Kohji Miyazaki

Hepatolithiasis in East Asia retrospective study

Hepatolithiasis is a major disease in Asia but differences in operative incidence between countries have not been examined. A retrospective study was conducted in Taiwan, Hong Kong, and Singapore, and the results were compared with those in Japan with the aim of defining factors involved in the etiology of the condition. In order to ensure uniformity of the data collected, the same form was used throughout the study and was completed by the same personnel after reviewing the patients record and radiographs in each case. The years 1976–1980 were chosen for the study, since the newer methods of diagnosis such as ultrasound, endoscopic retrograde cholangiography, and percutaneous transhepatic cholangiography became available during that period. The most significant finding was the difference in the relative prevalence of hepatolithiasis as a proportion of all gallstone cases in Taiwan, Hong Kong, and Singapore, where the majority of the population consisted of patients of Chinese descent. The highest prevalence, 53.5%, was found in Taiwan, while in Hong Kong it was 3.1% and in Singapore 1.7%. Environmental rather than ethnic factors are implicated in the cause of hepatolithiasis.

Hepatolithiasis associated with cholangiocarcinoma. Possible etiologic significance

Three cases of primary bile duct carcinomas (cholangiocarcinomas) were found among 61 cases of hepatolithiasis. Cholangiocarcinoma arose from the extrahepatic bile duct in one and from the dilated intrahepatic bile duct in two patients. Hyperplasia of the columnar cells was often present. These hyperplastic epithelial cells often show papillomatous or adenomatous pattern, which are frequently associated with the presence of stones and the contaminated bile, and may show malignant changes leading to the development of cholangiocarcinoma.

Effect of chenodeoxycholic and ursodeoxycholic acids on isolated adult human hepatocytes

Chenodeoxycholic and ursodeoxycholic are effective cholelitholytic agents, but differ in their side effects. Chenodeoxycholic acid administration induces diarrhea and a transient rise of GOT, which are virtually nonexistent with ursodeoxycholic acid treatment. Lithocholic acid, a bacterial metabolite of chenodeoxycholic acid, has been implicated as a possible hepatotoxin. In the present investigation, the effect of chenodeoxycholic acid or ursodeoxycholic acid and their glycine and taurine conjugates on isolated human hypatocytes was directly assessed. Chenodeoxycholic acid had drastic effects on isolated human hepatocytes by reducing the number of microvilli and disrupting cell membranes. Pronounced release of GOT was observed. In contrast, ursodeoxycholic acid produced only slight morphological changes and enzyme release. Conjugation of each respective bile acids had a moderating effect.

