Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians.

BACKGROUND: The genomes of present-day non-Africans are composed of 1-3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50-60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations. RESULTS: The high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19-1.54, P = 3.59 × 10-6), with a P-value close to a threshold that takes into account multiple testing. CONCLUSIONS: Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.

Surgical Management of Postoperative Grade C Pancreatic Fistula following Pancreatoduodenectomy.

Background: The incidence of Grade C postoperative pancreatic fistula ranges from 2 to 11% depending on the type of pancreatic resection. This complication may frequently require early relaparotomy and the surgical approach remains technically challenging and is still associated with a high mortality. Infectious complications and post-operative hemorrhage are the two most common causes of reoperation. Summary: The best management of grade C pancreatic fistulas remains controversial and ranges from conservative approaches up to completion pancreatectomy. The choice of the technique depends on the patient's conditions, intraoperative findings, and surgeon's discretion. A pancreas-preserving strategy appears to be attractive, including from simple to more complex procedures such as debridement and drainage, and external wirsungostomy. Completion pancreatectomy should be reserved for selected cases, including stable patients with severe infection complication or hemorrhage after pancreatic fistula who do not respond to pancreas-preserving procedures. Key Messages: This review describes the current options for management of grade C pancreatic fistula after pancreatoduodenectomy with regard to indication, choice of procedure and outcomes of the different approaches.

A Combination of Biochemical and Pathological Parameters Improves Prediction of Postresection Survival After Preoperative Chemotherapy in Pancreatic Cancer: The PANAMA-score.

OBJECTIVE: To build a prognostic score for patients with primary chemotherapy undergoing surgery for pancreatic cancer based on pathological parameters and preoperative Carbohydrate antigen 19-9 (CA19-9) levels. BACKGROUND: Prognostic stratification after primary chemotherapy for pancreatic cancer is challenging and prediction models, such as the AJCC staging system, lack validation in the setting of preoperative chemotherapy. METHODS: Patients with primary chemotherapy resected at the Massachusetts General Hospital between 2007 and 2017 were analyzed. Tumor characteristics independently associated with overall survival were identified and weighted by Cox-proportional regression. The pancreatic neoadjuvant Massachusetts-score (PANAMA-score) was computed from these variables and its performance assessed by Harrel concordance index and area under the receiving characteristics curves analysis. Comparisons were made with the AJCC staging system and external validation was performed in an independent cohort with primary chemotherapy from Heidelberg, Germany. RESULTS: A total of 216 patients constituted the training cohort. The multivariate analysis demonstrated tumor size, number of positive lymph-nodes, R-status, and high CA19-9 to be independently associated with overall survival. Kaplan-Meier analysis according to low, intermediate, and high PANAMA-score showed good discriminatory power of the new metrics (P < 0.001). The median overall survival for the three risk-groups was 45, 27, and 12 months, respectively. External validation in 258 patients confirmed the prognostic ability of the score and demonstrated better accuracy compared with the AJCC staging system. CONCLUSION: The proposed PANAMA-score, based on independent predictors of postresection survival, including pathologic variables and CA19-9, not only provides better discrimination compared to the AJCC staging system, but also identifies patients at high-risk for early death.

Global Survey on Pancreatic Surgery During the COVID-19 Pandemic.

OBJECTIVE: The aim of this study was to clarify the role of pancreatic surgery during the COVID-19 pandemic to optimize patients' and clinicians' safety and safeguard health care capacity. SUMMARY BACKGROUND DATA: The COVID-19 pandemic heavily impacts health care systems worldwide. Cancer patients appear to have an increased risk for adverse events when infected by COVID-19, but the inability to receive oncological care seems may be an even larger threat, particularly in case of pancreatic cancer. METHODS: An online survey was submitted to all members of seven international pancreatic associations and study groups, investigating the impact of the COVID-19 pandemic on pancreatic surgery using 21 statements (April, 2020). Consensus was defined as >80% agreement among respondents and moderate agreement as 60% to 80% agreement. RESULTS: A total of 337 respondents from 267 centers and 37 countries spanning 5 continents completed the survey. Most respondents were surgeons (n = 302, 89.6%) and working in an academic center (n = 286, 84.9%). The majority of centers (n = 166, 62.2%) performed less pancreatic surgery because of the COVID-19 pandemic, reducing the weekly pancreatic resection rate from 3 [interquartile range (IQR) 2-5] to 1 (IQR 0-2) (P < 0.001). Most centers screened for COVID-19 before pancreatic surgery (n = 233, 87.3%). Consensus was reached on 13 statements and 5 statements achieved moderate agreement. CONCLUSIONS: This global survey elucidates the role of pancreatic surgery during the COVID-19 pandemic, regarding patient selection for the surgical and oncological treatment of pancreatic diseases to support clinical decision-making and creating a starting point for further discussion.