Objective: To develop 2 distinct preoperative and intraoperative risk scores to predict postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) to improve preventive and mitigation... Show moreObjective: To develop 2 distinct preoperative and intraoperative risk scores to predict postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) to improve preventive and mitigation strategies, respectively.Background: POPF remains the most common complication after DP. Despite several known risk factors, an adequate risk model has not been developed yet.Methods: Two prediction risk scores were designed using data of patients undergoing DP in 2 Italian centers (2014-2016) utilizing multivariable logistic regression. The preoperative score (calculated before surgery) aims to facilitate preventive strategies and the intraoperative score (calculated at the end of surgery) aims to facilitate mitigation strategies. Internal validation was achieved using bootstrapping. These data were pooled with data from 5 centers from the United States and the Netherlands (2007-2016) to assess discrimination and calibration in an internal-external validation procedure.Results: Overall, 1336 patients after DP were included, of whom 291 (22%) developed POPF. The preoperative distal fistula risk score (preoperative D-FRS) included 2 variables: pancreatic neck thickness [odds ratio: 1.14; 95% confidence interval (CI): 1.11-1.17 per mm increase] and pancreatic duct diameter (OR: 1.46; 95% CI: 1.32-1.65 per mm increase). The model performed well with an area under the receiver operating characteristic curve of 0.83 (95% CI: 0.78-0.88) and 0.73 (95% CI: 0.70-0.76) upon internal-external validation. Three risk groups were identified: low risk (<10%), intermediate risk (10%-25%), and high risk (>25%) for POPF with 238 (18%), 684 (51%), and 414 (31%) patients, respectively. The intraoperative risk score (intraoperative D-FRS) added body mass index, pancreatic texture, and operative time as variables with an area under the receiver operating characteristic curve of 0.80 (95% CI: 0.74-0.85).Conclusions: The preoperative and the intraoperative D-FRS are the first validated risk scores for POPF after DP and are readily available at: . The 3 distinct risk groups allow for personalized treatment and benchmarking. Show less
Objectives: To investigate the effect of preoperative chemoradiotherapy on surgical complications in patients after pancreatic resection for (borderline-)resectable pancreatic cancer. Summary of... Show moreObjectives: To investigate the effect of preoperative chemoradiotherapy on surgical complications in patients after pancreatic resection for (borderline-)resectable pancreatic cancer. Summary of Background Data: Preoperative chemoradiotherapy is increasingly used in patients with (borderline-)resectable pancreatic cancer. concerns have been raised about the potential harmful effect of any preoperative therapy on the surgical complication rate after pancreatic resection. Methods: An observational analysis was performed within the multicenter randomized controlled PREOPANC trial (April 2013-July 2017). The trial randomly assigned (1:1) patients to preoperative chemoradiotherapy followed by surgery and the remaining adjuvant chemotherapy or to immediate surgery, followed by adjuvant chemotherapy. The main analysis consisted of a per-protocol approach. The endpoints of the present analyses were the rate of postoperative complications. Results: This study included 246 patients from 16 centers, of whom 66 patients underwent resection after preoperative therapy and 98 patients after immediate surgery. No differences were found regarding major complications (37.9% vs 30.6%, P=0.400), postpancreatectomy hemorrhage (9.1% vs 5.1%, P=0.352), delayed gastric emptying (21.2% vs 22.4%, P=0.930), bile leakage (4.5% vs 3.1%, P=0.686), intra-abdominal infections (12.1% vs 10.2%, P=0.800), and mortality (3.0% vs 4.1%, P=1.000). There was a significant lower incidence of postoperative pancreatic fistula in patients who received preoperative chemoradiotherapy (0% vs 9.2%, P=0.011). Conclusions: Preoperative chemoradiotherapy did not increase the incidence of surgical complications or mortality and reduced the rate of postoperative pancreatic fistula after resection in patients with (borderline-)resectable pancreatic cancer. Show less
