Impact of preoperative statin medication on long-term outcomes after pancreatoduodenectomy for ductal adenocarcinoma: an international multicentric cross-sectional study.

PURPOSE Statin treatment has been shown in certain population studies and meta-analyses to improve survival of patients with pancreatic ductal adenocarcinoma (PDAC). This study assessed if patients with statin treatment had better overall survival (OS) and disease-free survival (DFS) after upfront pancreatoduodenectomy for PDAC. METHODS Consecutive PDAC patients were retrospectively collected from three centers in Europe and USA (study period: 2000-2017). Adult patients who underwent upfront pancreatoduodenectomy and survived the first 90 postoperative days were included. Patients with metastasis at diagnosis or with macroscopic incomplete resection were excluded. Patients were considered under statin if started at least one month before pancreatoduodenectomy. Survival rates were calculated using Kaplan-Meier method and compared with log-rank test. RESULTS A total of 496 patients were included. Median age was 67 years (IQR 59-75), 48% (n = 236) were women, and 141 patients (28%) received statin treatment already preoperatively. Patients with and without statin treatment were comparable in terms of demographics and pre-/intraoperative characteristics, except for age and pre-existing diabetes. Median OS and DFS were similar in patients with and without statin treatment (OS: 29, 95% CI 22-36 vs. 27 months, 95% CI 22-32, p = 0.370, DFS: 18, 95% CI 14-22 vs. 16 months, 95% CI 14-18, p = 0.430). On multivariable Cox regression, lymph node involvement (HR 1.9, 95% CI 1.6-2.2, p < 0.001), tumor differentiation (HR 1.3, 95% CI 1.1-1.6, p = 0.003), and postoperative chemotherapy (HR 0.5, 95% CI 0.4-0.7, p < 0.001) were predictors of OS, whereas statin treatment was not a prognostic factor (HR 0.9, 95% CI 0.7-1.2, p = 0.376). CONCLUSION In this international cohort of PDAC patients, statin treatment did not influence survival after upfront pancreatoduodenectomy. Nodal involvement, tumor differentiation, and postoperative chemotherapy were independent predictors of OS

External validation of three lymph node ratio-based nomograms predicting survival using an international cohort of patients with resected pancreatic head ductal adenocarcinoma.

INTRODUCTION Lymph node ratio (LNR) is an important prognostic factor of survival in patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to validate three LNR-based nomograms using an international cohort. MATERIALS AND METHODS Consecutive PDAC patients who underwent upfront pancreatoduodenectomy from six centers (Europe/USA) were collected (2000-2017). Patients with metastases, R2 resection, missing LNR data, and who died within 90 postoperative days were excluded. The updated Amsterdam nomogram, the nomogram by Pu et al., and the nomogram by Li et al. were selected. For the validation, calibration, discrimination capacity, and clinical utility were assessed. RESULTS After exclusion of 176 patients, 1'113 patients were included. Median overall survival (OS) of the cohort was 23 months (95% CI: 21-25). For the three nomograms, Kaplan-Meier curves showed significant OS diminution with increasing scores (p < 0.01). All nomograms showed good calibration (non-significant Hosmer-Lemeshow tests). For the Amsterdam nomogram, area under the ROC curve (AUROC) for 3-year OS was 0.64 and 0.67 for 5-year OS. Sensitivity and specificity for 3-year OS prediction were 65% and 59%. Regarding the nomogram by Pu et al., AUROC for 3- and 5-year OS were 0.66 and 0.70. Sensitivity and specificity for 3-year OS prediction were 68% and 53%. For the Li nomogram, AUROC for 3- and 5-year OS were 0.67 and 0.71, while sensitivity and specificity for 3-year OS prediction were 63% and 60%. CONCLUSION The three nomograms were validated using an international cohort. Those nomograms can be used in clinical practice to evaluate survival after pancreatoduodenectomy for PDAC

Outcomes and risk score for distal pancreatectomy with celiac axis resection (DP-CAR) : an international multicenter analysis

