Amane Kitasato

Stenting versus non-stenting in pancreaticojejunostomy: a prospective study limited to a normal pancreas without fibrosis sorted by using dynamic MRI.

Objectives: We prospectively investigated the efficacy of an external pancreatic duct stent to prevent pancreatic fistula in the nonfibrotic pancreas after pancreaticojejunostomy, in which the degree of pancreatic fibrosis was assessed objectively by using dynamic magnetic resonance imaging (MRI). Methods: Among the 67 consecutive patients who underwent pancreatic head resection, 45 patients were judged to have a normal pancreas without fibrosis based on the preoperative assessment of pancreatic fibrosis based on MRI. The patients were randomly allocated to 1 of 2 groups with (n = 23) or without (n = 22) use of an external pancreatic duct stent in performing a pancreaticojejunostomy. Results: Pancreatic fistula developed in 8 (34.5%) patients in the stented group: 3 grade A and 5 grade B; whereas in the nonstented group, 9 (40.9%) patients developed pancreatic fistula: 3 grade A and 6 grade B. There were no significant differences in the incidence or severity of pancreatic fistula between the 2 groups. Conclusions: The utility of the external pancreatic duct stent after pancreaticojejunostomy was not found in the nonfibrotic pancreases, which were sorted according to the degree of pancreatic fibrosis using the pancreatic time-signal intensity curve analysis from MRI.

Laparoscopic spleen-preserving distal pancreatectomy with and without splenic vessel preservation: The role of the Warshaw procedure

BACKGROUND/OBJECTIVES Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) for low-grade malignant pancreas tumors was recently demonstrated. Although the procedure with splenic vessel preservation (SVP) is optimal for LSPDP, SVP is not always possible in patients with a large tumor or a tumor attached to splenic vessels. This study aimed to analyze the safety of two procedures: LSPDP without SVP, known as the Warshaw technique (lap-WT), and LSPDP with SVP (lap-SVP). METHODS Seventeen patients who underwent a lap-WT and seven patients who underwent a lap-SVP were investigated retrospectively. RESULTS The median follow-up duration was 45 (range 17-105) months. In the lap-WT and lap-SVP patients, the sizes of the tumors were 5 (1.3-12) and 1.5 (1-4) cm; the operative times were 304 (168-512) and 319 (238-387) min; the blood loss was 210 (5-3250) and 60 (9-210) gr; the length of the postoperative hospital stay was 15 (8-29) and 18 (5-24) days; the peak platelet counts were 37.2 (14.6-65.2) and 26.4 (18.8-41) × 10(4)/μL, and splenomegaly was observed in 10 (59%) and three (43%) patients, respectively. In both procedures, there was no local recurrence. In the lap-WT group, splenic infarctions were seen in four (24%) patients and perigastric varices were seen in two (12%) patients. All of these patients were observed conservatively. CONCLUSIONS Both the lap-WT and lap-SVP were found to be safe and effective, and in cases in which the tumor is relatively large or close to the splenic vessels, lap-WT can be used as the more appropriate procedure.

Evaluation of SOX9 Expression in Pancreatic Ductal Adenocarcinoma and Intraductal Papillary Mucinous Neoplasm

Objectives Sex-determining region Y (SRY) box 9 (SOX9) is an important transcription factor required for development and has been implicated in several types of cancer. Sex-determining region Y box 9 has never been linked to pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The aim of this study was to investigate the relationship between SOX9 and PDAC and that between SOX9 and IPMN. Methods Surgical specimens were obtained from 55 patients with PDAC and 68 patients with IPMN and were investigated using SOX9 immunohistochemical analysis. Results The rate of SOX9 positive cells to total pancreatic duct epithelial cells in a normal pancreas was 82.7%. On the other hand, the SOX9 positive rate in PDAC was 0.8%. There was a significant difference between the normal pancreas and PDAC (P = 0.0002). In IPMN, the SOX9 positive rate gradually decreased according to tumor progression, with the following rates observed: intraductal papillary mucinous adenoma (66.3%); noninvasive intraductal papillary mucinous carcinoma (46.3%); minimally invasive intraductal papillary mucinous carcinoma (30.5%); and invasive carcinoma originating in intraductal papillary mucinous carcinoma (2.3%). There were significant differences between each group (P < 0.05). Conclusions Our data suggested that SOX9 might contribute to carcinogenesis in PDAC and IPMN.

