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Contains fulltext : 251531.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To quantify the impact of individual complications on mortality, organ failure, hospital stay, and readmission after pancreatoduodenectomy. SUMMARY OF BACKGROUND DATA: An initial complication may provoke a sequence of adverse events potentially leading to mortality after pancreatoduodenectomy. This study was conducted to aid prioritization of quality improvement initiatives. METHODS: Data from consecutive patients undergoing pancreatoduodenectomy (2014-2017) were extracted from the Dutch Pancreatic Cancer Audit. Population attributable fractions (PAF) were calculated for the association of each complication (ie, postoperative pancreatic fistula, postpancreatectomy hemorrhage, bile leakage, delayed gastric emptying, wound infection, and pneumonia) with each unfavorable outcome [ie, in-hospital mortality, organ failure, prolonged hospital stay (>75th percentile), and unplanned readmission), whereas adjusting for confounders and other complications. The PAF represents the proportion of an outcome that could be prevented if a complication would be eliminated completely. RESULTS: Overall, 2620 patients were analyzed. In-hospital mortality occurred in 95 patients (3.6%), organ failure in 198 patients (7.6%), and readmission in 427 patients (16.2%). Postoperative pancreatic fistula and postpancreatectomy hemorrhage had the greatest independent impact on mortality [PAF 25.7% (95% CI 13.4-37.9) and 32.8% (21.9-43.8), respectively] and organ failure [PAF 21.8% (95% CI 12.9-30.6) and 22.1% (15.0-29.1), respectively]. Delayed gastric emptying had the greatest independent impact on prolonged hospital stay [PAF 27.6% (95% CI 23.5-31.8)]. The impact of individual complications on unplanned readmission was smaller than 11%. CONCLUSION: Interventions focusing on postoperative pancreatic fistula and postpancreatectomy hemorrhage may have the greatest impact on in-hospital mortality and organ failure. To prevent prolonged hospital stay, initiatives should in addition focus on delayed gastric emptying.

Contains fulltext : 232906.pdf (Publisher’s version ) (Open Access) BACKGROUND: Preoperative differentiation between neoplastic and nonneoplastic gallbladder polyps, and the subsequent indication for cholecystectomy remains a clinical dilemma. The current 1 cm size threshold for neoplasia is unspecific. The aim of this study was to improve diagnostic work-up for gallbladder polyps using sonographic and MRI characteristics of neoplastic and nonneoplastic polyps. METHODS: A prospective, exploratory study including patients undergoing cholecystectomy for gallbladder polyp(s) was conducted. Patients underwent targeted transabdominal ultrasound (TAUS) and MRI. Outcomes were sensitivity and specificity for polyp diagnosis, and the radiological characteristics of neoplastic and nonneoplastic polyp types. Histopathology after cholecystectomy was used as reference standard. RESULTS: Histopathology demonstrated gallbladder polyps in 20/27 patients (74%): 14 cholesterol polyps, three adenomyomatosis, two adenomas and one gastric heterotopia. Sensitivity of polyp identification were 72% (routine TAUS) and 86% (targeted TAUS and MRI). Both adenomas were identified as neoplastic on targeted TAUS and MRI. Sonographic presentation as multiple, pedunculated polyps, either heterogeneous or with hyperechoic foci, or as single polyps containing cysts were limited to nonneoplastic polyps. On MRI hyperintense polyps on T1-weighted image were cholesterol polyps. An adenoma with high-grade dysplasia showed foci of decreased ADC values. We propose a checklist for polyp evaluation by targeted TAUS and a flowchart for radiological work-up of gallbladder polyps. CONCLUSIONS: The presented checklist and flowchart could aid diagnostic work-up for gallbladder polyps compared to current routine ultrasound, by elimination of nonneoplastic polyps and ultimately improve treatment decision for patients with gallbladder polyps.

Introduction: Minimally invasive techniques have been suggested to achieve enhanced recovery and improved outcome after pancreaticoduodenectomy (PD). This study describes our experience and a stepw...

Background: While most of the evidence on minimally invasive liver surgery (MILS) is derived from expert centers, nationwide outcomes remain underreported. This study aimed to evaluate the implementation and outcome of MILS on a nationwide scale. Methods: Electronic patient files were reviewed in all Dutch liver surgery centers and all patients undergoing MILS between 2011 and 2016 were selected. Operative outcomes were stratified based on extent of the resection and annual MILS volume. Results: Overall, 6951 liver resections were included, with a median annual volume of 50 resections per center. The overall use of MILS was 13% (n = 916), which varied from 3% to 36% (P < 0.001) between centers. The nationwide use of MILS increased from 6% in 2011 to 23% in 2016 (P < 0.001). Outcomes of minor MILS were comparable with international studies (conversion 0–13%, mortality

Background: Abdominal drainage and the timing of drain removal in patients undergoing pancreatic resection are under debate. Early drain removal after pancreatic resection has been reported to be safe with a low risk for clinical relevant postoperative pancreatic fistula (CR-POPF) when drain amylase on POD1 is Methods: Patients registered in the Dutch Pancreatic Cancer Audit (2014-2016) who underwent pancreatoduodenectomy, distal pancreatectomy or enucleation were analysed. Data on post-operative drain amylase levels, drain removal, postoperative pancreatic fistulae were collected. Univariate and multivariate analysis using a logistic regression model were performed. The primary outcome measure was grade B/C pancreatic fistula (CR-POPF).Results: Among 1402 included patients, 433 patients with a drain fluid amylase level of 5000U/L the CR-POPF rate was 28%. When using a cut-off point of 2000U/L or 1000U/L during POD1-3, the CR-POPF rates were 6% and 5% respectively. For patients with an amylase level of >2000U/L and >1000UL during POD 1-3 the CR-POPF rates were 26% and 22% respectively (n = 223). Drain removal on POD4 or thereafter was associated with more complications (p = 0.004). Drain amylase level was shown to be the most statistically significant predicting factor for CR-POPF (Wald = 49.7; p Conclusion: Our data support early drain removal after pancreatic resection. However, a cut-off of 5000U/L drain amylase on POD1 was associated with a relatively high CR-POPF rate of 7%. A cut-off point of 1000U/L during POD1-3 resulted in 5% CR-POPF and might be a safer alternative. (C) 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Background: Laparoscopic pancreatoduodenectomy with open reconstruction (LPD-OR) has been suggested to lower the rate of postoperative pancreatic fistula reported after laparoscopic pancreatoduodenectomy with laparoscopic reconstruction (LPD). Propensity score matched studies are, lacking. Methods: This is a multicenter prospective cohort study including patients from 7 Dutch centers between 2014–2018. Patients undergoing LPD-OR were matched LPD patients in a 1:1 ratio based on propensity scores. Main outcomes were postoperative pancreatic fistulas (POPF) grade B/C and Clavien-Dindo grade ≥3 complications. Results: A total of 172 patients were included, involving the first procedure for all centers. All 56 patients after LPD-OR could be matched to a patient undergoing LPD. With LPD-OR, the unplanned conversion rate was 21% vs. 9% with LPD (P < 0.001). Median blood loss (300 vs. 400 mL, P = 0.85), operative time (401 vs. 378 min, P = 0.62) and hospital stay (10 vs. 12 days, P = 0.31) were comparable for LPD-OR vs. LPD, as were Clavien-Dindo grade ≥3 complications (38% vs. 52%, P = 0.13), POPF grade B/C (23% vs. 21%, P = 0.82), and 90-day mortality (4% vs. 4%, P > 0.99). Conclusion: In this propensity matched cohort performed early in the learning curve, no benefit was found for LPD-OR, as compared to LPD.

Rapamycin (sirolimus) is employed as an immunosuppressant following liver transplant, to inhibit the re-growth of cancer cells following liver resection for hepatocellular carcinoma (HCC), and for the treatment of advanced HCC. Rapamycin also induces the expression of antioxidant enzymes in the liver, suggesting that pretreatment with the drug could provide a potential strategy to reduce ischemia reperfusion injury following liver surgery. The aim of this study was to further investigate the actions of rapamycin in inducing expression of the antioxidant enzymes heme oxygenase-1 (HO-1) and peroxiredoxin-1 (Prx-1) in normal liver and in tumorigenic liver cells. A rat model of segmental hepatic ischemia and reperfusion, cultured freshly-isolated rat hepatocytes, and tumorigenic H4IIE rat liver cells in culture were employed. Expression of HO-1 and Prx-1 was measured using quantitative PCR and western blot. Rapamycin pre-treatment of normal liver in vivo or normal hepatocytes in vitro led to a substantial induction of mRNA encoding HO-1 and Prx-1. The dose-response curve for the action of rapamycin on mRNA expression was biphasic, showing an increase in expression at 0 - 0.1 μM rapamycin but a decrease from maximum at concentrations greater than 0.1 μM. By contrast, in H4IIE cells, rapamycin inhibited the expression of HO-1 and Prx-1 mRNA. Oltipraz, an established activator of transcription factor Nrf2, caused a large induction of HO-1 and Prx-1 mRNA. The dose response curve for the inhibition by rapamycin of HO-1 and Prx-4 mRNA expression, determined in the presence of oltipraz, was monophasic with half maximal inhibition at about 0.01 μM. It is concluded that, at concentrations comparable to those used clinically, pre-treatment of the liver with rapamycin induces the expression of HO-1 and Prx-1. However, the actions of rapamycin on the expression of these two antioxidant enzymes in normal hepatocytes are complex and, in tumorigenic liver cells, differ from those in normal hepatocytes. Further studies are warranted to evaluate preconditioning the livers of patients subject to liver resection or liver transplant with rapamycin as a viable strategy to reduce IR injury following liver surgery.

