Ichiro Makino

Rapid cholesterol nucleation time and cholesterol gall stone formation after subtotal or total colectomy in humans.

Changes in biliary lipid composition, pH, ionised calcium, total and unconjugated bilirubin, and cholesterol nucleation time of gall bladder bile samples were examined in six patients who had undergone subtotal or total colectomy between five months and seven years previously, and values were compared with those in control patients with no gall stones. The colectomy group mainly comprised patients with ulcerative colitis and familial adenomatosis coli, in whom only a short length of the terminal ileum (mean (SEM) 2.25 (0.57) cm) had been resected. The reconstruction procedures were ileoanal anastomosis in two patients, terminal ileostomy in two, ileorectal anastomosis in one, and J shaped ileal pouch-anal anastomosis in one patient. The distributions of age, sex, and relative body weight were similar in the two groups. The gall bladder bile was lithogenic in the post colectomy group--these patients had a significantly increased cholesterol saturation index (p < 0.01) and rapid cholesterol nucleation time (p < 0.05) compared with the control group. A significant increase in the molar percentage of cholesterol and a decrease in that of total bile acid associated with significantly decreased secondary bile acids (p < 0.05) were observed in the post colectomy group. Gall stones formed in two of six patients after colectomy were cholesterol stones containing more than 80% cholesterol by dry weight. Total and unconjugated bilirubin, pH, and ionised calcium values were similar in the two groups. The results indicate that after total or subtotal colectomy the composition of gall bladder bile increases the risk of cholesterol gall stone formation.

Differences in Gallbladder Bile Lithogenicity in Patients after Gastrectomy and Colectomy

The differences in lithogenicity of gallbladder bile, biliary lipid composition, cholesterol saturation index (CSI), cholesterol nucleation time (NT), bilirubin, and ionized calcium were compared in patients who had previously undergone gastrectomy or colectomy. The increased CSI and the rapid NT were absent in gastrectomized patients, while colectomy significantly increased the CSI and accelerated the NT. The levels of ionized calcium and unconjugated bilirubin, possibly responsible for pigment stone formation, were significantly higher in patients after gastrectomy, but were nearly absent in patients after colectomy. The results suggest that after gastrectomy the gallbladder bile indicates a trend towards pigment stone formation, whereas there is a trend towards cholesterol gallstones after colectomy. The different alterations of the gallbladder bile lithogenicity are clinically important.

Hepatic Adenine Nucleotides and DNA Synthesis during the Regenerative and Atrophic Process of the Liver Lobes after Selective Portal Vein Ligation

Selective portal vein occlusion prior to aggressive hepatic resection is now an alternative way to decrease postoperative morbidity and mortality rates. However, the detailed changes in the hepatic energy status and DNA synthesis rate in both portal vein ligated (PVL) and nonligated (PVNL) lobes of the liver are not clear. In rats, the portal branch that supplies 70% of the liver volume was ligated, and changes in arterial ketone body ratio (AKBR), liver weight, histology, DNA synthesis rate and adenine nucleotides of the PVL and PVNL liver lobes were determined before and 1, 2, 4 and 7 days after portal vein ligation, and compared with those in sham-operated rats. The weight of the PVL lobes decreased, while that of the PVNL lobes increased depending on time. The DNA synthesis rates of the PVNL lobes were significantly higher than those in sham-operated control liver during the first 4 days with the maximal value on the 2nd day, while those of PVL lobes were essentially similar to the control values. Energy charge (EC) in both PVL and PVNL lobes significantly decreased on day 1 and recovered gradually, but with less extent in the regenerating PVNL lobes. The concentrations of total adenine nucleotides (TAN) in both the PVL and PVNL lobes were essentially similar during the first 2 days, but became significantly lower in PVL lobes after day 4. A decrease in EC preceded an increase in DNA synthesis only in the PVNL lobes, in contrast to the PVL lobes. Mitosis of hepatocytes on day 2 and subsequently enlarged lobules with an increased number of hepatocytes were histologic features in the PVNL liver. The AKBR was not correlated with hepatic energy charge of the liver. In conclusion, PVNL liver regenerates preceded by a decrease in EC and a subsequent increase in DNA synthesis keeping TAN constant, while PVL liver becomes atrophic, with a similar change in EC of the PVNL liver but ultimately decreased TAN without any change in DNA synthesis. AKBR is not a parameter reflecting the hepatic EC after portal branch ligation.