Choice of treatment for hepatolithiasis based on pathological findings

The results of surgical treatment in 56 patients with hepatolithiasis are reported including a follow-up study on 53 patients who survived more than 1 year (median, 5 years and 8 months). Patients were treated by 4 different procedures, i.e., common duct exploration in 32 patients, hepatic resection in 13 patients, hepatic resection with intrahepatic cholangiojejunostomy in 6 patients, and endoscopic stone removal in 5 patients. These procedures were combined with additional procedures, i.e., sphincteroplasty and bilioenteric anastomosis when necessary. There were no operative deaths. The stones were completely removed in 51.8% of the patients. Follow-up study for 1 to 10 years showed good results in 70.8% of the patients. Residual stones were often observed in the cases with stricture at the liver hilum and this led to poor results at follow-up. The results of various procedures were evaluated in relation to the prevailing pathology such as bile duct stricture and the location of stones.RésuméLes résultats du traitement chirurgical de 56 malades atteints de lithiase biliaire intra-hépatique sont rapportés ainsi que létude des suites évolutives de 53 dentre eux qui ont survécu plus dun an après lintervention (médiane 5 ans et 8 mois). Ces malades furent traités de quatre faÇons différentes: 32 par exploration biliaire, 13 par résection hépatique, 6 par cholangio-jéjunostomie intra-hépatique, 5 par extraction endoscopique des calculs. Dans certains cas il fut pratiqué à titre complémentaire et par nécessité soit une sphinctéroplastie soit une anastomose bilio-digestive.Il ny eut pas de décès post-opératoire. Dans 51.8% des cas lablation des calculs fut complète. Létude des suites pendant une période sétendant de 1 à 10 ans a permis de dénombrer 70.8% de bons résultats. Les mauvais résultats furent observés quand existait un rétrécissement des canaux biliaires au niveau du hile du foie à lorigine dune lithiase résiduelle.Les résultats des différentes interventions ont été étudiés en fonction des lésions, en particulier rétrécissements des canaux biliaires intra-hépatiques et du siège des calculs.ResumenLa hepatolitiasis, o sea la presencia de cálculos intrahepáticos, es infrecuentemente informada en la literatura médica occidental; sin embargo, es una entidad frecuente en el oriente de Asia, incluyendo al Japón. La incidencia ha sido informada en 4.1 por ciento de todos 1os pacientes operados por colelitiasis en el Japón, pero en otros lugares de Asia oriental ha sido informada entre el 10 y el 30 por ciento. Se piensa que la estenosis de los canales biliares está relacionada con la estasis biliar y la formación de cálculos.Se presentan los resultados en 56 pacientes con hepatolitiasis, incluyendo el seguimiento en 53 pacientes que sobrevivieron más de un año (promedio 5 años y 8 meses); hubo 31 hombres y 28 mujeres, con edades entre 25 y 70 años (promedio 50). Se confirmó la presencia de estrechez de los canales biliares en 37 de 59 pacientes. Los pacientes fueron tratados mediante cuatro procedimientos diferentes: exploración del canal colédoco en 32 casos, resección hepática en 13, resección hepática con colangioyeyunostomía intrahepática en 6 y remoción endoscópica en 5. Estos procedimientos fueron combinados con otros adicionales, tales como esfinteroplastia y anastomosis bilioentérico, cuando se consideró necesario. No se presentaron muertes operatorias. Los cálculos fueron removidos en su totalidad en el 51.8 por ciento de los pacientes. El seguimiento de uno a diez años demostró buen resultado en el 70.8 por ciento. Cálculos residuales fueron frecuentemente observados en los casos que presentaban estrechez a nivel del hilio hepático, y esto dió lugar a resultados pobres en el seguimiento. Los resultados de los diferentes procedimientos se encuentran relacionados con la patología predominante, tal como la presencia de estrecheces en los canales biliares y la ubicación de los cálculos.

Isolation and primary culture of adult human hepatocytes

SummaryBiopsy tissue of adult human liver was gently dissociated with collagenase followed by Dispase. By repeated low g centrifugation, a large number of almost pure, viable hepatocytes was obtained. This is the first report of a successful procedure for obtaining adult human hepatocytes for study in tissue culture. The isolated cells have the typical morphology of liver parenchyma, and these characteristics persist throughout the period of culturing. Evidence of their function is indicated by albumin synthesis. This procedure is now being used to study human hepatocyte functions in vitro and the effects of a variety of agents including carcinogens and viruses.