Endoscopic transpapillary pancreatic stenting for internal pancreatic fistula with the disruption of the pancreatic ductal system

BACKGROUND Internal pancreatic fistula (IPF) is a well-recognized complication of pancreatic diseases. Although there have been many reports concerning IPF, the therapy for IPF still remains controversial. We herein report our experiences with endoscopic transpapillary pancreatic stent therapy for IPF and evaluate its validity. METHOD Six patients with IPF who presented at our department and received endoscopic transpapillary pancreatic stent therapy were investigated, focusing on the clinical and imaging features as well as treatment strategies, the response to therapy and the outcome. RESULTS All patients were complicated with stenosis or obstruction of the main pancreatic duct, and in these cases the pancreatic ductal disruption developed distal to the areas of pancreatic stricture. The sites of pancreatic ductal disruption were the pancreatic body in five patients and the pancreatic tail in one patient. All patients received endoscopic stent placement over the stenosis site of the pancreatic duct. Three patients improved completely and one patient improved temporarily. Finally, three patients underwent surgical treatment for IPF. All patients have maintained a good course without a recurrence of IPF. CONCLUSION Endoscopic transpapillary pancreatic stent therapy may be an appropriate first-line treatment to be considered before surgical treatment. The point of stenting for IPF is to place a stent over the stenosis site of the pancreatic duct to reduce the pancreatic ductal pressure and the pseudocysts pressure.

Gastric rupture with necrosis following acute gastric dilatation: report of a case

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.

A Method for Performing Islet Transplantation Using Tissue-Engineered Sheets of Islets and Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) are known to have a protective effect on islet cells. Cell sheets developed using tissue engineering help maintain the function of the cells themselves. This study describes a tissue engineering approach using islets with MSC sheets to improve the therapeutic effect of islet transplantation. MSCs were obtained from Fischer 344 rats and engineered into cell sheets using temperature-responsive culture dishes. The islets obtained from Fischer 344 rats were seeded onto MSC sheets, and the islets with MSC sheets were harvested by low-temperature treatment after coculture. The functional activity of the islets with MSC sheets was confirmed by a histological examination, insulin secretion assay, and quantification of the levels of cytokines. The therapeutic effects of the islets with MSC sheets were investigated by transplanting the sheets at subcutaneous sites in severe combined immunodeficiency (SCID) mice with streptozotocin-induced diabetes. Improvement of islet function and viability was shown in situ on the MSC sheet, and the histological examination showed that the MSC sheet maintained adhesion factor on the surface. In the recipient mice, normoglycemia was maintained for at least 84 days after transplantation, and neovascularization was observed. These results demonstrated that islet transplantation in a subcutaneous site would be possible by using the MSC sheet as a scaffold for islets.

Hand-assisted laparoscopic total pancreatectomy for a main duct intraductal papillary mucinous neoplasm of the pancreas.

The laparoscopic approach to pancreatectomy entails a number of restrictions in performing major pancreatic surgery. This report describes a hand-assisted laparoscopic total pancreatectomy performed for a main duct intraductal papillary mucinous neoplasm of the pancreas. Dissection of the gastroduodenal artery and splenic artery, and the transection of the duodenum were done through the midline mini-laparotomy, while mobilization of the spleen and the pancreatic tail and body, and Kocher’s maneuver were performed using the hand-assisted laparoscopic approach. Furthermore, dissection of lymph nodes in the hepatoduodenal ligament, removal of the gallbladder, division of the hepatic duct, tunneling of the pancreas, and dissection of the pancreas from the superior mesenteric vein and superior mesenteric artery were possible to perform safely under a pure laparoscopic technique with an excellent laparoscopic view. The reconstruction procedures were performed through the mini-laparotomy. The hand-assisted laparoscopic total pancreatectomy should be considered for the treatment of selected patients because it has various advantages as one type of minimally invasive surgery.