The levels of carbohydrate antigen 19-9 (CA19-9) are often tested to stage pancreatobiliary tumours or to monitor the effects of treatment of such tumours. Benign diseases can also be associated with elevated CA 19-9 levels, but extreme elevation is rare in such cases.An 84-year-old man was diagnosed with cholecystitis at the emergency department and received conservative treatment with antibiotics for this. After 5 weeks, the patient came to the outpatient clinic with unexplained icterus. Additional imaging revealed indications of malignancy and the CA19-9 concentration was 4240 kU/l. We suspected pancreatobiliary malignancy. However, ERCP revealed obstructive choledocholithiasis and we subsequently performed laparoscopic cholecystectomy. Based on histopathology examination of the gallbladder, a diagnosis of xanthogranulomatous cholecystitis was made. After surgery, CA19-9 levels decreased and the patient swiftly recovered.Significantly elevated CA19-9 levels are not proof of pancreatobiliary malignancy. Our case underscores that CA19-9 is not an ideal tumour marker and that the results of CA19-9 tests should therefore be interpreted with some caution.

Introduction: Definitions regarding resectability and hence indications for preoperative chemotherapy vary. Use of preoperative chemotherapy may influence postoperative outcomes. This study aimed to assess the variation in use of preoperative chemotherapy for CRLM and related postoperative outcomes in the Netherlands.Materials and methods: All patients who underwent liver resection for CRLM in the Netherlands between 2014 and 2018 were included from a national database. Case-mix factors contributing to the use of preoperative chemotherapy, hospital variation and postoperative outcomes were assessed using multivariable logistic regression. Postoperative outcomes were postoperative complicated course (PCC), 30day morbidity and 30-day mortality.Results: In total, 4469 patients were included of whom 1314 patients received preoperative chemotherapy and 3155 patients did not. Patients receiving chemotherapy were significantly younger (mean age (+SD) 66.3 (10.4) versus 63.2 (10.2) p < 0.001) and had less comorbidity (Charlson scores 2+ (24% versus 29%, p = 0.010). Unadjusted hospital variation concerning administration of preoperative chemotherapy ranged between 2% and 55%. After adjusting for case-mix factors, three hospitals administered significantly more preoperative chemotherapy than expected and six administered significantly less preoperative chemotherapy than expected. PCC was 12.1%, 30-day morbidity was 8.8% and 30-day mortality was 1.5%. No association between preoperative chemotherapy and PCC (OR 1.24, 0.98-1.55, p = 0.065), 30-day morbidity (OR 1.05, 0.81-1.39, p = 0.703) or with 30-day mortality (OR 1.22, 0.75-2.09, p = 0.467) was found.Conclusion: Significant hospital variation in the use of preoperative chemotherapy for CRLM was present in the Netherlands. No association between postoperative outcomes and use of preoperative chemotherapy was found. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Importance: All events that transpire during laparoscopic cholecystectomy (LC) cannot be adequately reproduced in the operative note. Video recording is already known to add important information regarding this operation. Objective: It is hypothesized that additional audio recordings can provide an even better procedural understanding by capturing the surgeons' considerations. Design, Setting, and Participants: The Simultaneous Video and Audio Recording of Laparoscopic Cholecystectomy Procedures (SONAR) trial is a multicenter prospective observational trial conducted in the Netherlands in which operators were requested to dictate essential steps of LC. Elective LCs of patients 18 years and older were eligible for inclusion. Data collection occurred from September 18, 2018, to November 13, 2018. Main Outcomes and Measures: Adequacy rates for video recordings and operative note were compared. Adequacy was defined as the competent depiction of a surgical step and expressed as the number of adequate steps divided by the total applicable steps for all cases. In case of discrepancies, in which a step was adequately observed in the video recording but inadequately reported in the operative note, an expert panel analyzed the added value of the audio recording to resolve the discrepancy. Results: A total of 79 patients (49 women [62.0%]; mean [SD] age, 54.3 [15.9] years) were included. Video recordings resulted in higher adequacy for the inspection of the gallbladder (note, 39 of 79 cases [49.4%] vs video, 79 of 79 cases [100%]; P

Background Based on excellent outcomes from high-volume centres, laparoscopic liver resection is increasingly being adopted into nationwide practice which typically includes low-medium volume centres. It is unknown how the use and outcome of laparoscopic liver resection compare between high-volume centres and low-medium volume centres. This study aimed to compare use and outcome of laparoscopic liver resection in three leading European high-volume centres and nationwide practice in the Netherlands. Method An international, retrospective multicentre cohort study including data from three European high-volume centres (Oslo, Southampton and Milan) and all 20 centres in the Netherlands performing laparoscopic liver resection (low-medium volume practice) from January 2011 to December 2016. A high-volume centre is defined as a centre performing >50 laparoscopic liver resections per year. Patients were retrospectively stratified into low, moderate- and high-risk Southampton difficulty score groups. Results A total of 2425 patients were included (1540 high-volume; 885 low-medium volume). The median annual proportion of laparoscopic liver resection was 42.9 per cent in high-volume centres and 7.2 per cent in low-medium volume centres. Patients in the high-volume centres had a lower conversion rate (7.4 versus 13.1 per cent; P Conclusion High-volume expert centres had a sixfold higher use of laparoscopic liver resection, less conversions, and shorter hospital stay, as compared to a nationwide low-medium volume practice. Stratification into Southampton difficulty score risk groups identified some differences but largely outcomes appeared better for high-volume centres in each risk group.

Current literature is characterized by a discrepancy between reported symptomatic and radiological recurrent hiatal hernia’s following primary repair. Crural augmentation using mesh is suggested to reduce recurrence rates. The aim of this trial is to analyze 1-year outcome of laparoscopic hiatal hernia repair using sutures versus sutures reinforced with non-absorbable mesh. Between 2013 and 2016, 72 patients with an objectified hiatal hernia were randomized for primary repair using non-absorbable sutures and sutures reinforced with non-absorbable mesh. Data regarding the incidence of recurrent hiatal hernia, need for endoscopic dilatation or surgical reintervention, postoperative dysphagia and/or reflux symptoms, general health, and use of acid-suppressing medication were analyzed. 72 patients (n = 36 vs. n = 36) were included. One year after primary repair and repair using non-absorbable mesh, there were no differences in the number of recurrent hiatal hernia’s demonstrated by barium swallow radiology (n = 4 [11.4%] vs. n = 6 [19.4%], p = 0.370) or upper gastrointestinal endoscopy (n = 5 [14.4%] vs. n = 5 [17.2%], p = 0.746), the number of surgical reinterventions (n = 2 [5.6%] vs. n = 1 [2.8%], p = 1.000), nor in chest pain and heartburn scores, with comparable dysphagia and satisfaction scores. Compared to the preoperative state, both groups demonstrated a comparable and significant reduction in chest pain score and Dakkak dysphagia score. Use of non-absorbable mesh to reinforce primary hiatal hernia repair results in equal hiatal hernia recurrence and symptomatic outcome compared to repair using sutures alone. During 1-year follow-up, there were no mesh-related complications. Follow-up beyond 1 year needs to demonstrate whether these findings are sustained.