Bypass procedure for bile duct cancer

In spite of the great advances made in diagnostic procedures and patient management, and the aggressive attitude adopted by most surgeons, a sizable portion of bile duct cancer remains unresectable and should be treated by palliative procedures. We reviewed 93 patients with bile duct cancer treated in our department during the 20-year period from 1965 to 1984, and found that biliary enteric anastomosis offers the best palliation with acceptable mortality and complication rates and increases length of survival and improves quality of life. For proximal third bile duct cancer, the approach in the plane of the falciform ligament by Bismuth and Corlette and the anastomosis of the duct of the lateral inferior segment, segment III, or anterior inferior segment, segment V, to a Roux-Y jejunal loop is recommended because of its sufficient size, accessibility, and distance from the tumor. For middle and distal thirds bile duct cancer, hepaticodochojejunostomy (Roux-Y) is preferred by first transecting the common hepatic or common bile duct and anastomosing it to the Roux-Y jejunal loop to delay encroachment by the distally located bile duct cancer.RésuméMalgré les grands progrès effectués dans les domaines du diagnostic, de la préparation du malade, et de lattitude chirurgicale (plus entreprenante que par le passé) de nombreux cancers de larbre biliaire ne peuvent Être traités par lexérèse et relèvent seulement dune intervention palliative. Les auteurs, en se livrant à létude analytique de 93 cas de cancer des voies biliaires traités dans leur département de 1965 à 1984, aboutissent à la conclusion que lanastomose bilio-digestive est la meilleure méthode de traitement palliatif car le taux de la mortalité et des complications est acceptable alors mÊme que la durée dune survie de qualité est prolongée. Les cancers de la partie haute de larbre biliaire relèvent dune anastomose entre une anse jéjunale montée en Y selon la technique de Roux et le canal du segment III abordé dans le plan du ligament falciforme (canal du segment latéral inférieur) et le canal du segment V (canal du segment antérieur inférieur) en raison du diamètre suffisant des canaux, de leu facilité daccès et de leur éloignement de la tumeur. En ce qui concerne les cancers de la partie moyenne ou de la partie inférieure de la voie biliaire principale, lintervention de choix est représentée par la constitution dune anastomose hépatico ou cholédoco-jéjunale sur anse en Y après section du canal hépatique ou du cholédoque de manière à retarder lextension à lanastomose du processus tumoral.ResumenA pesar del notable avance logrado en los procedimientos de diagnóstico, en el manejo general del paciente, y en la actitud de agresividad adoptada por la mayoría de los cirujanos, una porción considerable de los pacientes con cáncer de la vía biliar se mantiene no resecable y debe ser tratado mediante procedimientos paliativos. Hemos revisado 93 pacientes con cáncer de la vía biliar manejados en nuestro departamento en los Últimos 20 años, entre 1965 y 1984, y encontramos que la anastomosis bilioentérica ofrece la mejor paliación con tasas aceptables de mortalidad y de complicaciones, y provee una supervivencia de major calidad y más prolongada. Para el cancer del tercio proximal del canal biliar se recomienda el aproche en el piano del ligamento falciforme de Bismuth y Corlette y la anastomosis del canal del segmento lateral inferior, del segmento III, o segmento anterior inferior, del segmento V, a un asa yeyunal de Roux-en-Y, por ser de calibre suficiente, por su asequibilidad, y por la favorable distancia del tumor. Para los cánceres del tercio medio y del tercio distal se prefiere la hepaticoyeyunostomía (Roux-en-Y) con trasección del canal hepático comÚn o del colédoco y anastomosis al asa yeyunal de Roux-en-Y con el objeto de retardar la invasión o compresión por el cáncer ubicado en la porción distal.

Demonstration and maintenance of mucus secretion in cultured human gallbladder epithelial cells

SummaryThe method of human gallbladder epithelial cell culture has been developed successfully with active mucus secretory function. Human gallbladder epithelial cells were dissociated by Dispase digestion from the specimens obtained by cholecystectomy for uncomplicated gallbladder stone cases. The dissociated cells formed a monolayer in Eagle’fs minimum essential medium supplemented with 10% fetal bovine serum within 24 h after the inoculation. These cells were maintained for at least 2 wk without fibroblastic overgrowth. Cultured cells contained periodic acid Schiff-positive material in cellular cytoplasm for 3 d. On transmission electron microscopy these materials were identified as mucous secretory granules. Mucous secretory function was determined by [3H]glucosamine incorporation. Sixty percent of the secreted glycoproteins labeled with [3H]glucosamine was eluted in excluded fractions of Sepharose 4B gel filtration, which were considered to be mucous glycoprotein, because they were found to be resistant to proteoglycan-specific enzymes such as hyaluronidase, chondroitinase ABC, heparitinase, and heparinase. The mucous glycoprotein secretion was maintained for 3 d and found to be inhibited in a dose-dependent manner by monensin (10−7 to 10−5M) which is a known blocker of secretory function.

DNA repair synthesis in primary culture of bovine bile duct epithelial cells induced by chemical agents in relation to bile duct cancer

Unscheduled DNA synthesis (UDS) was measured autoradiographically in a primary culture of extrahepatic bile duct epithelial cells of Holstein cows following exposure to chemicals known to be capable of developing bile duct cancers in experimental animals, i.e., N-methyl-N-nitro-N-nitrosoguanidine (MNNG, CAS No. 70-25-7), N-ethyl-N-nitro-N-nitrosoguanidine (ENNG, CAS No. 4255-77-6), 20-methylcholanthrene (MCA, CAS No. 56-49-5), N-nitrosodimethylamine (DMN, CAS No. 62-75-9) and aflatoxin B1 (AFB1, CAS No. 1162-65-8). MNNG and ENNG induced UDS without addition of S9 mixture. MCA elicited UDS only if S9 mixture was added. Regardless of the presence or absence of S9 mixture, DMN failed to induce UDS. DNA repair by AFB1 was enhanced by the presence of S9 mixture. Therefore, for MNNG, ENNG and high doses of AFB1 activation by the liver is not necessary to exert genotoxic effects and they seem to be capable of direct action on bile duct epithelial cells in the presence of a bilioenteric fistula or anastomosis.

