Central pancreatectomy of the remnant pancreas without reconstruction after pancreatoduodenectomy.

BACKGROUND: There are several reports on the safety and feasibility of pancreatoduodenectomy (PD) without reconstruction of the small remnant pancreas. However, a few studies have explored central pancreatectomy (CP) for non-reconstructed small remnant pancreases after PD. This study presents a case of CP without pancreatic reconstruction after PD. CASE PRESENTATION: A 58-year-old man with cerebral palsy underwent PD for distal cholangiocarcinoma. Three years postoperatively, a 12-mm tumor was detected in the remnant pancreatic body and diagnosed as a pancreatic neuroendocrine neoplasm. Surgical resection was performed, because the tumor was enlarged and chemotherapy resistant. The afferent loop with pancreatojejunostomy anastomosis was dissected, and CP, including pancreatojejunostomy anastomosis, was performed. Given the remnant pancreas was hard and atrophic, the pancreatic tail was transected using a stapler without reconstructing the small remnant pancreas. The patient experienced no postoperative complications including postoperative pancreatic fistula, and the endocrine function of the pancreas was preserved. CONCLUSIONS: We present a case of remnant pancreatic CP that did not require reconstruction after PD. Preservation of the small remnant pancreas without reconstruction during CP may be feasible to maintain endocrine function in select patients after PD.

Overcoming immunotherapy resistance and inducing abscopal effects with boron neutron immunotherapy (B-NIT).

Immune checkpoint inhibitors (ICIs) are effective against many advanced malignancies. However, many patients are nonresponders to immunotherapy, and overcoming this resistance to treatment is important. Boron neutron capture therapy (BNCT) is a local chemoradiation therapy with the combination of boron drugs that accumulate selectively in cancer and the neutron irradiation of the cancer site. Here, we report the first boron neutron immunotherapy (B-NIT), combining BNCT and ICI immunotherapy, which was performed on a radioresistant and immunotherapy-resistant advanced-stage B16F10 melanoma mouse model. The BNCT group showed localized tumor suppression, but the anti-PD-1 antibody immunotherapy group did not show tumor suppression. Only the B-NIT group showed strong tumor growth inhibition at both BNCT-treated and shielded distant sites. Intratumoral CD8+ T-cell infiltration and serum high mobility group box 1 (HMGB1) levels were higher in the B-NIT group. Analysis of CD8+ T cells in tumor-infiltrating lymphocytes (TILs) showed that CD62L- CD44+ effector memory T cells and CD69+ early-activated T cells were predominantly increased in the B-NIT group. Administration of CD8-depleting mAb to the B-NIT group completely suppressed the augmented therapeutic effects. This indicated that B-NIT has a potent immune-induced abscopal effect, directly destroying tumors with BNCT, inducing antigen-spreading effects, and protecting normal tissue. B-NIT, immunotherapy combined with BNCT, is the first treatment to overcome immunotherapy resistance in malignant melanoma. In the future, as its therapeutic efficacy is demonstrated not only in melanoma but also in other immunotherapy-resistant malignancies, B-NIT can become a new treatment candidate for advanced-stage cancers.

BNCT pancreatic cancer treatment strategy with glucose-conjugated boron drug.

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.

Right Hepatic Vein Reconstruction with an Autologous Jugular Vein Graft to Expand the Surgical Indications for Liver Tumors.

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.