Inflammatory bowel disease, vascular disease, volvulus, adhesions, or abdominal trauma may necessitate extensive small-bowel resection resulting in an ultra-short distal duodenal or jejunal stump. If this distal duodenal or short jejunal stump is too short for stoma creation and bowel continuity restoration is hazardous or not possible at all, a distal duodenogastrostomy or proximal jejunogastrostomy in combination with drainage of the stomach is an option to prevent stump leakage. Although successful, this distal duodenogastrostomy has been described only in very few patients and in older records. We reintroduced this technique and describe a recent series of patients that confirms its usefulness in certain conditions. The technique of the distal duodenogastrostomy or proximal jejunogastrostomy with gastric drainage was used for the management of the difficult distal duodenum stump in five critically ill patients undergoing extensive bowel resection. Four patients with small-bowel ischemia and one patient suffering from perforating Crohn's disease and small-bowel volvulus were treated successfully. The gastrostomies were subsequently converted to a duodenotransversostomy (in two patients) or the patients underwent small-bowel transplantation (two patients). One patient still has a jejunogastrostomy just after the duodenal-jejunal transition. In all five patients, the distal duodenogastrostomy or proximal jejunogastrostomy in combination with gastric drainage functioned well up to restoration of bowel continuity. In one patient, distal duodenogastrostomy and transabdominal gastric drainage functioned well for 5 years. No anastomotic leakage occurred. This procedure provides a feasible solution for an ultra-short bowel at emergency laparotomy. It enhances the surgical armamentarium and provides treatment options for these patients that were perhaps previously deemed unsalvageable.

Background Kidney transplantation is associated with harmful processes affecting the viability of the graft. One of these processes is associated with the phenomenon of ischaemia–reperfusion injury. Anaesthetic conditioning is a widely described strategy to attenuate ischaemia–reperfusion injury. We therefore conducted the Volatile Anaesthetic Protection of Renal Transplants-1 trial, a pilot project evaluating the influence of two anaesthetic regimens, propofol- vs sevoflurane-based anaesthesia, on biochemical and clinical outcomes in living donor kidney transplantation. Methods Sixty couples were randomly assigned to the following three groups: PROP (donor and recipient propofol), SEVO (donor and recipient sevoflurane), and PROSE (donor propofol and recipient sevoflurane). The primary outcome was renal injury reflected by urinary biomarkers. The follow-up period was 2 yr. Results Three couples were excluded, leaving 57 couples for analysis. Concentrations of kidney injury molecule-1 (KIM-1), N-acetyl-β-d-glucosaminidase (NAG), and heart-type fatty acid binding protein (H-FABP) in the first urine upon reperfusion showed no differences. On day 2, KIM-1 concentrations were higher in SEVO [952.8 (interquartile range 311.8–1893.0) pg mmol−1] compared with PROP [301.2 (202.0–504.7) pg mmol−1]. This was the same for NAG: SEVO, 1.835 (1.162–2.457) IU mmol−1vs PROP, 1.078 (0.819–1.713) IU mmol−1. Concentrations of H-FABP showed no differences. Measured glomerular filtration rate at 3, 6, and 12 months showed no difference. After 2 yr, there was a difference in the acute rejection rate (P=0.039). Post hoc testing revealed a difference between PROP (35%) and PROSE (5%; P=0.020). The difference between PROP and SEVO (11%) was not significant (P=0.110). Conclusions The SEVO group showed higher urinary KIM-1 and NAG concentrations in living donor kidney transplantation on the second day after transplantation. This was not reflected in inferior graft outcome. Clinical trial registration NCT01248871.

Item does not contain fulltext BACKGROUND: Laparoscopic pancreatoduodenectomy may improve postoperative recovery compared with open pancreatoduodenectomy. However, there are concerns that the extensive learning curve of this complex procedure could increase the risk of complications. We aimed to assess whether laparoscopic pancreatoduodenectomy could reduce time to functional recovery compared with open pancreatoduodenectomy. METHODS: This multicentre, patient-blinded, parallel-group, randomised controlled phase 2/3 trial was performed in four centres in the Netherlands that each do 20 or more pancreatoduodenectomies annually; surgeons had to have completed a dedicated training programme for laparoscopic pancreatoduodenectomy and have done 20 or more laparoscopic pancreatoduodenectomies before trial participation. Patients with a benign, premalignant, or malignant indication for pancreatoduodenectomy, without signs of vascular involvement, were randomly assigned (1:1) to undergo either laparoscopic or open pancreatoduodenectomy using a central web-based system. Randomisation was stratified for annual case volume and preoperative estimated risk of pancreatic fistula. Patients were blinded to treatment allocation. Analysis was done according to the intention-to-treat principle. The main objective of the phase 2 part of the trial was to assess the safety of laparoscopic pancreatoduodenectomy (complications and mortality), and the primary outcome of phase 3 was time to functional recovery in days, defined as all of the following: adequate pain control with only oral analgesia; independent mobility; ability to maintain more than 50% of the daily required caloric intake; no need for intravenous fluid administration; and no signs of infection (temperature

Summary Background International guidelines advise laparoscopic cholecystectomy to treat symptomatic, uncomplicated gallstones. Usual care regarding cholecystectomy is associated with practice variation and persistent post-cholecystectomy pain in 10–41% of patients. We aimed to compare the non-inferiority of a restrictive strategy with stepwise selection with usual care to assess (in)efficient use of cholecystectomy. Methods We did a multicentre, randomised, parallel-arm, non-inferiority study in 24 academic and non-academic hospitals in the Netherlands. We enrolled patients aged 18–95 years with abdominal pain and ultrasound-proven gallstones or sludge. Patients were randomly assigned (1:1) to either usual care in which selection for cholecystectomy was left to the discretion of the surgeon, or a restrictive strategy with stepwise selection for cholecystectomy. For the restrictive strategy, cholecystectomy was advised for patients who fulfilled all five pre-specified criteria of the triage instrument: 1) severe pain attacks, 2) pain lasting 15–30 min or longer, 3) pain located in epigastrium or right upper quadrant, 4) pain radiating to the back, and 5) a positive pain response to simple analgesics. Randomisation was done with an online program, implemented into a web-based application using blocks of variable sizes, and stratified for centre (academic versus non-academic and a high vs low number of patients), sex, and body-mass index. Physicians and patients were masked for study-arm allocation until after completion of the triage instrument. The primary, non-inferiority, patient-reported endpoint was the proportion of patients who were pain-free at 12 months' follow-up, analysed by intention to treat and per protocol. A 5% non-inferiority margin was chosen, based on the estimated clinically relevant difference. Safety analyses were also done in the intention-to treat population. This trial is registered at the Netherlands National Trial Register, number NTR4022. Findings Between Feb 5, 2014, and April 25, 2017, we included 1067 patients for analysis: 537 assigned to usual care and 530 to the restrictive strategy. At 12 months' follow-up 298 patients (56%; 95% CI, 52·0–60·4) were pain-free in the restrictive strategy group, compared with 321 patients (60%, 55·6–63·8) in usual care. Non-inferiority was not shown (difference 3·6%; one-sided 95% lower CI −8·6%; pnon-inferiority=0·316). According to a secondary endpoint analysis, the restrictive strategy resulted in significantly fewer cholecystectomies than usual care (358 [68%] of 529 vs 404 [75%] of 536; p=0·01). There were no between-group differences in trial-related gallstone complications (40 patients [8%] of 529 in usual care vs 38 [7%] of 536 in restrictive strategy; p=0·16) and surgical complications (74 [21%] of 358 vs 88 [22%] of 404, p=0·77), or in non-trial-related serious adverse events (27 [5%] of 529 vs 29 [5%] of 526). Interpretation Suboptimal pain reduction in patients with gallstones and abdominal pain was noted with both usual care and following a restrictive strategy for selection for cholecystectomy. However, the restrictive strategy was associated with fewer cholecystectomies. The findings should encourage physicians involved in the care of patients with gallstones to rethink cholecystectomy, and to be more careful in advising a surgical approach in patients with gallstones and abdominal symptoms. Funding The Netherlands Organization for Health Research and Development, and CZ healthcare insurance.

Outcome following fundoplication for gastroesophageal reflux can be measured using objective tests, symptom scores and quality of life (QoL) measures. Which is best and how these assessments correlate is uncertain. To determine the utility of assessment measures we compared a general QoL measure (SF-36) and a disease-specific measure (GERD-hr-QoL) with symptom and satisfaction scores in individuals following fundoplication.329 individuals underwent fundoplication between 2000 and 2015 in 2 centres in Australia and the Netherlands. Patients were assessed before and 3, 12 and 24 months after surgery using 10-point Likert scales to assess heartburn and satisfaction, the SF-36 questionnaire and the GERD-hr-QoL questionnaire. SF-36 scores were converted into component scores: Physical Component Scale (PCS) score and Mental Component Scale (MCS) score. Correlations between QoL measures and clinical outcomes were determined.Surgery relieved heartburn (7.0 vs. 0.0 median, P0.001) and patients were highly satisfied with the outcome (median 9.0). PCS and MCS scores improved after surgery (PCS 40.9 vs. 46.0, P0.001; MCS 47.6 vs. 50.3, P = 0.027). GERD-hr-QoL scores also improved after surgery (15.7 vs. 3.7, P0.001). Correlations between PCS and MCS scores versus heartburn and satisfaction scores were generally weak or absent. However, correlations between GERD-hr-QoL versus heartburn and satisfaction scores were moderate to strong.Despite improvements in scores, the SF-36 correlated poorly with clinical outcome measures, and its use to measure outcome following fundoplication is questioned. However, the GERD-hr-QoL correlated well with the symptom scores, suggesting this disease-specific QoL measure is a better tool for assessing anti-reflux surgery outcome.

