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BACKGROUND: Laparoscopic and robotic minimally invasive liver surgery (MILS) is gaining popularity. Recent data and views on the implementation of laparoscopic and robotic MILS throughout Europe are lacking.METHODS: An anonymous survey consisting of 46 questions was sent to all members of the European-African Hepato-Pancreato-Biliary Association.RESULTS: The survey was completed by 120 surgeons from 103 centers in 24 countries. Median annual center volume of liver resection was 100 [IQR 50-140]. The median annual volume of MILS per center was 30 [IQR 16-40]. For minor resections, laparoscopic MILS was used by 80 (67%) surgeons and robotic MILS by 35 (29%) surgeons. For major resections, laparoscopic MILS was used by 74 (62%) surgeons and robotic MILS by 33 (28%) surgeons. The majority of the surgeons stated that minimum annual volume of MILS per center should be around 21-30 procedures/year. Of the surgeons performing robotic surgery, 28 (70%) felt they missed specific equipment, such as a robotic-CUSA. Seventy (66%) surgeons provided a formal MILS training to residents and fellows. In 5 years' time, 106 (88%) surgeons felt that MILS would have superior value as compared to open liver surgery.CONCLUSION: In the participating European liver centers, MILS comprised about one third of all liver resections and is expected to increase further. Laparoscopic MILS is still twice as common as robotic MILS. Development of specific instruments for robotic liver parenchymal transection might further increase its adoption.

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.

BACKGROUND: Pancreatic tumors are frequently diagnosed in a locally advanced stage with poor prognosis if untreated. This study assesses the safety and oncological outcomes of pancreatic surgery with arterial en-bloc resection.METHODS: We retrospectively reviewed a prospectively maintained database of patients who underwent a pancreatic resection with arterial resection between 2011 and 2020. Univariable analyses were used to assess prognostic factors for survival.RESULTS: Forty consecutive patients (22 female; 18 male) undergoing arterial resections were included. Surgical procedures consisted of 19 pancreatoduodenectomies (PD, 48%), 16 distal splenopancreatectomy (DSP, 40%), and 5 total pancreatectomies (TP, 12%). Arterial resection included hepatic arteries (HA, N = 23), coeliac trunk (TC, N = 15) and superior mesenteric artery (SMA, N = 2). Neoadjuvant therapy was applied in 22 patients (58%). Major complications after surgery were observed in 15% of cases. 90-day mortality was 5%. Median disease-free survival and median overall survival were for the R0/CRM- group 22.8 months and 27.9 months, 9.5 and 19.8 months for the R0/CRM+ group, and 10.1 and 13.1 months for the R1 group, respectively.CONCLUSION: In highly selected patients, arterial en-bloc resection can be performed with acceptable mortality and morbidity rates and beneficial oncological outcome.

OBJECTIVE: To evaluate whether detection of recurrent pancreatic ductal adenocarcinoma (PDAC) in an early, asymptomatic stage increases the number of patients receiving additional treatment, subsequently improving survival.SUMMARY OF BACKGROUND DATA: International guidelines disagree on the value of standardized postoperative surveillance for early detection and treatment of PDAC recurrence.METHODS: A nationwide, observational cohort study was performed including all patients who underwent PDAC resection (2014-2016). Prospective baseline and perioperative data were retrieved from the Dutch Pancreatic Cancer Audit. Data on follow-up, treatment, and survival were collected retrospectively. Overall survival (OS) was evaluated using multivariable Cox regression analysis, before and after propensity-score matching, stratified for patients with symptomatic and asymptomatic recurrence.RESULTS: Eight hundred thirty-six patients with a median follow-up of 37 months (interquartile range 30-48) were analyzed. Of those, 670 patients (80%) developed PDAC recurrence after a median follow-up of 10 months (interquartile range 5-17). Additional treatment was performed in 159/511 patients (31%) with symptomatic recurrence versus 77/159 (48%) asymptomatic patients (P < 0.001). After propensity-score matching on lymph node ratio, adjuvant therapy, disease-free survival, and recurrence site, additional treatment was independently associated with improved OS for both symptomatic patients [hazard ratio 0.53 (95% confidence interval 0.42-0.67); P < 0.001] and asymptomatic patients [hazard ratio 0.45 (95% confidence interval 0.29-0.70); P < 0.001].CONCLUSIONS: Additional treatment of PDAC recurrence was independently associated with improved OS, with asymptomatic patients having a higher probability to receive recurrence treatment. Therefore, standardized postoperative surveillance aiming to detect PDAC recurrence before the onset of symptoms has the potential to improve survival. This provides a rationale for prospective studies on standardized surveillance after PDAC resection.