Background: Distal pancreatectomy with celiac axis resection (DP-CAR) is a treatment option for selected patients with pancreatic cancer involving the celiac axis. A recent multicenter European study reported a 90-day mortality rate of 16%, highlighting the importance of patient selection. The authors constructed a risk score to predict 90-day mortality and assessed oncologic outcomes. Methods: This multicenter retrospective cohort study investigated patients undergoing DP-CAR at 20 European centers from 12 countries (model design 2000-2016) and three very-high-volume international centers in the United States and Japan (model validation 2004-2017). The area under receiver operator curve (AUC) and calibration plots were used for validation of the 90-day mortality risk model. Secondary outcomes included resection margin status, adjuvant therapy, and survival. Results: For 191 DP-CAR patients, the 90-day mortality rate was 5.5% (95 confidence interval [CI], 2.2-11%) at 5 high-volume (1 DP-CAR/year) and 18% (95 CI, 9-30%) at 18 low-volume DP-CAR centers (P=0.015). A risk score with age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) score, multivisceral resection, open versus minimally invasive surgery, and low- versus high-volume center performed well in both the design and validation cohorts (AUC, 0.79 vs 0.74; P=0.642). For 174 patients with pancreatic ductal adenocarcinoma, the R0 resection rate was 60%, neoadjuvant and adjuvant therapies were applied for respectively 69% and 67% of the patients, and the median overall survival period was 19months (95 CI, 15-25months). Conclusions: When performed for selected patients at high-volume centers, DP-CAR is associated with acceptable 90-day mortality and overall survival. The authors propose a 90-day mortality risk score to improve patient selection and outcomes, with DP-CAR volume as the dominant predictor

International Validation of a Nomogram to Predict Recurrence after Resection of Grade 1 and 2 Nonfunctioning Pancreatic Neuroendocrine Tumors

Background: Despite the low recurrence rate of resected nonfunctional pancreatic neuroendocrine tumors (NF-pNETs), nearly all patients undergo long-term surveillance. A prediction model for recurrence may help select patients for less intensive surveillance or identify patients for adjuvant therapy. The objective of this study was to assess the external validity of a recently published model predicting recurrence within 5 years after surgery for NF-pNET in an international cohort. This prediction model includes tumor grade, lymph node status and perineural invasion as predictors. Methods: Retrospectively, data were collected from 7 international referral centers on patients who underwent resection for a grade 1-2 NF-pNET between 1992 and 2018. Model performance was evaluated by calibration statistics, Harrel's C-statistic, and area under the curve (AUC) of the receiver operating characteristic curve for 5-year recurrence-free survival (RFS). A sub-analysis was performed in pNETs >2 cm. The model was improved to stratify patients into 3 risk groups (low, medium, high) for recurrence. Results: Overall, 342 patients were included in the validation cohort with a 5-year RFS of 83% (95% confidence interval [CI]: 78-88%). Fifty-eight patients (17%) developed a recurrence. Calibration showed an intercept of 0 and a slope of 0.74. The C-statistic was 0.77 (95% CI: 0.70-0.83), and the AUC for the prediction of 5-year RFS was 0.74. The prediction model had a better performance in tumors >2 cm (C-statistic 0.80). Conclusions: External validity of this prediction model for recurrence after curative surgery for grade 1-2 NF-pNET showed accurate overall performance using 3 easily accessible parameters. This model is available via www.pancreascalculator.com

The Comprehensive Complication Index (CCI®) is a Novel Cost Assessment Tool for Surgical Procedures

OBJECTIVE The aim of this study was to identify a readily available, reproducible, and internationally applicable cost assessment tool for surgical procedures. SUMMARY OF BACKGROUND DATA Strong economic pressure exists worldwide to slow down the rising of health care costs. Postoperative morbidity significantly impacts on cost in surgical patients. The comprehensive complication index (CCI), reflecting overall postoperative morbidity, may therefore serve as a new marker for cost. METHODS Postoperative complications and total costs from a single tertiary center were prospectively collected (2014 to 2016) up to 3 months after surgery for a variety of abdominal procedures (n = 1388). CCI was used to quantify overall postoperative morbidity. Pearson correlation coefficient (rpears) was calculated for cost and CCI. For cost prediction, a linear regression model based on CCI, age, and type of surgery was developed and validated in an international cohort of patients. RESULTS We found a high correlation between CCI and overall cost (rpears = 0.75) with the strongest correlation for more complex procedures. The prediction model performed very well (R = 0.82); each 10-point increase in CCI corresponded to a 14% increase to the baseline cost. Additional 12% of baseline cost must be added for patients older than 50 years, or 24% for those over 70 years. The validation cohorts showed a good match of predicted and observed cost. CONCLUSION Overall postoperative morbidity correlates highly with cost. The CCI together with the type of surgery and patient age is a novel and reliable predictor of expenses in surgical patients. This finding may enable objective cost comparisons among centers, procedures, or over time obviating the need to look at complex country-specific cost calculations (www.assessurgery.com)

Definition and classification of chyle leak after pancreatic operation: A consensus statement by the International Study Group on Pancreatic Surgery