Rapamycin is employed as an immunosuppressant following organ transplant and, in patients with hepatocellular carcinoma, to inhibit cancer cell regrowth following liver surgery. Preconditioning the liver with rapamycin to induce the expression of antioxidant enzymes is a potential strategy to reduce ischemia reperfusion (IR) injury. However, pre-treatment with rapamycin inhibits bile flow, especially following ischemia. The aim was to investigate the mechanisms involved in this inhibition. In a rat model of segmental hepatic ischemia and reperfusion, acute administration of rapamycin by intravenous injection did not inhibit the basal rate of bile flow. Pre-treatment of rats with rapamycin for 24 h by intraperitoneal injection inhibited the expression of mRNA encoding the sinusoidal influx transporters Ntcp, Oatp1 and 2 and the canalicular efflux transporter Bsep, and increased expression of canalicular Mrp2. Dose-response curves for the actions of rapamycin on the expression of Bsep and Ntcp in cultured rat hepatocytes were biphasic, and monophasic for effects on Oatp1. In cultured tumorigenic H4IIE liver cells, several bile acid transporters were not expressed, or were expressed at very low levels compared to hepatocytes. In H4IIE cells, rapamycin increased expression of Ntcp, Oatp1 and Mrp2, but decreased expression of Oatp2. It is concluded that the inhibition of bile flow recovery following ischemia observed in rapamycin-treated livers is principally due to inhibition of the expression of sinusoidal bile acid transporters. Moreover, in tumorigenic liver tissue the contribution of tumorigenic hepatocytes to total liver bile flow is likely to be small and is unlikely to be greatly affected by rapamycin.

Contains fulltext : 181861.pdf (Publisher’s version ) (Closed access) BACKGROUND: Infected necrotising pancreatitis is a potentially lethal disease and an indication for invasive intervention. The surgical step-up approach is the standard treatment. A promising alternative is the endoscopic step-up approach. We compared both approaches to see whether the endoscopic step-up approach was superior to the surgical step-up approach in terms of clinical and economic outcomes. METHODS: In this multicentre, randomised, superiority trial, we recruited adult patients with infected necrotising pancreatitis and an indication for invasive intervention from 19 hospitals in the Netherlands. Patients were randomly assigned to either the endoscopic or the surgical step-up approach. The endoscopic approach consisted of endoscopic ultrasound-guided transluminal drainage followed, if necessary, by endoscopic necrosectomy. The surgical approach consisted of percutaneous catheter drainage followed, if necessary, by video-assisted retroperitoneal debridement. The primary endpoint was a composite of major complications or death during 6-month follow-up. Analyses were by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN09186711. FINDINGS: Between Sept 20, 2011, and Jan 29, 2015, we screened 418 patients with pancreatic or extrapancreatic necrosis, of which 98 patients were enrolled and randomly assigned to the endoscopic step-up approach (n=51) or the surgical step-up approach (n=47). The primary endpoint occurred in 22 (43%) of 51 patients in the endoscopy group and in 21 (45%) of 47 patients in the surgery group (risk ratio [RR] 0.97, 95% CI 0.62-1.51; p=0.88). Mortality did not differ between groups (nine [18%] patients in the endoscopy group vs six [13%] patients in the surgery group; RR 1.38, 95% CI 0.53-3.59, p=0.50), nor did any of the major complications included in the primary endpoint. INTERPRETATION: In patients with infected necrotising pancreatitis, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing major complications or death. The rate of pancreatic fistulas and length of hospital stay were lower in the endoscopy group. The outcome of this trial will probably result in a shift to the endoscopic step-up approach as treatment preference. FUNDING: The Dutch Digestive Disease Foundation, Fonds NutsOhra, and the Netherlands Organization for Health Research and Development.

Background: Chronic pancreatitis is a complex disease with many unanswered questions regarding the natural history and therapy. Prospective longitudinal studies with long-term follow-up are warranted.Methods: The Dutch Chronic Pancreatitis Registry (CARE) is a nationwide registry aimed at prospective evaluation and follow-up of patients with chronic pancreatitis. All patients with (suspected) chronic or recurrent pancreatitis are eligible for CARE. Patients are followed-up by yearly questionnaires and review of medical records. Study outcomes are pain, disease complications, quality of life, and pancreatic function. The target sample size was set at 500 for the first year and 1000 patients within 3 years.Results: A total of 1218 patients were included from February 2010 until June 2013 by 76 participating surgeons and gastroenterologist from 33 hospitals. Participation rate was 90% of eligible patients. Eight academic centers included 761 (62%) patients, while 25 community hospitals included 457 (38%). Patient centered outcomes were assessed by yearly questionnaires, which had a response rate of 85 and 82% for year 1 and 2, respectively. The median age of patients was 58 years, 814 (67%) were male, and 38% had symptoms for less than 5 years.Discussion: The CARE registry has successfully recruited over 1200 patients with chronic and recurrent pancreatitis in about 3 years. The defined inclusion criteria ensure patients are included at an early disease stage. Participation and compliance rates are high. CARE offers a unique opportunity with sufficient power to investigate many clinical questions regarding natural course, complications, and efficacy and timing of treatment strategies. Copyright (C) 2014, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.

OBJECTIVE The aim of the current study was to assess symptomatic outcome and need for surgical reintervention for patients identified with pathological esophageal acid exposure by routine postoperative 24-hour pH-monitoring. BACKGROUND Although laparoscopic fundoplication is associated with excellent short- and midterm results, recurrent symptoms pose an important challenge. Postoperative pH-monitoring is considered the "gold standard" for diagnosing recurrent GERD and frequently used for routine postoperative follow up. METHODS Analysis of prospectively collected data from patients who underwent laparoscopic fundoplication between April 1994 and June 2015 and underwent routine postoperative 24-hour pH-monitoring was performed. Symptomatic outcome and need for surgical reintervention up to 5 years was compared between patients with pathological and physiological postoperative esophageal acid exposure. Primary endpoints were heartburn score and need for surgical reintervention for recurrent reflux. RESULTS A total of 309 patients in whom routine postoperative 24-hour pH-monitoring was performed were included. Pathological acid exposure was present in 33 patients (11%) compared with 276 patients (89%) with physiological acid exposure. During 5-year follow up, there were no differences in heartburn, dysphagia, or satisfaction scores. Eighteen percent of all patients with abnormal postoperative pH-studies underwent redo fundoplication during 5-year follow up. CONCLUSIONS Pathological acid exposure demonstrated by routine postoperative pH-monitoring was not associated with worse symptomatic outcome in terms of reflux control and satisfaction. A possible explanation for this finding is that laparoscopic fundoplication reduces the patients' ability to perceive reflux. This underlines the importance of assessing the association between symptomatic outcome and esophageal function tests in determining outcome of antireflux surgery.

Background:Combination therapy of thiopurines and anti-tumor necrosis factor alpha (TNF-) antibodies is the most effective medical treatment of Crohn's disease (CD). Data on thiopurines and anti-TNF- antibodies in preventing surgical recurrence (need for re-resection) of CD are scarce. Therefore, we analyzed which factors were involved in surgical recurrence of CD in a large cohort of patients with CD operated in a regional and a university hospital.Methods:This is a retrospective cohort study of 567 patients who underwent surgery for CD. Clinical data and risk factors for surgical recurrence were analyzed, focusing on medical therapy and hospital type.Results:Overall, 237 (41.8%) patients developed a surgical recurrence, after a median of 70 (2-482) months. Before surgical recurrence, 235 patients (41.4%) and 116 patients (20.5%) used thiopurines and anti-TNF- antibodies, respectively. Multivariate analysis identified 3 independent risk factors associated with surgical recurrence of CD. A higher risk was seen in patients with colonic disease compared with patients with ileal disease (hazard ratio, 1.56; 95% confidence interval, 1.10-2.21; P = 0.012) and in patients using multiple types of medication (hazard ratio, 1.38; 95% confidence interval, 1.25-1.54; P

BACKGROUND: There is resistance to routine intraoperative cholangiography (IOC) during cholecystectomy because it prolongs surgery and may be experienced as cumbersome. An alternative instrument may help to reduce these drawbacks and lower the threshold for IOC. This trial compared the Kumar cannulation technique to the more commonly used Olsen clamp for IOC (KOALA trial; Dutch Trial Register NTR2582). METHODS: Patients undergoing elective laparoscopic cholecystectomy were randomized between IOC using the Kumar clamp and the Olsen clamp. Primary end points were the time that the IOC procedure took and its perceived ease as measured on a visual analog scale from 0 (impossible) to 10 (effortless). To detect a difference of 33 % in IOC time, a total sample size of 40 patients was required. RESULTS: Fifty-nine patients were randomized. Nine were excluded because of conversion to open cholecystectomy before the IOC procedure. Twenty-eight patients underwent IOC with the Kumar clamp and 22 with the Olsen clamp. The success rate was 23 (82.1 %) of 28 for the Kumar clamp and 19 (86.4 %) of 22 for the Olsen clamp (p > 0.999). The mean IOC time was 10 min 27 s ± 6 min 17 s using the Kumar clamp and 11 min 34 s ± 7 min 27 s using the Olsen clamp (p = 0.537). Surgeons graded the ease of the Kumar clamp as 6.8 ± 2.7 and the Olsen clamp as 6.8 ± 2.1 (p = 0.977). CONCLUSIONS: IOC using the Kumar clamp was neither faster nor easier than using the Olsen clamp. Both clamps facilitated IOC in just over 10 min. Individual surgeon preference should dictate which clamp is used.