Introduction: Since current studies on locally advanced pancreatic cancer (LAPC) mainly report from single, high-volume centers, it is unclear if outcomes can be translated to daily clinical practice. This study provides treatment strategies and clinical outcomes within a multicenter cohort of unselected patients with LAPC.Materials and methods: Consecutive patients with LAPC according to Dutch Pancreatic Cancer Group criteria, were prospectively included in 14 centers from April 2015 until December 2017. A centralized expert panel reviewed response according to RECIST v1.1 and potential surgical resectability. Primary outcome was median overall survival (mOS), stratified for primary treatment strategy.Results: Overall, 422 patients were included, of whom 77% (n = 326) received chemotherapy. The majority started with FOLFIRINOX (77%, 252/326) with a median of six cycles (IQR 4-10). Gemcitabine monotherapy was given to 13% (41/326) of patients and nab-paclitaxel/gemcitabine to 10% (33/326), with a median of two (IQR 3-5) and three (IQR 3-5) cycles respectively. The mOS of the entire cohort was 10 months (95%CI 9-11). In patients treated with FOLFIRINOX, gemcitabine monotherapy, or nab-paclitaxel/gemcitabine, mOS was 14 (95%CI 13-15), 9 (95%CI 8-10), and 9 months (95%CI 8-10), respectively. A resection was performed in 13% (32/252) of patients after FOLFIRINOX, resulting in a mOS of 23 months (95%CI 12-34).Conclusion: This multicenter unselected cohort of patients with LAPC resulted in a 14 month mOS and a 13% resection rate after FOLFIRINOX. These data put previous results in perspective, enable us to inform patients with more accurate survival numbers and will support decision-making in clinical practice. (C) 2020 The Authors. Published by Elsevier Ltd.

Background: The threshold to perform total pancreatectomy is rather high, predominantly because of concerns for long-term consequences of brittle diabetes on patients' quality of life. Contemporary data on postoperative outcomes, diabetes management, and long-term quality of life after total pancreatectomy from large nationwide series are, however, lacking.Methods: We performed a nationwide, retrospective cohort study among adults who underwent total pancreatectomy in 17 Dutch centers (2006-2016). Morbidity and mortality were analyzed, and long-term quality of life was assessed cross-sectionally using the following generic and disease-specific questionnaires: the 5-level version European quality of life 5-dimension and the European Organization for Research and Treatment in Cancer Quality of Life Questionnaire Cancer. Several questionnaires specifically addressing diabetic quality of life included the Problem Areas in Diabetes Scale 20, the Diabetes Treatment Satisfaction Questionnaire-status version, and the Hypoglycemia Fear Survey-II. Results were compared with the general population and patients with type 1 diabetes.Results: Overall, 148 patients after total pancreatectomy were included. The annual nationwide volume of total pancreatectomy increased from 5 in 2006 to 32 in 2015 (P < .05). The 30-day and 90-day mortality were 5% and 8%, respectively. The major complication rate was 32%. Quality of life questionnaires were completed by 60 patients (85%, median follow-up of 36 months). Participants reported lower global (73 vs 78, P = .03) and daily health status (0.83 vs 0.87, P < .01) compared to the general population. Quality of life did not differ based on time after total pancreatectomy (5 years). In general, patients were satisfied with their diabetes therapy and experienced similar diabetes-related distress as patients with type 1 diabetes.Conclusion: This nationwide study found increased use of total pancreatectomy with a relatively high 90-day mortality. Long-term quality of life was lower compared to the general population, although differences were small. Diabetes-related distress and treatment satisfaction were similar to patients with type 1 diabetes. (C) 2019 Elsevier Inc. All rights reserved.

OBJECTIVES: Large biobanks with uniform collection of biomaterials and associated clinical data are essential for translational research. The Netherlands has traditionally been well organized in multicenter clinical research on pancreatic diseases, including the nationwide multidisciplinary Dutch Pancreatic Cancer Group and Dutch Pancreatitis Study Group. To enable high-quality translational research on pancreatic and periampullary diseases, these groups established the Dutch Pancreas Biobank.METHODS: The Dutch Pancreas Biobank is part of the Parelsnoer Institute and involves all 8 Dutch university medical centers and 5 nonacademic hospitals. Adult patients undergoing pancreatic surgery (all indications) are eligible for inclusion. Preoperative blood samples, tumor tissue from resected specimens, pancreatic cyst fluid, and follow-up blood samples are collected. Clinical parameters are collected in conjunction with the mandatory Dutch Pancreatic Cancer Audit.RESULTS: Between January 2015 and May 2017, 488 patients were included in the first 5 participating centers: 4 university medical centers and 1 nonacademic hospital. Over 2500 samples were collected: 1308 preoperative blood samples, 864 tissue samples, and 366 follow-up blood samples.CONCLUSIONS: Prospective collection of biomaterials and associated clinical data has started in the Dutch Pancreas Biobank. Subsequent translational research will aim to improve treatment decisions based on disease characteristics.

Background: Future remnant liver volume is used to predict the risk for liver failure in patients who will undergo major liver resection. Formulas to estimate total liver volume based on biometric data are widely used to calculate future remnant liver volume; however, it remains unclear which formula is most accurate. This study evaluated published estimate total liver volume formulas to determine which formula best predicts the actual future remnant liver volume based on measurements in a large number of patients who underwent associating liver partition and portal vein ligation for staged hepatectomy surgery.Methods: All patients with complete liver volume data in the associating liver partition and portal vein ligation for staged hepatectomy registry were included in this study. Estimate total liver volume and estimated future remnant liver volume were calculated for 16 published formulas. The median over- or underestimation compared with actual measured volumes were determined for estimate total liver volume and future remnant liver volume. The proportion of patients with an under- or overestimated future remnant liver volume for each formula were compared with each other using a 25% cut-off for each formula.Results: Among 529 studied patients, the formulas ranged from a 19% underestimation to a 63% overestimation of estimate total liver volume. Estimation of future remnant liver volume lead to a 10% underestimation to a 5% overestimation among the formulas. Of all studied formulas, the Vautheyl formula was the most accurate, generating underestimation of future remnant liver volume in 20% and overestimation of future remnant liver volume in 6% of patients.Conclusion: Validation of 16 published total liver volume formulas in a multicenter international cohort of 529 patients that underwent staged hepatectomy revealed that the Vauthey formula (estimate total liver volume =18.51 x body weight + 191.8) provides the most accurate prediction of the actual future remnant liver volume. (C) 2019 Elsevier Inc. All rights reserved.

