Dietary zinc supplementation to the donor improves insulin secretion after islet transplantation in chemically induced diabetic rats.

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.

A novel animal model of long-term sustainable anal sphincter dysfunction.

BACKGROUND: Although intersphincteric resection can avoid the need for permanent colostomy in patients with lower rectal cancer, it sometimes causes anal sphincter dysfunction, thus resulting in a lifelong, debilitating disorder due to incontinence of solid and liquid stool. The development of regenerative medicine could improve this condition by regenerating impaired anal muscle. In order to prove this hypothesis, preliminary experiments in animals will be indispensable; however, an adequate animal model is currently lacking. The purpose of this study was to establish a novel animal model with long-term sustainable anal sphincter dysfunction. MATERIALS AND METHODS: Twenty male Sprague-Dawley rats were allocated into sham operation (n = 10) and anal sphincter resection (ASR) (n = 10) groups. The ASR group underwent removal of the left half of both the internal and external anal sphincters. Both groups were evaluated for anal function by measuring their resting pressure before surgery and on postoperative day (POD) 1, 7, 14, and 28. RESULTS: The rats in the sham operation group recovered their anal pressure up to baseline on POD 7. The rats in the ASR group showed a significant decrease in anal pressure on POD 1 (P < 0.0001) compared with the baseline, and kept this low pressure until POD 28 (P < 0.0001). The defect of the anal sphincter muscle was confirmed histologically in the ASR group on POD 28. CONCLUSIONS: The present novel model exhibits continuous anal sphincter dysfunction for at least 1 mo and may contribute to further studies evaluating the efficacy of therapies such as regenerative medicine.

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.

Limited pancreatectomy for metastatic pancreatic tumors from renal cell carcinoma.

BACKGROUND/AIMS: 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. METHODOLOGY: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

Intraductal papillary mucinous neoplasm of the pancreas with a bifid pancreatic duct.

A bifid pancreatic duct presenting a major bifurcation in the main pancreatic duct is one of the anatomical variations of the pancreatic ducts. We encountered a 71-year-old female with a 5-cm-diameter branch duct intraductal papillary mucinous neoplasm of the pancreas in whom preoperative endoscopic retrograde pancreatography demonstrated an anomalous bifurcation of the main pancreatic duct at the body of the pancreas. We performed a distal pancreatectomy, instead of a middle pancreatectomy, with a cutting line at the downstream pancreas to the duct bifurcation point. Intraoperative ultrasonography was useful to confirm the exact location of the pancreatic duct bifurcation as well as the tumor extension. The procedure resulted in a favorable outcome without any postoperative complications. Although a bifid pancreatic duct is an unusual anomalous condition, this case should alert surgeons to be aware of such anatomical variants when performing pancreatic resection, otherwise, incurable pancreatic complications may occur postoperatively.

Chemopreventative effect of hochu-ekki-to (TJ-41) on chemically induced biliary carcinogenesis in hamsters.

BACKGROUND: Bilioenterostomy is a common surgical technique that is widely used. Recently, clinical studies have revealed that biliary carcinomas can occur after bilioenterostomy. The present study was designed to evaluate whether hochu-ekki-to (TJ-41), a Japanese herbal drug, could prevent chemically induced biliary carcinomas in bilioenterostomized hamsters. MATERIALS AND METHODS: Syrian golden hamsters were subjected to choledochojejunostomy and then received subcutaneous injections of N-nitrosobis(2-oxopropyl) amine every 2 weeks at a dose of 10 mg/kg. N-nitrosobis(2-oxopropyl) amine administration was started 4 weeks after surgery. The animals were simultaneously p.o. administered TJ-41 in water every day at a dose of 1000 mg/kg (TJ-41 group). The control hamsters were administered water alone. The hamsters were sacrificed 22 weeks after surgery, and the development of biliary carcinomas, the presence and degree of cholangitis, and the cell kinetic status of the biliary epithelium were evaluated histologically. RESULTS: Intrahepatic bile duct carcinomas developed in 15/17 (88%) hamsters in the control group and in only 8/17 (47%) hamsters in the TJ-41 group (P < 0.05). The degree of cholangitis was not different between the two groups. However, the proliferating cell nuclear antigen labeling index of the biliary epithelium in the TJ-41 group (6.46%) was significantly lower than the controls (9.67%) (P < 0.05). These findings indicated that TJ-41 reduced accelerated biliary epithelial cell kinetics after bilioenterostomy, resulting in the prevention of carcinogenesis. CONCLUSION: TJ-41 has a preventive effect on chemically induced carcinoma of the biliary tract after bilioenterostomy.

