Irene M. Mulder

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

Guidelines of Diagnostics and Treatment of Acute Left-Sided Colonic Diverticulitis

Background: The incidence of acute left-sided colonic diverticulitis (ACD) is increasing in the Western world. To improve the quality of patient care, a guideline for diagnosis and treatment of diverticulitis is needed. Methods: A multidisciplinary working group, representing experts of relevant specialties, was involved in the guideline development. A systematic literature search was conducted to collect scientific evidence on epidemiology, classification, diagnostics and treatment of diverticulitis. Literature was assessed using the classification system according to an evidence-based guideline development method, and levels of evidence of the conclusions were assigned to each topic. Final recommendations were given, taking into account the level of evidence of the conclusions and other relevant considerations such as patient preferences, costs and availability of facilities. Results: The natural history of diverticulitis is usually mild and treatment is mostly conservative. Although younger patients have a higher risk of recurrent disease, a higher risk of complications compared to older patients was not found. In general, the clinical diagnosis of ACD is not accurate enough and therefore imaging is indicated. The triad of pain in the lower left abdomen on physical examination, the absence of vomiting and a C-reactive protein >50 mg/l has a high predictive value to diagnose ACD. If this triad is present and there are no signs of complicated disease, patients may be withheld from further imaging. If imaging is indicated, conditional computed tomography, only after a negative or inconclusive ultrasound, gives the best results. There is no indication for routine endoscopic examination after an episode of diverticulitis. There is no evidence for the routine administration of antibiotics in patients with clinically mild uncomplicated diverticulitis. Treatment of pericolic or pelvic abscesses can initially be treated with antibiotic therapy or combined with percutaneous drainage. If this treatment fails, surgical drainage is required. Patients with a perforated ACD resulting in peritonitis should undergo an emergency operation. There is an ongoing debate about the optimal surgical strategy. Conclusion: Scientific evidence is scarce for some aspects of ACD treatment (e.g. natural history of ACD, ACD in special patient groups, prevention of ACD, treatment of uncomplicated ACD and medical treatment of recurrent ACD), leading to treatment being guided by the surgeons personal preference. Other aspects of the management of patients with ACD have been more thoroughly researched (e.g. imaging techniques, treatment of complicated ACD and elective surgery of ACD). This guideline of the diagnostics and treatment of ACD can be used as a reference for clinicians who treat patients with ACD.

Systematic review of trocar-site hernia

Broad implementation of laparoscopic surgery has made trocar‐related complications clinically important. Trocar‐site hernia (TSH) is an uncommon, but potentially serious, complication that occasionally requires emergency surgery. This systematic review was conducted to establish the prevalence and risk factors for TSH.

Early experience with laparoscopic lavage for perforated diverticulitis

Laparoscopic lavage has recently emerged as a promising alternative to sigmoid resection in the treatment of perforated diverticulitis. This study examined an early experience with this technique.

Systematic review of the technique of colorectal anastomosis.

Many different techniques of colorectal anastomosis have been described in search of the technique with the lowest incidence of anastomotic leak. A systematic review of leak rates of techniques of hand-sewn colorectal anastomosis was conducted to provide a guideline for surgical residents and promote standardization of its technique. Clinical and experimental articles on colorectal anastomotic techniques and anastomotic healing published in the past 4 decades were searched. We included evidence on suture material, suture format, single- vs double-layer sutures, interrupted vs continuous sutures, hand-sewn vs stapled and compression colorectal anastomosis, and anastomotic configuration. In total, 3 meta-analyses, 26 randomized controlled trials, 11 nonrandomized comparative studies, 20 cohort studies, and 57 experimental studies were found. Results show that, for many aspects of the hand-sewn colorectal anastomosis technique, evidence is lacking. A single-layer continuous technique using inverting sutures with slowly absorbable monofilament material seems preferable. However, in contrast to stapled and compression colorectal anastomoses, the technique for hand-sewn colorectal anastomoses is nonstandardized with regard to intersuture distance, suture distance to the anastomotic edge, and tension on the suture. We believe detailed documentation of the anastomotic technique of all colorectal operations is needed to determine the role of the hand-sewn colorectal anastomosis.

Experimental study on synthetic and biological mesh implantation in a contaminated environment

Implantation of meshes in a contaminated environment can be complicated by mesh infection and adhesion formation.

In vitro model to study the biomaterial‐dependent reaction of macrophages in an inflammatory environment

Macrophages play an important role in the reaction to biomaterials, which sometimes have to be used in a surgical field at risk of contamination. The macrophage phenotype in reaction to biomaterials in an inflammatory environment was evaluated in both an in vivo and in vitro setting.