Objective: To quantify the impact of individual complications on mortality, organ failure, hospital stay, and readmission after pancreatoduodenectomy. Summary of Background Data: An initial... Show moreObjective: 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. Show less
The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110... Show moreThe First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: . Show less
Mungroop, T.H.; Klompmaker, S.; Wellner, U.F.; Steyerberg, E.W.; Coratti, A.; D'Hondt, M.; ... ; European Consortium Minimally Inva 2021
Objective: The aim of the study was to validate and optimize the alternative Fistula Risk Score (a-FRS) for patients undergoing minimally invasive pancreatoduodenectomy (MIPD) in a large pan... Show moreObjective: The aim of the study was to validate and optimize the alternative Fistula Risk Score (a-FRS) for patients undergoing minimally invasive pancreatoduodenectomy (MIPD) in a large pan-European cohort.Background: MIPD may be associated with an increased risk of postoperative pancreatic fistula (POPF). The a-FRS could allow for risk-adjusted comparisons in research and improve preventive strategies for high-risk patients. The a-FRS, however, has not yet been validated specifically for laparoscopic, robot-assisted, and hybrid MIPD.Methods: A validation study was performed in a pan-European cohort of 952 consecutive patients undergoing MIPD (543 laparoscopic, 258 robot-assisted, 151 hybrid) in 26 centers from 7 countries between 2007 and 2017. The primary outcome was POPF (International Study Group on Pancreatic Surgery grade B/C). Model performance was assessed using the area under the receiver operating curve (AUC; discrimination) and calibration plots. Validation included univariable screening for clinical variables that could improve performance.Results: Overall, 202 of 952 patients (21%) developed POPF after MIPD. Before adjustment, the original a-FRS performed moderately (AUC 0.68) and calibration was inadequate with systematic underestimation of the POPF risk. Single-row pancreatojejunostomy (odds ratio 4.6, 95 confidence interval [CI] 2.8-7.6) and male sex (odds ratio 1.9, 95 CI 1.4-2.7) were identified as important risk factors for POPF in MIPD. The updated a-FRS, consisting of body mass index, pancreatic texture, duct size, and male sex, showed good discrimination (AUC 0.75, 95 CI 0.71-0.79) and adequate calibration. Performance was adequate for laparoscopic, robot-assisted, and hybrid MIPD and open pancreatoduodenectomy.Conclusions: The updated a-FRS (www.pancreascalculator.com) now includes male sex as a risk factor and is validated for both MIPD and open pancreatoduodenectomy. The increased risk of POPF in laparoscopic MIPD was associated with single-row pancreatojejunostomy, which should therefore be discouraged. Show less
Macroencapsulation of islets of Langerhans is a promising strategy for transplantation of insulin-producing cells in the absence of immunosuppression to treat type 1 diabetes. Hollow fiber... Show moreMacroencapsulation of islets of Langerhans is a promising strategy for transplantation of insulin-producing cells in the absence of immunosuppression to treat type 1 diabetes. Hollow fiber membranes are of interest there because they offer a large surface-to-volume ratio and can potentially be retrieved or refilled. However, current available fibers have limitations in exchange of nutrients, oxygen, and delivery of insulin potentially impacting graft survival. Here, multibore hollow fibers for islets encapsulation are designed and tested. They consist of seven bores and are prepared using nondegradable polymers with high mechanical stability and low cell adhesion properties. Human islets encapsulated there have a glucose induced insulin response (GIIS) similar to nonencapsulated islets. During 7 d of cell culture in vitro, the GIIS increases with graded doses of islets demonstrating the suitability of the microenvironment for islet survival. Moreover, first implantation studies in mice demonstrate device material biocompatibility with minimal tissue responses. Besides, formation of new blood vessels close to the implanted device is observed, an important requirement for maintaining islet viability and fast exchange of glucose and insulin. The results indicate that the developed fibers have high islet bearing capacity and can potentially be applied for a clinically applicable bioartificial pancreas. Show less