A jejunal wall-covering method following central pancreatectomy for prevention of a pancreatic fistula: a novel technique.

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.

Multifocal branch-duct pancreatic intraductal papillary mucinous neoplasms.

The appropriate management for patients with multifocal branch-duct intraductal papillary mucinous neoplasms (IPMNs) of the pancreas involving the entire pancreatic gland remains unclear. We present a 66-year-old woman who underwent pylorus-preserving pancreaticoduodenectomy for a branch-duct intraductal papillary mucinous carcinoma demonstrating a grape-like multilocular cyst, 35 mm in diameter, in the head of the pancreas along with numerous number of small branch-duct IPMNs in the whole pancreas. Histologically, the multifocal cystic lesions were lined by a single row of columnar mucin-containing epithelial cells without atypia. The patient has been doing well without any recurrence during 9-year follow-up after surgery. Surgical removal of the prominent lesions suspicious of malignancy and a close observation of the remaining lesions in the remnant pancreas may be a reasonable treatment plan for patients with multifocal branch-duct IPMNs involving the entire pancreatic gland.

Chemopreventive effects of a selective cyclooxygenase-2 inhibitor (etodolac) on chemically induced intraductal papillary carcinoma of the pancreas in hamsters.

The present study was designed to determine whether etodolac, a selective cyclooxygenase-2 inhibitor, prevents chemically induced intraductal papillary carcinoma (IPC) in the main pancreatic duct of hamsters. Hamsters were subjected to cholecystoduodenostomy with dissection of the distal end of the common duct. Four weeks after surgery, the surviving hamsters received subcutaneous injections of N-nitrosobis(2-oxopropyl)amine four times at a dose of 10 mg/kg body wt, every 2 weeks. The animals were divided into three groups according to the simultaneous oral intake of a standard pelleted diet containing etodolac at 0% (group CE, n = 30), 0.01% (group ET, n = 21) and 0.04% (group ET4, n = 25), respectively. Hamsters were killed for pathological examination at 36 weeks after the operation. The incidence of induced pancreatic carcinoma was 93, 81 and 72% in groups CE, ET and ET4, respectively. The pancreatic carcinomas were histologically classified into four types, i.e. tubular, papillary, cyst adenocarcinoma and IPC. The incidence of IPC and the number of IPCs per animal were significantly lower in groups ET4 (36% and 0.48) and ET (48% and 0.62) when compared with group CE (67% and 1.30). The proliferating cell nuclear antigen labeling indices in the non-cancerous epithelial cells of the main pancreatic duct were 2.8 and 6.8% in groups ET4 and ET, respectively, and were significantly lower than that in group CE (10.8%). In conclusion, etodolac inhibited N-nitrosobis(2-oxopropyl)amine-induced IPC in hamsters. Suppression of epithelial cell proliferation of the main pancreatic duct was considered as a possible mechanism of cancer prevention in this hamster model.

Inflammatory cytokines promote inducible nitric oxide synthase-mediated DNA damage in hamster gallbladder epithelial cells.