Background Cancer cachexia and skeletal muscle wasting are related to poor survival. In this study, quantitative body composition measurements using computed tomography (CT) were investigated in relation to survival, post-operative complications, and surgical site infections in surgical patients with cancer of the head of the pancreas. Methods A prospective cohort of 199 patients with cancer of the head of the pancreas was analysed by CT imaging at the L3 level to determine (i) muscle radiation attenuation (average Hounsfield units of total L3 skeletal muscle); (ii) visceral adipose tissue area; (iii) subcutaneous adipose tissue area; (iv) intermuscular adipose tissue area; and (v) skeletal muscle area. Sex-specific cut-offs were determined at the lower tertile for muscle radiation attenuation and skeletal muscle area and the higher tertile for adipose tissues. These variables of body composition were related to overall survival, severe post-operative complications (Dindo–Clavien ≥ 3), and surgical site infections (wounds inspected daily by an independent trial nurse) using Cox-regression analysis and multivariable logistic regression analysis, respectively. Results Low muscle radiation attenuation was associated with shorter survival in comparison with moderate and high muscle radiation attenuation [median survival 10.8 (95% CI: 8.8–12.8) vs. 17.4 (95% CI: 14.7–20.1), and 18.5 (95% CI: 9.2–27.8) months, respectively; P

Background Sarcopenia, obesity and sarcopenic obesity have been linked to impaired outcome after liver surgery. Preoperative liver function of sarcopenic, obese and sarcopenic-obese patients might be reduced, possibly leading to more post-operative morbidity. The aim of this study was to explore whether liver function and volume were influenced by body composition in patients undergoing liver resection. Methods In 2011 and 2012, all consecutive patients undergoing the methacetin breath liver function test were included. Liver volumetry and muscle mass analysis were performed using preoperative CT scans and Osirix® software. Muscle mass and body-fat% were calculated. Predefined cut-off values for sarcopenia and the top two body-fat% quintiles were used to identify sarcopenia and obesity, respectively. Histologic assessment of the resected liver gave insight in background liver disease. Results A total number of 80 patients were included. Liver function and volume were comparable in sarcopenic(-obese) and non-sarcopenic(-obese) patients. Obese patients showed significantly reduced liver function [295 (95–508) vs. 358 (96–684) µg/kg/h, P = 0.018] and a trend towards larger liver size [1694 (1116–2685) vs. 1533 (869–2852) mL, P = 0.079] compared with non-obese patients. Weight (r = −0.40), body surface area (r = −0.32), estimated body-fat% (r = −0.43) and body mass index (r = −0.47) showed a weak but significant negative (all P

Despite the established advantages of laparoscopy, bleeding control during laparoscopic liver resection (LLR) is a liver-specific improvement. The 2nd International Consensus Conference on Laparoscopic Liver Resection was held in October 2014 at Morioka, Japan. One of the most capital questions was: What is essential in bleeding control during LLR? In order to correctly address this question, we conducted a comprehensive review of the literature. Essential points based on personal experience of the expert panel are also discussed. A total of 54 publications were identified. Based on this analysis, the working group built these recommendations: (1) a pneumoperitoneum of 10-14 mmHg should be used as it allows a good control of the bleeding without significant modifications of hemodynamics; (2) a low central venous pressure (

BACKGROUND: An enhanced recovery after surgery (ERAS) program aims to reduce the stress response to surgery and thereby accelerate recovery. It is unclear whether these programs can be safely implemented for elderly patients, especially in highly complex surgery such as pancreaticoduodenectomy (PD). The objective of this study was to evaluate the feasibility of an ERAS program in elderly patients undergoing PD. METHODS: Implementation of the ERAS protocol was studied prospectively in a consecutive series of patients undergoing PD between January 2009 and August 2013. Patients were divided into two groups: /= 70 years. Endpoints were length of stay (LOS), readmissions, morbidity, mortality, and compliance with ERAS targets. RESULTS: Of a total of 110 patients, 55 were /= 70 years (median 77). Median LOS was 14 days in both groups. In patients without complications median LOS was 9 days. Both mortality and readmissions did not differ between groups (mortality n = 3 (5.5 %) in younger versus n = 6 (10.9 %) in older patients, p = 0.49, readmissions: n = 11 (20 %) versus n = 7 (12.7 %), p = 0.44). CT-drainage and relaparotomy-rates were not different between groups, nor was overall morbidity (n = 31 (56.3 %) in the older versus n = 35 (63.3 %) in the younger group, p = 0.44). There were no differences in compliance with elements of the ERAS protocol between groups. CONCLUSION: An ERAS program seems feasible and safe for patients >/= 70 years of age undergoing PD.

