ABSTRACT
Multidisciplinary therapy centered on radical surgery for resectable pancreatic cancer is expected to prolong prognosis, but relies on CA19-9 biomarker levels to determine treatment strategy. Boron neutron capture therapy (BNCT) is a chemoradiotherapy using tumor hyperaccumulator boron drugs and neutron irradiation. The purpose of this study is to investigate novel boron drug agents for BNCT for pancreatic cancer. Bioinformatics was used to evaluate the uptake of current boron amino acid (BPA) drugs for BNCT into pancreatic cancer. The expression of the amino acid transporter LAT1, a BPA uptake transporter, was low in pancreatic cancer and even lower in high CA19-9 pancreatic cancer. In contrast, the glucose transporter was high in high CA19-9 pancreatic cancers and inversely correlated with LAT1 expression. Considering the low EPR effect in pancreatic cancer, we synthesized a small molecule Glucose-BSH, which is boron BSH bound to glucose, and confirmed its specific uptake in pancreatic cancer. uptake of Glucose-BSH was confirmed in an environment compatible with the tumor microenvironment. The therapeutic efficacy and safety of Glucose-BSH by therapeutic neutron irradiation were confirmed with BNCT. We report Glucose-BSH boron drug discovery study of a Precision Medicine BNCT with application to high CA19-9 pancreatic cancer.
Subject(s)
Boron Neutron Capture Therapy , Glucose , Pancreatic Neoplasms , Boron Neutron Capture Therapy/methods , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/pathology , Humans , Glucose/metabolism , Cell Line, Tumor , Animals , Boron Compounds/chemistry , Boron Compounds/therapeutic use , Boron/chemistry , Female , Mice, NudeSubject(s)
Barium Sulfate/adverse effects , Biliary Tract , Cholangiopancreatography, Endoscopic Retrograde/methods , Cholelithiasis/prevention & control , Contrast Media/adverse effects , Double-Balloon Enteroscopy/methods , Duodenal Neoplasms/surgery , Foreign Bodies/therapy , Intestinal Neoplasms/surgery , Neuroendocrine Tumors/surgery , Pancreatic Neoplasms/surgery , Stomach Neoplasms/surgery , Aged , Gastric Bypass , Humans , Male , Pancreaticoduodenectomy , Pancreaticojejunostomy , Plastic Surgery ProceduresABSTRACT
PURPOSE: We herein report 3 cases in which the right hepatic vein (RHV) involved with a liver tumor was reconstructed using an autologous jugular vein graft to raise the curability and to increase the functional volume of the liver remnant (LR). CASE 1: Cholangiocellular carcinoma (diameter 6.0 cm) in the left lobe invaded the RHV, the branch of the RHV which drains segment 7 (V7) and the middle hepatic vein (MHV). Because the ratio of the LR drained by the inferior right hepatic vein (IRHV) was 26.7%, extended left lobectomy including MHV with RHV and V7 reconstruction was carried out, resulting in a good outcome and an uneventful operative course. Surgical margins on the liver resection plane and at the IVC were 5 mm and partially zero, respectively. CASE 2: Cholangiolocellular carcinoma (diameter 9.0 cm) in the left lobe and the anterior segment invaded the RHV, V7, IVC and bile duct. In this case, the IRHV was present and not involved with the tumor. Because the ratio of the LR drained by the IRHV was 26.1%, left hepatic trisectionectomy with RHV, V7, IVC, and bile duct reconstruction was performed, leading to a good operative course. Surgical margins on the liver resection plane and at the IVC were 8 mm and partially zero, respectively. CASE 3: Hepatocellular carcinoma (diameter 2.7 cm) in segment 7 invaded the RHV. Because the hepatic functional reserve had decreased due to the presence of hepatitis C virus, extended subsegmentectomy (segment 7) with RHV reconstruction was performed, thus resulting in a sufficiently maintained LR function. Surgical margin on the liver resection plane was 7 mm. CONCLUSION: RHV reconstruction with an autologous jugular vein graft is considered to be useful for safely expanding the surgical indications for liver tumors.
