Osteopenia in primary biliary cirrhosis and cirrhosis of the liver in women,evaluated by dual-energy X-ray absorptiometry

To study bone involvement in primary biliary cirrhosis (PBC), we used dual-energy X-ray absorptiometry to measure bone mineral density (BMD) in Japanese women with PBC and with cirhosis of the liver. In both groups, in each decade up to 60 years of age, the mean BMD of the lumbar spine was not significantly different from that in healthy Japanese women; however, in patients aged 60 years or more, the level was significantly lower both in the patients with PBC (P<0.001) and in those with cirrhosis of the liver (P<0.01). Patients with PBC were also examined by single-photon absorptiometry. The BMD of the radius in the patients with PBC was less changed than that of the lumbar vertebrae; thus, the bone changes in PBC seem to be greater in spongy than in cortical bone.     

Cell kinetic study of the gallbladder epithelium,with special reference to the pancreaticobiliary maljunction

The bromodeoxyuridine labelling index (BrdU-LI), ornithine decarboxylase (ODC) activity, and bile elements in the gallbladder were examined in 23 patients to investigate cell kinetics and oncogenesis in gallbladder epithelium with pancreaticobiliary maljunction (PBMJ). The patients were classified into five groups: group I (4 patients without biliary disorder), group II (8 patients with cholecystolithiasis), group III (4 patients with PBMJ), group IV (3 patients with gallbladder cancer and PBMJ), and group V (4 patients with gallbladder cancer). In non-cancerous epithelium, the BrdU-LI in groups III (2.88±3.07%), IV (4.92±2.73), and V (5.93±2.08) was significantly higher than in group I (0.06±0.12), and the ODC activity in groups III (7.83±6.82 pmole CO₂/h per mg protein), IV (17.21±9.44), and V (11.27±12.33) was also significantly higher than that in group I (1.39±1.78). Both BrdU-LI and ODC activity were high in epithelium showing metaplasia in 3 patients from groups III and IV. In groups I and II, the lithocholic acid (LCA) fraction showed a positive correlation with BrdU-LI (correlation coefficient, 0.90) and ODC activity (correlation coefficient, 0.91). From these results, it can be concluded that the gallbladder epithelium in patients with PBMJ, and its metaplastic changes, show an increase in cell proliferation, which is important in the progression of cancer.     

Biosynthesis and secretion of mucin-related products in Hs746T gastric cancer cells

We have previously studied the biosynthesis and secretion of mucin in the normal human stomach and reported that the tetramer of the 60-kDa subunit of mucin core protein was synthesized and highly glycosylated, and that only high molecular weight mucin was secreted. In this study, we investigated the mucin-related products of a gastric cancer cell line (Hs746T). Analysis of intracellular and extracellular products immunoprecipitated with an anti-apomucin monoclonal antibody revealed that a 110-kDa protein, the dimer of the 55-kDa subunit, was synthesized and secreted. Tunicamycin treatment inhibited the secretion of the 110-kDa protein. These findings suggest thatN-glycosylation may be involved in the secretory mechanism of the mucin-related product.     

Histogenesis of hyperplastic polyps of the stomach in terms of cellular proliferation

We investigated the histogenesis of hyperplastic polyps of the stomach, in terms of cellular proliferation, by studying endoscopically removed and gastrectomized human gastric polyps either labeled with bromodeoxyuridine (BrdU) by in vitro flash labeling techniques or labeled in an isolated organ circulation system, in both of which, perfluorochemical artificial blood was employed. Immunohistochemistry with antibodies against BrdU and proliferating cell nuclear antigen (PCNA) was simultaneously employed. The generative cell zone of pedunculated and semipedunculated polyps was markedly expanded compared with that of the background mucosa, and this change also appeared in sessile polyps, although to a lesser degree. Enhanced proliferative activity was observed in both epithelial and stromal cells in areas of erosion. Our results demonstrate that the initial change in the histogenesis of hyperplastic polyps is an expansion of the generative cell zone, followed by interstitial edema and stromal cell proliferation, and that erosion can facilitate these changes. No correlation was found between the size of the polyps and the labeling indices. This finding explains, in part, the diversity of chronological changes in the size and shape of hyperplastic polyps.     

