Pancreatic Inflammation and Proenzyme Activation Are Associated With Clinically Relevant Postoperative Pancreatic Fistulas After Pancreas Resection.

OBJECTIVE: We investigated the activation of pancreatic proenzymes and signs of peripancreatic inflammation in patients with clinically relevant postoperative pancreatic fistulas (POPFs). SUMMARY BACKGROUND DATA: An increase of systemic amylase concentration was associated with POPFs. This suggested parallels in the pathomechanisms between the development of POPFs and pancreatitis. METHODS: Trypsinogen, procathepsin B, and IL-6 concentrations as well as cathepsin B, myeloperoxidase and trypsin activities were determined throughout the first 7 postoperative days in drain fluids of 128 consecutive patients after pancreas resection. Histology and immunohistochemistry were performed in pancreatic specimens after total pancreatectomy due to complications and after placing experimental pancreatic sutures in the pancreatic tail of C57/Bl6 mice. RESULTS: Trypsin activity, cathepsin B activity and myeloperoxidase activity on the first postoperative day were elevated and predictive for clinically relevant pancreatic fistulas. Drain fluid stabilized trypsin activity and prevented the activation of the cascade of digestive enzymes. Leukocytes were the source of cathepsin B in drain fluid. Findings differed between fistulas after distal pancreatectomy and pancreatoduodenectomy. Immunohistochemistry of the pancreatic remnant revealed an inflammatory infiltrate expressing cathepsin B, independent of the presence of pancreatic fistulas. The infiltrate could be reproduced experimentally by sutures placed in the pancreatic tail of C57/Bl6 mice. CONCLUSIONS: Trypsinogen activation, increased cathepsin B activity and inflammation around the pancreato-enteric anastomosis on post operative day 1 are associated with subsequent clinically relevant POPFs after pancreatoduodenectomy. The parenchymal damage seems to be induced by placing sutures in the pancreatic parenchyma during pancreatic surgery.

Curative-intent pancreas resection for pancreatic metastases: surgical and oncological results.

BACKGROUND: Pancreatic metastasis is a rare cause for pancreas surgery and often a sign of advanced disease no chance of curative-intent treatment. However, surgery for metastasis might be a promising approach to improve patients' survival. The aim of this study was to analyze the surgical and oncological outcome after pancreatic resection of pancreatic metastasis. METHODS: This is a retrospective cohort analysis of a prospectively-managed database of patients undergoing pancreatic resection at the University of Freiburg Pancreatic Center from 2005 to 2017. RESULTS: In total, 29 of 1297 (2%) patients underwent pancreatic resection due to pancreatic metastasis. 20 (69%) patients showed metastasis of renal cell carcinoma (mRCC), followed by metastasis of melanoma (n = 5, 17%), colon cancer (n = 2, 7%), ovarian cancer (n = 1, 3%) and neuroendocrine tumor of small intestine (n = 1, 3%). Two (7%) patients died perioperatively. Median follow-up was 76.4 (range 21-132) months. 5-year and overall survival rates were 82% (mRCC 89% vs. non-mRCC 67%) and 70% (mRCC 78% vs. non-mRCC 57%), respectively. Patients with mRCC had shorter disease-free survival (14 vs. 22 months) than patients with other primary tumor entities. CONCLUSION: Despite malignant disease, overall survival of patients after metastasectomy for pancreatic metastasis is acceptable. Better survival appears to be associated with the primary tumor entity. Further research should focus on molecular markers to elucidate the mechanisms of pancreatic metastasis to choose the suitable therapeutic approach for the individual patient.

Bio-absorbable sealants for reinforcing the pancreatic stump after distal pancreatectomy are critical.

BACKGROUND: Bio-absorbable sealants are widely used to reduce the rate and severity of postoperative pancreatic fistulas after distal pancreatectomy. However, numerous clinical trials have failed to demonstrate their clinical benefit. We therefore investigated stability and bio-compatibility of absorbable sealants in vitro and in vivo. METHODS: In vitro, polymerized compounds were incubated in pancreatic juice before their stability was tested. In vivo, two compounds were used to seal the pancreatic stump after distal pancreatectomy in nine pigs. Burst pressure of the pancreatic stump, surgical outcome, histology of the pancreatic stump, systemic inflammation, and drain fluid was examined. RESULTS: Products based on fibrin or collagen were unstable in the presence of active pancreatic enzymes and completely dissolved within 2 h. Sealants using chemical cross-linking of proteins showed improved stability for 7 days. In vivo, application of polyethylenglycol-based sealant leads to complete closure of the pancreatic duct after 5 days, while a glutaraldehyde-based sealant prevented physiological closure of the pancreatic main duct. CONCLUSIONS: Many compounds used clinically to reinforce the pancreatic stump after distal pancreatectomy are inadequate due to instability in the presence of pancreatic enzymes. While selected bio-absorbable sealants inhibited the natural healing of the pancreatic stump, polyethylenglycol-based sealants should be tested in further clinical trials.