Advances in the Perioperative Management of Pancreatic Cancer

Abstract: Surgery is currently the only form of curative treatment for pancreatic cancer, yet five-year survival rates following resection are just 15-20%. Improved hospital care has decreased postoperative mortality to 2% yet morbidity remains high at 50%. Poor survival and high morbidity are driven by several perioperative factors. The aims of this thesis were to (I) understand the impact of waiting times between imaging and surgery, (II) evaluate the best strategy for patients deemed unresectable at surgery, (III) explore novel pancreaticojejunal anastomotic techniques and (IV) to evaluate systemic treatment options for patients with borderline resectable pancreatic cancer.  In paper I, the time between diagnosis and surgical treatment was evaluated with regards to cancer progression at the time of surgery. The rate of unresectable disease at surgery was significantly lower with a waiting of time of 32 days or less compared with longer waiting times (13.9 vs 32.5%). Tumor size and vascular involvement also increased the risk of unresectable disease at surgery. In paper II, the palliative double bypass (PDB) and just an exploratory laparotomy were compared in cases of unresectable disease at surgery. Perioperative mortality and initiation of chemotherapy were similar between the groups. Patients undergoing chemotherapy following exploratory laparotomy alone had longer median overall survival compared to patients undergoing chemotherapy following a PDB (16.3 versus 10.3 months).In paper III, an end-to-end invaginated pancreaticojejunostomy was compared to the traditional duct to mucosa anastomosis in the setting of a randomized controlled trial. Patients at high risk for developing a post-operative pancreatic fistula (POPF) were selected The results showed no difference in clinically significant pancreatic leaks. There were however significantly fewer cases of grade C POPF associated with the invaginated pancreaticojejunostomy. In paper IV the role of neoadjuvant chemotherapy (NACT) and upfront resection was retrospectively evaluated for patients with borderline resectable pancreatic tumors. Patients who underwent upfront resection versus NACT had comparable median overall survival rates when drop-outs were included in an intention-to-treat principle (9 vs 10.9 months respectively). Per-protocol analysis of patients that completed their intended therapy revealed no difference in the upfront surgery group (9.5 months) and a significantly longer survival in the NACT group (21.8 months).