AIM: To investigate the link between chronic biliary inflammation and carcinogenesis using hamster gallbladder epithelial cells. METHODS: Gallbladder epithelial cells were isolated from hamsters and cultured with a mixture of inflammatory cytokines including interleukin-1beta, interferon-gamma, and tumor necrosis factor-alpha. Inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO) generation, and DNA damage were evaluated. RESULTS: NO generation was increased significantly following cytokine stimulation, and suppressed by an iNOS inhibitor. iNOS mRNA expression was demonstrated in the gallbladder epithelial cells during exposure to inflammatory cytokines. Furthermore, NO-dependent DNA damage, estimated by the comet assay, was significantly increased by cytokines, and decreased to control levels by an iNOS inhibitor. CONCLUSION: Cytokine stimulation induced iNOS expression and NO generation in normal hamster gallbladder epithelial cells, which was sufficient to cause DNA damage. These results indicate that NO-mediated genotoxicity induced by inflammatory cytokines through activation of iNOS may be involved in the process of biliary carcinogenesis in response to chronic inflammation of the biliary tree.

Biliary navigation surgery using endoscopic nasobiliary drainage tube for the prevention of bile duct injury in laparoscopic cholecystectomy.

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.

Evaluation and management of thoracopancreatic fistula.

BACKGROUND: Thoracopancreatic fistula is a rare clinical entity but a serious complication of inflammatory pancreatic diseases, caused by a disruption of the pancreatic ductal system. Its diagnosis is frequently misleading, however, and thus is often delayed. METHODS: Seven patients with thoracopancreatic fistula who presented at our department between March 2002 and July 2005 were investigated, focusing on the diagnostic work-up as well as the treatment strategies, the response to therapy, and the outcome. RESULTS: Thoracopancreatic fistulas developed secondary to alcohol-related chronic pancreatitis in 6 patients and acute severe pancreatitis in 1. The disruption sites of the pancreatic ductal system were the head of the pancreas in 2 patients, the pancreatic body in 2 patients, and the pancreatic tail in 3 patients. All patients, except 1, were complicated with stricture of the main pancreatic duct, with ductal disruptions developing distal to the pancreatic strictures. The precise demonstration of the pancreatic ductal anatomy with ultrasonography, computed tomography (CT), conventional magnetic resonance imaging (MRI), and endoscopic retrograde cholangiopancreatography was limited. In contrast, MR-cholangiopancreatography (MRCP) provided excellent mapping of the pancreatic ductal stricture, disruption, and fistula in 6 patients. Various medical therapies failed to close the fistula in all patients. Subsequent treatments, based on the assessment of pancreatic ductal anatomy with MRCP, included endoscopic transpapillary implantation of a pancreatic stent, a longitudinal pancreaticojejunostomy, distal pancreatectomy, and peritoneal drainage. All patient outcomes were favorable. CONCLUSIONS: MRCP is an essential diagnostic modality in all suspected cases of thoracopancreatic fistula. The goal of treatment should be directed toward a sufficient decompression of the obstructed pancreas. If severe pancreatic stricture is present, then surgical decompression may be required in accordance with the individual pancreatic ductal anatomy.

Acute suppuration of the pancreatic duct associated with pancreatic ductal obstruction due to pancreas carcinoma.

Acute obstructive suppurative cholangitis is a well-known clinical entity; however, acute suppuration of the pancreatic duct in the setting of pancreatic ductal obstruction is an uncommon pancreatic disorder. We report a case of acute suppuration of the pancreatic duct without either a concomitant pancreatic abscess or an infected pseudocyst, presenting as acute relapsing pancreatitis. In this case, the underlying cause of suppuration of the pancreatic duct was pancreatic ductal obstruction and chronic pancreatitis secondary to pancreas head carcinoma along with infection of Escherichia coli. Endoscopic placement of a pancreatic stent resulted in an evacuation of grayish thick pus from the distal pancreatic duct with a dramatic improvement of the disease. This case proposes the concept that acute suppuration of the pancreatic duct is a complex process involving the chronically damaged pancreas, pancreatic outflow obstruction, and subsequent bacterial infection. Antibiotic treatment is effective but temporary; therefore, the immediate drainage of the infected pancreatic duct is mandatory.

Bile-reflux into the pancreatic ducts is associated with the development of intraductal papillary carcinoma in hamsters.