BACKGROUND: An increasing number of patients undergo major liver resection following preoperative chemotherapy. Liver regeneration may be impaired in these patients, predisposing them to postoperative liver dysfunction. The aim of the present study was to evaluate the effects of preoperative chemotherapy on liver regeneration after partial liver resection. METHODS: Patients planned to receive right hepatectomy either with (group B) or without (group A) prior chemotherapy were identified retrospectively from a prospective multi-institutional database created in the conduct of a national randomized controlled trial (RCT). Prior chemotherapy was neither an inclusion nor an exclusion criterion of the trial. Future remnant liver volume (FRLV) was calculated by measuring total functional liver volume and resection specimen on preoperative computed tomography (CT) scans. Remnant liver volume after 7 days (V RLV7days) was measured on scheduled postoperative CT scans. The early regeneration index 7 days after surgery (RI early) was calculated as [(V RLV7days - FRLV) / FRLV] x 100 %. Data are expressed as median (interquartile range). RESULTS: A total of 72 patients were enrolled: 45 in group A and 27 in group B. For the whole group, the liver remnant showed a 58 % (39 %) increase in volume at day 7 (1) day. The RI early was not significantly different between groups A and B, 60 % (36 %) and 50 % (43 %), respectively (p = 0.47). The RI early was significantly lower in patients who had undergone more than six cycles of chemotherapy. CONCLUSIONS: Preoperative chemotherapy does not seem to have a negative impact on early liver regeneration after partial liver resection.

Objectives Enhanced recovery after surgery (ERAS) or fast‐track protocols have been implemented in different fields of surgery to attenuate the surgical stress response and accelerate recovery. The objective of this study was to systematically review the literature on outcomes of ERAS protocols applied in liver surgery. Methods The MEDLINE, EMBASE, PubMed and Cochrane Library databases were searched for randomized controlled trials (RCTs), case–control studies and case series published between January 1966 and October 2011 comparing adult patients undergoing elective liver surgery in an ERAS programme with those treated in a conventional manner. The primary outcome measure was hospital length of stay (LoS). Secondary outcome measures were time to functional recovery, and complication, readmission and mortality rates. Results A total of 307 articles were found, six of which were included in the review. These comprised two RCTs, three case–control studies and one retrospective case series. Median LoS ranged from 4 days in an ERAS group to 11 days in a control group. Morbidity, mortality and readmission rates did not differ significantly between the groups. Only two studies assessed time to functional recovery. Functional recovery in these studies was reached 2 days before discharge. conclusions This systematic review suggests that ERAS protocols can be successfully implemented in liver surgery. Length of stay is reduced without compromising morbidity, mortality or readmission rates.

IMPORTANCE Postoperative pancreatic fistula is a potentially life-threatening complication after pancreatoduodenectomy. Evidence for best management is lacking.OBJECTIVE To evaluate the clinical outcome of patients undergoing catheter drainage compared with relaparotomy as primary treatment for pancreatic fistula after pancreatoduodenectomy.DESIGN, SETTING, AND PARTICIPANTS A multicenter, retrospective, propensity-matched cohort study was conducted in 9 centers of the Dutch Pancreatic Cancer Group from January 1, 2005, to September 30, 2013. From a cohort of 2196 consecutive patients who underwent pancreatoduodenectomy, 309 patients with severe pancreatic fistula were included. Propensity score matching (based on sex, age, comorbidity, disease severity, and previous reinterventions) was used to minimize selection bias. Data analysis was performed from January to July 2016.EXPOSURES First intervention for pancreatic fistula: catheter drainage or relaparotomy.MAIN OUTCOMES AND MEASURES Primary end point was in-hospital mortality; secondary end points included new-onset organ failure.RESULTS Of the 309 patients included in the analysis, 209 (67.6%) were men, and mean (SD) age was 64.6 (10.1) years. Overall in-hospital mortality was 17.8%(55 patients): 227 patients (73.5%) underwent primary catheter drainage and 82 patients (26.5%) underwent primary relaparotomy. Primary catheter drainage was successful (ie, survival without relaparotomy) in 175 patients (77.1%). With propensity score matching, 64 patients undergoing primary relaparotomy were matched to 64 patients undergoing primary catheter drainage. Mortality was lower after catheter drainage (14.1% vs 35.9%; P = .007; risk ratio, 0.39; 95% CI, 0.20-0.76). The rate of new-onset single-organ failure (4.7% vs 20.3%; P = .007; risk ratio, 0.15; 95% CI, 0.03-0.60) and new-onset multiple-organ failure (15.6% vs 39.1%; P = .008; risk ratio, 0.40; 95% CI, 0.20-0.77) were also lower after primary catheter drainage.CONCLUSIONS AND RELEVANCE In this propensity-matched cohort, catheter drainage as first intervention for severe pancreatic fistula after pancreatoduodenectomy was associated with a better clinical outcome, including lower mortality, compared with primary relaparotomy.

