time and technique, reintroduction of diet, postoperative pain, use of analgesia, hospital stay, and complications were documented. Results: 104 patients were allocated to the OA group and 97 to the LA group. Postoperative pain was significantly less in the LA group on the 1st (p < 0.001) and 2nd (p < 0.001) postoperative day, resulting in less use of analgesics on both days (p < 0.001). Restoration of diet was similar in both groups. Mean operative time was longer in the LA group: 61 vs 41 min (p < 0.001). Postoperative complications did not differ in either group, except for wound infections (six OA group vs zero LA group, p < 0.05). Mean hospital stay was similar in both groups. Conclusions: LA results in less postoperative pain and fewer wound infections. The laparoscopic procedure is technically more demanding to perform, resulting in longer operative time.

Intraperitoneal polypropylene mesh hernia repair complicates subsequent abdominal surgery.

BackgroundProsthetic incisional hernia repair (PIHR) is superior to primary closure in preventing hernia recurrence. Serious complications have been associated with the use of prosthetic material. Complications of subsequent surgical interventions after prior PIHR in relation to its anatomical position were the objectives of this study.Patients and MethodsPatients who underwent subsequent laparotomy/laparoscopy after PIHR between January 1992 and February 2005 at our institution were evaluated. Intraperitoneal and preperitoneal mesh was related to complication rates after subsequent surgical interventions.ResultsSixty-six of 335 patients underwent re-laparotomy after PIHR. The perioperative course was complicated in 76% (30/39) of procedures with intraperitoneal placed grafts compared to 29% (8/27) of interventions with preperitoneally positioned meshes (P < 0.001). Small bowel resections were necessary in 21% of the intraperitoneal group (8/39) versus 0% in the preperitoneal group. Surgical site infection rates were higher in the intraperitoneal group (10/39, 26%, versus 1/27, 4%). Enterocutaneous fistula formation was rare and occurred in two patients after subsequent laparotomy (5%).ConclusionsRe-laparotomy after PIHR with polypropylene meshes are associated with more preoperative and postoperative complications when the mesh is placed intraperitoneally. Therefore 0intraperitoneal positioning of polypropylene mesh at incisional hernia repair should be avoided if possible.

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

BACKGROUND Incisional 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. METHODS We 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. FINDINGS Between 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. INTERPRETATION Our 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. FUNDING Erasmus University Medical Center and Ethicon.

Restoration of bowel continuity after surgery for acute perforated diverticulitis: should Hartmann’s procedure be considered a one‐stage procedure?

Objective  Hartmann’s procedure (HP) still remains the most frequently performed procedure in acute perforated diverticulitis, but it results in a end colostomy. Primary anastomosis (PA) with or without defunctioning loop ileostomy (DI) seems a good alternative. The aim of this study was to assess differences in the rate of stomal reversal after HP and PA with DI and to evaluate factors associated with postreversal morbidity in patients operated for acute perforated diverticulitis.

Impact of incisional hernia on health-related quality of life and body image: a prospective cohort study

BACKGROUND We investigated the impact of incisional hernia (IH) on quality of life and body image. METHODS Open abdominal surgery patients were included in a prospective cohort study performed between 2007 and 2009 in an academic hospital. Main outcomes were incidence of IH after approximately 12 months and Short-Form 36 and body image questionnaire results. RESULTS There were 374 patients who were examined after a median follow-up period of 16 months (range, 10-24 mo). Seventy-five patients had developed IH (20%); 63 (84%) were symptomatic. Adjusted for age, sex, and Charlson Comorbidity Index score, patients with IH reported significantly lower mean scores for components physical functioning (P = .033), role physical (P = .002), and physical component summary (P = .010). A trend toward significance was found for general health (P = .061). Patients with IH reported significantly lower mean cosmetic scores (P = .002), and body image and total body image scores (both P < .001). CONCLUSIONS Patients with IH reported lower mean scores on physical components of health-related quality of life and body image.

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