Optimizing clinical outcomes after pancreatic resection

In recent years, nationwide outcomes after pancreatic resection have improved since centralization to high-volume centers has been implemented, driven by a focus on surgical performance, process measures, optimizing the quality of postoperative care, and intensive multidisciplinary collaboration. However, postoperative complications after pancreatic resection still occur in 30-73%. If not treated in time, postoperative complications may provoke a sequence of adverse events eventually leading to death, as discussed in this thesis.

Since complications are not always preventable, it has been suggested that focus for further improving outcomes should include timely recognition and adequate management of complications. This was shown in the nationwide PORSCH trial, a stepped-wedge randomized trial that investigated the implementation of an algorithm focusing on these two concepts after pancreatic resection. The algorithm considerably improved clinical postoperative outcomes, including a nearly 50% reduction in nationwide mortality. The algorithm is incorporated in a smartphone application and can be used all over the world. We showed that preoperative risk models for postoperative complications do not yet have the potential to stratify patients for a particular treatment strategy.

Specifically for patients developing a dirty leak, i.e. mixed leakage of pancreatic juice and bile through a defect hepatojejunostomy or pancreatojejunostomy, we have shown that percutaneous transhepatic drainage is a clinically and technically successful procedure. Also, little was known about cholangitis, another invalidating complication after pancreatoduodenectomy. We proved it to be frequent (i.e. 10% of patients) and recurrent with multiple readmissions. Diagnostic and treatment guidelines for postoperative cholangitis are much needed to improve outcomes in these patients.

A subgroup of patients, in whom physical condition and frailty may contribute even more to the risk of complications and worsened survival rates, are elderly. This thesis showed that pancreatic resection can be safely performed in elderly patients with pancreatic cancer, as short-term outcomes and mortality are similar to those in younger patients. However, adjuvant chemotherapy is more often omitted in elderly due to various reasons, resulting in suboptimal treatment and worse long-term survival.

On the long-term, postoperative complications affect the patient’s eligibility for adjuvant chemotherapy and thereby influence the oncological prognosis. Adequate treatment of short-term complications in order to prevent long-term effects is crucial to improve recurrence-free and overall survival of these patients.

Studies in this thesis clearly demonstrate the substantial progress in pancreatic care in the Netherlands over the past decade. Nevertheless, postoperative complications remain an inevitable threat for every patient undergoing pancreatic resection. Given that, as shown in this thesis, failure to rescue continues to be the leading cause of mortality after pancreatic surgery, this remains the key for further improvement of postoperative care. The promising results in this thesis give enough reason to continue the development of innovative postoperative treatment strategies to decrease failure to rescue.