Contains fulltext : 117870.pdf (Publisher’s version ) (Closed access) BACKGROUND: To warrant the adoption or rejection of health care interventions in daily practice, it is important to establish the point at which the available evidence is considered sufficiently conclusive. This process must avoid bias resulting from multiple testing and take account of heterogeneity across studies. The present paper addresses the issue of whether the available evidence may be considered sufficiently conclusive to continue or discontinue the current practice of postoperative abdominal drainage after pancreatic resection. METHODS: A systematic review was conducted of randomized and non-randomized studies comparing outcomes after routine intra-abdominal drainage with those after no drainage after pancreatic resection. Studies were retrieved from the PubMed, Cochrane Central Trial Register and EMBASE databases and meta-analysed cumulatively, adjusting for multiple testing and heterogeneity using the iterated logarithm method. RESULTS: Three reports, describing, respectively, one randomized and two non-randomized studies with a comparative design, met the inclusion criteria predefined for primary studies reporting on drain management and complications after pancreatic resection. These studies included 89, 179 and 226 patients, respectively. The absolute differences in rates of postoperative complications in these studies were -6.4%, -9.5% and -6.3%, respectively, in favour of the no-drain groups. The cumulative risk difference in major complications, adjusted for multiple testing and heterogeneity, was -7.8%, with a 95% confidence interval of -20.2% to 4.7% (P = 0.214). CONCLUSIONS: The routine use of abdominal drains after pancreatic resection may result in a higher risk for major complications, but the evidence is inconclusive.

Item does not contain fulltext OBJECTIVE: To study the feasibility and impact of a nationwide training program in minimally invasive distal pancreatectomy (MIDP). SUMMARY OF BACKGROUND DATA: Superior outcomes of MIDP compared with open distal pancreatectomy have been reported. In the Netherlands (2005 to 2013) only 10% of distal pancreatectomies were in a minimally invasive fashion and 85% of surgeons welcomed MIDP training. The feasibility and impact of a nationwide training program is unknown. METHODS: From 2014 to 2015, 32 pancreatic surgeons from 17 centers participated in a nationwide training program in MIDP, including detailed technique description, video training, and proctoring on-site. Outcomes of MIDP before training (2005-2013) were compared with outcomes after training (2014-2015). RESULTS: In total, 201 patients were included; 71 underwent MIDP in 9 years before training versus 130 in 22 months after training (7-fold increase, P < 0.001). The conversion rate (38% [n = 27] vs 8% [n = 11], P < 0.001) and blood loss were lower after training and more pancreatic adenocarcinomas were resected (7 [10%] vs 28 [22%], P = 0.03), with comparable R0-resection rates (4/7 [57%] vs 19/28 [68%], P = 0.67). Clavien-Dindo score >/=III complications (15 [21%] vs 19 [15%], P = 0.24) and pancreatic fistulas (20 [28%] vs 41 [32%], P = 0.62) were not significantly different. Length of hospital stay was shorter after training (9 [7-12] vs 7 [5-8] days, P < 0.001). Thirty-day mortality was 3% vs 0% (P = 0.12). CONCLUSION: A nationwide MIDP training program was feasible and followed by a steep increase in the use of MIDP, also in patients with pancreatic cancer, and decreased conversion rates. Future studies should determine whether such a training program is applicable in other settings.

Background Cancer cachexia and skeletal muscle wasting are related to poor survival. In this study, quantitative body composition measurements using computed tomography (CT) were investigated in relation to survival, post‐operative complications, and surgical site infections in surgical patients with cancer of the head of the pancreas. Methods A prospective cohort of 199 patients with cancer of the head of the pancreas was analysed by CT imaging at the L3 level to determine (i) muscle radiation attenuation (average Hounsfield units of total L3 skeletal muscle); (ii) visceral adipose tissue area; (iii) subcutaneous adipose tissue area; (iv) intermuscular adipose tissue area; and (v) skeletal muscle area. Sex‐specific cut‐offs were determined at the lower tertile for muscle radiation attenuation and skeletal muscle area and the higher tertile for adipose tissues. These variables of body composition were related to overall survival, severe post‐operative complications (Dindo–Clavien ≥ 3), and surgical site infections (wounds inspected daily by an independent trial nurse) using Cox‐regression analysis and multivariable logistic regression analysis, respectively. Results Low muscle radiation attenuation was associated with shorter survival in comparison with moderate and high muscle radiation attenuation [median survival 10.8 (95% CI: 8.8–12.8) vs. 17.4 (95% CI: 14.7–20.1), and 18.5 (95% CI: 9.2–27.8) months, respectively; P

Studies on the impact of comorbidity and age on postoperative outcome after gastrointestinal tumor resection are scarce. In this study we investigated the impact of comorbidity and age on 30-, 60-, and 90-day mortality after resection of esophageal, gastric, periampullary, colon, and rectal cancer.The study included 8,583 patients recorded in the population-based Netherlands Cancer Registry, regions Eindhoven (Eindhoven Cancer Registry) and Mid and South Limburg, who underwent resection for cancer stage I-III. Patients were diagnosed between 2005 and 2010. Age was categorized as65, 65-74, and ≥75 years.Comorbidity was present in more than two-thirds (n = 5,910) of patients. The 30-day mortality rates ranged from 0.5 % for rectal cancer patients65 years to 12.8 % for gastric cancer patients ≥75 years. Patients with comorbidity who underwent esophageal tumor resection had the highest mortality rates, ranging from 8.4 % for 30-day to 12.0 % for 90-day mortality, while rectal cancer patients had the lowest rates, that is, 4.3-6.4 %, respectively. In multivariable analyses, cardiac disease (odds ratio [OR] = 1.74, 95 % confidence interval [95 % CI] = 1.32-2.30), vascular disease (OR = 1.41, 95 % CI = 1.02-1.95) and previous malignancies (OR = 1.38, 95 % CI = 1.02-1.86) in colon cancer, and cardiac disease (OR = 1.81, 95 % CI = 1.10-2.98) and vascular disease (OR = 1.95, 95 % CI = 1.11-3.42) in rectal cancer were associated with the highest 30-day mortality.Postoperative mortality extends beyond 30 days. Comorbidity and older age are associated with early postoperative mortality after gastrointestinal cancer resection. Underlying comorbidity should be identified preoperatively with attention to patients' specific needs to optimally attenuate risk prior to surgery. A less aggressive treatment approach may well be considered in these groups.

