Microbiome Patterns in Matched Bile, Duodenal, Pancreatic Tumor Tissue, Drainage, and Stool Samples: Association with Preoperative Stenting and Postoperative Pancreatic Fistula Development.

Melanie Langheinrich,Georg F Weber,Abbas Agaimy,Robert Schierwagen,Olaf Tyc,Stefan Wirtz,Christian Pilarsky,Robert Grützmann,Matthias M Gittler,Jonel Trebicka,Barbara Kneis,Maximilian Brunner,Christian Krautz,Stephan Kersting

doi:10.3390/jcm9092785

Abstract

Postoperative complications after pancreatic surgery are still a significant problem in clinical practice. The aim of this study was to characterize and compare the microbiomes of different body compartments (bile duct, duodenal mucosa, pancreatic tumor lesion, postoperative drainage fluid, and stool samples; preoperative and postoperative) in patients undergoing pancreatic surgery for suspected pancreatic cancer, and their association with relevant clinical factors (stent placement, pancreatic fistula, and gland texture). For this, solid (duodenal mucosa, pancreatic tumor tissue, stool) and liquid (bile, drainage fluid) biopsy samples of 10 patients were analyzed using 16s rRNA gene next-generation sequencing. Our analysis revealed: (i) a distinct microbiome in the different compartments, (ii) markedly higher abundance of Enterococcus in patients undergoing preoperative stent placement in the common bile duct, (iii) significant differences in the beta diversity between patients who developed a postoperative pancreatic fistula (POPF B/C), (iv) patients with POPF B/C were more likely to have bacteria belonging to the genus Enterococcus, and (v) differences in microbiome composition with regard to the pancreatic gland texture. The structure of the microbiome is distinctive in different compartments, and can be associated with the development of a postoperative pancreatic fistula.

Highlights

Pancreatic cancer (PC) is currently the seventh leading cause of cancer-related mortality worldwide, and is projected to become the second leading cause of cancer-related death by 2030 [1]
We performed an exploratory study on the first patients with pancreatic head resection in order to characterize the microbiome in different compartments related to the pancreas, and to see if the local microbiome is associated with the development of postoperative complications under different clinical conditions
We have shown that preoperative biliary stenting influences the local microbiome, and the microbiome of the pancreas, and that dysbiosis affects patient outcome for pancreatic surgery

Summary

Introduction

Pancreatic cancer (PC) is currently the seventh leading cause of cancer-related mortality worldwide, and is projected to become the second leading cause of cancer-related death by 2030 [1]. Despite the improvement in surgical techniques, new devices and technologies, and intensive care management, postoperative complications and morbidity remain a challenge after pancreatic surgery. Data from the prospective StuDoQ Pancreas registry of the German Society of General and Visceral Surgery yield a rate of 15% (12–19%) for major complications (Clavien-Dindo Classification (CDC) grades 3b and 4) in elective pancreatoduodenectomy [2]. A postoperative pancreatic fistula (POPF) is the most dangerous complication, and leads to a risk of sepsis, prolonged hospitalization, increased morbidity and mortality, and higher hospital costs [3,4,5,6]. The microbiome of the gut has been linked to anastomotic leakages after colorectal surgeries [7], and to surgical complications in pancreatic operations [8]

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