Changes in bile salt composition after cholecystectomy and ileal resection

The effect of ileal resection and cholecystectomy on bile salt metabolism was studied in female prairie dogs 4 weeks after either a sham laparotomy, cholecystectomy, ileal resection, or cholecystectomy and ileal resection. Bile was collected from a common bile duct cannula at hourly intervals for 12 hours. Pool sizes and synthetic rates of primary and secondary bile salts were determined from washout curves. Cholate, chenodeoxycholate, deoxycholate, and lithocholate levels were determined by gas chromatography from pooled collections of bile. After cholecystectomy and ileal resection, the pool sizes of primary and secondary bile salts were significantly reduced to amounts that were much less than the pool sizes after either procedure alone. Primary bile salt synthesis was significantly increased after combined cholecystectomy and ileal resection, to the same degree as cholecystectomy alone. After the combined procedures, there was a decrease in the proportion of cholate in hepatic bile associated with an increase in chenodeoxycholate, deoxycholate, and lithocholate levels. The data suggest that after the loss of both ileum and gallbladder the bile salt pool sizes are drastically reduced, the synthesis of primary bile salts is increased, and the proportion of secondary bile salts is increased. Cholecystectomy should be avoided, if possible, in patients with ileal resection in order to conserve the bile salt pool and prevent severe fat malabsorption.     

Biliary cholesterol and lithogeneity of bile in patients after ileal resection

For determination of the factors that regulate biliary cholesterol secretion and the lithogenity of bile in ileal dysfunction, plasma and biliary lipids and fecal excretion of bile acids were studied in 29 patients who had undergone ileal resection. Seven patients with ileal resection had normal bile acid excretion (less than 10 mg/kg/day), and 22 had various degrees of bile acid malabsorption. None of the patients had gallstones when examined with abdominal sonography. LDL cholesterol levels were decreased in bile acid malabsorption and demonstrated a positive correlation with the molar percentage of biliary cholesterol. Biliary cholesterol (mol percent) was inversely correlated with fecal bile acid excretion. This finding suggests that biliary cholesterol secretion decreases with increasing loss of bile acids to feces in ileal dysfunction, leading to an actual decrease in the lithogenic index and to hyposaturation of cholesterol in bile. The reduction in biliary cholesterol, regarded as protecting the gallbladder mucosa against the detergent properties of bile acids, may play an important role in the pathogenesis of increased gallstone formation in ileal dysfunction.     

The relationship of cholecystectomy and taurocholic acid feeding to bile composition and hepatocyte function in prairie dogs

The prairie dog was used as a model for human gallstone formation. Stones formed in the gallbladder of all animals on a lithogenic diet. Hepatic bile was nonlithogenic, whereas gallbladder bile promoted cholesterol precipitation. Addition of taurocholate to the diet reduced the number of stones and lithogenicity. Cholecystectomy resulted in an increased bile flow and reduced secretion of cholesterol in the animals on a high cholesterol diet. Reduction of cholesterol and bile acid synthesis by negative feedback was demonstrated in isolated hepatocyte culture. The shift of bile salt production to chenodeoxycholates on a high cholesterol intake was demonstrated both in vivo and in vitro. A theory of gallstone formation is presented which hypothesizes a defect in hepatocyte storage of cholesterol rather than bile acid synthesis as the primary effect, relegating the problems to one of a disease of lipid metabolism.     

The role of hepatic resection in the management of bile duct injuries following laparoscopic cholecystectomy

The creation of a specialized hepatobiliary surgery unit at our medical center has resulted in referral of 16 patients with bile duct complications following laparoscopic cholecystectomy over the last 18 months. No patient required conversion to open cholecystectomy. Although no injury was recognized at the time of surgery, 15 of 16 patients became symptomatic within the first 30 days. Two patients died from sepsis and multisystem organ failure after protracted hospital courses. Endoscopic retrograde cholangiopancreatography and/or percutaneous transhepatic cholangiography determined diagnosis and level of injury. Six of seven patients with cystic duct leak underwent successful endoscopic stent placement and one patient sealed spontaneously after percutaneous drainage of a large biloma. Nine patients required surgery that included hepaticojejunostomy (five), T-tube insertion and drainage of abscess (two), or segmental hepatic resection (two). Timely recognition of bile duct complications following laparoscopic cholecystectomy is critical to a successful long-term outcome. Although the majority of cystic duct leaks can be managed with endoscopic stenting, patients with ductal injuries require hepaticojejunostomy. Segmental liver resection may serve an important role in the management of carefully selected patients with high intrahepatic injuries to avoid long-term transhepatic stenting and complications such as episodic cholangitis and late stricture formation.     