A retrospective study of the preventive effect of transarterial chemotherapy for intrahepatic recurrence of hepatocellular carcinoma after partial hepatectomy

A major problem in treating hepatocellular carcinoma (HCC) is intrahepatic recurrence after partial hepatectomy, despite the relatively early detection now possible due to recent developments in non-invasive diagnostic modalities. The present study evaluated the usefulness of preventive therapy for intrahepatic recurrence of HCC. In order to suppress intrahepatic recurrence in HCC patients at high risk of recurrence after tumor removal, we performed preventive transarterial chemotherapy in 23 such patients. Doxorubicin, at a dose of 0.5 mg/kg body weight, was administered, via a catheter inserted at the junction of the common hepatic artery and the gastroduodenal artery, every 2 weeks for the first 2 months, and every month thereafter for at least 1 year. The control group consisted of 30 patients with similar risk of recurrence who underwent partial hepatectomy during the same period without receiving transarterial preventive therapy. The 1-, 2-, 3-, and 5-year cumulative cancer-free survival rates in patients who received transarterial preventive chemotherapy after partial hepatectomy were 87.0%, 47.1%, 21.2%, and 21.2%, respectively, compared to 53.3%, 30.0%, 20.0%, and 13.3%, respectively, in the control group (P<0.05). The 1-, 2-, 3-, and 5-year cumulative overall survival rates were 95.7%, 81.2%, 58.4%, and 48.7%, respectively, in the preventive chemotherapy group, compared to 70.0%, 49.4%, 41.7%, and 19.5%, respectively, in the control group (P<0.05). Thus, the present study demonstrates the limited but significant effect of preventive transarterial chemotherapy for the intrahepatic recurrence of HCC after partial hepatectomy.     

Long-Term survivor of ruptured hepatocellular carcinoma after two hepatic resections

We report here a long-term survivor of ruptured hepatocellular carcinoma (HCC). A 37-year-old Japanese man complained of sudden abdominal pain after taking an alcoholic drink. Ultrasonographic examination showed a large amount of fluid in the abdominal cavity. Emergency laparotomy was performed. A solid mass showing extrahepatic growth was present in the right lobe of the liver. No active bleeding site was detected, but the tumor was covered with old blood coagula. The tumor was covered with the greater omentum to prevent further hemorrhage. Following assessment of the extent of the tumor and of liver function, delayed hepatectomy was performed. Histological examination indicated the tumor to be HCC. Twenty-six months after initial hepatic resection, partial resection of the liver was performed again for recurrent tumor. The patient has survived without recurrence for more than 5 years. The long survival was due, we believe to the liver being non-cirrhotic, the delayed hepatic resection, and the early detection of the recurrent tumor.     

Biochemical and metabolic assessments of liver graft preserved with oncotic oxygen carrier

The effect of an oxygen-carrying agent, as a component of the preservation solution, on the biochemical viability and energy metabolism of the graft in liver preservation was evaluated. Two preservation methods, simple hypothermic storage and continuous machine perfusion, both performed at 4°C for 48 h, were studied in male Lewis rats. Pyridoxylated hemoglobin-polyoxyethylene conjugate (PHP) was used as the oncotic oxygen carrier. University of Wisconsin (UW) solution served as a control solution. The test solution (PHP+UW) was a 1∶1 mixture of PHP and UW solutions with 4.0g% of hemoglobin. We observed that oxygen consumption during perfusion was significantly higher in the PHP+UW than in the UW group. Hepatic mitochondrial function and tissue adenosine-5′-triphosphate (ATP) levels were better preserved in the PHP+UW than in the UW group, and were also better preserved in continuous machine perfusion than in simple hypothermic storage. No significant differences were observed in perfusate biochemical parameters. These results indicate that the incorporation of an oxygen-carrying agent into preservation solution provides significantly better oxygen delivery to liver grafts, and may improve hepatic viability.     

