Safety and Efficacy of Laser Lithotripsy for Complicated Biliary Stones Using Direct Choledochoscopy

Background

The first-line therapy for choledocholithiasis is endoscopic retrograde cholangiopancreatography (ERCP) with stone extraction, which is successful in over 90 % of cases. However, large biliary stones often require extracorporeal shockwave lithotripsy, electrohydraulic lithotripsy (EHL), or laser lithotripsy. The objective of our study was to assess the safety and efficacy of laser lithotripsy with choledochoscopy guidance.

Methods

Between March 2001 and November 2009, laser lithotripsy with a holmium laser was used for complicated bile stones in 20 patients. All patients included had failed standard stone extraction techniques after a mean of 2.1 ± 1.1 ERCP sessions. Main outcome measures included complete stone clearance and complications post-procedure.

Results

Twenty patients (mean age 61.0 ± 22.3 years, six men) underwent laser lithotripsy with a mean stone size was 2.2 cm (range 1.1–3.5 cm) and a mean number of stones of 2.2 (range 1–6). A mean of 0.25 ± 0.20 kJ was applied during laser lithotripsy sessions with a mean procedure time of 85.3 ± 23.0 min. The majority (18/20, 90 %) achieved final clearance after a mean of 1.4 ± 0.8 (29 total) laser sessions and a mean of 1.9 ± 0.8 (38 total) ERCP sessions. Five complications occurred: two patients required post-procedure admission for pain and three patients had bile leaks. All bile leaks were minor and resolved after biliary stenting.

Conclusions

Laser lithotripsy using the holmium laser is safe and effective with direct cholangioscopic guidance. Further prospective studies are warranted.     

Effect of ursodeoxycholic acid administration on biliary lipid secretion in primary biliary cirrhosis

Ursodeoxycholic acid (UDCA) has been reported to improve liver function tests when administered to patients with cholestatic liver diseases, such as primary biliary cirrhosis (PBC). However, its effects on biliary lipid metabolism in patients with PBC are still unknown. In this study we report the effect that UDCA (600 mg/day, for four weeks) had on biliary cholesterol saturation index, biliary bile acid pattern and pool size, and biliary lipid output in seven female patients (ages 34–58 years) with PBC, stages I to III. A significant improvement of liver function tests was observed after four weeks of treatment. Saturation index was significantly decreased from 1.23±0.1 to 0.7±0.08 (P<0.02); this effect was due to the significant decrease of biliary cholesterol concentration from 6.7±0.36 to 3.6±0.37 percent molar (P<0.02). A significant decrease of cholesterol output (from 88±9 to 55±10 μmol/hr, P<0.02) was also observed. The amount of cholic acid, the predominant bile acid in bile, significantly decreased (from 47.3±3.5 to 35.4±2.6 percent molar, P<0.02), as did amounts of chenodeoxycholic and deoxycholic acids, while the amount of UDCA rose from 1.6±1.0 to 34.0±1.3 percent molar (P<0.02). Total bile acid pool size was not affected by UDCA, but the evaluation of individual bile acid pool sizes showed an increased proportion of UDCA relative to the endogenous bile acids. The results of the study confirm the beneficial effect of UDCA on liver function tests in PBC patients and support the hypothesis that the improvement of these measurements may be due to replacement of toxic endogenous bile acids with UDCA.     

Clinical Significance and Long-Term Outcome of Incidentally Found Bile Duct Dilatation

Background and Aim

The significance of incidentally detected bile duct dilatation has not yet been elucidated and there are only a few studies on asymptomatic patients with a dilated bile duct. This study aimed to investigate the causes and natural course of bile duct dilatation in asymptomatic patients.

Methods

A retrospective review of medical records was conducted for individuals in whom bile duct dilatation was detected by routine screening abdominal ultrasound at a health promotion center in Samsung Medical Center from January 2005 to April 2008.

Results

A total of 514 patients were included; the mean age was 60.1 ± 9.9 and the median follow-up period was 72 (interquartile range 56–85) months. Thirty-eight individuals who had a definite cause or biliary disease requiring treatment at the time of detection of bile duct dilatation were compared with 476 individuals who did not have a definitive cause or who did not need treatment. Both common bile duct (CBD) dilatation and intrahepatic bile duct (IHBD) dilatation were significantly related to the presence of a definitive causative lesion (OR 3.95; 95 % CI 1.77–8.82; p = 0.001). In the IHBD dilatation group, the severity of dilatation was also associated with the presence of a definitive causative lesion (OR 5.77; 95 % CI 1.32–25.26; p = 0.020).