Long-term effects of bile on the gastric mucosa of the dog

Bile was allowed to act on the gastric mucosa of dogs for periods of time ranging from 60 to 540 days. Then the mucosa was studied by light microscopy and morphometric techniques to determine height of the mucosa, infundibulum and glands, number of mast cells, and number of interepithelial lymphocytes. Marked acute inflammatory lesions and decrease in cellular mucin content were observed mainly in the antral mucosa exposed to bile for up to 130 days. Other changes appearing both in the antrum and fundus of the same dogs included an increase in the number of interepithelial lymphocytes, architectural distortion, and decrease in the height of the mucosa, the infundibulum being the most affected component in the antrum and the glands in the fundus. Positive alkaline phosphatase activity was observed in the antral area up to 130 days. With continuous exposure to bile, the gastric mucosa appeared to undergo adaptation, since all the described alterations gradually disappeared.     

The effects of triazolam on cerebral blood flow and metabolism in the dog

The new benzodiazepine triazolam was given to six initially awake dogs maintained with spinal anaesthesia and mechanical ventilation. Both cerebral blood flow (CBF) and cerebral metabolic rate for O2 (CMRO2) were significantly reduced after the initial dose of 0.1 mg X kg-1 triazolam, and the EEG changed from an awake to a sleep pattern in less than 20 s. CMRO2 was gradually reduced with increasing doses of triazolam (0.3, 1.0, 10.0 and 30.0 mg X kg-1) to 76% of control after the final 30 mg X kg-1 dose. CBF did not decrease further after the initial dose, and the addition of N2O after the final dose did not cause any significant change in CBF or CMRO2. The dogs were hemodynamically stable during the study. Small increases in brain lactate and pyruvate levels, but not in the L/P ratio were the only significant changes in brain metabolite levels. Triazolam appears to be a safe and rapidly acting induction agent in the dog.     

Effect of glucagon on bile acid metabolism after resection of liver cancer in patients with cirrhosis

After hepatectomy patients with cirrhosis and liver cancer may develop progressive hepatic dysfunction and eventually hepatic failure. Insulin and glucagon are often used to treat certain kinds of hepatic dysfunction and hepatic insufficiency. We investigated the effect of glucagon on bile acid metabolism and pancreatic endocrine function. In 7 patients with severe cirrhosis and cancer of the liver, 1 mg of glucagon was injected intravenously pre- and post-operatively, and total bile acids, C-AMP, and bile acid fractions were determined. In the pre-operative glucagon tolerance test, the C-AMP level rose from a baseline of 14 +/- 0.8 PMol/ml to 362 +/- 94 PMol/ml 30 min after the injection of glucagon (p less than 0.01); and the level of total bile acids decreased from a baseline of 28 +/- 9 microMol/ml to 11 +/- 3 microMol/ml 60 min after the injection of glucagon. The post-operative C-AMP level increased from a baseline of 13 +/- 1 PMol/ml to 192 +/- 58 PMol/ml level of 30 min after the injection of glucagon (p less than 0.01), and the post-operative level of total bile acids decreased from a baseline of 64 +/- 20 microMol/ml to 26 +/- 7 microMol/ml 60 min after the injection of glucagon. There was a significant correlation between the 5-min increment ratio of C-AMP and the decrement ratio of total bile acids (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Relative effects of ileal resection and bypass on intestinal adaptation and carcinogenesis

Since ileal resection and ileal bypass are commonly performed in man and might stimulate colonic hyperplasia, their co-carcinogenic potential was explored in male Sprague-Dawley rats (n = 135). One week after 33 per cent distal small-bowel resection, 33 per cent distal small-bowel bypass or distal ileal transection (control), animals started a 6-week course of azoxymethane injections (total dose 90 mg/kg ip). Findings in rats killed at 20 and 25 weeks were similar: bypass produced a higher yield of colorectal tumours (4.0 +/- 0.6 per rat: mean +/- s.e.) than controls (2.4 +/- 0.4; P less than 0.05), but resection caused maximal enhancement (5.2 +/- 0.5: P less than 0.01). In rats killed at 30 weeks, however, tumour yields were almost identical. Overall, resection increased colonic tumour yield by 55 per cent (P less than 0.02) and bypass by 32 per cent. Stathmokinetic measurements of crypt cell production rate (CCPR) at 20 weeks showed similar increases after resection and bypass both in residual functioning small bowel (109-200 per cent: P less than 0.01) and in colorectum (63-100 per cent: P less than 0.05). At 30 weeks these adaptive effects persisted, despite an overall increase in CCPR with age. Loss of functioning ileum enhances experimental colorectal carcinogenesis principally by reducing the latent period for tumour development. Resection has a greater effect than bypass probably by producing earlier hyperplasia, though later adaptive effects are similar.     

