Case Report: Myxedema Coma Caused by Immunoglobulin A Vasculitis in a Patient With Severe Hypothyroidism.

Myxedema coma is a critical disorder with high mortality rates. Disruption of the compensatory mechanism for severe and long-term hypothyroidism by various causes leads to critical conditions, including hypothermia, respiratory failure, circulatory failure, and central nervous system dysfunction. Infectious diseases, stroke, myocardial infarction, sedative drugs, and cold exposure are considered the main triggers for myxedema coma. A 59-year-old Japanese woman presented with bilateral painful purpura on her lower legs. She was diagnosed with coexisting immunoglobulin A (IgA) vasculitis and severe IgA vasculitis with nephritis and was consequently treated with intravenous methylprednisolone (125 mg/day). However, she rapidly developed multiple organ failure due to the exacerbation of severe hypothyroidism, i.e., myxedema. Her condition improved significantly following oral administration of prednisolone along with thyroxine. There was a delayed increase in the serum free triiodothyronine level, while the serum free thyroxine level was quickly restored to normal. Rapid deterioration of the patient's condition after admission led us to diagnose her as having myxedema coma triggered by IgA vasculitis. Hence, clinicians should be aware of the risks of dynamic exacerbations in patients with hypothyroidism. Furthermore, our study suggested that combination therapy with thyroxine and liothyronine might prove effective for patients with myxedema coma, especially for those who require high-dose glucocorticoid administration.

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.

Gastric wall-covering method for the prevention of pancreatic fistula after pancreatic resection.

A pancreatic fistula is one of the most frequent complications and is still responsible for most mortality after pancreatic surgery. We propose a gastric wall-covering method, a new and novel surgical technique in pancreatic surgery for the prevention of pancreatic fistula, in which the pancreatic cutting surface is covered completely with the gastric wall. Ten patients underwent our new surgical technique, gastric wall-covering method, in 7 patients with distal pancreatectomy and in 3 with partial resection of the head of the pancreas. There were no episodes of pancreatic fistula or any complications. Our novel technique is simple, technically feasible, and useful for the prevention of the pancreatic leakage following pancreatic surgery.

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.

Risk factors for pancreatic anastomotic leakage: the significance of preoperative dynamic magnetic resonance imaging of the pancreas as a predictor of leakage.

BACKGROUND: The histologic degree of pancreatic fibrosis can be assessed preoperatively by using the time-signal intensity curve (TIC) of the pancreas obtained from dynamic magnetic resonance imaging. STUDY DESIGN: To identify risk factors for postoperative pancreatic anastomotic leakage and to assess the impact of pancreatic TIC on this complication, 89 patients who underwent a pancreatic head resection with an end-to-side pancreaticojejunostomy between December 1998 and August 2005 were retrospectively reviewed. The pancreatic TIC profiles were classified into 3 types: type I, indicating a normal pancreas without fibrosis; and types II and III indicating fibrotic pancreas. RESULTS: Pancreaticojejunal anastomotic leakage occurred in 14 patients (16%). In a univariate analysis, pancreatic texture (hard, 3% versus intermediate, 20% versus soft, 23%; p = 0.046), pancreatic duct size (> 3 mm, 8% versus 6.0%) than in those with a normal hemoglobin A1c level. CONCLUSIONS: Pancreatic TIC from dynamic MRI provides reliable information for predicting risk of pancreatic anastomotic leakage after pancreatic head resection. Especially in patients with type I pancreatic TIC, the presence of uncontrolled diabetes is considered a primary risk factor for postoperative pancreatic leakage.

Parapapillary choledochoduodenal fistula associated with cholangiocarcinoma.

Parapapillary choledochoduodenal fistula is a rare disorder. We herein report a case of parapapillary choledochoduodenal fistula associated with cholangiocarcinoma. A 61-year-old woman was admitted to our hospital for further examination of a liver tumor. She had no clinical symptoms, but computed tomography scans showed an irregularly contoured liver tumor which was histologically confirmed to be adenocarcinoma, by a needle biopsy examination. Duodenal fiberscopy revealed a fistula orifice 1.0 cm proximal to the orifice of the papilla of Vater, and endoscopic retrograde cholangiography through the fistula showed a communication to the common bile duct. Hypotonic duodenography demonstrated reflux of contrast material into the choledochoduodenal fistula. The bile sample collected from the common bile duct showed extremely high levels of pancreatic enzymes, including amylase, phospholipase-A2, and elastase-I. Furthermore, Helicobacter DNA was detected in bile by polymerase chain reaction (PCR) analysis. This experience suggests to us that parapapillary choledochoduodenal fistula may be a risk factor for biliary tract carcinoma, and surgical management is the treatment of choice for this rare condition, even when the patient has no significant clinical symptoms.

Chemopreventative effect of a cyclooxygenase-2-specific inhibitor (etodolac) on chemically induced biliary carcinogenesis in hamsters.