Conclusion

Incidentally found biliary dilatation could be a prodrome of significant biliary tree disease. Therefore, further evaluation and regular follow up should be considered especially for marked IHBD dilatation or concomitant dilatation of CBD and IHBD detected on ultrasound.     

Bile loss does not affect serum and bile pefoloxacin levels in external biliary drainage patients

Although the excretion of an antibiotic into the bile is an important factor for the therapy of patients suffering biliary infections, recent findings suggest that external biliary drainage of the obstructed biliary tree leads to a progressive reduction of the antibiotic levels in the excreted bile, probably due to bile loss. Since pefloxacin, a broad spectrum antibiotic excreted mainly into the bile, seems to be useful for such infections, it would be of great interest to investigate its concentration human serum and bile throughout a 6-day treatment. Fourteen biliary lithiasis patients were enrolled in the study; 7 were subjected to cholecystectomy (group A) and 7 to cholecystectomy plus common bile duct exploration and 7 to cholecystectomy plus common bile duct exploration and external biliary drainage through a specially diesgned custommade T-tube (group B). The distal end of the horizontal part of this tube could be occluded by the incorporation of an inflatable ballon, thus facilitating the complete diversion of the bile flow from the duodenum. Pefloxacin was given intravenously at a single loading dose of 800 mg, followed, after 24h, by 400 mg bi.i.d. for 5 days. Blood and bile (group B only) saples were obtained before and at various time intervals after drug infusion. Pefloxacin assays, detemined by high performance liquid chromatography, revealed no variation in perfoxacin concentrations in the bile throughout the entire study period, despite a bile loss of about 700 ml daily. Serum levels in both groups ad bile levels in group B wer found to be equally high, being many times above the minimum inhibitory concentrations for sensitive pathogens. Additionally, the elimination half-life of pefloxacin was found to be similar for both groups (25.5±6.7 h vs 27.9±15.6h, for goups A and B, respectively). It is concluded that bile loss does not affect serum and bile pefloxacin levels in patients subjected to external biliary drainage.     

The Effect of Biliary Pressure on Antibiotic Excretion into Bile

Abstract: Biliary obstruction has been recognized to inhibit excretion of antibiotics into bile. In the present study, using cefpirome sulfate (CPR), we sought to determine the effect of biliary pressure on antibiotic transfer into bile in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Thirty-six patients with a variety of biliopancreatic diseases (free of renal disease or hypoproteinemia) received a single intravenous dose of CPR (1 g) prior to ERCP. Under fluoroscopy a diagnostic catheter with a metal ball tip was advanced into the middle portion of the extrahepatic bile duct or, in cases of common bile duct obstruction, above the obstruction. Biliary pressure was measured via the same catheter using duodenal pressure as a reference. Subsequently, bile was aspirated, and blood was withdrawn simultaneously. The mean interval between CPR administration and the bile and blood samplings was 67±12 minutes. The bile CPR concentration and the bile/serum ratio of CPR concentrations showed a significant inverse correlation with biliary pressure, but the serum CPR concentration did not. The bile CPR concentration and the bile/serum ratio of CPR concentrations differed significantly between the group with normal biliary pressures, below 10 mmHg, and that with biliary pressures exceeding 10 mmHg. The serum CPR concentrations of the two groups were similar. These results suggest that biliary pressure plays an important role in determining antibiotic transfer into bile.     

Effects of a concanavalin A-binding biliary glycoprotein on nucleation time of gallbladder bile

A study was performed to determine quantitative differences in the total protein concentration of gallbladder bile from gallstone patients and to isolate nucleation-promoting factors from the bile. Total protein concentrations in cholesterol gallstone bile (3.6±0.6 mg/ml, mean±SD, n=10), calcium bilirubinate gallstone bile (4.2±1.1 mg/ml, n=10), black pigment gallstone bile (1.9±0.6 mg/ml, n=4) and control gallbladder bile (2.3±0.5 mg/ml, n=9) were not significantly different. Also no statistically significant differences in cholesterol saturation index were found among these groups. Gallbladder bile from cholesterol gallstone patients showed significantly faster nucleation than that of contorls, calcium bilirubinate gallstone, or black pigment gallstone patients. We partially purified biliary glycoproteins from cholesterol gallstone bile or calcium bilirubinate gallstone bile by chromatography on concanavalin A Sepharose. Nucleation time was measured following the addition of these proteins to control bile in vitro. The glycoproteins obtained from cholesterol gallstone bile had significant nucleation-promoting activity, but nucleation time was not changed following the addition of biliary glycoproteins from calcium bilirubinate gallstone patients. These results suggest that qualitative differences in individual proteins of gallbladder bile are responsible for nucleation-promoting activity in vitro.     