Recent literature suggests that chyle leak may complicate up to 10% of pancreatic resections. Treatment depends on its severity, which may include chylous ascites. No international consensus definition or grading system of chyle leak currently is available. The International Study Group on Pancreatic Surgery, an international panel of pancreatic surgeons working in well-known, high-volume centers, reviewed the literature and worked together to establish a consensus on the definition and classification of chyle leak after pancreatic operation. Chyle leak was defined as output of milky-colored fluid from a drain, drain site, or wound on or after postoperative day 3, with a triglyceride content ≥110 mg/dL (≥1.2 mmol/L). Three different grades of severity were defined according to the management needed: grade A, no specific intervention other than oral dietary restrictions; grade B, prolongation of hospital stay, nasoenteral nutrition with dietary restriction, total parenteral nutrition, octreotide, maintenance of surgical drains, or placement of new percutaneous drains; and grade C, need for other more invasive in-hospital treatment, intensive care unit admission, or mortality. This classification and grading system for chyle leak after pancreatic resection allows for comparison of outcomes between series. As with the other the International Study Group on Pancreatic Surgery consensus statements, this classification should facilitate communication and evaluation of different approaches to the prevention and treatment of this complicatio

Outcomes After Distal Pancreatectomy with Celiac Axis Resection for Pancreatic Cancer: A Pan-European Retrospective Cohort Study

BACKGROUND: Western multicenter studies on distal pancreatectomy with celiac axis resection (DP-CAR), also known as the Appleby procedure, for locally advanced pancreatic cancer are lacking. We aimed to study overall survival, morbidity, mortality and the impact of preoperative hepatic artery embolization (PHAE). METHODS: Retrospective cohort study within the European-African Hepato-Pancreato-Biliary-Association, on DP-CAR between 1-1-2000 and 6-1-2016. Primary endpoint was overall survival. Secondary endpoints were radicality (R0-resection), 90-day mortality, major morbidity, and pancreatic fistulae (grade B/C). RESULTS: We included 68 patients from 20 hospitals in 12 countries. Postoperatively, 53% of patients had R0-resection, 25% major morbidity, 21% an ISGPS grade B/C pancreatic fistula, and 16% mortality. In total, 82% received (neo-)adjuvant chemotherapy and median overall survival in 62 patients with pancreatic ductal adenocarcinoma patients was 18 months (CI 10-37). We observed no impact of PHAE on ischemic complications. CONCLUSIONS: DP-CAR combined with chemotherapy for locally advanced pancreatic cancer is associated with acceptable overall survival. The 90-day mortality is too high and should be reduced. Future studies should investigate to what extent increasing surgical volume or better patient selection can improve outcomes

Evidence Map of Pancreatic Surgery-A living systematic review with meta-analyses by the International Study Group of Pancreatic Surgery (ISGPS)

Background: Pancreatic surgery is associated with considerable morbidity and, consequently, offers a large and complex field for research. To prioritize relevant future scientific projects, it is of utmost importance to identify existing evidence and uncover research gaps. Thus, the aim of this project was to create a systematic and living Evidence Map of Pancreatic Surgery. Methods: PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science were systematically searched for all randomized controlled trials and systematic reviews on pancreatic surgery. Outcomes from every existing randomized controlled trial were extracted, and trial quality was assessed. Systematic reviews were used to identify an absence of randomized controlled trials. Randomized controlled trials and systematic reviews on identical subjects were grouped according to research topics. A web-based evidence map modeled after a mind map was created to visualize existing evidence. Meta-analyses of specific outcomes of pancreatic surgery were performed for all research topics with more than 3 randomized controlled trials. For partial pancreatoduodenectomy and distal pancreatectomy, pooled benchmarks for outcomes were calculated with a 99% confidence interval. The evidence map undergoes regular updates. Results: Out of 30,860 articles reviewed, 328 randomized controlled trials on 35,600 patients and 332 systematic reviews were included and grouped into 76 research topics. Most randomized controlled trials were from Europe (46%) and most systematic reviews were from Asia (51%). A living meta-analysis of 21 out of 76 research topics (28%) was performed and included in the web-based evidence map. Evidence gaps were identified in 11 out of 76 research topics (14%). The benchmark for mortality was 2% (99% confidence interval: 1%–2%) for partial pancreatoduodenectomy and <1% (99% confidence interval: 0%–1%) for distal pancreatectomy. The benchmark for overall complications was 53% (99%confidence interval: 46%–61%) for partial pancreatoduodenectomy and 59% (99% confidence interval: 44%–80%) for distal pancreatectomy. Conclusion: The International Study Group of Pancreatic Surgery Evidence Map of Pancreatic Surgery, which is freely accessible via www.evidencemap.surgery and as a mobile phone app, provides a regularly updated overview of the available literature displayed in an intuitive fashion. Clinical decision making and evidence-based patient information are supported by the primary data provided, as well as by living meta-analyses. Researchers can use the systematic literature search and processed data for their own projects, and funding bodies can base their research priorities on evidence gaps that the map uncovers

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

ASSISTANCE HEPATIQUE PAR XENOPERFUSION EXTRACORPORELLE DE FOIE DE PORC (MODELES D'ETUDES EXPERIMENTALES ET PRE-CLINIQUES)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF