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Background: Despite the fact that primary percutaneous catheter drainage has become standard practice, some patients with pancreatic fistula after pancreatoduodenectomy ultimately undergo a relaparotomy. The aim of this study was to compare completion pancreatectomy with a pancreas-preserving procedure in patients undergoing relaparotomy for pancreatic fistula after pancreatoduodenectomy. Methods: This retrospective cohort study of nine institutions included patients who underwent relaparotomy for pancreatic fistula after pancreatoduodenectomy from 2005-2018. Furthermore, a systematic review and meta-analysis were performed according to the PRISMA guidelines. Results: From 4877 patients undergoing pancreatoduodenectomy, 786 (16 per cent) developed a pancreatic fistula grade B/C and 162 (3 per cent) underwent a relaparotomy for pancreatic fistula. Of these patients, 36 (22 per cent) underwent a completion pancreatectomy and 126 (78 per cent) a pancreas-preserving procedure. Mortality was higher after completion pancreatectomy (20 (56 per cent) versus 40 patients (32 per cent); P=0.009), which remained after adjusting for sex, age, BMI, ASA score, previous reintervention, and organ failure in the 24 h before relaparotomy (adjusted odds ratio 2.55, 95 per cent c.i. 1.07 to 6.08). The proportion of additional reinterventions was not different between groups (23 (64 per cent) versus 84 patients (67 per cent); P=0.756). The meta-analysis including 33 studies evaluating 745 patients, confirmed the association between completion pancreatectomy and mortality (Mantel-Haenszel random-effects model: odds ratio 1.99, 95 per cent c.i. 1.03 to 3.84). Conclusion: Based on the current data, a pancreas-preserving procedure seems preferable to completion pancreatectomy in patients in whom a relaparotomy is deemed necessary for pancreatic fistula after pancreatoduodenectomy. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including single-agent chemotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer patients.Methods: This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤ 90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤ 270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients assuming an accrual period of 3 years and 1.5 years follow-up.Discussion: The PREOPANC-2 trial directly compares two neoadjuvant regimens for patients with resectable and borderline resectable pancreatic cancer. Our study will provide evidence on the neoadjuvant treatment of choice for patients with resectable and borderline resectable pancreatic cancer.Trial Registration: Primary registry and trial identifying number: EudraCT: 2017-002036-17 . Date of registration: March 6, 2018. Secondary identifying numbers: The Netherlands National Trial Register - NL7094 , NL61961.078.17, MEC-2018-004. [ABSTRACT FROM AUTHOR]

Aim: Anastomotic leakage (AL) is one of the most feared complications after rectal resection. This study aimed to assess a combination of biomarkers for early detection of AL after rectal cancer resection. Method: This study was an international multicentre prospective cohort study. All patients received a pelvic drain after rectal cancer resection. On the first three postoperative days drain fluid was collected daily and C‐reactive protein (CRP) was measured. Matrix metalloproteinase‐2 (MMP2), MMP9, glucose, lactate, interleukin 1‐beta (IL1β), IL6, IL10, tumour necrosis factor alpha (TNFα), Escherichia coli, Enterococcus faecalis, lipopolysaccharide‐binding protein and amylase were measured in the drain fluid. Prediction models for AL were built for each postoperative day using multivariate penalized logistic regression. Model performance was estimated by the c‐index for discrimination. The model with the best performance was visualized with a nomogram and calibration was plotted. Results: A total of 292 patients were analysed; 38 (13.0%) patients suffered from AL, with a median interval to diagnosis of 6.0 (interquartile ratio 4.0–14.8) days. AL occurred less often after partial than after total mesorectal excision (4.9% vs 15.2%, P = 0.035). Of all patients with AL, 26 (68.4%) required reoperation. AL was more often treated by reoperation in patients without a diverting ileostomy (18/20 vs 8/18, P = 0.03). The prediction model for postoperative day 1 included MMP9, TNFα, diverting ileostomy and surgical technique (c‐index = 0.71). The prediction model for postoperative day 2 only included CRP (c‐index = 0.69). The prediction model for postoperative day 3 included CRP and MMP9 and obtained the best model performance (c‐index = 0.78). Conclusion: The combination of serum CRP and peritoneal MMP9 may be useful for earlier prediction of AL after rectal cancer resection. In clinical practice, this combination of biomarkers should be interpreted in the clinical context as with any other diagnostic tool. [ABSTRACT FROM AUTHOR]