Novel photodynamic therapy against biliary tract carcinoma using mono-l-aspartyl chlorine e6: basic evaluation for its feasibility and efficacy

Background

Recently, a second-generation photosensory agent for photodynamic therapy (PDT), mono-l-aspartyl chlorine e6 (NPe6), which degrades rapidly in vivo, has been developed. We evaluated its feasibility and efficacy for treatment in biliary tract carcinoma.

Methods

A transmittance of semiconductor laser light (664 nm), sensitivity of a human biliary tract carcinoma cell line, and disorder to normal tissue including Glissonian constructs and adjacent hepatocytes were investigated.

Results

The transmittance of the laser was 85-91% through yellow clear bile and that of the bile including 50 μg/ml NPe6 was 17–48%. The effective concentration of NPe6 which showed LD50 for a cell line was 12.5 μg/ml, and that of LD95 was 25 μg/ml. NPe6 in the supernatant reduced laser transmissiveness, but it had little influence on the antitumor effect in supernatant with or without NPe6. The NOZ cell-tumor volume was reduced significantly 14 days after irradiation in the PDT group (PDT 69.9 ± 44.6 mm³ vs control 296.3 ± 239.9 mm³ P < 0.05). No severe hepatic disorder including Glisson components was observed by the histological findings.

Conclusion

NPe6 PDT was effective in carcinomas even in the presence of bile, and causes no serious complication for the liver and Glisson structure. Therefore, NPe6 PDT will be a useful candidate as a new therapy for biliary tract carcinomas.     

Influence of portacaval anastomosis on serum and biliary unsulfated bile acid composition in patients with liver cirrhosis

Serum and biliary unsulfated bile acids were studied using a gaschromatographic method in 8 patients before and 2 months after portacaval anastomosis. Total serum bile acids were 21.6±3.6 μmol/liter before and 68.0±8.6 μmol/liter after surgery (P<0.005). Cholic acid rose from 26.5±3.4% to 33.8±4.8% (P<0.02) of the total serum bile acids, while chenodeoxycholic acid decreased from 67.9±4.1% to 60.8±4.3% (P<0.05). The relative concentration of cholic and chenodeoxycholic acids in bile increased slightly but not significantly after surgery, while deoxycholate fell from 8.5±1.7% to 2.1±0.6%. Conclusions: (1) in cirrhosis the serum and biliary bile acid composition are markedly different, the cholic-chenodeoxycholic ratio being much lower in serum than in bile; (2) after portacaval anastomosis serum and biliary bile acid patterns tend to become similar; (3) percent biliary deoxycholate decreases significantly after surgery.     

Biliary lithotripsy with a new electromagnetic shock wave source

During a two-year study period 170 consecutive patients with gallbladder stones, suitable for lithotripsy, were treated with a new electromagnetic lithotriptor (Modulith) and oral bile acids; 142 patients were treated as outpatients. Sufficient fragmentation were obtained in 94% when 2112±137 shocks in 211 sessions with an energy setting of 17.8±0.8 kV were administered. Only 4/170 patients needed transient analgesia. Overall, side effects were transient and mild, but three patients developed biliary pancreatitis, which was treated by endoscopic sphincterotomy in two of them. A total of 67/100 patients were free of stones after one year. Subgroup analysis showed that 80% of the patients (stone diameter 5–20 mm), 64% (20–30 mm) and 65% (multiple stones), respectively, can expected to be free of stones after 12 months. In addition, 25 patients with large, endoscopically not extractable common bile duct stones were treated by lithotripsy with the Modulith. After endoscopic placement of a nasobiliary tube, stone targeting was possible by ultrasonography in 14 patients and by fluoroscopy in another 11 cases. In 23 of the 25 patients (92%) stone clearance by endoscopy was achieved after application of 2516±565 shocks with an energy preset of 18 kV. One patient refused further endoscopic procedures after successful fragmentation and another required local stone dissolution therapy. Side effects occurred more frequently (P<0.05) after lithotripsy of bile duct stones than of gallbladder stones, but they were without major clinical relevance. The new lithotriptor Modulith thus enables safe and highly effective lithotripsy of gallbladder calculi on an outpatient basis. Moreover, the device also allows successful lithotripsy of bile duct stones.     