Laparoscopic hiatal hernia repair has become standard practice for most surgeons performing antireflux surgery. Hiatal hernia repair consists of cruroplasty with sutures only or additional reinforcement using mesh. Use of mesh was initiated to reduce recurrence rates. Recent analyses show that use of mesh may influence radiologic recurrence rates, but it does not seem to prevent symptomatic recurrences and the need for reoperation. This study compares clinical and radiologic outcomes of primary cruroplasty and cruroplasty with non-absorbable mesh after laparoscopic hiatal hernia repair. Retrospective analysis of prospectively followed cohort of patients undergoing laparoscopic correction of hiatal hernia type II–IV in two tertiary referral centers was carried out. Radiologic recurrence, symptomatic recurrence, reoperation rate, complications and patient-reported outcome measures were analyzed for all patients. A total of 189 patients were analyzed after laparoscopic hiatal hernia correction with an additional fundoplication [127 (67.2%) primary correction, 62 (32.8%) with mesh reinforcement]. After a mean follow-up of 39.3 months, the overall radiologic recurrence rate was 24.3%, which was equal in both groups [25.8% (mesh) vs 23.6% (no mesh), P = 0.331]. Symptomatic recurrence rate was 13.2% (16.1 vs 11.8%, P = 0.495) and reoperation rate 7.4% (9.7 vs 6.3%), which was comparable between the two groups. Complication rates were equal, and no serious mesh-related complications were reported. Health-related quality of life improved after surgery, dysphagia decreased and patient satisfaction was high for both groups without significant differences. Radiologic recurrences, symptomatic recurrences and reoperation rates are equal after laparoscopic hiatal hernia repair with or without non-absorbable mesh reinforcement, irrespective of hernia size and type. Quality of life, dysphagia and patient satisfaction were comparable. No serious mesh-related complications occurred. The results of this study do not support the routine use of mesh in hiatal hernia repair.

BACKGROUND: This study aimed to identify safety measures practiced by Dutch surgeons during laparoscopic cholecystectomy. METHOD: An electronic questionnaire was sent to all members of the Dutch Society of Surgery with a registered e-mail address. RESULTS: The response rate was 40.4% and 453 responses were analyzed. The distribution of the respondents with regard to type of hospital was similar to that in the general population of Dutch surgeons. The critical view of safety (CVS) technique is used by 97.6% of the surgeons. It is documented by 92.6%, mostly in the operation report (80.0%), but often augmented by photography (42.7%) or video (30.2%). If the CVS is not obtained, 50.9% of surgeons convert to the open approach, 39.1% continue laparoscopically, and 10.0% perform additional imaging studies. Of Dutch surgeons, 53.2% never perform intraoperative cholangiography (IOC), 41.3% perform it incidentally, and only 2.6% perform it routinely. A total of 105 bile duct injuries (BDIs) were reported in 14,387 cholecystectomies (0.73%). The self-reported major BDI rate (involving the common bile duct) was 0.13%, but these figures need to be confirmed in other studies. CONCLUSION: The CVS approach in laparoscopic cholecystectomy is embraced by virtually all Dutch surgeons. The course of action when CVS is not obtained varies. IOC seems to be an endangered skill as over half the Dutch surgeons never perform it and the rest perform it only incidentally.

Background Hiatal hernias (HH) are more common among elderly patients, with an increase in incidence with advancing age. Elderly patients frequently suffer from comorbidity, causing them to have an increased risk of perioperative mortality and morbidity. The aim of this study is to assess the safety of this procedure within elderly patients. Methods We performed a retrospective analysis of all patients with HH operated between July 2009 and May 2015 at two hospitals in the Netherlands specialized in antireflux surgery and HH repair. Mortality rates and short- and long-term morbidity rates were compared between patients aged under 70 years and aged over 70 years. Results A total of 204 consecutive patients underwent laparoscopic HH repair at our institutions, of whom 121 were aged under 70 years and 83 were aged over 70 years. There was no mortality intraoperatively, nor during 30-days follow-up. Intraoperative complications occurred in 7 patients aged 70 years and over, with no significant differences compared to the patients aged under 70. The 30-day morbidity rate did not significantly differ between the age groups, with an overall postoperative complication rate of 9.3 %. Only length of stay (LOS) was significantly longer in the elderly patients. Performing univariate analysis, only the occurrence of intraoperative complications was associated with 30-day morbidity. Conclusion In the present study, age was not associated with increased 30-day morbidity or mortality following HH repair. Therefore, in carefully selected patients, age should not be used as an argument to withhold laparoscopic HH repair.

Background & aims: Exact data on Dutch patients with chronic intestinal failure (CIF) and after intestinal transplantation (ITx) have been lacking. To improve standard care of these patients, a nationwide collaboration has been established. Objectives of this study were obtaining an up-to-date prevalence of CIF and characterizing these patients using the specially developed multicenter web-based Dutch Registry of Intestinal Failure and Intestinal Transplantation (DRIFT).Methods: Cross-sectional study. CIF was defined as type 3 intestinal failure in which >75% of nutritional requirements were given as home parenteral nutrition (HPN) for >= 4 weeks in children and >50% for >= 3 months in adults. All patients with CIF receiving HPN care by the three Dutch specialized centers on January 1, 2013 and all ITx patients were registered in DRIFT (https://drift.darmfalen.nl).Results: In total, 195 patients with CIF (158 adults, 37 children) were identified, of whom 184 were registered in DRIFT. The Dutch point prevalence of CIF was 11.62 per million (12.24 for adults, 9.56 for children) on January 1, 2013. Fifty-seven patients (31%) had one or more indications for ITx, while 12 patients actually underwent ITx since its Dutch introduction. Four patients required transplantectomy of their intestinal graft and 3 intestinal transplant patients died.Conclusion: The multicenter registry DRIFT revealed an up-to-date prevalence of CIF and provided nationwide insight into the patients with CIF during HPN and after ITx in the Netherlands. DRIFT will facilitate the multicenter monitoring of individual patients, thereby supporting multidisciplinary care and decision-making. (C) 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Background/Aims. Rapamycin, which is employed in the management of patients undergoing liver surgery, induces the synthesis of heme oxygenase-1 (HO-1) in some non-liver cell types. The aim was to investigate whether rapamycin can induce HO-1 expression in the liver, and to test the effects of rapamycin on liver function in the early phase of ischemia reperfusion (IR) injury.Methods. Isolated rat hepatocytes and a rat model of segmental hepatic ischemia and reperfusion were employed. Bile flow was measured gravimetrically or by using indocyanine green. mRNA and protein (by quantitative PCR and Western blot, respectively) and blood concentrations of rapamycin, bilirubin, and liver marker enzymes were measured.Results. In isolated hepatocytes, rapamycin induced a 6-fold increase in HO-1, comparable to that induced by cobalt proporphyrin (CoPP), and a 2-fold increase in peroxiredoxin-1. Pretreatment of rats with rapamycin resulted in a small increase in liver HO-1 expression, a 20% inhibition of the basal rate of bile flow, and a 50% inhibition in the rate of bile flow recovery after ischemia. CoPP increased basal bile flow by 20% and inhibited bile flow recovery by 50%. These effects were associated with small increases in the blood concentrations of bilirubin and liver marker enzymes.Conclusions. Rapamycin, through HO-1 induction, has the potential to protect the liver against damage in the late phase of IR. The inhibition by rapamycin of bile flow indicates that its actions on liver function in the acute phase of IR injury are complex. (C) 2012 Elsevier Inc. All rights reserved.

