Total Pancreatectomy with islet Autotransplantation as an Alternative to high-risk Pancreatojejunostomy after Pancreaticoduodenectomy: A Prospective Randomized Trial

Objective: To compare pancreaticoduodenectomy (PD) and total pancreatectomy (TP) with islet autotransplantation (IAT) in patients at high risk of postoperative pancreatic fistula (POPF). Background: Criteria to predict the risk of POPF occurrence after PD are available. However, even when a high risk of POPF is predicted, TP is not currently accepted as an alternative to PD, because of its severe consequences on glycaemic control. Combining IAT with TP may mitigate such consequences. Methods: Randomized, open-label, controlled, bicentric trial (NCT01346098). Candidates for PD at high-risk pancreatic anastomosis (ie, soft pancreas and duct diameter ≤3 mm) were randomly assigned (1:1) to undergo either PD or TP-IAT. The primary endpoint was the incidence of complications within 90 days after surgery. Results: Between 2010 and 2019, 61 patients were assigned to PD (n=31) or TP-IAT (n=30). In the intention-to-treat analysis, morbidity rate was 90·3% after PD and 60% after TP-IAT (P=0.008). According to complications' severity, PD was associated with an increased risk of grade ≥2 [odds ratio (OR)=7.64 (95% CI: 1.35-43.3), P=0.022], while the OR for grade ≥3 complications was 2.82 (95% CI: 0.86-9.24, P=0.086). After TP-IAT, the postoperative stay was shorter [median: 10.5 vs 16.0 days; P<0.001). No differences were observed in disease-free survival, site of recurrence, disease-specific survival, and overall survival. TP-IAT was associated with a higher risk of diabetes [hazard ratio=9.1 (95% CI: 3.76-21.9), P<0.0001], but most patients maintained good metabolic control and showed sustained C-peptide production over time. Conclusions: TP-IAT may become the standard treatment in candidates for PD, when a high risk of POPF is predicted.