Clinical features of pancreaticobiliary maljunction: update analysis of 2nd Japan-nationwide survey

Introduction

Pancreaticobiliary maljunction (PBM) is a congenital anomaly, which can be defined as a union of the pancreatic and biliary ducts located outside off the duodenal wall. We herein investigate clinical features of PBM including as the 2nd report of a Japanese nationwide survey.

Patients and methods

During a period of 18 years (from 1990 to 2007), 2,561 patients with PBM were registered at 141 medical institutions in Japan. Among them, eligible patients (n = 2,529) were divided into two groups: adult (n = 1,511) and pediatric patients (n = 1,018). Comparisons of clinical features including associated biliary cancers were performed according to the biliary dilatation (BD), age factor, and time era.

Results

Only one case in pediatric patients with BD combined with a bile duct cancer (0.1 %). In adult patients, the bile duct cancer and the gallbladder cancer was seen in 6.9 and 13.4 % patients with BD and in 3.1 and 37.4 % patients without BD, respectively. In adult patients with BD, the occurrence rates of biliary cancers were increased in latter period (00’–07’) compared with former period (90’–99’). The ratio of biliary cancer localization was changed between former and latter period, and the bile duct cancer was increased in latter period (from 5.5 to 9.3 %).

Conclusions

The largest series of PBM were evaluated to clarify the clinical features including the associated biliary cancer in this Japan-nationwide survey. This report could be widely used in the future as a reference data for diagnosis and treatment of PBM.     

Biliary lipid composition in patients with non-cirrhotic portal fibrosis – a comparison with compensated cirrhosis of the liver

ABSTRACT— Patients with non-cirrhotic portal fibrosis (NCPF) are known to have mild hepatic functional abnormalities. To study the biliary lipid composition in these patients, duodenal bile was collected from 18 patients with NCPF, 15 patients with non-alcoholic compensated cirrhosis of the liver and 18 matched, non-obese, healthy control subjects. There were no significant differences in the mean (± SD) concentrations of cholesterol, phospholipids and bile acids in patients with NCPF and healthy controls. On the other hand, patients with cirrhosis had significantly lower concentrations of all the three biliary lipids as compared with the NCPF patients and controls (p<0.05). The cholesterol solubilizing capacity of the bile was the same in NCPF patients, cirrhotics and controls. It is concluded that the relative proportions of the three biliary lipids remain unchanged in patients with NCPF despite mild hepatic derangement.     

Ursodeoxycholic acid administration on bile acid metabolism in patients with early stages of primary biliary cirrhosis

Ursodeoxycholic acid has been proposed for the treatment of primary biliary cirrhosis. The aim of this study was to evaluate the effect of ursodeoxycholic acid administration on bile acid metabolism in patients with early-stage primary biliary cirrhosis. Biliary bile acid composition, primary bile acid pool sizes, synthesis, and fractional turnover rate were measured before and after four weeks of ursodeoxycholic acid administration (600 mg/day) in nine patients with biopsy-proven primary biliary cirrhosis (stages I-III). Molar percentages of chenodeoxycholic, cholic, and deoxycholic acids in bile were significantly decreased by ursodeoxycholic acid administration, while its biliary concentration increased to 34.2% at the end of the same four-week period. The cholic and chenodeoxycholic acid pools decreased, although not significantly, while the deoxycholic acid pool was reduced by 60% (from 0.7±0.12 to 0.29±0.07 mmol,P<0.002). Primary bile acid synthesis was slightly increased, and fractional turnover rate was significantly increased. The conversion rate of cholic to deoxycholic acid was measured and found to be significantly increased (P<0.05) after ursodeoxycholic acid administration; however, serum levels of both free and conjugated deoxycholic acid were significantly decreased (from 23.2±9.7 to 3.8±1.9 μmol/liter,P<0.001). We conclude that in patients with primary biliary cirrhosis, ursodeoxycholic acid administration replaces endogenous bile acids in the enterophepatic circulation by increasing bile acid fractional turnover rate without significant increments of their hepatic synthesis.     