Bile duct carcinoma following abdominal radiation for urologic neoplasms

This report concerns three cases of bile duct carcinoma which occurred 15–40 years after patients received treatment for urogenital neoplasia. All three patients had initially received radiation therapy in addition to urological surgery. Jaundice was the major clinical symptom of the second tumor. Two of the three patients were able to be surgically treated when presenting with their second carcinoma (partial pancreaticoduodenectomy, bile duct resection; central liver resection), whereas the third patient was in such a poor state of health that he was biopsied only and treated with a pigtail drain. All three patients died within 3 months to 3 years following the diagnosis of the second tumor. The more than coincidential occurrence of the rare bile duct carcinoma in our three patients with previous urogenital neoplasia warrants a new discussion concerning the connection between primary carcinoma, radiation therapy, and the occurrence of a second tumor.     

Lymphatic drainage of the gallbladder

Based upon detailed dissections of the lymphatic system in adult cadavers, the lymphatic drainage of the gallbladder was divided into three pathways: (1) The cholecystoretropancreatic pathway, which had two routes, one running spirally from the anterior surface of the common bile duct to the right rear, and the other running almost straight down from the posterior surface of the common bile duct. These routes converged at the principal retroportal node at the posterior surface of the head of the pancreas. (2) The cholecysto-celiac pathway; this was the route running to the left through the hepatoduodenal ligament to reach the celiac nodes. (3) The cholecysto-mesenteric pathway; this was the route running to the left in front of the portal vein to connect with the nodes at the superior mesenteric root. The cholecysto-retropancreatic pathway can be regarded as the main pathway, and the principal retroportal node appeared to be critical as the main terminal node in the visceral lymphatic system of the gallbladder. These three pathways converged with the abdomino-aortic lymph nodes near the left renal vein, and the nodes in the interaortico-caval space were considered to be of particular importance.     

Treatment of cholelithiasis with acetylcysteine,a new gallstone solvent

An improved technique for making thin sections of gallstones has enabled us to examine their morphology microscopically. Using this technique in various types of gallstones, we found a network of mucin, which was considered to play an important role in gallstone formation. The effectiveness of a mucolytic agent, acetylcysteine, for the direct dissolution of gallstones was evaluated in this study. Immersion in acetycysteine led to the prompt disintegration of various types of gallstones into small fragments. As acetylcysteine is commercially available as a mucolytic agent, a clinical trial was undertaken for the treatment of cholelithiasis (hepatolithiasis,n=5; choledocholithiasis,n=1). Because of the disintegrating effect of acetylcysteine, after the injection of this agent, many fragments flowed out through the percutaneous transhepatic biliary drainage tube. Acetylcysteine gallstone dissolution combined with percutaneous transhepatic cholangioscopic lithotripsy significantly aided the lithotriptic action, due to the disappearance of mucin from the bile duct. No side effects were observed either during or after the treatment. We concluded that acetylcysteine can be used as a new agent for the direct dissolution of most types of gallstones in patients with cholelithiasis.     

Comparison of Euro-Collins and University of Wisconsin solutions in adult human cadaveric liver transplantation

To characterize the potential utility of the University of Wisconsin (UW) solution, 37 grafts preserved in UW solution (UW group) were compared with 38 grafts preserved in Euro-Collins (EC) solution (EC group). Patients in both groups underwent similar perioperative management. Donor and recipient data in the two groups were similar. The mean cold ischemia time (CIT) of the UW group was 6.51±2.06 h (range: 3.17–14.65 h); this was significantly longer than that of the EC group, of 4.80±1.68 h (range: 1.67–8.83h) (P<0.05). There were no significant differences in actuarial patient or graft survival between the two groups. Blood concentrations of aspartate aminotransferase (AST) within 12 h and lactic dehydogenase (LDH) within 6 h of reperfusion were significantly lower in the UW group than in the EC group, each being (P<0.05). The total bilirubin (TBR) concentration was lower in the UW group than in the EC group, but the difference was not significant. Alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGTP), and prothrombin time (PT) showed no significant differences between the two groups. There was no difference in the frequency of complications or rejection episodes between the two groups. However, gender identical grafts had a lower rejection than gender non-identical grafts in the UW group (P<0.05). Our data suggest that the UW solution reduces transplantation-related graft injury compared with the EC solution.     

