Non-Cross-Linked Collagen Mesh Performs Best in a Physiologic, Noncontaminated Rat Model.

BACKGROUND: In laparoscopic incisional hernia repair, direct contact between the prosthesis and abdominal viscera is inevitable and may lead to adhesions. Despite the large variety of mesh prosthesis, little is known about their in vivo behavior. Biological meshes are considered to have many advantages, but due to their price they are rarely used. A rat model was used to assess biological and conventional synthetic meshes on their in vivo characteristics. DESIGN: One-hundred twenty male Wistar rats were randomized into five groups of 24 rats. A mesh was implanted intraperitoneally and fixated with nonresorbable sutures. The following five meshes were implanted: Parietene (polypropylene), Permacol (cross-linked porcine acellular dermal matrix), Strattice (non-cross-linked porcine acellular dermal matrix), XCM Biologic (non-cross-linked porcine acellular dermal matrix), and Omyra Mesh (condensed polytetrafluoroethylene). The rats were sacrificed after 30, 90, or 180 days. Incorporation, shrinkage, adhesions, abscess formation, and histology were assessed for all meshes. RESULTS: All animals thrived postoperatively. After 180 days, Permacol, Parietene, and Omyra Mesh had a significantly better incorporation than Strattice ( P = .001, P = .019, and P = .037 respectively). After 180 days, Strattice had significantly fewer adhesions on the surface of the mesh than Parietene ( P < .001), Omyra Mesh ( P = .011), and Permacol ( P = .027). After 30 days, Permacol had significantly stronger adhesions than Strattice ( P = .030). However, this difference was not significant anymore after 180 days. After 180 days, there was significantly less shrinkage in Permacol than in Strattice ( P = .001) and Omyra Mesh ( P = .050). CONCLUSION: Based on incorporation, adhesions, mesh shrinkage, and histologic parameters, Strattice performed best in this experimental rat model.

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 Hartmann's 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, Hartmann's 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.

The prevention of colorectal anastomotic leakage with tissue adhesives in a contaminated environment is associated with the presence of anti-inflammatory macrophages.

BACKGROUND: Colorectal anastomoses created in a contaminated environment result in a high leakage rate. This study investigated whether using anastomotic sealants (TissuCol(®), Histoacryl(®) Flex, and Duraseal(®)) prevents leakage in a rat peritonitis model. STUDY DESIGN: Sixty-seven Wistar rats were divided into control and experimental groups (TissuCol, Histoacryl, and Duraseal groups). Peritonitis was induced 1 day before surgery with the cecal ligation puncture model. On day 0, colonic anastomosis was constructed with sutures and then sealed with no adhesive (control group) or one select adhesive (experimental groups). Bursting pressure, abscess formation, and adhesion severity were evaluated on day 3 or day 14. Hematoxylin and eosin staining and immunohistochemical staining for CD4, CD8, CD206, and iNOS were performed. RESULTS: On day 3, bursting pressures of the TissuCol group (120.1 ± 25.3 mmHg), Histoacryl group (117.3 ± 20.2 mmHg), and Duraseal group (123.6 ± 35.4 mmHg) were significantly higher than the that of the control group (24.4 ± 31.7 mmHg, p < 0.001). Abscesses around the anastomosis were found in the control group (6/7) and Duraseal group (2/9) but not in the TissuCol group or Histoacryl group. A higher number of CD206+ cells (M2 macrophages), a lower number of iNOS+ cells (M1 macrophages), a higher M2/M1 index, and a higher CD4+/CD8+ index were seen at the anastomotic site in all experimental groups compared with the control group on day 3. On day 14, abscesses were only found in the control group. Adhesion severity in the Duraseal group was significantly lower than that in the control group (p = 0.001). CONCLUSIONS: Anastomotic sealing using TissuCol(®), Histoacryl(®) Flex, or Duraseal(®) seems to be an effective and safe option to prevent leakage in contaminated colorectal surgery. The presence of large numbers of anti-inflammatory macrophages seems to be involved in preventing the leakage.

Routine histopathology for carcinoma in cholecystectomy specimens not evidence based: a systematic review.

BACKGROUND: Routine histopathological examination of gallbladder specimens is mainly performed to identify unexpected gallbladder carcinoma (GBC). This systematic review assesses the prevalence and characteristics of GBC in cholecystectomy specimens. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched for all articles reporting on the finding of GBC in cholecystectomy specimens. RESULTS: Of the 30 articles included, 20 were from Europe and the United States, and 10 were of Asian origin. In the Western studies, 276 cases of GBC were found in 61,542 specimens (median prevalence 0.4%, 95% confidence interval [CI] 0.3-0.6). Of these, 65% were expected pre- or intraoperatively. In the Asian studies, 344 cases of GBC were found in 37,365 specimens (median prevalence 1.2%, 95% CI 0.8-1.7). Of these, 45% were expected pre- or intraoperatively. In a subgroup analysis, identification of previously unexpected GBC affected treatment in only a minority of patients. In total, 72% of the patients received no further treatment and 32 patients (22%) received secondary surgery, of whom 15 patients survived at least 1 year. CONCLUSIONS: The histopathological finding of GBC after cholecystectomy appears to be a rare event. The prevalence of unexpected GBC was higher in Asian studies than in Western studies. The pre- and intraoperative sensitivity for this carcinoma is low. Moreover, the diagnosis of GBC at the time of histopathology is usually inconsequential. The results of this systematic review do not support routine histopathology of cholecystectomy specimens in clinical practice.