BACKGROUND: Reflux of pancreatic juice into the biliary tract is a well-known risk factor for the development of biliary carcinoma. In this study, we investigated the significance of bile-reflux into the pancreatic ducts in pancreatic carcinogenesis, especially in the development of carcinoma in the main pancreatic duct in hamsters. MATERIALS AND METHODS: Syrian hamsters were subjected to three different surgical procedures: cholecystoduodenostomy with dissection of the extrahepatic bile duct on the distal end of the common duct (Model A); cholecystoduodenostomy along with a dissection of the common bile duct (Model B); or simple laparotomy (Model C). The animals then received weekly subcutaneous injections of N-nitrosobis(2-oxopropyl)amine (BOP), for 9 weeks, and were killed for pathological investigation at 16 weeks after the initial BOP administration. RESULTS: Pancreas carcinomas developed in 95, 88, and 90% of the Model A hamsters (n = 22), B (n = 24), and C (n = 21), respectively. The induced pancreatic tumors were histologically classified into four types: papillary; tubular; cystic adenocarcinoma; or intraductal carcinoma of the main pancreatic duct consisting of intraductal papillary carcinoma (IPC) and intraductal tubular carcinoma (ITC). The number and the incidence of IPCs induced in Model A hamsters were 24 lesions and 77% and were statistically higher than those in Model B (7 lesions and 29%) and C hamsters (7 lesions and 33%) (P < 0.01). Bile-reflux into the pancreatic ducts was clearly demonstrated in only hamsters of Model A by means of Indocyanine green injection via the portal vein. Proliferative cell nuclear antigen labeling indices of the epithelial cells in the main pancreatic duct in hamsters, with no BOP treatment, were 3.8, 0.8, and 1.1% in Models A (n = 10), B (n = 10), and C (n = 10), respectively, and the difference was statistically significant (P < 0.01). CONCLUSIONS: Our findings suggest that bile-reflux into the pancreatic ducts is a significant factor predisposing to the development of IPC of the pancreas through an acceleration of epithelial cell kinetics of the main pancreatic duct.

Intraoperative pancreatography and gastric-wall-covering method for the prevention of pancreatic leakage after enucleation of insulinoma in the pancreas.

Pancreatic leakage is one of the most common complications following pancreatic surgery. Although several surgical techniques and several devices for the management of pancreatic ducts have been advocated to prevent pancreatic leakage, its incidence is still not acceptable. We report our new surgical technique, a gastric-wall-covering method, for the prevention of pancreatic leakage in the enucleation of insulinoma in the pancreas, along with intraoperative pancreatography for navigation surgery of the pancreatic duct. Our novel techniques help to prevent pancreatic leakage following pancreatic surgery, including partial resection of the pancreas.

Demonstration of a biliobronchial fistula with a hepatoiminodiacetic acid scan.

Biliobronchial fistula (BBF) is a rare complication after hepatic resection. A 68-year-old woman who had undergone a right hepatic trisegmentectomy followed by a hepaticojejunostomy with a Roux-en-Y anastomosis for gallbladder cancer and liver metastasis from colon cancer was admitted to our hospital for further investigation of persistent bilioptysis. We could not detect the cause of the bilioptysis on computed tomography or magnetic resonance cholangiopancreatography, but a hepatoiminodiacetic scan clearly showed the BBF. Endoscopic retrograde cholangiography is thought to be suitable for diagnosing BBF, but it is invasive and unavailable in patients who have undergone digestive reconstruction, such as a Roux-en-Y anastomosis. In such cases, hepatoiminodiacetic scanning should be used for diagnosing BBF.

Inferior branch-preserving superior head resection of the pancreas with gastric wall-covering method for intraductal papillary mucinous adenoma.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas showed significantly less aggressive pathologic features compared with common pancreatic cancer. Therefore, several organ-preserving techniques, including duodenum-preserving pancreatic head resection, have been advocated in surgical procedures for IPMN. We describe a surgical technique of superior head resection of the pancreas with inferior branch preservation followed by a gastric wall-covering method for the prevention of pancreatic leakage in patients with IPMN of the pancreas head.