Takehiro Mishima

182 Background: Chemotherapy-induced peripheral neuropathy (CIPN) has become a substantial problem because of specific cytotoxic agents such as nab-paclitaxel, oxaliplatin, and eribulin. In addressing CIPN-related side effects caused by nab-PTX, we previously reported better CTCAE v4.0 grades and superior nab-PTX dose maintenance in breast cancer treatment adopting our 3S approach. Our 3S approach combines compression therapy (stockings and sleeves applied 24 hours from the beginning of nab-PTX administration) with medication therapy (selected prophylactic medications goshajinkigan, lafutidine, and mecobalamin applied over the course of treatment). In revisiting how stocking use restored skin perfusion levels decreased by nab-PTX chemotherapy, we examined whether the skin perfusion increases differ by CIPN grade. Methods: Using a laser Doppler blood flow meter with integrated probe (NL-101 Nahri Nexis Japan), we measured the skin perfusion of the lower limbs before and after stocking use across four groups: three groups of 3S prophylactics-treated nab-PTX patients divided by CIPN grade (Grade 0 [G0, n=12], Grade 1 [G1, n=20], Grades 2 and 3 combined [G2+3, n=12]), and one control group of healthy volunteers (GH, n=50). Results: In the control group (GH), the mean increase in skin perfusion level (mL/min/100g) after wearing stockings was 0.90 (SD= 3.36). For the 3S prophylactic treatment patients, the mean increase was 4.25 (4.98) in the G0 group, 2.11 (4.93) in the G1 group, and 2.69 (2.53) in the G2+3 group. ANOVA analysis indicated a significant difference in skin perfusion increase among the groups (p=0.0493). Analysis between the groups indicated significance in the G0 group increase over the control group increase (p=0.0255). Conclusions: CIPN was previously shown to decrease skin perfusion; in the current study skin perfusion responsiveness to stockings differed significantly between chemotherapy patients and healthy volunteers. Restorative skin perfusion increase is potentially related with alleviating CIPN grade, for which further evaluation is needed.

Objectives Zinc (Zn) is related to insulin synthesis, storage, and secretion. This study demonstrates the effects of Zn supplementation in donor rats on the outcomes of islet transplantation. Methods Donor rats received 3 different regimens of dietary Zn supplementation for 2 weeks before undergoing pancreas donation: a standard diet containing Zn at 50 ppm (control), 1 ppm (low-Zn group) or 1000 ppm (high-Zn group), respectively. Diabetic recipient rats underwent islet transplantation, and the blood glucose levels and insulin secretion were monitored for 7 days after transplantation. Results The serum and pancreatic Zn levels at the time of donation were significantly lower in the low-Zn group (48.8 ± 25.5 µg/dL and 11.3 ± 1.9 µg/g) and higher in the high-Zn group (147.3 ± 17.6 µg/dL and 18.7 ± 2.2 µg/g) when compared with those observed in the controls (118.7 ± 7.9 µg/dL and 14.6 ± 2.0 µg/g) (P < 0.05). The blood glucose levels became re-elevated 2 days after transplantation in rats receiving islet grafts from the controls and the low-Zn groups. In contrast, in the rats that received islets from the high-Zn groups, these were maintained within a reference range (P < 0.01). Conclusions These data indicate that a Zn-rich diet for donor rats improves the function of islet grafts in chemically induced diabetic rats.

Gastric rupture with necrosis following acute gastric dilatation (AGD) is a rare and potentially fatal event; usually seen in patients with eating disorders such as anorexia nervosa or bulimia. A 12-year-old lean boy with no remarkable medical history was brought to our Emergency Department suffering acute abdominal symptoms. Emergency laparotomy revealed massive gastric dilatation and partial necrosis, with rupture of the anterior wall of the fundus of the stomach. We performed partial gastrectomy and the patient recovered uneventfully. We report this case to demonstrate that AGD and subsequent gastric rupture can occur in patients without any underlying disorders and that just a low body mass index is a risk factor for this potentially fatal condition.