Background: Radical gastrectomy is the cornerstone of the treatment of gastric cancer. For tumors invading the pancreas, en-bloc partial pancreatectomy may be needed for a radical resection. The aim of this study was to evaluate the outcome of gastrectomies with partial pancreatectomy for gastric cancer.Methods: Patients who underwent gastrectomy with or without partial pancreatectomy for gastric or gastro-oesophageal junction cancer between 2011 and 2015 were selected from the Dutch Upper GI Cancer Audit (DUCA). Outcomes were resection margin (pR0) and Clavien-Dindo grade ≥ III postoperative complications and survival. The association between partial pancreatectomy and postoperative complications was analyzed with multivariable logistic regression. Overall survival of patients with partial pancreatectomy was estimated using the Kaplan-Meier method.Results: Of 1966 patients that underwent gastrectomy, 55 patients (2.8%) underwent en-bloc partial pancreatectomy. A pR0 resection was achieved in 45 of 55 patients (82% versus 85% in the group without additional resection, P = 0.82). Clavien-Dindo grade ≥ III complications occurred in 21 of 55 patients (38% versus 17%, P < 0.001). Median overall survival [95% confidence interval] was 15 [6.8-23.2] months. For patients with and without perioperative systemic therapy, median survival was 20 [12.3-27.7] and 10 [5.7-14.3] months, and for patients with pR0 and pR1 resection, it was 20 [11.8-28.3] and 5 [2.4-7.6] months, respectively.Conclusions: Gastrectomy with partial pancreatectomy is not only associated with a pR0 resection rate of 82% but also with increased postoperative morbidity. It should only be performed if a pR0 resection is feasible. [ABSTRACT FROM AUTHOR]

Aim This study used a national registry to compare the outcome after a low Hartmann's procedure ( LHP), defined as removal of most of the rectum to leave a short anorectal stump and an end colostomy, and low anterior resection (LA) with or without a diverting ileostomy ( DI) in rectal cancer patients all of whom had received preoperative neoadjuvant radiotherapy ( RT). Method Patients who underwent LHP or LA with or without DI for rectal cancer after RT between 2009 and 2013 were identified from the Dutch Surgical Colorectal Audit. The postoperative outcome was compared between the three groups and risk of complications, reoperation and mortality were analysed in a multivariable model. Results The study included 4288 patients were included, of whom 27.8% underwent LHP, 20.2% LA and 52.0% LA with DI. Thirty-day mortality was higher after LHP (3.2% vs 1.3% and 1.3% for LA with or without DI, P < 0.001), but LHP was not an independent predictor of mortality in multivariable analysis. LHP and LA with DI were associated with a lower rate of abdominal infective complications (6.5% and 10.1% vs 16.2%, P < 0.001) and reoperation (7.3% and 8.1% vs 16.5%, P < 0.001). In multivariable analysis, LHP ( OR 0.35, 95% CI 0.26-0.47) and LA with DI ( OR 0.43, 95% CI 0.33-0.54) were associated with a lower risk of reoperation than LA alone. LHP was associated with a lower risk of any postoperative complication than LA with or without DI ( OR 0.81, 95% CI 0.66-0.98). Conclusion LHP and LA with DI were associated with fewer infective complications and reoperations than LA alone. The rate of any complication was less after LHR than LA with or without DI. [ABSTRACT FROM AUTHOR]

The article reports on a trial comparing early nasoenteric tube feeding (ENTF) in acute pancreatic patients at 72 hours after emergency department presentation in 2014. Topics discussed include the 30% primary end point in the early group and 27% in the on-demand group, and the absence of significant differences in major infection rates between the two groups. The article states that ENTF showed no superiority over an oral diet in reducing infection or death rate in patients.