Polyvinyl Alcohol Hydrogel Decreases Formation of Adhesions in a Rat Model of Peritonitis

BACKGROUND Adhesion formation after surgery for peritonitis-related conditions, with such associated complications as intestinal obstruction, pain, and infertility, remains an important problem. Applying a liquid barrier intra-peritoneally might reduce initial adhesion formation. METHODS A combination of the cecal ligation and puncture model of peritonitis with the side-wall defect (SWD) model of adhesion formation was performed. Forty rats were assigned randomly to receive no barrier or 1 mL or 2 mL of the cross-linked polyvinyl alcohol and carboxymethylcellulose (PVA/CMC) hydrogel A-Part(®) Gel (B. Braun Aesculap AG, Tuttlingen, Germany). After 14 days, the animals were sacrificed, and adhesion formation and abscess formation were scored. RESULTS Thirty animals survived, distributed equally among the groups. There were significantly fewer adhesions to the SWD in the PVA/CMC groups (median 0) than in the control group (median 26%-50%) (p<0.05). The median tenacity of the adhesions was significantly higher in the control group (Zühlke score 2) than in the PVA/CMC groups (Zühlke score 0) (p<0.05). The amount and size of intra-abdominal abscesses were not significantly different in the three groups. CONCLUSION In this experiment, PVA/CMC hydrogel reduced the amount of adhesions to the SWD and between viscera significantly with equal risk of abscess formation.

Postoperative adhesion prevention with a new barrier: an experimental study.

Introduction: Postoperative adhesion formation remains a major clinical problem. The aim of this study was to test the effect of a new hydrogel on adhesion formation in a rat model. Materials and Methods: A reproducible rat model was used to induce standardized adhesion formation in three experiments. In experiment 1, a cross-linked polyvinyl alcohol (PVA) and carboxymethylcellulose (CMC) hydrogel (PVA/CMC, A-Part®; B. Braun Aesculap, Germany) was tested in different dosages. In experiment 2, PVA/CMC gel was compared to icodextrin 4% (Adept®; Baxter USA). In both groups, animals were sacrificed after 2 weeks. In experiment 3, histological examination after 4 and 6 weeks was performed. The percentage of adhesions to the defect was measured and the density was determined according to the Zühlke scale. During histological examination of the abdominal wall, the formation of neoperitoneum and potential residues of the agents were assessed. Results: In experiment 1, a significant reduction in amount as well as density of the adhesions was visible with all dosages of PVA/CMC gel. In experiment 2, again quantity and density of the adhesions were diminished by PVA/CMC hydrogel compared to the control group. Icodextrin 4% showed no significant reduction in adhesion formation. In experiment 3, no residues of PVA/CMC gel or icodextrin 4% were found during histological examination after 4 and 6 weeks and neoperitoneum was present in all cases. Conclusion: PVA/CMC hydrogel appears to be a novel effective adhesion prevention agent. Together with an upcoming safety study, these data encourage to start clinical efficacy studies.

Effects of New Anti-Adhesion Polyvinyl Alcohol Gel on Healing of Colon Anastomoses in Rats

BACKGROUND Adhesions follow abdominal surgery with an incidence as high as 95%, resulting in invalidating complications such as bowel obstruction, female infertility, and chronic pain. Searches have been performed for a safe and effective adhesion barrier; however, such barriers have impaired anastomotic site healing. The primary aim of this study was to investigate the effect of a new adhesion barrier, polyvinyl alcohol gel, on healing of colonic anastomoses using a rat model. METHODS Thirty-two Wistar rats were divided in two groups. In all animals, an anastomosis was constructed in the ascending colon. The first group received no adhesion barrier, whereas in the second group, 2 mL of polyvinyl alcohol gel (A-Part Gel(®); Aesculap AG, Tuttlingen, Germany) was applied circularly around the anastomosis. All animals were sacrificed on the seventh post-operative day, and the abdomen was inspected for signs of anastomotic leakage. The anastomotic bursting pressure, the adhesions around the anastomosis, and the collagen content of the excised anastomosis were measured. RESULTS No significant differences were observed between the two groups in the incidence of anastomotic leakage, the anastomotic bursting pressure (p=0.08), or the collagen concentration (p=0.91). No significant reduction in amount of adhesions was observed in the rats receiving polyvinyl alcohol gel. CONCLUSIONS This experimental study showed no significant differences in anastomotic leakage, anastomotic bursting pressure, or collagen content of the anastomosis when using the adhesion barrier polyvinyl alcohol around colonic anastomoses. The barrier did not prevent adhesion formation.