To ensure a sufficient barrier between a host and noxious luminal content, the intestinal epithelium must be equipped with efficient mechanisms to limit damage to the epithelial lining. Using a human model, we were able to investigate these mechanisms in the human gut exposed to ischaemia-reperfusion (IR) over the time course of 150 min. In 10 patients a part of jejunum, to be removed for surgical reasons, was selectively exposed to IR. Control tissue was collected, as well as tissue exposed to 30 min of ischaemia with 0, 30 or 120 min of reperfusion. Haematoxylin/eosin staining demonstrated the appearance of subepithelial spaces following 30 min of ischaemia, while the epithelial lining remained intact at this stage. Western blot for myosin light chain kinase (MLCK) revealed a significant increase in protein levels after ischaemia (p < 0.01), and selective staining of MLCK and phosphorylated MLC (pMLC) in lamina propria muscle fibres indicated that appearance of subepithelial spaces was a consequence of active villus contraction. Early during reperfusion, accumulation of pMLC was observed exclusively at the basal side of enterocytes that had lost contact with the collagen-IV-positive basement membrane. These epithelial sheets were pulled together like a zipper, even before these cells were shed. This constriction, verified by increased F-actin and pMLC double staining, accounted for a 45% reduction in virtual wound surface (p < 0.001) at 30 min of reperfusion. In addition, these mechanisms were involved in resealing remaining small epithelial defects, resulting in a fully restored epithelial lining within 120 min of reperfusion. In conclusion, we show in a human in vivo model that the human jejunum has the ability to preserve the epithelial lining during intestinal IR by rapid lamina propria contraction and zipper-like constriction of epithelial cells that are to be shed into the lumen. These newly described phenomena limit exposure to noxious luminal content. Copyright (c) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Human intestinal ischemia-reperfusion (IR) is a frequent phenomenon carrying high morbidity and mortality. Although intestinal IR-induced inflammation has been studied extensively in animal models, human intestinal IR induced inflammatory responses remain to be characterized. Using a newly developed human intestinal IR model, we show that human small intestinal ischemia results in massive leakage of intracellular components from ischemically damaged cells, as indicated by increased arteriovenous concentration differences of intestinal fatty acid binding protein and soluble cytokeratin 18. IR-induced intestinal barrier integrity loss resulted in free exposure of the gut basal membrane (collagen IV staining) to intraluminal contents, which was accompanied by increased arteriovenous concentration differences of endotoxin. Western blot for complement activation product C3c and immunohistochemistry for activated C3 revealed complement activation after IR. In addition, intestinal IR resulted in enhanced tissue mRNA expression of IL-6, IL-8, and TNF-alpha, which was accompanied by IL-6 and IL-8 release into the circulation. Expression of intercellular adhesion molecule-1 was markedly increased during reperfusion, facilitating influx of neutrophils into IR-damaged villus tips. In conclusion, this study for the first time shows the sequelae of human intestinal IR-induced inflammation, which is characterized by complement activation, production and release of cytokines into the circulation, endothelial activation, and neutrophil influx into IR-damaged tissue.

Bile duct injury in patients undergoing laparoscopic cholecystectomy is a rare but serious complication. Concomitant vascular injury worsens the outcome of bile duct injury repair. Near-infrared fluorescence imaging using indocyanine green (ICG) is a promising, innovative, and noninvasive method for the intraoperative identification of biliary and vascular anatomy during cholecystectomy. The results from our clinical feasibility study illustrate that biliary and vascular fluorescence imaging in laparoscopic cholecystectomy, using the D-Light P System (Tricam SLII; Karl Storz Endoscopes) and preoperative administration of ICG, is easily applicable in clinical practice, can be helpful for earlier visualization of the biliary tree and is useful for the confirmation of the arterial anatomy.

Few randomized controlled trials (RCTs) have been performed in patients undergoing pancreaticoduodenectomy (PD). An important factor contributing to this is the large number of patients needed to adequately power RCTs for relevant clinical single endpoints. A PD-specific composite endpoint (CEP) could solve this problem. The aim of the present study was to develop a PD-specific CEP, consisting of complications related to PD, allowing reduction in sample sizes and improving the ability to compare outcomes. PD-specific CEP components were selected after a systematic review of the literature and consensus between 25 international pancreatic surgeons. Ultimately, prospective cohorts of patients who underwent PD in two high-volume HPB centers (London, UK, and Maastricht, NL) were used to assess the event rate and effect of implementing a PD-specific CEP. From a total of 18 single-component endpoints, intra-abdominal abscess, sepsis, post-PD hemorrhage, bile leakage, gastrojejunostomy leakage, leakage of the pancreatic anastomosis, delayed gastric emptying, and operative mortality within 90 days were selected to be included the PD-specific CEP. All eight components had consensus definitions and a Dindo–Clavien classification of 3 or more. The incidence of the PD-specific CEP was 24.7 % in the Maastricht cohort and 23.3 % in the London cohort. These incidence rates led to a twofold reduction in the theoretical calculated sample size for an adequately powered RCT on PD using this CEP as a primary endpoint. The proposed PD-specific CEP enables clinical investigators to adequately power RCTs on PD and increases the feasibility, comparability, and utility in meta-analysis.