BACKGROUND: Our university medical center is the only center in The Netherlands that has adopted a policy of routine intraoperative cholangiography (IOC) during cholecystectomy. This study aimed to describe the rate of bile duct injury (BDI) and management of common bile duct (CBD) stones before and after implementation of a routine IOC policy.STUDY DESIGN: Medical records were reviewed of all patients undergoing cholecystectomy in the 3 years before implementation of routine IOC and 3 years after. Dissection with the goal to achieve the critical view of safety was the standard operative technique during the entire study period.RESULTS: Four hundred and twenty-one patients underwent cholecystectomy with selective IOC and 435 patients with routine IOC. Groups were similar in age, sex, comorbidity, indication for surgery, and surgical approach. IOC was attempted in 5.9% in the selective IOC group and 59.8% in the routine IOC group (p CONCLUSIONS: Implementation of routine IOC policy was followed by fewer major BDIs and higher rates of intraoperative CBD stone management. (J Am Coll Surg 2011;213:267-274. (C) 2011 by the American College of Surgeons)

Background Boerhaave's syndrome has a high mortality rate (14-40%). Surgical treatment varies from a minimal approach consisting of adequate debridement with drainage of the mediastinum and pleural cavity to esophageal resection. This study compared the results between a previously preferred open minimal approach and a video-assisted thoracoscopic surgery (VATS) procedure currently considered the method of choice.Methods In this study, 12 consecutive patients treated with a historical nonresectional drainage approach (1985-2001) were compared with 12 consecutive patients treated prospectively after the introduction of VATS during the period 2002-2009. Baseline characteristics were equally distributed between the two groups.Results In the prospective group, 2 of the 12 patients had the VATS procedure converted to an open thoracotomy, and 2 additional patients were treated by open surgery. In the prospective group, 8 patients experienced postoperative complications compared with all 12 patients in the historical control group. Four patients (17%), two in each group, underwent reoperation. Six patients, three in each group, were readmitted to the hospital. The overall in-hospital mortality was 8% (1 patient in each group), which compares favorably with other reports (7-27%) based on drainage alone.Conclusions Adequate surgical debridement with drainage of the mediastinum and pleural cavity resulted in a low mortality rate. The results for VATS in this relatively small series were comparable with those for an open thoracotomy.

Contains fulltext : 80886.pdf (Publisher’s version ) (Closed access) SUMMARY BACKGROUND DATA: The role of early endoscopic retrograde cholangiopancreatography (ERCP) in acute biliary pancreatitis (ABP) remains controversial. Previous studies have included only a relatively small number of patients with predicted severe ABP. We investigated the clinical effects of early ERCP in these patients. METHODS: We performed a prospective, observational multicenter study in 8 university medical centers and 7 major teaching hospitals. One hundred fifty-three patients with predicted severe ABP without cholangitis enrolled in a randomized multicenter trial on probiotic prophylaxis in acute pancreatitis were prospectively followed. Conservative treatment or ERCP within 72 hours after symptom onset (at discretion of the treating physician) were compared for complications and mortality. Patients without and with cholestasis (bilirubin: >2.3 mg/dL [40 mumol/L] and/or dilated common bile duct) were analyzed separately. RESULTS: Of the 153 patients, 81 (53%) underwent ERCP and 72 (47%) conservative treatment. Groups were highly comparable at baseline. Seventy-eight patients (51%) had cholestasis. In patients with cholestasis, ERCP (52/78 patients: 67%), as compared with conservative treatment, was associated with fewer complications (25% vs. 54%, P = 0.020, multivariate adjusted odds ratio [OR]: 0.35, 95% confidence interval [CI]: 0.13-0.99, P= 0.049). This included fewer patients with >30% pancreatic necrosis (8% vs. 31%, P = 0.010). Mortality was nonsignificantly lower after ERCP (6% vs. 15%, P = 0.213, multivariate adjusted OR: 0.44, 95% CI: 0.08-2.28, P = 0.330). In patients without cholestasis, ERCP (29/75 patients: 39%) was not associated with reduced complications (45% vs. 41%, P = 0.814, multivariate adjusted OR: 1.36; 95% CI: 0.49-3.76; P = 0.554) or mortality (14% vs. 17%, P = 0.754, multivariate adjusted OR: 0.78; 95% CI: 0.19-3.12, P = 0.734). CONCLUSIONS: Early ERCP is associated with fewer complications in predicted severe ABP if cholestasis is present.

BackgroundlAims. Ischemic preconditioning (IPC) and intermittent ischemia (INT) reduce liver injury following ischemia reperfusion in liver resections. Aged livers are at higher risk for ischemia reperfusion injury, but little is known of the effectiveness of IPC and INT in aged livers. The aim of this study was to investigate the effects of IPC and INT on ischemia reperfusion injury in aged livers.Methods. A rat model of segmental hepatic ischemia (45 min) and reperfusion (60 min) was used. Bile flow, as an indicator of early hepatocyte damage and dynamic liver function, plasma concentrations of bilirubin, liver marker enzymes, and liver histology were assessed.Results. In young rats (8-13 weeks), IPC regimes of 10 min clamping and 10 min reperfusion, and 5 min clamping and 30 min reperfusion, restored bile flow to 23 and 42%, respectively, of the initial value, compared to 14 and 88% for continuous clamping and controls, respectively. An M regime of three cycles of alternating 15 min perfusion and 15 min clamping gave a substantially greater (70%) restoration of bile flow. In aged rats (20-24 months), the IPC regimes did not give any restoration of bile flow. By contrast, the INT regime restored bile flow to 68%. Plasma bilirubin concentrations were lowest in the INT groups, whereas alanine transaminase concentrations for the IPC and INT groups compared with the continuous clamping groups showed no significant differences.Conclusions. In young rats, INT is more effective than IPC in restoring the immediate consequences of IP-induced damage to hepatocytes and liver function after ischemia-reperfusion. In aged rats INT, but not IPC, reverses hepatocyte damage and restores liver function. INT may promote better hepatocyte and liver function than IPC following the surgical resection of aged livers. (c) 2009 Elsevier Inc. All rights reserved.

Background/Aims: Intermittent ischemia (INT) can improve liver function following inflow occlusion. The aim was to test whether the number of cycles of INT can be increased without impairing liver function. Methods:Liver function in the acute phase of ischemia reperfusion injury was assessed by measuring bile flow in rat livers. Phospholipid and bile salts in bile, liver marker enzymes in blood, and liver histology were measured. Aged livers were compared with young livers. Results: Clamping for 45 min reduced postperfusion bile flow to 13% of the initial value compared with 88 ± 5% for control livers (means ± SEM, n = 5–8), and substantially reduced the phospholipid:bile salt ratio in bile. Application of 3, 4, 5 and 6 cycles of INT (15 min) restored bile flow to 70 ± 11, 61 ± 4, 48 ± 2 and 35 ± 3% (p < 0.01) of the initial value, respectively, and restored the phospholipid:bile salt ratio. Multiple cycles of INT were less effective in aged rats. Conclusion: Several cycles of INT, through promotion of bile flow recovery and reduction in the cytotoxic actions of bile salts, may provide an effective clinical strategy for increasing clamping time in liver resections.

Contains fulltext : 152695.pdf (Publisher’s version ) (Closed access) BACKGROUND: In patients with mild gallstone pancreatitis, cholecystectomy during the same hospital admission might reduce the risk of recurrent gallstone-related complications, compared with the more commonly used strategy of interval cholecystectomy. However, evidence to support same-admission cholecystectomy is poor, and concerns exist about an increased risk of cholecystectomy-related complications with this approach. In this study, we aimed to compare same-admission and interval cholecystectomy, with the hypothesis that same-admission cholecystectomy would reduce the risk of recurrent gallstone-related complications without increasing the difficulty of surgery. METHODS: For this multicentre, parallel-group, assessor-masked, randomised controlled superiority trial, inpatients recovering from mild gallstone pancreatitis at 23 hospitals in the Netherlands (with hospital discharge foreseen within 48 h) were assessed for eligibility. Adult patients (aged >/=18 years) were eligible for randomisation if they had a serum C-reactive protein concentration less than 100 mg/L, no need for opioid analgesics, and could tolerate a normal oral diet. Patients with American Society of Anesthesiologists (ASA) class III physical status who were older than 75 years of age, all ASA class IV patients, those with chronic pancreatitis, and those with ongoing alcohol misuse were excluded. A central study coordinator randomly assigned eligible patients (1:1) by computer-based randomisation, with varying block sizes of two and four patients, to cholecystectomy within 3 days of randomisation (same-admission cholecystectomy) or to discharge and cholecystectomy 25-30 days after randomisation (interval cholecystectomy). Randomisation was stratified by centre and by whether or not endoscopic sphincterotomy had been done. Neither investigators nor participants were masked to group assignment. The primary endpoint was a composite of readmission for recurrent gallstone-related complications (pancreatitis, cholangitis, cholecystitis, choledocholithiasis needing endoscopic intervention, or gallstone colic) or mortality within 6 months after randomisation, analysed by intention to treat. The trial was designed to reduce the incidence of the primary endpoint from 8% in the interval group to 1% in the same-admission group. Safety endpoints included bile duct leakage and other complications necessitating re-intervention. This trial is registered with Current Controlled Trials, number ISRCTN72764151, and is complete. FINDINGS: Between Dec 22, 2010, and Aug 19, 2013, 266 inpatients from 23 hospitals in the Netherlands were randomly assigned to interval cholecystectomy (n=137) or same-admission cholecystectomy (n=129). One patient from each group was excluded from the final analyses, because of an incorrect diagnosis of pancreatitis in one patient (in the interval group) and discontinued follow-up in the other (in the same-admission group). The primary endpoint occurred in 23 (17%) of 136 patients in the interval group and in six (5%) of 128 patients in the same-admission group (risk ratio 0.28, 95% CI 0.12-0.66; p=0.002). Safety endpoints occurred in four patients: one case of bile duct leakage and one case of postoperative bleeding in each group. All of these were serious adverse events and were judged to be treatment related, but none led to death. INTERPRETATION: Compared with interval cholecystectomy, same-admission cholecystectomy reduced the rate of recurrent gallstone-related complications in patients with mild gallstone pancreatitis, with a very low risk of cholecystectomy-related complications. FUNDING: Dutch Digestive Disease Foundation.