Impact of Diabetes Mellitus on the Clinical Response to Cardiac Resynchronization Therapy in Elderly People

Heart failure (HF) and type 2 diabetes mellitus (T2DM) exhibit a well-established interrelationship and a growing prevalence, in particular in elderly people. Cardiac resynchronization therapy (CRT) has been shown to improve myocardial function in patients with HF and cardiac dyssynchrony. However, reports on CRT in diabetic elderly patients are limited and controversial. Therefore, the aim of the present study was to investigate the functional role of T2DM on the effectiveness of CRT at advanced age. In this single-center prospective study, we enrolled 72 HF patients over 75 years old with and without T2DM who underwent CRT implant. Detailed clinical and instrumental data, including cardiac ultrasound analysis, 6-min walk test, and quality-of-life evaluation, were collected at baseline and at 1-year follow-up. At the time of implantation, 44.4 % of patients had T2DM, of which 62.5 % were well controlled with diet and hypoglycemic drugs and 37.5 % were treated by insulin therapy. After 1 year, CRT improved myocardial ventricular geometry and functional capacity in a comparable proportion of diabetic and non-diabetic patients alongside with a similar amelioration in the functional status. Taken together, our findings demonstrate that diabetic patients >75 years old exhibit a response to CRT that is comparable to non-diabetic subjects.     

Gross dissection and radiological studies of abnormal pancreatico-choledocho-ductal junction

The reliability of radiological diagnosis of abnormal pancreatico-choledocho-ductal junction (APCDJ) in comparison with findings of gross dissection of the pancreatic choledocho-ductal junction was studied in 8 patients, based on comparison between radiologic and macroscopic findings of the junction in 99 patients who had received pancreatoduodenectomy. APCDJ, that is the joining of the common bile duct and the pancreatic duct in the pancreatic parenchyma extraduodenally, was identified in 5 patients both radiologically and macroscopically. Macroscopically, the length of their common channel ranged from 20 to 32 mm. with a mean of 29 mm. In the other three patients, APCDJ was misdiagnosed radiologically, for the following reasons. In a patient with pancreatic carcinoma, a rather long common channel, 15 mm in length, while ran in the submucosal layer of the duodenum, was though to be APCDJ on radiologic examinations. In a patient with bile duct carcinoma, an abnormal closing between the common bile duct and the pancreatic duct due to carcinomatous infiltration of the pancreas led to a radiologication misinterpretation for APCDJ. In the last patient, APCDJ was identified only macroscopically, not radiologically, because of a relatively short common channel and the location of common bile duct carcinoma. Thus, APCDJ was clearly identified in patients with a long common channel, whereas it was difficult to identify in patients with a short common channel.     

Spinal Cord Stimulation for Heart Failure: Preclinical Studies to Determine Optimal Stimulation Parameters for Clinical Efficacy

Spinal cord stimulation with implantable devices has been used worldwide for decades to treat regional pain conditions and cardiac angina refractory to conventional therapies. Preclinical studies with spinal cord stimulation in experimental animal models of heart disease have described interesting effects on cardiac and autonomic nervous system physiology. In canine and porcine animals with failing hearts, spinal cord stimulation reverses left ventricular dilation and improves cardiac function, while suppressing the prevalence of cardiac arrhythmias. In this paper, we present further canine studies that determined the optimal site and intensity of spinal cord stimulation that produced the most robust and beneficial clinical response in heart failure animals. We then explore and discuss the clinically relevant aspects and potential impediments that may be encountered in translating spinal cord stimulation to human patients with advanced cardiac disease.     

Distinguishing Hypertrophic Cardiomyopathy-Associated Mutations from Background Genetic Noise

Despite the significant progress that has been made in identifying disease-associated mutations, the utility of the hypertrophic cardiomyopathy (HCM) genetic test is limited by a lack of understanding of the background genetic variation inherent to these sarcomeric genes in seemingly healthy subjects. This study represents the first comprehensive analysis of genetic variation in 427 ostensibly healthy individuals for the HCM genetic test using the “gold standard” Sanger sequencing method validating the background rate identified in the publically available exomes. While mutations are clearly overrepresented in disease, a background rate as high as ～5 % among healthy individuals prevents diagnostic certainty. To this end, we have identified a number of estimated predictive value-based associations including gene-specific, topology, and conservation methods generating an algorithm aiding in the probabilistic interpretation of an HCM genetic test.     