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 surgeon's 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.

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

BACKGROUND: Recently, 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/DESIGN: In this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmann's 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 Hartmann's 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. DISCUSSION: The 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 REGISTRATION: Nederlands Trial Register NTR2037.

Hartmann's procedure versus sigmoidectomy with primary anastomosis for perforated diverticulitis with purulent or faecal peritonitis (LADIES): a multicentre, parallel-group, randomised, open-label, superiority trial.

BACKGROUND: Previous studies have suggested that sigmoidectomy with primary anastomosis is superior to Hartmann's procedure. The likelihood of stoma reversal after primary anastomosis has been reported to be higher and reversal seems to be associated with lower morbidity and mortality. Although promising, results from these previous studies remain uncertain because of potential selection bias. Therefore, this study aimed to assess outcomes after Hartmann's procedure versus sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy, for perforated diverticulitis with purulent or faecal peritonitis (Hinchey III or IV disease) in a randomised trial. METHODS: A multicentre, randomised, open-label, superiority trial was done in eight academic hospitals and 34 teaching hospitals in Belgium, Italy, and the Netherlands. Patients aged between 18 and 85 years who presented with clinical signs of general peritonitis and suspected perforated diverticulitis were eligible for inclusion if plain abdominal radiography or CT scan showed diffuse free air or fluid. Patients with Hinchey I or II diverticulitis were not eligible for inclusion. Patients were allocated (1:1) to Hartmann's procedure or sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy. Patients were enrolled by the surgeon or surgical resident involved, and secure online randomisation software was used in the operating room or by the trial coordinator on the phone. Random and concealed block sizes of two, four, or six were used, and randomisation was stratified by age (<60 and ≥60 years). The primary endpoint was 12-month stoma-free survival. Patients were analysed according to a modified intention-to-treat principle. The trial is registered with the Netherlands Trial Register, number NTR2037, and ClinicalTrials.gov, number NCT01317485. FINDINGS: Between July 1, 2010, and Feb 22, 2013, and June 9, 2013, and trial termination on June 3, 2016, 133 patients (93 with Hinchey III disease and 40 with Hinchey IV disease) were randomly assigned to Hartmann's procedure (68 patients) or primary anastomosis (65 patients). Two patients in the Hartmann's group were excluded, as was one in the primary anastomosis group; the modified intention-to-treat population therefore consisted of 66 patients in the Hartmann's procedure group (46 with Hinchey III disease, 20 with Hinchey IV disease) and 64 in the primary anastomosis group (46 with Hinchey III disease, 18 with Hinchey IV disease). In 17 (27%) of 64 patients assigned to primary anastomosis, no stoma was constructed. 12-month stoma-free survival was significantly better for patients undergoing primary anastomosis compared with Hartmann's procedure (94·6% [95% CI 88·7-100] vs 71·7% [95% CI 60·1-83·3], hazard ratio 2·79 [95% CI 1·86-4·18]; log-rank p<0·0001). There were no significant differences in short-term morbidity and mortality after the index procedure for Hartmann's procedure compared with primary anastomosis (morbidity: 29 [44%] of 66 patients vs 25 [39%] of 64, p=0·60; mortality: two [3%] vs four [6%], p=0·44). INTERPRETATION: In haemodynamically stable, immunocompetent patients younger than 85 years, primary anastomosis is preferable to Hartmann's procedure as a treatment for perforated diverticulitis (Hinchey III or Hinchey IV disease). FUNDING: Netherlands Organisation for Health Research and Development.

Infection susceptibility of crosslinked and non-crosslinked biological meshes in an experimental contaminated environment.

BACKGROUND: This experimental study investigates infectious complications and functional outcome of biological meshes in a contaminated environment. METHODS: In 90 rats peritonitis was induced, and after 24 hours, a biological mesh was implanted intraperitoneally including 2 non-crosslinked mesh groups (Strattice and Surgisis) and 2 crosslinked mesh groups (CollaMendFM and Permacol). Sacrifice was after 90 and 180 days. RESULTS: More mesh infections occurred in crosslinked meshes compared with non-crosslinked meshes (70% vs 4%; P < .001). Mesh infection was the highest in crosslinked CollaMendFM (81.2%) and lowest in non-crosslinked Strattice groups (0%). Incorporation into the abdominal wall was poor in all meshes (0% to 39%). After 180 days no residue of non-crosslinked Surgisis mesh was found. After 180 days, shrinkage was .8% in crosslinked Permacol and 20% in Strattice groups. Strattice showed the least adhesion formation (median 5%). CONCLUSIONS: Infection rate of biological meshes in a contaminated field was the highest in crosslinked meshes. All biological meshes showed poor incorporation, which makes long-term abdominal wall repair questionable.

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.

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.

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.