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Background/Aims: The enterohepatic circulation of bile acids is related to normal inter-digestive gastrointestinal motility, with the gut peptide motilin also being involved. This study aimed to investigate the effect of intraduodenal artificial bile infusion on antroduodenal and gallbladder motility so as to further elucidate the controlling factors. Methods: Twelve fasting, healthy male volunteers received artificial bile (80 mol% bile acids; 15 mol% phospholipids; 5 mol% cholesterol) or placebo (saline) intraduodenally for 10 min starting 30 min after the end of phase III, according to a double-blind, randomised, cross-over design. Antroduodenal motility, gallbladder volumes, and plasma motilin levels were measured. All values are means ± SEM. Results: The interval between infusion and the subsequent phase III, as well as the origin of this phase III were not significantly different between bile and saline. Antral pressure waves were significantly more frequent during and immediately after bile infusion compared with saline infusion (p < 0.05). The duration of phase I following infusion was significantly longer after bile (24.8 ± 3.7 min) than after saline infusion (13.1 ± 1.7 min; p < 0.05). The mean gallbladder volume tended to increase in the hours following bile infusion, but to decrease after saline infusion (p = 0.06). Plasma motilin increased after bile and saline infusion in an almost identical way. Conclusion: This study provides no clear evidence for a role of intraduodenal artificial bile (i.e. its main constituents) in the regulation of migrating motor complex cycling or feedback inhibition of inter-digestive gallbladder emptying.

Objective: To develop a standardised and reproducible model of intra-abdominal infection and abscess formation in rats. Design: Experimental study. Setting: University hospital, The Netherlands. Subjects: 36 adult male Wistar rats. Interventions: In 32 rats, peritonitis was produced using two different concentrations of Escherichia coli (E. coli) and Bacteroides fragilis (B. fragilis) incorporated in fibrin clots (E. coli: 1 x 10(5) colony forming units (CFU) /ml or 1 x 10(8) CFU/ml, B. fragilis: 1 x 10(8) CFU/ml). Four rats with fibrin clots without bacteria served as uninfected controls. Main outcome measurements: Macroscopy and bacterial counts in peritoneal fluid, blood, and fibrin clots after 24 hours, 4 days, 7 days, and 4 weeks. Results: Macroscopically, there were signs of intra-abdominal infection and abscesses. With the higher starting concentration of E. coli, macroscopic signs were more pronounced and in nearly all rats bacterial counts in peritoneal fluid and fibrin clots showed persistently high numbers of E. coli and B. fragilis for at least 7 days (E. coli = 2 x 10(3) to 1 x 10(6) CFU/ml and 5 x 10(7) to 9 x 10(8) CFU/clot; B. fragilis = 1 x 10(3) to 1 x 10(6) CFU/ml and 5 x 10(7) to 6 x 10(8) CFU/clot). Conclusion: This standardised and reproducible model of intra-abdominal infection and abscess formation seems well suited for further use and development in experiments on the pathophysiology of intra-abdominal infection and abscesses.

Background/Aims: Translocation of gut bacteria occurs in obstructive jaundice, the underlying mechanisms are unclear. We designed this experimental study to investigate the association between interdigestive motility and the pathogenesis of bacterial translocation during biliary obstruction. Methods: Rats were fitted with jejunal myoelectrodes for the measurement of the interdigestive migrating motor complex (MMC) and with two cannulas in the proximal common bile duct (CBD) for exteriorization of biliary flow. This allowed measurement of MMCs under control conditions with an intact enterohepatic circulation and during 3 days of CBD obstruction without surgical intervention. Mesenteric lymph nodes, liver, spleen and segments of the duodenum, the jejunum and the caecum were removed for microbial culturing. Results: The MMC cycle length increased from 17.3 min before CBD obstruction to 31.9, 34.1, and 25.3 min on days 1, 2 and 3, respectively, after CBD obstruction (p < 0.05 for all days). Bacterial levels in the jejunum were significantly higher in CBD-obstructed rats than in control rats. The translocation incidence was significantly higher in rats with CBD obstruction (6/8) than in control rats (1/8). The bacterial levels in the jejunum correlated significantly with the MMC cycle length (r = 0.60, p Conclusion: Experimental biliary obstruction is associated with disturbance of MMCs, small-bowel bacterial overgrowth and increased bacterial translocation.

OBJECTIVE: To clarify the role of the migrating motor complex (MMC) in the regulation of small intestinal microflora and bacterial translocation. SUMMARY BACKGROUND DATA: The intestinal microflora may serve as a source of infectious microorganisms. Failure of regulatory mechanisms of the intestinal flora could therefore play an important role in the pathogenesis of gut-derived infections. METHODS: Rats were fitted with small intestinal myoelectrodes. MMCs were measured on a control day and 3 consecutive days during continuous administration of morphine or placebo. Mesenteric lymph nodes, liver, spleen, peripheral blood, duodenum, and ileum samples were cultured quantitatively. RESULTS: The mean MMC cycle length in placebo-treated animals was 15.1+/-0.5 minutes. MMCs were completely disrupted after morphine treatment. Total bacterial growth in the duodenum was 7.27+/-0.34 10log colony-forming units (CFU)/g with placebo and 8.28+/-0.27 CFU/g with morphine. In placebo-treated animals, the mean MMC cycle length the day before culturing correlated with total bacterial growth in the duodenum. Translocation incidences to the mesenteric lymph nodes, liver, spleen, and blood were 0/8, 1/8, 0/8, and 0/8 with placebo and 7/8, 6/8, 5/8, and 0/8 with morphine. The overall translocation incidence was 1/8 in placebo-treated animals and 8/8 in morphine-treated animals. CONCLUSIONS: The MMC is an important mechanism controlling bacterial growth in the upper small bowel. Its disruption with morphine promotes duodenal bacterial overgrowth and bacterial translocation.

Intermittent ischemia is known to promote post perfusion bile flow, and hence recovery of liver function following ischemia reperfusion of the liver. However, the mechanisms involved are not well understood. The aim of this study was to identify the step(s) in the bile acid transport pathway altered by intermittent ischemia.Arat model of segmental hepatic ischemia in which the bilateral median and left lateral lobes were made ischemic by clamping the blood vessels was used. Indocyanine green (ICG), infrared spectroscopy, and compartmental kinetic analysis, were used to indirectly monitor the movement of bile acids across hepatocytes in situ. Rates of bile flow were measured gravimetrically.In control livers (not subjected to ischemia), the movement of ICG from the blood to bile fluid could be described by a three compartment model comprising the blood, a rapidly-exchangeable compartment, and the hepatocyte cytoplasmic space. In livers subjected to continuous clamping, the rates of ICG uptake to the liver, and outflow from the liver, were greatly reduced compared with those in control livers. Intermittent clamping (three episodes of 15 min clamping) compared with continuous clamping substantially increased the rate of ICG uptake from the blood but had less effect on the rate of ICG outflow from hepatocytes.It is concluded that intermittent ischemia promotes post reperfusion bile flow in the early phase of ischemia reperfusion injury principally by enhancing the movement of bile acids from the blood to hepatocytes.

