Intraoperative ultrasound examination is useful for monitoring transplanted islets
A 39 y-old man who had an episode of severe abdominal pain and pancreatic bleeding due to chronic pancreatitis (CP) and pancreatic arteriovenous malformation (AVM) was admitted to our institution to undergo TP with IAT. Before hospitalization, he received an elemental diet therapy to prevent CP attack. Although he had no past history and no complication of diabetes, he had episodes of alcohol abuse and smoking. Preoperative serum insulin was 48.3 µU/ml and serum C-peptide was 3.15 ng/mL. Glucose tolerance was at a normal level.\nPreoperative CT revealed enriched abnormal vessels (approximately 2.0 cm-sized) in pancreatic head and the portal vein was enhanced at an early stage. It also showed a 2.5 cm cystic lesion in the pancreatic tail, which was suspected to be a pancreatic pseudocyst. The pseudocyst oppressed the posterior wall of the stomach. These image findings indicated AVM, and it was considered that the pancreatitis was caused by AVM. We considered that total pancreatectomy (TP) could not be prevented because there were findings associated with AVM in the pancreatic head and tail. To prevent brittle pancreatic diabetes caused by total islet loss, islet autotransplantation (IAT) was planned at the same time. We already had approval of the Ethics Committee of Tohoku University School of Medicine for the clinical project of TP with IAT.\nBefore performing TP with IAT for this patient, we had already decided on the procedure to be used follows: (1) a double lumen catheter (for central vein, sized 14 gauze and 30 cm length) was inserted into the portal vein via the superior mesenteric vein for transplantation and monitoring the portal vein pressure, (2) the tip of the catheter was positioned at the bifurcation of the anterior and posterior branch of the portal vein and the islets were selectively infused into the right lobe of the liver to prevent total liver embolization and (3) intraoperative US examination was performed for detecting islets in the portal vein and determining whether the portal vein was embolized or not. The patient had no preoperative events of CP attack or bleeding. After the preoperative examinations, the operation was performed.\nIn general, en-bloc resection of the pancreas is recommended for islet isolation. However, TP for AVM is technically difficult to perform en-bloc resection due to the existence of many abnormal vessels and pancreatic inflammation. In addition, extensive blood loss is difficult to prevent because the feeding arteries (gastroduodenal artery for the head and splenic artery for the body and tail) must be ligated at the last step of the operation to shorten the warm ischemia time (WIT). Thus, we selected a two-step TP method: distal pancreatectomy (DP) was performed first and then pancreaticoduodenectomy (PD) was done to decrease the blood loss and to shorten the WIT. After the exposure of the pancreas, by following the gastroduodenal and common hepatic artery, the root of the splenic artery (SPA) was picked up but not ligated to preserve the blood flow. The pancreatic neck was then separated from the anterior surface of the porto-mesenteric vein. After gentle mobilization of the body and tail of the pancreas and spleen, pancreatic transection in the neck followed by ligation of the splenic vein was performed before ligation of the SPA (final step of the DP). After removal of the distal pancreas, the proximal pancreas with the duodenum was then removed by the standard Whipple’s procedure. The total weight of the pancreas was 86 g. An 8 Fr. size catheter was cannulated into the main pancreatic duct and ductal injection was performed at the procurement site using ET-K solution (Otsuka Pharmaceutical Factory Inc.). The pancreas was immersed into the cold ET-K solution, packed in a cooler box with crushed ice and carried to the cell-processing center of our institution. After performing TP and tract reconstructions, a double lumen central venous catheter was inserted into the main portal vein via the superior mesenteric vein. The operative time was 670 min and the blood loss volume was 2,070 mL. The WIT was within 10 min and the cold ischemia time was 167 min.\nIslets were isolated from the body/tail and head of the pancreas with a semi-circuit digestion system using Liberase MTF-C/T (Roche Diagnostics K.K.). Purification using COBE 2991 was performed in order to reduce the risk of portal embolism and successfully decreased graft volume (600 µL). Two hundred twenty-nine thousand five hundred thirty-eight islet equivalents (IEQs) with the purity of 30% were acquired from the pancreas. The islets were packed in one bag containing 200 mL of heparinized (containing 1,500 units of heparin) transplantation solution. We connected the bag to one side of the portal vein catheter and dripped the islets into the portal vein. The other side of the catheter was connected to a pressure monitor and the portal vein pressure was measured during the whole procedure of transplantation. The portal vein pressure during transplantation was 8–9 mmHg and no elevation was detected. The IAT was finished safely and the transplantation time was 50 min.\nIntraopetative US was done during the IAT using a Diagnostic Ultrasound System (Nemio™ XG, Toshiba Medical System Co.). The central frequency of the US probe was 7.5 MHz. We performed the US examination by putting the probe on the liver directly and confirmed the tip of the catheter, detected as a high echoic tube, at the bifurcation between the anterior and posterior branches of the portal vein. Transplanted islets, which flowed toward the periphery of the portal vein from the tip of the catheter, were visualized as hyperechoic clusters (). No portal thrombosis or bleeding was detected during and after transplantation.\nAfter finishing the transplantation, the patient was moved to the intensive care unit where he stayed for 3 d. He received intensive insulin therapy (keeping the blood glucose under 130 mg/dL) and was medicated with 0.9 mg / day of GLP-1 analog (Victoza®, Novo Nordisk Pharma Ltd.) during admission. He had no adverse events during admission and was discharged with no complications. The insulin doses at discharge were 6 units/day of an ultra-rapid type (Humulin R®, Eli Lilly Japan K.K.) and 7 units/day of a long lasting type (Lebemir®, Novo Nordisk Pharma Ltd.). After discharge, his blood glucose and HbA1c levels gradually increased, but he has had no symptoms suggesting hypoglycemia till 1 y after transplantation. The blood glucose, HbA1c and serum C-peptide at 3 mo were 142 mg/dL, 6.5% and 0.31 ng/mL.