Pancreatoduodenectomy for pancreatic head carcinoma with or without pylorus preservation.

BACKGROUND/AIMS: With the concept of less invasive surgery, PpPD (pylorus-preserving pancreatoduodenectomy) has taken the place of conventional Whipple pancreatoduodenectomy (Whipple) as a standard operation for pancreatic head carcinoma. The aim of this paper is to compare early and late postoperative results of PpPD and Whipple for pancreatic head carcinoma. METHODOLOGY: Postoperative clinical follow-up data and outcome of 50 Japanese patients with pancreatic head carcinoma who underwent pancreatoduodenectomy with or without pylorus preservation were reviewed to scrutinize the demerits and merits of the pylorus preservation. RESULTS: Preoperative and postoperative serum chemistry was not different between the two groups. Mean operation time of the Whipple group was 517 minutes, which was significantly shorter than 624 minutes of the PpPD group (P = 0.0006). Cumulative stage was not different between the two groups. Cumulative curability of the PpPD group was superior to the Whipple group; of the 27 patients with Whipple, A in 4, B in 5 and C in 18, while of the 23 patients with PpPD, A in 12, B in 2 and C in 9 (P = 0.0182). Gastric tube was removed on POD 6.0 in the Whipple group, while on POD 39 in the PpPD group (P < 0.0001). Oral intake was started on POD 14.0 in the Whipple group, while on POD 28.3 in the PpPD group (P = 0.0018). Discharge was on POD 57.8 in the Whipple group, while POD 86.9 in the PpPD group (P = 0.0023). At the time of discharge and postoperative 6, 12, and 18 months, body weight loss from the preoperative level was 1kg smaller in the PpPD group than in the Whipple group. 1-year and 3-year survival rates of the Whipple group was 53.8% and 15.8%, while 62.8% and 19.6% of the PpPD group, showing no significant difference. CONCLUSIONS: These data show that delayed gastric emptying is evident in the PpPD group, resulting in longer hospital stay, while long-term body weight loss is smaller in this group. The clinical outcome is similar between the two groups. PpPD can be accepted as a standard operation for pancreatic head carcinoma.

Modulation of cholesterol metabolism affects tumor growth in hamsters.

To investigate the effects of cholesterol and cholesterol-lowering agents on cholesterol metabolism and tumor growth, 0.5% cholesterol, 2% cholestyramine, or 0.01% simvastatin was fed to hamsters with transplanted Simian virus40 transformed tumor cells. Tumor weight, tissue cholesterol and DNA concentrations, and HMG-CoA reductase activities were determined. Cholesterol or cholestyramine feeding did not affect the tumor growth, however, the tumor weight and DNA concentration were decreased and tumor HMG-CoA reductase activity was increased in the simvastatin group. In conclusion, simvastatin may inhibit the DNA synthesis and growth of the Simian virus40 transformed tumor cells possibly through the inhibition of cholesterol and isoprenoids synthesis in the hamster.

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.

Effect of biliary drainage on serum 7 alpha-hydroxycholesterol level in patients with obstructive jaundice.

Percutaneous transhepatic biliary drainage was performed in 15 patients with obstructive jaundice and the serum 7 alpha-hydroxycholesterol level was monitored for 2 weeks by capillary gas-liquid chromatography-mass spectrometry. Before biliary drainage, the serum 7 alpha-hydroxycholesterol level was 130 +/- 52 pmole/ml, which was significantly lower than the normal value (238 +/- 100 pmole/ml). After biliary drainage, the serum 7 alpha-hydroxycholesterol level was decreased to 117 +/- 48 pmole/ml on the first day. There were two groups of patients as classified by the behavior of the serum 7 alpha-hydroxycholesterol level after the third day. In one group of patients (responders), the serum level increased significantly up to 525 +/- 83 pmole/ml at the end of the 2 weeks. In another group (nonresponders), the serum level did not increase and remained 145 +/- 86 pmole/ml. The serum bilirubin level tended to improve faster in the responders (decline index = -0.234 +/- 0.152) than in the nonresponders (decline index = -0.057 +/- 0.067; P < 0.05) and a statistically significant correlation was found between the decline index and the total 7 alpha-hydroxycholesterol level on Days 7 or 14. As the serum 7 alpha-hydroxycholesterol level is considered to reflect hepatic bile acid synthesis, which is one of the important functions of the liver, we conclude that the increased serum 7 alpha-hydroxycholesterol level after biliary drainage in the responders indicates recovered liver function and that the low serum level in the nonresponders suggests more severe hepatocellular damage in patients with obstructive jaundice.

High concentrations of conjugated bile acids inhibit bacterial growth of Clostridium perfringens and induce its extracellular cholylglycine hydrolase.