Traumatic injury of the pancreas is rare in children. It is often difficult to diagnose due to the lack of signs and symptoms, and shortly after trauma laboratory values may be normal. In addition, ultrasound and CT are often not specific. The treatment of grade 1 and 2 injury is non-operative. Although there seems to be a shift towards non-operative management of grade 3-5 injuries (with injury of the pancreatic duct), this is still a matter of debate. We describe 3 children, a girl of 2.5 years-old and a boy of 7 years-old, with grade 3 pancreatic injuries and an 8-year-old boy with a grade 2 injury. We demonstrate that the diagnosis is hard to establish, while the consequences of this injury can be serious. Thinking of pancreatic injury is most important to its diagnosis. We advocate referral to or consultation of specialized centres in these cases.

BackgroundSurgery for chronic pancreatitis is indicated for intractable pain or the treatment of complications. This retrospective cohort study evaluated the applicability of pain coping and quality-of-life (QOL) scoring in patients with chronic pancreatitis.MethodsBetween 1995 and 2008, 155 patients underwent surgery for chronic pancreatitis in two Dutch university hospitals. Medical charts were reviewed, and QOL and coping with pain were assessed by two validated questionnaires.ResultsMedian follow-up was 5·6 years. The aetiology was alcohol related in 48·3 per cent. Some 111 resections and 46 drainage procedures were performed. Fifty-seven patients had major complications and the hospital mortality rate was 1·3 per cent. After surgery the number of patients needing analgesics was reduced (P < 0·001). Alcohol consumption significantly reduced pain coping mechanisms (P = 0·032). Overall, QOL remained poor after surgery. Scores on three dimensions of the QOL questionnaire were significantly better after drainage than after resection procedures.ConclusionIn general, QOL after surgery for chronic pancreatitis remains poor, owing to pre-existing lifestyle and co-morbidity. Patients selected for a pancreatic duct drainage procedure have a better postoperative QOL than those undergoing resectional procedures. Alcohol consumption is associated with poor ability to cope with pain after surgery and should be discouraged.

Background: Ischaemic preconditioning (IPC) and intermittent ischaemia (INT) reduce liver injury after ischaemia reperfusion (IR). Steatotic livers are at a higher risk of IR injury, but the protection offered by IPC and INT is not well understood. The aim of the present study was to determine the effectiveness of IPC and INT in maintaining liver function in steatotic livers.Material and methods: A model of segmental hepatic ischaemia (45 min) and reperfusion (60 min) was employed using lean and obese Zucker rats. Bile flow recovery was measured to assess dynamic liver function, hepatocyte fat content quantified and blood electrolytes, metabolites and bile calcium measured to assess liver and whole body physiology. Liver marker enzymes and light and electron microscopy were employed to assess hepatocyte injury.Results: IPC was not effective in promoting bile flow recovery after IR in either lean or steatotic livers, whereas INT promoted good bile flow recovery in steatotic as well as lean livers. However, the bile flow recovery in steatotic livers was less than that in lean livers. In steatotic livers, ischaemia led to a rapid and substantial decrease in fat content. Steatotic livers were more susceptible to IR injury than lean livers, as indicated by increased blood ALT concentrations and major histological injury.Conclusion: INT is more effective than IPC in restoring liver function in the acute phase of IR in steatotic livers. In obese patients, INT may be useful in promoting better liver function after IR after liver resection.

Background: Results of liver transplantation have improved significantly over the last three decades. Hospital volume has been cited as an important outcome factor. The South Australian (SA) programme commenced in 1992 as the fourth centre in Australia. Methods: Patient and graft survival curves were computed from the Australian and New Zealand (ANZ) Liver Transplant Registry. SA results were compared with the rest of ANZ. All recipients of a cadaveric liver from the start of the SA programme in 1992 until the 100th case in 2005 were included and compared with recipients from ANZ in the same period. Results: In SA, 100 recipients received 104 grafts (average 8.0/year). In the same period 1438 recipients received 1530 grafts in ANZ (mean 23.4/year per unit). The median follow up was 6.2 years. Patient and graft survival curves were similar (P = 0.51, log-rank test.) Survival rates at 1, 5 and 10 years were 0.93, 0.83, 0.61 and 0.88, 0.80, 0.72 for SA and ANZ, respectively (P = NS). There was trend towards a higher mortality rate of recurrent hepatitis C in SA patients when compared with the rest of ANZ (4.0 vs 1.3% respectively, P = 0.06). Recipient variables, such as age and primary liver disease did not differ between SA and ANZ. For the SA patients the biliary anastomotic stricture rate was 20%, primary non-function rate was 2%, hepatic artery thrombosis 1% and portal vein thrombosis 1%. Conclusion: Good results are possible in a small-volume unit for cadaveric adult liver transplant.

Ischemia and reperfusion (IR) injury of the liver is associated with impaired bile secretion, but the effects of ischemic preconditioning (IPC) and intermittent ischemia (INT) on bile flow are unknown. A rat model of segmental (60%-70%) hepatic ischemia and reperfusion was employed to test the effects of IPC and INT on bile flow. Continuous clamping for 45 min (CC) substantially reduced bile flow, and this did not recover after 60 min of reperfusion. IPC and INT caused a significant recovery of bile flow. The elevation in plasma liver marker enzymes induced by CC was not reduced by IPC and INT. Light microscopy showed mild hepatocyte damage in all groups. In the CC group, the amount of F-actin localized around the bile canaliculi in the ischemic lobes was less than that in the nonischemic lobes, but this difference was not observed in the IPC and INT groups. It is concluded that IPC and INT substantially alleviate the decrease in bile flow induced by ischemia. Bile flow may be useful in the assessment of IR injury.

Ischemia and reperfusion (IR) injury of the liver is associated with impaired bile secretion, but the effects of ischemic preconditioning (IPC) and intermittent ischemia (INT) on bile flow are unknown. A rat model of segmental (60%-70%) hepatic ischemia and reperfusion was employed to test the effects of IPC and INT on bile flow. Continuous clamping for 45 min (CC) substantially reduced bile flow, and this did not recover after 60 min of reperfusion. IPC and INT caused a significant recovery of bile flow. The elevation in plasma liver marker enzymes induced by CC was not reduced by IPC and INT. Light microscopy showed mild hepatocyte damage in all groups. In the CC group, the amount of F-actin localized around the bile canaliculi in the ischemic lobes was less than that in the nonischemic lobes, but this difference was not observed in the IPC and INT groups. It is concluded that IPC and INT substantially alleviate the decrease in bile flow induced by ischemia. Bile flow may be useful in the assessment of IR injury.

Objectives: The colon is considered a major source of bacteria causing infection of pancreatic necrosis in acute pancreatitis (AP). Subtotal colectomy before AP in rats reduces mortality, but its role in affecting small bowel flora, bacterial translocation, and infection of pancreatic necrosis is unknown. Our aim was to study these phenomena in rats with AP. Methods: Fifty rats, allocated in 4 groups, underwent 2 laparotomies: group 1, sham laparotomy and saline biliopancreatic duct infusion; group 2, subtotal colectomy and saline infusion; group 3, sham laparotomy and AP ( ductal infusion of glycodeoxycholic acid and intravenous cerulein); group 4, subtotal colectomy and AP. Seventy-two hours later, samples were collected for microbiological analysis. Results: Subtotal colectomy caused small bowel bacterial overgrowth with gram-positive cocci ( group 1 versus group 2, duodenum: P = 0.030, ileum: P = 0.029). Bacterial counts of gram-negative rods/anaerobes in the duodenum and ileum and pancreatic bacterial counts of rats with colectomy and AP were significantly higher than in rats with AP only ( group 3 versus group 4, duodenum: P = 0.040, ileum: P = 0.029, pancreas: P = 0.017). Duodenal bacterial overgrowth and pancreatic infection correlate significantly (r = 0.45, P = 0.004). Conclusions: Subtotal colectomy induces small bowel bacterial overgrowth, which is associated with increased bacterial translocation to the pancreas.

authors are to be congratulated for performing a mediumsized series of cholecystectomies for acute pathology with no bile duct injuries or leaks. We, too, fully endorse the practice of careful dissection in the triangle of Calot and achievement of the CVS before clipping and dividing any tubular structures. However, rather than viewing the CVS as a replacement for routine intraoperative cholangiography (IOC), we feel that the two safety measures complement each other. Sanjay and colleagues rightly argue that the large population-based studies often used to propagate routine IOC date from the pre-CVS era. 2,3 They continue to suggest that this protective effect is therefore not to be expected in modern surgical practice. In our point of view, this is an unlikely assertion. The CVS has been standard practice in the Netherlands for several years. A recent nationwide survey by our group confirmed that 98% of the Dutch surgeons use this technique. 4 Nonetheless, common bile duct (CBD) injuries remain a substantial problem in the Netherlands with an incidence that is estimated to be higher than the 0.5% often quoted in literature. 5 Referrals to the largest tertiary referral center for bile duct injury (BDI) in the Netherlands show no decreasing trend in the course of the past decade. 6 In our