Postoperative pancreatic fistula (POPF) remains one of the most dreaded complications after pancreatoduodenectomy (PD), especially in patients with soft pancreatic parenchyma and a small main pancreatic duct. In this context, total pancreatectomy (TP) has been proposed to prevent the occurrence of POPF, although its metabolic consequences limit its widespread adoption.

To compare the postoperative outcomes of PD and TP in patients at high risk of POPF, assessing morbidity, mortality, and metabolic consequences.

A systematic literature search was conducted according to the PRISMA recommendations, including comparative studies of PD versus TP in a high-risk population. The criteria analyzed included morbidity, mortality, oncological outcomes and the occurrence of insulin-dependent diabetes mellites.

The available data suggest a reduction in overall morbidity and severe complications after TP, but at the cost of a high rate of postoperative diabetes mellites. Islet cell auto-transplantation (IAT) could mitigate these metabolic consequences, and has shown encouraging results on glycemia control and the preservation of residual insulin secretion.

In patients at high risk of POPF, TP may be a pertinent alternative to PD, especially in complex anatomical or oncological situations. However, the metabolic benefit–risk balance needs to be carefully assessed, and strategies such as TP-IAT may improve functional outcomes. Additional randomized controlled trials are needed, including an accurate assessment of postoperative quality of life.