To investigate the effects of conjugated bile acid on bacterial growth and cholylglycine hydrolase activity, Clostridium perfringens from human feces was exposed to varying concentrations of taurine- or glycine-conjugated chenodeoxycholic acid. Extracellular enzyme activity was determined by deconjugation of radiolabeled taurocholic acid and viable cells were counted after anaerobic culture at 37 degrees C for 24 h. Viable cells were decreased with more than 1.0 mg of conjugated chenodeoxycholic acid per mL and there were no viable cells with 10.0 mg of bile acid per mL. Although total enzyme activity was decreased according to the bile acid concentration, enzyme activity per bacterium was increased between 1.0 and 4.0 mg/mL. There were no statistically significant differences between the types of conjugation. It was concluded that conjugated bile acids may exert inhibitory effect on bacterial growth and extracellular cholylglycine hydrolase activity in Clostridium perfringens. However, under the physiologic condition in the human intestine, conjugated bile acid might induce production of extracellular cholyglycine hydrolase per bacterium.

Serum 7 alpha-hydroxycholesterol reflects hepatic bile acid synthesis in patients with obstructive jaundice after external biliary drainage.

To examine the hypothesis that serum levels of 7 alpha-hydroxycholesterol reflect bile acid synthesis in the liver, we analyzed serum 7 alpha-hydroxycholesterol and bile acid output in 13 patients with obstructive jaundice after relief of biliary obstruction. Before biliary drainage, the serum level of 7 alpha-hydroxycholesterol was 92 +/- 12 pmol/ml (mean +/- S.E.M.) and was significantly lower than the control value (226 +/- 26 pmol/ml, p < 0.01). After biliary drainage, serum 7 alpha-hydroxycholesterol level and biliary bile acid outputs began to rise in some patients, indicating reversible liver dysfunction. In other patients, serum 7 alpha-hydroxycholesterol levels and bile acid outputs did not increase, suggesting severe or irreversible liver dysfunction. On and after the third day of biliary decompression, serum 7 alpha-hydroxycholesterol levels correlated well with bile acid excretion (p < 0.01, r = 0.93). Other liver function parameters, such as serum bilirubin, serum bile acids, albumin, and bile flow, also revealed significant correlation with serum 7 alpha-hydroxycholesterol levels. We conclude that the serum 7 alpha-hydroxycholesterol level clearly reflects bile acid synthesis in the liver and that it may serve as a useful parameter for the assessment of hepatic functional recovery in patients with obstructive jaundice after biliary drainage.

Effects of pravastatin and ursodeoxycholic acid on cholesterol and bile acid metabolism in patients with cholesterol gallstones.

To investigate the effects of pravastatin and ursodeoxycholic acid (UDCA) on cholesterol and bile acid metabolism in humans, 41 patients with cholesterol gallstone disease were allocated to four groups and treated with pravastatin (20 mg/day), UDCA (600 mg/day), both pravastatin and UDCA, or neither drug (control) for 1-2 weeks prior to elective cholecystectomy. Cholesterol 7 alpha-hydroxylase activity and serum levels of total 7 alpha-hydroxycholesterol were significantly increased by pravastatin and unaffected by UDCA. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity was markedly increased by pravastatin and decreased by UDCA. UDCA significantly decreased biliary cholesterol concentration and the cholesterol saturation index and prolonged the nucleation time; however, pravastatin alone had little effect on biliary lithogenicity. Serum total and low-density lipoprotein (LDL)-cholesterol levels were reduced most by the combined administration of pravastatin and UDCA. In conclusion, at a dose of 20 mg/day, pravastatin increased bile acid synthesis but did not decrease biliary lithogenicity. UDCA had no significant effect on bile acid synthesis, but markedly decreased biliary lithogenicity.

Metabolism of intravenously administered 7 alpha-hydroxycholesterol-3 beta-stearate in the hamster.

In order to investigate the metabolic fate of serum esterified 7 alpha-hydroxycholesterol, [4-14C]7 alpha-hydroxycholesterol-3 beta-stearate was synthesized from labeled cholesterol and administered to bile fistula hamsters intravenously. Bile samples were collected at every 20 min for 7 h. Radioactivity was detected in bile 40 min after the beginning of the infusion of the labeled compound and 56.5 +/- 5.7% (48.7-66.0%) of the administered radioactivity was recovered in bile during 7 h. The liver contained appreciable radioactivity (19.5 +/- 7.6% of the administered dose) at the time of sacrifice. Only a trace amount of radioactivity was detected in urine and blood. Cumulative recovery of the radioactivity was 76.3 +/- 8.6% (63.3-90.4%). Major radioactive metabolites in the bile samples were identified to be taurine- and glycine-conjugated cholic acid and chenodeoxycholic acid by radioactive thin-layer chromatographic analysis of the bile samples before and after enzymatic hydrolysis and 3 alpha-hydroxysteroid dehydrogenase treatment. The conversion was nearly complete and we could not detect neutral metabolites, such as the mother compound, free 7 alpha-hydroxycholesterol and bile alcohols, as well as glucuronidated or sulfated bile acids. It is concluded that serum esterified 7 alpha-hydroxycholesterol could be effectively taken up by the liver, hydrolyzed by cholesterol esterase and metabolized via the normal biosynthetic pathway to taurine- or glycine-conjugated primary bile acids to be excreted into bile.