Mechanism,management, and prevention of bile duct injury in laparoscopic cholecystectomy

Injury to the bile duct is one of the most serious complications of laparoscopic cholecystectomy. The incidence of bile duct injury during laparoscopic cholecystectomy may be higher than during open cholecystectomy. Most of these injuries occur early in a surgeon’s experience with the new technique. The classical laparoscopic bile duct injury occurs when the common duct is mistaken for the cystic duct; the common bile duct is transected and a part of the extrahepatic biliary system is resected. The bile duct may also be injured by excessive diathermy, resulting in a bile leak or a stricture. Insecure clipping of the cystic duct may also result in bile leakage. If these injuries are not recognized at the time of surgery, they present as bile collections or jaundice postoperatively. ERCP will delineate the exact injury accurately. These injuries are preventable by careful attention to technique and a willingness to convert to open surgery when difficulties are encountered. To minimize the risk to patients, programs of training, proctoring, and accreditation in laparoscopic surgery should be established.     

Integration of CAD models with product assembly planning in a Web-based 3D visualized environment

Product assembly planning plays an important role in the product life cycle management. Product assembly planning consists of the product representation, assembly sequence generation, and the sequence optimization. An efficient assembly planning depends on the integration of CAD models with product assembly analysis. However, existing product modeling systems are separated from the product assembly planning. 3D CAD models cannot be directly used by most of the product assembly planning systems. The data extraction from CAD models becomes a critical process in the integrated product development system. This paper presents an integration method of CAD models with product assembly planning. Product data are extracted from product CAD-VRML models and stored in MySQL database. The extracted data are regrouped for product assembly reasoning and 3D visualization. The 3D animation is developed to visually validate the generated assembly plan. The product assembly process is simulated by manipulating the geometry using VRML external authoring interface.     

Clinicopathological studies of anomalous arrangement of the pancreaticobiliary ductal system with pancreas divisum

We examined the morphological aspects of the pancreaticobiliary ductal system in 13 patients with both anomalous arrangement of the pancreaticobiliary ductal system (AAPB) and associated pancreas divisum (PD), and compared their clinicopathological findings with those of patients with either AAPB or PD alone. PD is classified into three types, i.e., separate pancreas, nonfusion of the ventral and dorsal pancreatic ducts, and partial fusion of the ventral and dorsal pancreatic ducts. Of the 13 patients with AAPB and associated PD, 5 were male and 8 female; their mean age was 57 years. Nine of the 13 had clinical symptoms. Five of the 13 had gallbladder cancer, 3 had cholecystolithiasis, and 2 choledochal cyst. One patient showed nonfusion of both pancreatic ducts and the others showed partial fusion of the ducts. The length of the common duct from the orifice of the papilla of Vater to the junction of the common bile duct with the ventral pancreatic duct and the location of the union varied. The presence of both AAPB and PD made the arrangement of the pancreaticobiliary ducts very complicated. Clinical aspects were similar to those of AAPB and the patients were likely to be treated for a condition other than PD. However, since relapsing acute pancreatitis and intermittent epigastric pain are typical symptoms in patients with AAPB as well as in those with PD, we should carefully follow up those patients with both AAPB and PD.     

Hepatic hilar bile duct cancer treated by multidisciplinary approach

The effects of a multidisciplinary approach in the treatment of hepatic hilar bile duct cancer were evaluated in 24 of 31 resected patients operated from 1985 through 1992. Our multidisciplinary treatment included preoperative biliary drainage, hepatic hilar resection with hepatic portajejunostomy, intraoperative targeting chemotherapy, and postoperative intracavitary irradiation, using a remote after loading system. Before surgical resection, percutaneous transhepatic biliary drainage was performed in patients with hyperbilirubinemia to reduce their serum bilirubin level and to improve hepatic function. Six patients underwent pancreatoduodenectomy, due to cancer invasion, in addition to hepatic hilar resection. Postoperative intracavitary irradiation with⁶⁰Co was performed via bile duct and inferior vena cava. There were no serious postoperative complications or postoperative deaths among patients treated by our multidisciplinary approach. The overall 1-, 2-, and 5-year survival rates were 71%, 58%, and 24%, respectively. In curatively resected patients, the 1-, 2-, and 5-year survival rates were 100%, 80% and 53%, respectively. These results demonstrate that our multidisciplinary therapeutic modality gives better survival rates than those reported previously.