The effects of prolonged isoflurane anaesthesia on cerebral blood flow and metabolism in the dog

To determine whether cerebral blood flow (CBF) changed with time under isoflurane anaesthesia, as has been reported for halothane, CBF and cerebral metabolic rate for oxygen (CMRO2) were studied in five dogs under prolonged isoflurane anaesthesia. CBF was measured with a modified sagittal sinus technique and CMRO2 was calculated as the product of CBF and the arteriovenous O2 difference. Maintaining this experimental dog model with 1% isoflurane in oxygen and nitrogen for 3 h in five dogs and for 4 h in three dogs did not cause any significant changes in CMRO2 or CBF. Cerebral metabolite levels were consistent with earlier reports from short-time studies and the EEG recordings showed a continuous sleep pattern with no pathological changes. It is concluded that there is no change in CBF or CMRO2 in our modified sagittal outflow model during 3-4 h of 1% isoflurane anaesthesia.     

腹腔镜胆囊切除术胆管损伤术后胆漏的处理

目的:总结腹腔镜胆囊切除术(laparoscopic cholecystectomy,LC)胆管损伤术后胆漏的预防与处理。方法:回顾分析2000年1月至2008年6月我院9例LC胆管损伤术后胆漏患者的临床资料,总结胆漏的原因、预防措施及处理。结果:9例全部痊愈出院。随访3~60个月无黄疸、发热等胆管炎症状。结论:LC胆管损伤后胆漏重在预防。肝内胆管分支损伤及肝外胆管侧壁损伤可采取保守治疗,腹腔引流联合内镜治疗明显缩短病程。肝外胆管横断伤需腹腔引流4周,周围炎症基本消退再行肝门胆管盆式空肠内引流术。     

The effect of massive intestinal resection on the dog skeleton

In order to explain a risk factor for osteoporosis, effects of chronic malabsorption on bone mass were experimentally assessed. In beagles, the distal three quarters of the small intestine was resected, and effects of the deficit on bone mass was studied. After double tetracycline labelling each dog was sacrificed, and sections of undecalcified lumbar vertebra were prepared for bone morphometry. Effects of postoperative treatment with ursodesoxycholic acid(UDCA) and 1α(OH)D₃ or with 1α(OH)D₃ alone were also evaluated. The massive resection of the distal small intestine resulted in a decrease of serum lipid level and apparent malabsorption, leading to prominent changes in metabolism of vitamin D such as decreased production of 25(OH)D and 24,25(OH)₂D. Six months after the resection, neither a decrease in bone mass nor impaired calcification could be documented in agreement with the lasting normal 1,25 (OH)₂D level. Decreases in osteoid volume and thickness, as well as low bone formation rates, suggested insufficient bone matrix synthesis presumably associated with malabsorption. Consequently, bone mass would eventually decrease after massive intestinal resection. UDCA and vit.D₃ supplements produced no clear effect on the bone.     

腹腔镜胆囊切除术胆漏的防治

目的:探讨预防腹腔镜胆囊切除术(laparoscop ic cholecystectomy,LC)胆漏的有效措施。方法:回顾分析我院2000年1月至2006年1月512例LC中8例胆漏患者的临床资料。结果:8例患者全部治愈,2例经过非手术治愈,占25%,2例行再次腹腔镜探查,占25%,4例开腹探查手术,占50%。结论:严格掌握LC手术适应证,良好显露Calot三角,靠胆囊钝性分开Calot三角,认准胆囊壶腹与胆囊管交汇部并游离出其延伸段是确认胆囊管的可行方法,适时把握中转开腹手术时机是预防胆漏等并发症的关键。     

Lovastatin inhibits gallstone formation in the cholesterol-fed prairie dog.

The efficacy of lovastatin, an inhibitor of hepatic cholesterol synthesis in the prevention of cholesterol gallstone formation, was evaluated in the prairie dog model. Two groups of animals were maintained on either nonlithogenic or 1.2% cholesterol-enriched chow for 21 days. Seven of the animals in each group received lovastatin, and the remaining six received only distilled water. All of the cholesterol-fed/water-treated animals had crystals and 83% had gallstones, but none of the cholesterol-fed/lovastatin-treated animals had gallstones and only three had microscopic crystals. These data indicate that lovastatin inhibits cholesterol gallstone formation in a diet-induced model of gallstone disease.