Radical surgery for middle and distal thirds bile duct cancer

AbstractA total of 38 patients with middle and distal thirds bile duct cancer treated in our department during a period of 20 years were reviewed and analyzed in respect to the type of operative procedures employed and the long-term results. The purpose of the study was to evaluate the impact of various recently available modalities for diagnosis and treatment on the prognosis of patients with these malignancies.nThe longest mean survival was 22.8 months after resection and the shortest was 3.5 months after intubation. Resectability increased during the course of the study, especially for distal bile duct cancer, and reached 70% in the last 10 years. Either local excision of the bile duct or pancreatoduodenectomy was chosen as a radical operative procedure for middle bile duct cancer, however, curative resection was obtained only by the latter. Pancreatoduodenectomy was the only choice of radical treatment for distal thirds bile duct cancer. Postoperative morbidity decreased during the last 10 years and preoperative biliary decompression significantly improved the postoperative survival time.RésuméLes auteurs ont étudié à posteriori et analysé les 38 cas de cancers de la partie moyenne et de la partie inférieure de la voie biliaire principale quils ont traités au cours des 20 dernières années. Leur analyse concerne les opérations pratiquées et leurs résultats à long terme de faÇon à évaluer limpact sur le pronostic des différentes interventions devenues disponibles.La survie la plus longue fut de 22.8 mois après exérèse et 3.5 mois après intubation. Le taux dexérèse sest accru avec le temps, en particulier en ce qui concerne les cancers de la partie inférieure, pour atteindre 70% au cours des 10 dernières années. Lexérèse du segment intermédiaire de la voie bilaire principale et la duodéno-pancréatectomie à titre curatif ont été employées pour traiter les cancers de ce segment mais en fait cest cette dernière opération qui a un potentiel curatif. Elle représente dailleurs lopération de choix pour les cancers de la partie inférieure de la voie biliaire principale. La morbidité postopératoire a diminué dans les 10 dernière années, le drainage biliaire décompressif préopératoire ayant été à lorigine dune augmentation de la survie post-opératoire selon les auteurs.ResumenUn total de 38 casos de cáncer del canal biliar medio y distal tratados en nuestro departamento en el curso de los Últimos 20 años fue revisado y analizado en cuanto al tipo del procedimiento operatorio empleado y los resultados a largo plazo; ésto con el fin de valorar el impacto de las diversas modalidades de terapia quirÚrgica recientemente asequibles sobre el pronóstico de los pacientes con cancer de la vía biliar de los tercios medio distal.La supervivencia media más prolongada fue de 22.8 meses después de la resección, y la más corta fue de 3.5 meses después de intubación. La resectabilidad se vio aumentar en una etapa del estudio, especialmente para los cánceres del tercio distal, y alcanzó a ser de 70% en los Últimos 10 años. La resección local del canal biliar o la pancreatoduodectomía fue escogida para los cánceres del tercio medio como forma radical de procedimiento operatorio. Sin embargo, resección curativa sólo pudo ser realizada mediante la pancreaticoduodenectomía, y para los cánceres del tercio distal ésta es la Única escogencia de tratamiento radical. La morbilidad postoperatoria decreció en el curso del ultimo decenio y la descompresión biliar mejoró en forma significativa el tiempo de supervivencia postoperatoria.

Chemotaxis of Kupffer cells isolated from rodent liver.

Kupffer cells (KC) were isolated from the liver of guinea pigs, rats, and mice using enzymatic digestion with collagenase, followed by differential centrifugation and plastic adherence. Purity of the isolated KC was 96.0±2.2, 97.2±2.1, and 96.0±2.3 per cent in guinea pigs, rats, and mice respectively. These isolated KC were tested for migratory response to bacterial factor, which is one of the representative chemotactic factors for inflammatory macrophages, using a modified Boyden chamber technique. KC from the three animal species similarly migrated to the bacterial factor. The migratory response of the KC to the bacterial factor is due to Chemotaxis but not chemokinesis. These results show the possibility that KC may recognize a chemoattractant and directionally migrate to it.