Metastasis of renal cell carcinoma (RCC) to distant organs occurs commonly, even after radical nephrectomy, but metastatic lesions are rarely detected in the pancreas. The present study aim was to improve the postoperative quality of life of a patient with pancreatic metastasis of RCC through limited resection of the pancreas. Since therapeutic modalities including chemotherapy or radiation are ineffective for metastatic tumors, surgical intervention is a treatment of choice in selected patients. In patients with multiple pancreatic metastases, however, near-total or total pancreatectomy may result in a lower quality of life postoperatively due to endocrine and exocrine pancreatic insufficiency. We used limited resection of the pancreas combined with removal of the uncinate process and distal pancreatectomy for a 65-year-old woman with multifocal pancreatic metastases located in the uncinate process, body, and tail of the pancreas, which were detected 6 years after radical nephrectomy for RCC. This surgical procedure allowed preservation of about 40% of the pancreatic parenchyma, with complete excision of metastatic tumors in the pancreas. The patient has had an excellent quality of life with well-preserved pancreatic function and no evidence of tumor recurrence for 31 months after pancreatic surgery.

The present study was designed to investigate whether an inducible nitric oxide synthase (iNOS)-specific inhibitor, ONO-1714 [(1S, 5S, 6R, 7R)-7-chloro-3-imino-5-methyl-2-azabicyclo[4.1.0] heptane], could prevent inflammation-associated biliary carcinogenesis in bilioenterostomized hamsters. Syrian golden hamsters underwent choledochojejunostomy and then received subcutaneous injections of the chemical carcinogen N-nitrosobis(2-oxopropyl)amine every 2 weeks at a dose of 10 mg/kg body wt, starting 4 weeks after surgery and continuing for 18 weeks. The hamsters were divided into two groups according to their oral intake of either a standard pelleted diet containing ONO-1714 at 100 p.p.m. for 18 weeks (ONO group, n = 15) or an ordinary diet alone (control group, n = 15). The animals were killed 22 weeks after surgery, and the development of biliary tumors was examined histologically. The presence and degree of cholangitis, cell kinetic status of the biliary epithelium and iNOS expression were evaluated. Intrahepatic biliary adenomas developed in all control animals, whereas they developed in only seven (47%) hamsters treated with ONO-1714 (P < 0.05). Intrahepatic biliary carcinomas were present in 13 (87%) hamsters in the control group and in only 6 (40%) hamsters in the ONO groups (P < 0.05). Histological and immunohistochemical examinations demonstrated a significant decrease in the degree of cholangitis, biliary epithelial cell kinetics and the expression of iNOS in the biliary epithelium in the ONO group in comparison with the control (P < 0.05). These results indicate that ONO-1714 represses N-nitrosobis(2-oxopropyl)amine-induced biliary carcinogenesis in bilioenterostomized hamsters and inhibits iNOS expression in the biliary epithelium. ONO-1714 may therefore be a promising agent for the prevention of biliary carcinoma in various inflammation-associated biliary disorders.

To preserve pancreatic endocrine and exocrine function, various types of pancreatic resection, including central pancreatectomy, have been introduced as less invasive surgeries. However, postoperative pancreatic leakage has been demonstrated to be the most frequent complication following pancreas-preserving surgery. The authors' new surgical technique, a jejunal wall-covering method, helps to prevent pancreatic leakage following central pancreatectomy.

Bile duct injury is the most troublesome complication in laparoscopic cholecystectomy (LC). The identification of the anatomical relationship between the cystic duct and common bile duct is one of the most important points for the safe LC. Therefore, we introduced a biliary navigation surgery using endoscopic nasobiliary drainage (ENBD) tube to avoid bile duct injury during LC. The benefit of intraoperative cholangiography using an ENBD tube is that the identification of the anatomical relationship between the cystic duct and common bile duct can be confirmed by using intraoperative cholangiography through the ENBD tube. We consider that ENBD tube is useful for identifying the biliary tract by repeated intraoperative cholangiography and, thus, for preventing injury to the bile duct in LC.