Laparoscopic hepatectomies have seen a worldwide proliferation. Major anatomic resections, which were initially considered unsuitable for laparoscopy, are currently confined to a few centers of expertise. The aim of this study was to discuss the current trends and techniques in laparoscopic major hepatectomy in Europe.The prospective databases of ten European centers were combined to provide answers to a questionnaire that had been addressed to all European teams known to perform laparoscopic liver surgery.Between 1996 and 2011 a total of 2245 laparoscopic liver resections have been carried out, of which 495 (22 %) were major resections. The proportion of laparoscopic right and left hepatectomies varied between 4 and 40 % of all major hepatectomies of the same type. Benign, primary malignant and metastatic lesions were, respectively, 22.4, 19.6 and 58 % of all indications. The different techniques and approaches, as regards hand assistance, hepatic inflow and outflow control, liver mobilization and concomitant colectomies, are discussed.To date, an important level of experience of laparoscopic liver resection has been accumulated in Europe, and experience of major hepatectomies is constantly increasing. However, they remain technically very demanding procedures which should be confined to expert surgeons who have already acquired considerable experience with simpler laparoscopic liver resections.

Objectives: Sarcopenia may negatively affect short-term outcomes after liver resection. The present study aimed to explore whether total functional liver volume (TFLV) is related to sarcopenia in patients undergoing partial liver resection. Methods: Analysis of total liver volume and tumour volume and measurements of muscle surface were performed in patients undergoing liver resection using OsiriX((R)) and preoperative computed tomography. The ratio of TFLV to bodyweight was calculated as: [TFLV (ml)/bodyweight (g)]*100%. The L3 muscle index (cm(2)/m(2)) was then calculated by normalizing muscle areas (at the third lumbar vertebral level) for height. Results: Of 40 patients, 27 (67.5%) were classified as sarcopenic. There was a significant correlation between the L3 skeletal muscle index and TFLV (r= 0.64, P < 0.001). Median TFLV was significantly lower in the sarcopenia group than in the non-sarcopenia group [1396 ml (range: 1129-2625 ml) and 1840 ml (range: 867-2404 ml), respectively; P < 0.05]. Median TFLV : bodyweight ratio was significantly lower in the sarcopenia group than in the non-sarcopenia group [2.0% (range: 1.4-2.5%) and 2.3% (range: 1.5-2.5%), respectively; P < 0.05]. Conclusions: Sarcopenic patients had a disproportionally small preoperative TFLV compared with non-sarcopenic patients undergoing liver resection. The preoperative hepatic physiologic reserve may therefore be smaller in sarcopenic patients.

To ensure a sufficient barrier between a host and noxious luminal content, the intestinal epithelium must be equipped with efficient mechanisms to limit damage to the epithelial lining. Using a human model, we were able to investigate these mechanisms in the human gut exposed to ischaemia-reperfusion (IR) over the time course of 150 min. In 10 patients a part of jejunum, to be removed for surgical reasons, was selectively exposed to IR. Control tissue was collected, as well as tissue exposed to 30 min of ischaemia with 0, 30 or 120 min of reperfusion. Haematoxylin/eosin staining demonstrated the appearance of subepithelial spaces following 30 min of ischaemia, while the epithelial lining remained intact at this stage. Western blot for myosin light chain kinase (MLCK) revealed a significant increase in protein levels after ischaemia (p0.01), and selective staining of MLCK and phosphorylated MLC (pMLC) in lamina propria muscle fibres indicated that appearance of subepithelial spaces was a consequence of active villus contraction. Early during reperfusion, accumulation of pMLC was observed exclusively at the basal side of enterocytes that had lost contact with the collagen-IV-positive basement membrane. These epithelial sheets were pulled together like a zipper, even before these cells were shed. This constriction, verified by increased F-actin and pMLC double staining, accounted for a 45% reduction in virtual wound surface (p0.001) at 30 min of reperfusion. In addition, these mechanisms were involved in resealing remaining small epithelial defects, resulting in a fully restored epithelial lining within 120 min of reperfusion. In conclusion, we show in a human in vivo model that the human jejunum has the ability to preserve the epithelial lining during intestinal IR by rapid lamina propria contraction and zipper-like constriction of epithelial cells that are to be shed into the lumen. These newly described phenomena limit exposure to noxious luminal content.