Deoxycholic acid in gall bladder bile does not account for the shortened nucleation time in patients with cholesterol gall stones.

The relations between the concentration of deoxycholic acid (DCA), the cholesterol saturation index, and the nucleation time in gall bladder bile were measured to determine the role of DCA in bile in the pathogenesis of cholesterol gall stone disease. Bile was obtained from patients with cholesterol gall stones (n = 30), subjects without gall stones (n = 35), and patients with pigment gall stones (n = 9). Three of 30 cholesterol gall stone patients and 10 of 35 gall stone free subjects were treated with antibiotics by mouth to decrease the concentration of bile DCA and determine the effect of DCA on biliary lithogenecity. Both the percentage and concentration of DCA in bile were similar in patients with and without cholesterol gall stones despite significant differences in their cholesterol saturation indices and nucleation times. Neither the percentage nor the concentration of DCA in bile correlated with either the cholesterol saturation index or the nucleation time. Analysis of subgroups with matching cholesterol saturation indices showed no correlation between the proportion of DCA in the bile and the cholesterol nucleation time. The proportion of DCA in bile was decreased by antibiotic treatment, but this had no effect on the cholesterol saturation index or nucleation time. These results suggest that DCA in bile is not responsible for biliary cholesterol saturation or cholesterol nucleation time.

Gallstones and their composition in patients with ileoanal anastomosis

Cholelithiasis is known to occur in 15%–24.5% of proctocolectomized patients. However, the clinical features and chemical analysis of gallstones in these patients have not been reported. We describe two cases of cholelithiasis that developed in patients after proctocolectomy with ileoanal anastomosis. These patients had a high output of watery stools and more frequent bowel movements than the average for Japanese patients with ileoanal anastomosis. The chemical composition of the resected gallstones was 93.0% cholesterol and 80.9%, respectively, in the two patients, indicating that cholesterol gallstones are formed in patients with ileoanal anastomosis after proctocolectomy.

Carcinoma of the ampulla of Vater synchronously associated with early gastric cancer—a report of two cases

We report two cases of carcinoma of the ampulla of Vater synchronously associated with early gastric cancers. The gastric lesions were diagnosed pre-operatively in one patient and at the time of examination of the resected specimen following pancreatoduodenectomy in the other. Specific problems in the diagnosis and management of these multiple primary carcinomas are discussed. Careful evaluation of the stomach prior to the surgical treatment for ampullary carcinoma is recommended.

Cholesterol crystal appearance time of gallbladder bile in middle-aged women

The aim of our study was to examine the hypothesis that the cholesterol nucleation time of gallbladder bile might be rapid in women in their fourth and fifth decades, which increases their risk of cholesterol gallstones. Fifty-four gallbladder bile samples were collected from gallstone-free patients and patients with cholesterol gallstones in a functioning gallbladder. We examined the relations of nucleation time to age and sex in each group. The nucleation time of gallbladder bile tended to be prolonged with age, but there was no correlation between nucleation time and age in each group. Cholesterol nucleation time was not significantly different between age-matched females and males in each group, nor was it faster in middle-aged females than in older females. Thus, nucleation time was not rapid in middle-aged females even in the gallstone-free group. These results indicate that cholesterol nucleation time is not significantly influenced by either sex or age, and cannot therefore account for the higher frequency of cholesterol gallstone disease in females in the fourth and fifth decades.