The present study was designed to evaluate whether etodolac, a cyclooxgenase-2 (COX-2)-specific inhibitor, could prevent chemically induced biliary carcinogenesis in bilioenterostomized hamsters. Syrian golden hamsters were subjected to choledochojejunostomy and then received subcutaneous injections of N-nitrosobis(2-oxopropyl)amine (BOP) every 2 weeks at a dose of 10 mg/kg body wt. BOP administration was started 4 weeks after surgery, and continued for 18 weeks. The animals were simultaneously orally administered etodolac three times per week at a dose of 10 mg/kg body wt in 0.5% methylcellose solution (etodolac group). The control hamsters were administered methylcellose solution alone. The hamsters were killed 22 weeks after surgery, and the biliary carcinomas were evaluated histologically. The presence and degree of cholangitis and the cell kinetic status of the biliary epithelium were also evaluated with special reference to biliary carcinogenesis. Intrahepatic bile duct carcinomas developed in 15 of 17 (88%) hamsters in the control group, and in only six of 18 (33%) hamsters in the etodolac group (P < 0.01). The incidence and number of developing biliary carcinomas were well correlated with the degree of cholangitis, and severe cholangitis was evident in the controls. The cell kinetic study demonstrated that the proliferating cell nuclear antigen-labeling index of the biliary epithelium was 9.67 and 5.14% in the control and etodolac groups, respectively (P < 0.05). The mean levels of prostaglandin E(2) (PGE(2)) products in the liver tissue were 14.14 +/- 3.31 pg/total protein (TP) mg in the control group, and 7.46 +/- 2.34 pg/TP mg in the etodolac group (P < 0.05). These findings indicated that etodolac reduced both the occurrence of severe cholangitis and the acceleration of biliary epithelial cell kinetics after bilioenterostomy, resulting in the prevention of BOP-induced biliary carcinogenesis in hamsters. In conclusion, COX-2-specific inhibitor (etodolac) may be a possible agent against not only reflux cholangitis, but also biliary carcinoma after bilioenterostomy.

Comparative analysis of Helicobacter DNAs and biliary pathology in patients with and without hepatobiliary cancer.

Several Helicobacter species have recently been isolated from the bile and hepatobiliary systems of murine species, and are well recognized as a pathogen of the hepatobiliary disorder. This study was planned to investigate whether Helicobacter species possess a causative potential for human hepatobiliary disease, especially for hepatobiliary carcinogenesis. Bile and hepatobiliary tissue samples from 19 patients with hepatobiliary cancer and 19 patients with benign biliary diseases were subjected to polymerase chain reaction analyses for the detection of Helicobacter DNAs. Using a proliferating cell nuclear antigen (PCNA) staining technique, we also investigated the biliary epithelial cell kinetics with special reference to the presence of Helicobacter DNAs in the hepatobiliary system. We found that Helicobacter DNAs were positive in 10 (52.6%) of the 19 patients with hepatobiliary cancer. The incidence was significantly higher than that (15.7%) in the benign cases (P = 0.03). The PCNA labeling index in the biliary epithelium in Helicobacter DNA-positive patients was statistically higher than that in Helicobacter DNA-negative ones, regardless of whether the patient was suffering from hepatobiliary cancer and/or biliary inflammation. A close correlation between the presence of Helicobacter DNAs and an elevation of the PCNA labeling index in the biliary epithelium was demonstrated by multiple regression analysis. Our findings suggest that Helicobacter species may play a role in the pathogenesis of hepatobiliary cancer through an acceleration of biliary cell kinetics.

Helicobacter pylori accelerates the biliary epithelial cell proliferation activity in hepatolithiasis.

BACKGROUND/AIMS: Several authors have reported the presence of H. pylori in the human biliary tract. The aim of this study was to investigate the influence of the presence of H. pylori on the epithelial cell proliferation activity in the biliary tract with hepatolithiasis. METHODOLOGY: A histopathological examination and polymerase chain reaction were used to detect the presence of H. pylori from fourteen patients with hepatolithiasis. The cell proliferation activity in the biliary epithelia was determined using proliferating cell nuclear antigen staining. RESULTS: A histopathological examination and polymerase chain reaction analysis demonstrated H. pylori to be detected in 5 (37%) and 4 (29%) out of 14 patients, respectively. The proliferating cell nuclear antigen labeling index was significantly higher in the H. pylori-positive patients (28.3%) than in the H. pylori-negative individuals (4.9%). CONCLUSIONS: H. pylori is present in the biliary tract of patients with hepatolithiasis, while H. pylori promotes the formation of stones in the biliary tract. The development of intrahepatic cholangiocarcinoma might therefore be linked to the presence of H. pylori because of the accelerated activity of cell kinetics in the epithelium of the biliary tract.

Pre- and intraoperative evaluation of biliary system for successful laparoscopic cholecystectomy in porcelain gallbladder patients.

BACKGROUND/AIMS: A porcelain gallbladder is generally thought to be a relative contraindication for laparoscopic cholecystectomy because of the difficulties in grasping the calcified wall of the gallbladder with forceps and making a retraction which would create a good operation field. The aim of this study was to define the clinical criteria for safe laparoscopic cholecystectomy in the treatment of porcelain gallbladders. METHODOLOGY: Between January 1993 and December 2000, 4 patients with porcelain gallbladders underwent laparoscopic cholecystectomy in our department. The significant features of the biliary system which contributed to the surgical results were investigated in these patients. RESULTS: All 4 patients were successfully treated by means of laparoscopic cholecystectomy. The confluence of the cystic duct was clearly demonstrated on the preoperative cholangiogram in all patients. Furthermore, the neck portion of the gallbladder wall, revealed no calcification on the CT scans of 3 patients, although the whole wall of the gallbladder, including the neck portion, showed a circumferential calcification in the remaining patient. Laparoscopic exposure and dissection of the Calot's triangle was relatively easy to perform in the former and was difficult in the latter, and thus, an anterograde laparoscopic cholecystectomy was the procedure of choice. Intraoperative cholangiography clearly demonstrated the confluence of the cystic duct in all of the patients. CONCLUSIONS: Porcelain gallbladder is an indication for laparoscopic cholecystectomy, especially in cases of a patent cystic duct and an uncalcified wall in the neck portion of the gallbladder. Laparoscopic cholecystectomy might be an indication for selected patients with porcelain gallbladder when an uncalcified and patent cystic duct are evident in pre- and intraoperative cholangiograms.