Efficacy and safety of total pancreatectomy with islet autotransplantation: A clinical study in Japan

Abstract

Total pancreatectomy with islet autotransplantation (TPIAT) is considered for chronic pancreatitis (CP) patients, particularly those with hereditary pancreatitis, diffuse small pancreatic duct disease, or previous failed surgery. In TPIAT, pancreatectomy is performed with the aim of relieving pain and restoring quality of life, followed by islet autotransplantation with the aim of reducing the burden of postoperative diabetes. According to the first report from the Collaborative Islet Transplant Registry, more than 800 cases of TPIAT had been performed by 2015, mainly in Europe and the United States (https://citregistry.org/system/files/1st_ AR_Auto.pdf). However, TPIAT is rarely performed in Japan or other parts of Asia. Only 10 Korean cases (nine with cystic neoplasms and one with pancreatic injury) and recently a first case in India for CP have been reported. The limited number of cases is primarily due to the lack of surgical teams for total pancreatectomy and clinical islet isolation and transplantation. Against this background, we established a system of islet transplantation at the clinical level, which is the biggest challenge for autologous islet transplantation in Japan, and recently started performing allogeneic islet transplantations. We hypothesized that TPIAT could be safely and effectively performed in Japan if there was a facility for allogeneic islet transplantation. In collaboration with the departments of gastroenterology and pancreatic surgery, we conducted a clinical trial called “Clinical Study of Pancreatectomy with Autologous Islet Transplantation for Treatment of Chronic Pancreatitis” (UMIN000014368) to evaluate the safety and efficacy of TPIAT in terms of pain and glycemic control. Between August 2016 and June 2019, we performed TPIAT in five patients. Islet isolation and islet transplantation were performed using a previously reported method with modification. All patients were followed up for 12 months. The median islet yield was 270 967 islet equivalents (IEQ; range, 116 068-467 042), and the median number of transplanted islets was 4149 IEQ/kg body weight (range, 2038-10 836). Major adverse events during follow-up were abdominal wall hemorrhage, intestinal obstruction, intra-abdominal abscess, and abdominal pain requiring hospitalization, none of which had sequelae. There were no major complications due to islet transplantation. The primary end point was achieved in four patients. Pain scores and Izbicki pain score improved postoperatively in all patients (Table 1). One patient (20%) became insulin independent from the second postoperative month, whereas the remaining four patients required insulin; C-peptide was present in the blood in all cases and good glycemic control was possible without severe hypoglycemia (Table 1). As a result, symptoms of pancreatitis, pain in particular, were significantly improved in all patients. Furthermore, transplantation of autologous pancreatic islets isolated from the resected pancreas resulted in preservation of endogenous insulin secretion postoperatively in all cases. These findings suggest that TPIAT is a viable treatment option for Japanese and other East Asian patients with CP when pain is difficult to manage.