Anastomotic leakage after colorectal surgery is correlated with considerable morbidity and mortality. Although many studies focus on risk factors and detection, studies on the treatment strategy for colorectal anastomotic leakage are scarce. A national questionnaire amongst 350 members of the Dutch Society for Gastrointestinal Surgery was undertaken on the current treatment of colorectal anastomotic leakage. The response was 40% after two anonymous rounds. 27% of the respondents state that a leaking anastomosis above the level of the promontory should be salvaged in ASA 1-2 patients <80 years of age, for ASA 3 and/or >80 years of age this percentage is 7.3%. For an anastomosis under the promontory, 50% of the respondents choose preserving the anastomosis for ASA 1-2 compared to 17% for ASA 3 and/or >80 years of age. In ASA 1-2 patients with a local abscess after a rectum resection without protective ileostomy, 31% of the respondents will create an protective ileostomy, 40% break down the anastomosis to create a definite colostomy, in ASA 3 and/or >80 years of age 14% of the respondents create a protective ileostomy and 63% a definitive colostomy. In ASA 1-2 patients with peritonitis after a rectum resection with deviating ileostomy, 31% prefer a laparotomy for lavage and repair of the anastomosis, 25% for lavage without repair and 36% of the respondents prefer to break down the anastomosis. When the patient is ASA 3 and/or >80 years of age, 13% prefer repair, 9% a lavage and 74% breaking down the anastomosis. This questionnaire shows that in contrast to older people, more surgeons make an effort to preserve the anastomosis in younger people., (Copyright © 2013 S. Karger AG, Basel.)

Objective: Despite improvements in anesthesiology and intensive care medicine, mortality for perforated gastroduodenal ulcer disease remains high. This study was designed to evaluate the results of surgery for perforated ulcer disease and to identify prognostic factors for mortality in order to optimize treatment., Patients and Methods: The medical records of 272 patients undergoing emergency surgery for perforated ulcer disease from 2000 to 2005 in two large teaching hospitals and one university hospital in the Netherlands were retrospectively analyzed. Information on 89 pre-, peri- and postoperative data were recorded. Statistical analysis was performed using multiple logistic regression analysis. The primary endpoint was 30-day mortality., Results: The 30-day mortality rate was 16%. Variables associated with 30-day mortality were age, shock, tachycardia, anemia and ASA class., Conclusions: A relatively low 30-day mortality rate was achieved. Age, shock, tachycardia and anemia were significantly associated with 30-day mortality. Finding that shock, tachycardia and anemia are independently associated with 30-day mortality could indicate that patients are septic upon admission. Improvements in survival might be achieved by early sepsis treatment., (Copyright © 2011 S. Karger AG, Basel.)

Background: The disruption of the hepatocyte tight junctions observed in biliary obstruction suggests altered permeability of the blood-bile barrier. In this study the role of biliary obstruction and increased biliary pressure on the translocation of bacteria from biliary tract to bloodstream and lymphatic system were evaluated., Materials and Methods: Rats underwent distal bile duct ligation (BDL, n = 33) for two weeks or a sham celiotomy (n = 21). Seventeen of the 33 BDL rats underwent subsequent biliary decompression by a choledochojejunostomy (CJ). Two weeks after the final operation, a laparotomy was performed again and the CBD, the thoracic duct, and the caval vein were canulated. Next, a suspension containing 10(8) Escherichia coli/ml was retrogradely infused in the CBD for 5 min at 5 or 20 cm H2O above the secretory biliary pressure., Results: A higher biliary infusion pressure resulted in a significant increase of cfu E.coli per milliliter of blood in all the three groups (Sham, BDL, CJ). BDL rats showed significantly more bacterial translocation to the bloodstream than the shams. After biliary decompression, translocation normalized to the control levels. At 5 cm H2O infusion pressure only one lymph culture was positive (CJ group). At 20 cm H2O overpressure, nine lymph cultures were E.coli positive (P = 0.03). These were found mainly in groups with a nonobstructed bile duct (Sham and CJ 40% vs BDL 10%)., Conclusion: Translocation of bacteria from biliary tract to bloodstream increased at higher intrabiliary pressures. Longstanding bile duct obstruction was an independent determinant for cholangiovenous reflux. Bacterial translocation to the lymphatic system did not parallel translocation to the bloodstream, although in the nonobstructed biliary tract, increased bacterial translocation to the lymphatic system was pressure related.

Objective: To analyse the outcome of preoperative biliary drainage in patients being operated on for a tumour in the pancreatic head., Design: Retrospective study., Setting: University hospital, The Netherlands., Subjects: Consecutive series of 241 patients., Main Outcome Measures: Decline in bilirubin concentrations and bacterial contamination of bile as a result of preoperative drainage. Incidence of postoperative complications in patients who underwent preoperative drainage and those who did not., Results: 184/241 patients underwent preoperative biliary drainage. Endoscopic drainage was the most effective, shown by a median reduction in bilirubin concentrations of 82%, 74%, and 50% after endoscopic drainage (n = 149), papillotomy (n = 25) and external drainage (n = 10), respectively. Bacterial contamination of bile was significantly more common when an endoprosthesis was used, but did not result in a higher rate of infective complications. 163 Whipple's resections, 33 total pancreatectomies, and 45 biliary-enteric bypasses were performed. 137/241 (57%) patients had postoperative complications. There was no significant difference in the incidence of postoperative complications between patients who had preoperative biliary drainage and those who did not (p = 0.4).