Groeneweg, K.E.; Au, Y.W.; Duijs, J.M.G.J.; Florijn, B.W.; Kooten, C. van; Fijter, J.W. de; ... ; Bijkerk, R. 2020
Simultaneous pancreas-kidney transplantation (SPKT) replaces kidney function and restores endogenous insulin secretion in patients with diabetic nephropathy (DN). Here, we aimed to identify... Show moreSimultaneous pancreas-kidney transplantation (SPKT) replaces kidney function and restores endogenous insulin secretion in patients with diabetic nephropathy (DN). Here, we aimed to identify circulating long noncoding RNAs (lncRNAs) that are associated with DN and vascular injury in the context of SPKT. Based on a pilot study and a literature-based selection of vascular injury-related lncRNAs, we assessed 9 candidate lncRNAs in plasma samples of patients with diabetes mellitus with a kidney function >35 mL/min/1.73 m(2) (DM; n = 12), DN (n = 14), SPKT (n = 35), healthy controls (n = 15), and renal transplant recipients (KTx; n = 13). DN patients were also studied longitudinally before and 1, 6, and 12 months after SPKT. Of 9 selected lncRNAs, we found MALAT1, LIPCAR, and LNC-EPHA6 to be higher in DN compared with healthy controls. SPKT caused MALAT1, LIPCAR, and LNC-EPHA6 to normalize to levels of healthy controls, which was confirmed in the longitudinal study. In addition, we observed a strong association between MALAT1, LNC-EPHA6, and LIPCAR and vascular injury marker soluble thrombomodulin and a subset of angiogenic microRNAs (miR-27a, miR-130b, miR-152, and miR-340). We conclude that specific circulating lncRNAs associate with DN-related vascular injury and normalize after SPKT, suggesting that lncRNAs may provide a promising novel monitoring strategy for vascular integrity in the context of SPKT. Show less
Klompmaker, S.; Hilst, J. van; Wellner, U.F.; Busch, O.R.; Coratti, A.; D'Hondt, M.; ... ; European Consortium Minimally Inva 2020
Objective: To assess short-term outcomes after minimally invasive (laparoscopic, robot-assisted, and hybrid) pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy (OPD) among European... Show moreObjective: To assess short-term outcomes after minimally invasive (laparoscopic, robot-assisted, and hybrid) pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy (OPD) among European centers. Background: Current evidence on MIPD is based on national registries or single expert centers. International, matched studies comparing outcomes for MIPD and OPD are lacking. Methods: Retrospective propensity score matched study comparing MIPD in 14 centers (7 countries) performing >= 10 MIPDs annually (2012-2017) versus OPD in 53 German/Dutch surgical registry centers performing >= 10 OPDs annually (2014-2017). Primary outcome was 30-day major morbidity (Clavien-Dindo >= 3). Results: Of 4220 patients, 729/730 MIPDs (412 laparoscopic, 184 robot-assisted, and 130 hybrid) were matched to 729 OPDs. Median annual case-volume was 19 MIPDs (interquartile range, IQR 13-22), including the first MIPDs performed in 10/14 centers, and 31 OPDs (IQR 21-38). Major morbidity (28% vs 30%,P= 0.526), mortality (4.0% vs 3.3%,P= 0.576), percutaneous drainage (12% vs 12%,P= 0.809), reoperation (11% vs 13%,P= 0.329), and hospital stay (mean 17 vs 17 days,P> 0.99) were comparable between MIPD and OPD. Grade-B/C postoperative pancreatic fistula (POPF) (23% vs 13%,P< 0.001) occurred more frequently after MIPD. Single-row pancreatojejunostomy was associated with POPF in MIPD (odds ratio, OR 2.95,P< 0.001), but not in OPD. Laparoscopic, robot-assisted, and hybrid MIPD had comparable major morbidity (27% vs 27% vs 35%), POPF (24% vs 19% vs 25%), and mortality (2.9% vs 5.2% vs 5.4%), with a fewer conversions in robot-assisted- versus laparoscopic MIPD (5% vs 26%,P< 0.001). Conclusions: In the early experience of 14 European centers performing >= 10 MIPDs annually, no differences were found in major morbidity, mortality, and hospital stay between MIPD and OPD. The high rates of POPF and conversion, and the lack of superior outcomes (ie, hospital stay, morbidity) could indicate that more experience and higher annual MIPD volumes are needed. Show less