Human intestinal ischemia-reperfusion (IR) is a frequent phenomenon carrying high morbidity and mortality. Although intestinal IR-induced inflammation has been studied extensively in animal models, human intestinal IR induced inflammatory responses remain to be characterized. Using a newly developed human intestinal IR model, we show that human small intestinal ischemia results in massive leakage of intracellular components from ischemically damaged cells, as indicated by increased arteriovenous concentration differences of intestinal fatty acid binding protein and soluble cytokeratin 18. IR-induced intestinal barrier integrity loss resulted in free exposure of the gut basal membrane (collagen IV staining) to intraluminal contents, which was accompanied by increased arteriovenous concentration differences of endotoxin. Western blot for complement activation product C3c and immunohistochemistry for activated C3 revealed complement activation after IR. In addition, intestinal IR resulted in enhanced tissue mRNA expression of IL-6, IL-8, and TNF-alpha, which was accompanied by IL-6 and IL-8 release into the circulation. Expression of intercellular adhesion molecule-1 was markedly increased during reperfusion, facilitating influx of neutrophils into IR-damaged villus tips. In conclusion, this study for the first time shows the sequelae of human intestinal IR-induced inflammation, which is characterized by complement activation, production and release of cytokines into the circulation, endothelial activation, and neutrophil influx into IR-damaged tissue.

Background This report describes a human in vivo ischemia reperfusion (IR) model of the small intestine. Animal models of intestinal IR are indispensable for our understanding of sequelae of IR induced organ damage. However, a functional experimental IR model of the human small intestine, allowing for translational research, can be considered critical for our pathophysiologic understanding of intestinal IR in man. Materials and Methods Patients with a healthy gut undergoing abdominal surgery with a Roux-Y or similar reconstruction were included, creating the opportunity to study IR of an isolated jejunal segment in a harmless model. Results Ischemia was induced by nontraumatic vascular clamping followed by reperfusion. This model can be adapted using variable ischemia and reperfusion times. Similarly, tissue and plasma can be collected at any given time point during ischemia until end of reperfusion, only determined by progress of the original, intended surgical procedure. Conclusion A unique and harmless human IR model of the jejunum was created, which enables the study of acute damage to the epithelial lining and its subsequent repair mechanisms.

interacts with the E-cadherin mRNA and regulates its expression posttranscriptionally, thus implicating in control of the epithelial barrier function. Methods: Caco-2 cells were used in these studies. The binding of HuR with E-Cadherin mRNA was examined by biotin pulldown assays and ribonucleoprotein/IP analysis. E-cadherin mRNA stability was examined by measuring its half-life with real-time PCR analysis, and its translation was examined by chimeric luciferaseE-cadherin 3'UTR reporter assays. HuR function was investigated by its gene silencing and overexpression. Barrier function was detected by paracellular tracer flux assay and trans epithelial electric resistant. Results: HuR bound to the E-cadherin mRNA by directly interacting with the E-cadherin 3'UTR rather than its 5'UTR and coding region. Ectopic overexpression of HuR by transient transfection increased [HuR/ E-cadherin mRNA] complex, enhanced E-cadherin translation (by~3 times), and up-regulated its protein level (by~3 times), but it failed to alter E-cadherin mRNA stability and total E-cadherin mRNA level. In contrast, silencing HuR decreased HuR/ E-cadherin mRNA association, inhibited E-cadherin translation, and down-regulated its protein abundance without affecting the stability and level of E-cadherin mRNA. Ectopic overexpression of HuR also promoted the epithelial barrier function as indicated by a decrease in paracellular permeability. Decreased E-cadherin translation by silencing HuR disrupted the barrier function and increased paracellular permeability. Conclusions: These results indicate: 1) E-cadherin mRNA is a target of HuR; 2) increased HuR/ E-cadherin mRNA association enhances E-cadherin mRNA translation; and 3) HuR plays an important role in the regulation of intestinal epithelial barrier function.

BACKGROUND & AIMS: In the intestine, Paneth cells participate in the innate immune response. Their highly secretory function makes them susceptible to environmental conditions that cause endoplasmic reticulum (ER) stress. We investigated whether intestinal ischemia/reperfusion (I/R) induces ER stress, thereby activating the unfolded protein response (UPR), and whether excessive UPR activation affects Paneth cells. In addition, we investigated the consequences of Paneth cell compromise during physical barrier damage. METHODS: Jejunal I/R was studied using a human experimental model (n = 30 patients). Activation of the UPR was assessed using immunofluorescence for binding protein and quantitative polymerase chain reaction analyses for C/EBP homologous protein (CHOP), growth arrest and DNA-damage inducible protein 34 (GADD34), and X-box binding protein 1 (XBP1) splicing. Paneth cell apoptosis was assessed by double staining for lysozyme and M30. Male Sprague-Dawley rats underwent either intestinal I/R to investigate UPR activation and Paneth cell apoptosis, or hemorrhagic shock with or without intraperitoneal administration of dithizone, to study consequences of Paneth cell compromise during physical intestinal damage. In these animals, bacterial translocation and circulating tumor necrosis factor-alpha and interleukin-6 levels were assessed. RESULTS: In jejunum samples from humans and rats, I/R activated the UPR and resulted in Paneth cell apoptosis. Apoptotic Paneth cells showed signs of ER stress, and Paneth cell apoptosis correlated with the extent of ER stress. Apoptotic Paneth cells were shed into the crypt lumen, significantly lowering their numbers. In rats, Paneth cell compromise increased bacterial translocation and inflammation during physical intestinal damage. CONCLUSIONS: ER stress-induced Paneth cell apoptosis contributes to intestinal I/R-induced bacterial translocation and systemic inflammation.