From 1983 to 1992 a total of 240 patients with a pancreatic head tumor underwent laparotomy to assess the resectability of the tumor. In 44 patients the tumor was not resected because of distant metastases (n = 20) or major vascular involvement or local tumor infiltration (n = 24) not detected during the preoperative workup. A palliative biliary and gastric bypass was performed in these patients. All other patients underwent a subtotal (Whipple's resection, n = 164) or total (n = 32) pancreaticoduo-denectomy. However, in 56 cases after Whipple's resection, microscopic examination of the specimen showed tumor invasion in the dissection margins. For this reason, these resections were considered palliative. We compared hospital mortality, morbidity, and long-term survival of patients who had undergone a biliary and gastric bypass for a locally advanced tumor (group A, n = 24) with a matched group of patients who had undergone a macroscopically radical Whipple's resection that on microscopic examination proved to be nonradical (group B, n = 36). Both groups were comparable with regard to age (mean 61 years in both groups), duration of symptoms (8 weeks in group A and 10 weeks in group B), and tumor size (mean 4.25 cm in group A and 4.30 cm in group B). Median postoperative hospital stay was 18 days in group A and 25 days in group B. Postoperative complications (intraabdominal abscess, gastrointestinal hemorrhage, anastomotic leakage, delayed gastric emptying) occurred in 33% of patients in group A and in 44% of patients in group B. Hospital mortality was 0% and 3% in group A and group B, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Despite the widespread use of transpapillary biliary endoprostheses, little is known about their effect on the extrahepatic bile ducts. In an experimental study in dogs, we induced inflammatory changes in the bile ducts by stent insertion and studied the reversibility of these changes after stent removal. In addition, the consequences of a period of preoperative stenting for subsequent operation of the biliary tract and the eventual detrimental effects of stenting on the histologic factors of the liver were studied. Twenty-six mongrel dogs were randomly divided into four groups: group 1, stenting during four weeks; group 2, after four weeks stenting, construction of a hepaticojejunostomy; group 3, four days of common bile duct (CBD) ligation, four weeks stenting and hepaticojejunostomy, and group 4, four days of CBD ligation and hepaticojejunostomy. All dogs were sacrificed two months after the last procedure. Hepatic biopsies were obtained during each procedure and bile duct biopsies during hepaticojejunostomy and upon sacrifice. Four weeks of stenting of a normal or obstructed CBD resulted in fibrosed bile ducts, showing severe chronic inflammation with papillary hyperplasia of the epithelium. All bile cultures grew fecal bacteria. Two months after stent removal, inflammation was still present, albeit less severe. Stenting and subsequent surgical treatment resulted in a higher incidence of postoperative complications (54 percent) compared with the control group (14 percent), although this did not reach statistical significance. Hepatic histologic factors were not markedly changed after transpapillary endoprosthesis placement, but after hepaticojejunostomy cholangiolitis was observed. Whenever transpapillary biliary endoprostheses are used, the local effects on the extrahepatic bile ducts and the subsequent bacterial contamination of the bile should be considered.

The morphologic changes of the extrahepatic biliary tract during obstruction and the effects of biliary decompression by means of an endoprosthesis on the bile duct wall were studied by light microscopy and scanning electron microscopy. Common hepatic duct biopsy specimens and bile cultures were obtained during surgery from 30 patients with a distal common bile duct obstruction caused by a tumor. Thirteen patients had obstructed bile ducts of 3 weeks' duration (group A). Seventeen patients had had jaundice for a period of 4 weeks and had subsequently undergone preoperative endoscopic biliary stenting for a period of 4 weeks (group B). Three autopsy specimens from patients without hepatobiliary disease served as controls. The results showed that the initial dilatation and thickening of the obstructed ducts in group A were associated with a mild inflammation, a moderate degree of fibrosis, and local epithelial disintegration. The presence of an endoprosthesis, however (group B), induced severe inflammatory changes with considerable fibrosis and ulcerative lesions, resulting in markedly thickened ducts with lumina approximating the diameter of the stent. Three of 13 (24%) bile cultures in group A were positive and 14 of 17 (82%) in group B were positive.