Hybrid procedure in living donor liver transplantation.

BACKGROUND We have previously reported a hybrid procedure that uses a combination of laparoscopic mobilization of the liver and subsequent hepatectomy under direct vision in living donor liver transplantation (LDLT). We present the details of this hybrid procedure and the outcomes of the procedure. METHODS Between January 1997 and August 2014, 204 LDLTs were performed at Nagasaki University Hospital. Among them, 67 recent donors underwent hybrid donor hepatectomy. Forty-one donors underwent left hemihepatectomy, 25 underwent right hemihepatectomy, and 1 underwent posterior sectionectomy. First, an 8-cm subxiphoid midline incision was made; laparoscopic mobilization of the liver was then achieved with a hand-assist through the midline incision under the pneumoperitoneum. Thereafter, the incision was extended up to 12 cm for the right lobe and posterior sector graft and 10 cm left lobe graft procurement. Under direct vision, parenchymal transection was performed by means of the liver-hanging maneuver. The hybrid procedure for LDLT recipients was indicated only for selected cases with atrophic liver cirrhosis without a history of upper abdominal surgery, significant retroperitoneal collateral vessels, or hypertrophic change of the liver (n = 29). For total hepatectomy and splenectomy, the midline incision was sufficiently extended. RESULTS All of the hybrid donor hepatectomies were completed without an extra subcostal incision. No significant differences were observed in the blood loss or length of the operation compared with conventional open procedures. All of the donors have returned to their preoperative activity level, with fewer wound-related complaints compared with those treated with the use of the conventional open procedure. In recipients treated with the hybrid procedure, no clinically relevant drawbacks were observed compared with the recipients treated with a regular Mercedes-Benz-type incision. CONCLUSIONS Our hybrid procedure was safely conducted with the same quality as the conventional open procedure in both LDLT donors and recipients.

Chemopreventative effect of an inducible nitric oxide synthase inhibitor, ONO-1714, on inflammation-associated biliary carcinogenesis in hamsters

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.

Sox9 expression in carcinogenesis and its clinical significance in intrahepatic cholangiocarcinoma

BACKGROUND Intrahepatic cholangiocarcinomas develop through a multi-step carcinogenesis. Precancerous lesions are defined as biliary intraepithelial neoplasia. Sex determining region Y-box9 (Sox9) is required for the normal differentiation of the biliary tract. AIMS To evaluate the Sox9 expression in carcinogenesis and its correlation with clinicopathological features in intrahepatic cholangiocarcinoma. METHODS Sox9 expression in normal epithelium, biliary intraepithelial neoplasia, and intrahepatic cholangiocarcinoma were investigated immunohistochemically using 43 specimens of intrahepatic cholangiocarcinoma. Sox9 expression in intrahepatic cholangiocarcinoma was compared with the clinicopathological features. The molecular effects of Sox9 were investigated by gene transfection to intrahepatic cholangiocarcinoma cell lines. RESULTS Sox9 expression was decreased from the normal epithelium to the biliary intraepithelial neoplasia in a stepwise fashion. In 51.2% (22/43) of the patients with intrahepatic cholangiocarcinoma, Sox9 expression was positive, and Sox9 expression was significantly associated with the biliary infiltration (P=0.034) and poor overall survival (P=0.039). Upregulation of Sox9 promoted the cell migration and invasion, and decreased the E-cadherin expression and increased the vimentin and α-SMA expression in cell lines. CONCLUSIONS Decreased Sox9 expression may be related to the early stage of the carcinogenesis of intrahepatic cholangiocarcinoma. Sox9 overexpression in intrahepatic cholangiocarcinoma is related to biliary infiltration and poorer prognosis, and it promotes cell migration and invasion, via the epithelial-to-mesenchymal transition.