Fumio Nakayama

Complete ten-year postgastrectomy follow-up of early gastric cancer

The postoperative courses of 109 patients with early gastric carcinoma treated from 1970 through 1976 were followed for 10 years. The cumulative 5-year survival rate was 96 percent and the 10-year survival rate was 92 percent. In this series, there was no significant difference in the survival rates between the mucosal cancer and submucosal invasion groups or between patients with and without lymph node metastasis. Five patients died from the recurrent cancer. The other causes of death were metachronous primary cancer in eight patients, synchronous primary cancer of sigmoid colon or rectum in two, cerebrovascular accident in six, heart disease in six, other causes in four, and unknown causes in four. Although the prognosis of early gastric cancer is remarkably good, patients should be carefully followed over a long period for late recurrence of the primary cancer and possible metachronous cancer of the other organs.

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.

Bacteria and gallstones

Two hundred consecutive gallstone cases have been subjected to bacteriological study employing improved anaerobic culture techniques. In addition toClostridia species, species of anaerobes such asBacteroides fragilis, Peptococcus, Veillonella, andEubacterium are found to be present, some of which possessed β-glucuronidase activity. This finding has a certain bearing on the etiology of bile pigment calcium stones. In addition toEscherichia coli, Bacteroides andClostridium often found in the biliary tract may contribute to the formation of bile pigment calcium stones by producing β-glucuronidase and thus deconjugating bilirubin diglucuronide to form free unconjugated bilirubin which in turn combines with calcium, leading to stone formation. In contrast, very low bacterial incidence was associated with cholesterol stones and so-called black stones—sometimes called pure pigment stones- and thus bacteria play little role, if any, in their formation. Therefore, bile pigment calcium stones and so-called black stones, which are often classified as pigment stones indiscriminately, should be differentiated not only because of their difference in their appearance and composition but also in their etiological background. Regardless of the kind of stones present in the common duct, the incidence of bacteria was found to be increased.

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.

Changing state of gallstone disease in Japan: Composition of the stones and treatment of the condition

Summary The long held impression that the composition of gallstones in Japan is gradually changing from the once predominant bile pigment to cholesterol, thus approaching that of the West, has been confirmed by actual chemical analysis of gallstone samples collected forty years apart. Factors responsible for this change are not clearly known at present, but may include the rapidly proceeding urbanization and changing food habits in postwar Japan. These two groups of stones, that is, cholesterol stone and bile pigment stone, should be considered as two separate entities having different etiologies, and operative treatment should therefore be instituted accordingly.

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.

Change in Bile Duct Pressure Responses After Cholecystectomy: Loss of Gallbladder as a Pressure Reservoir

Coordination of gallbladder and sphincter of Oddi and effect of cholecystectomy on biliary pressure physiology were investigated in 7 patients using an indwelling microtransducer catheter placed in the bile duct by duodenoscopy. Intramuscular morphine (0.2 mg/kg) to induce a sphincter of Oddi spasm produced no change before cholecystectomy but intravenous caerulein (0.1 microgram/kg) induced pressure elevation coincident with gallbladder contraction on echogram. After cholecystectomy, however, morphine caused a pressure rise and a coarse and irregular change of the tracings, which seemed attributable to sphincter of Oddi spasm. Caerulein promptly reduced the pressure and eliminated the irregularity. These results show (a) the sphincter of Oddi relaxes when the gallbladder contracts in response to caerulein and (b) the gallbladder acts as a pressure reservoir against the sphincter of Oddi spasm caused by morphine. The latter implies that the spasm of the sphincter of Oddi readily leads to a pressure rise if the gallbladder is absent, which may partly explain a development of postcholecystectomy syndrome.

Quantitative determination of bile acids in bile with reversed-phase high-performance liquid chromatography

Separation and quantitation of glycine and taurine conjugates of commonly occurring bile acids in bile, i.e. lithocholic, deoxycholic, chenodeoxycholic, ursodeoxycholic and cholic acids in their naturally occurring states have been successfully accomplished using high-performance liquid chromatography. No preliminary purification of bile acids is required except ethanol extraction of bile. A muBondapak C18 column and acetonitrile--methanol--phosphate buffer and ultraviolet detector at 200 nm were used. Detection limit weas 0.05 microgram and linearity was observed in the range up to 16 microgram. Bile acid composition of ten randomly chosen normal human gallbladder bile samples is given. A large difference in bile acid composition between glycine and taurine conjugates was found to be present.

Hepatolithiasis in Japan: Present status

Intrahepatic gallstone or hepatolithiasis is one of the most difficult conditions encountered by surgeons in daily practice. A nationwide survey was conducted recently to document the state of hepatolithiasis in Japan and to establish proper methods of treatment. Over 160 institutions participated and 1,590 cases were collected. The stones were mostly of the bile pigment calcium stone variety and were found mainly in the left hepatic duct. The incidence was found to differ considerably from area to area. Pathologic features, diagnostic procedures and treatments currently available for hepatolithiasis are discussed.

Microanalysis of bile acid in human liver tissue by selected ion monitoring

A method of microquantitative determination of bile acid in 5–30 mg of human liver tissue was developed. Bile acids were converted to their ethyl ester dimethylethylsilyl ether derivatives and analyzed by capillary gas chromatography-selected ion monitoring, using [2H4]-lithocholic (LCA), [2H5]deoxycholic (DCA), [2H4]chenodeoxycholic (CDCA), [2H4]-ursodeoxycholic (UDCA), and [2H3]cholic (CA) acids as internal standards. Precision and reproducibility of the present method were tested using surgically obtained liver specimens. The results were statistically analyzed according to one-way layout and the orthogonal polynomial equation. Bile acids except LCA were determined with 2.3 to 11.4% of the coefficient of variation. Recoveries of conjugated bile acids ranged from 72.2 to 96.0% with a mean of 84.3%. The amount of bile acids present in histologically normal liver specimens (n = 10) was found to be 29.56 ± 8.62 μg/g liver. The relative compositions (%) of CDCA and CA were 38.8 ± 8.9 and 41.1 ± 11.0, respectively.