Intravenous 64-multi-detector row CT-cholangiography of porcine livers: a feasibility study with definition of the temporal window for optimal bile duct delineation

Background/purpose

To assess the feasibility of intravenous 64-multi-detector row computed tomography (CT)-cholangiography of porcine livers with definition of the temporal window for optimal bile duct delineation.

Methods

Six healthy Landrace pigs, each weighing 28.97 ± 2.99 kg, underwent 64-multi-detector row CT-cholangiography. Each pig was infused with 50 ml of meglumine iotroxate continuously over a period of 20 min and, starting with the initiation of the infusion, 18 consecutive CT scans of the abdomen at 2-min intervals were acquired. All series were evaluated for bile duct visualization scores and maximum bile duct diameters as primary study goals and bile duct attenuation and liver enhancement as secondary study goals.

Results

Of the 16 analyzed biliary tract segments, maximum bile duct visualization scores ranged between 4.00 ± 0.00 and 2.83 ± 1.47. Time to maximum bile duct visualization scores ranged between 10 and 34 min. Average bile duct visualization scores for the 10- to 34-min interval ranged between 3.99 ± 0.05 and 2.78 ± 0.10. Maximum bile duct diameters ranged between 6.47 ± 1.05 and 2.65 ± 2.23 mm. Time to maximum bile duct diameters ranged between 24 and 34 min. Average bile duct diameters for the 10- to 34-min interval ranged between 6.00 ± 0.38 and 2.40 ± 0.13 mm.

Conclusions

Intravenous 64-multi-detector row CT-cholangiography of non-diseased porcine liver is feasible, with the best bile duct delineation acquired between 10 and 34 min after initiation of the contrast agent infusion.     

Effect of Glutathione Administration on Hepatic Biliary and Plasmatic Glutathione Levels in the Rat

Vendemiale G, Palmieri V, Palasciano G, Altomare E. Effect of glutathione administration on hepatic biliary and plasmatic glutathione levels in the rat. Scand J Gastroenterol 1994;29:1034-1038.

Background: Since the effect of exogenous glutathione (GSH) on overall hepatic GSH homeostasis is not known, the present study investigated the changes in the hepatic, biliary, and plasmatic GSH levels during GSH administration in intact rats

Methods: An exteriorized biliary-duodenal fistula was established, and GSH (1 mmol/kg over 2 h) or saline was administered intraperitoneally to rats with or without pretreatment with 5 mmol/kg L-serine borate, an inhibitor of gamma-glutamyltransferase (GGT).

Results: Three hours after GSH administration, biliary GSH efflux and bile flow rose from 104.7 ± 5.6 to 290.6 ± 8.6μg/ml bile and from 20.2 ± 1.3 to 30.2 ± 2.1 μl/min, respectively; GSH-treated rats also showed increased liver (35%) and posthepatic vein plasma (68%) GSH concentrations compared with controls. By contrast, in rats pretreated with the GGT inhibitor GSH administration appeared to be devoid of any effect, except for a modest biliary GSH increase.

Conclusions: This study indicates that significant changes occur in the hepatic GSH homeostasis after intraperitoneal GSH administration. The activity of hepatic GGT. most likely through degradation of circulating GSH, followed by an increase in cysteine availability, seems to account, at least partially, for the reported effects.     

Insulin-Induced Choleresis in Relation to Insulin Concentrations in Plasma and Bile in the Cat

In experiments on fasting, chloralose-anesthetized cats the concentrations of insulin and glucagon in arterial or portal plasma and bile were studied during insulin-induced choleresis. The administration of insulin in single doses (0.1–1.0 U · kg^-1) and infusions (0.001–0.01 U · kg^-1 · min^-1) resulted in parallel increases in bile flow and ¹⁴C-erythritol clearances of 17%–96%, whereas the net ductular fluid transport and the biliary excretion rate of bile acids remained unchanged. Insulin therefore stimulated the bile acid-independent fraction of the canalicular bile formation. When corrected for the hepatic transit time of insulin (25 min) the initial phase of insulin choleresis was closely related in time to the plasma (30–5000 μU · ml^-1) and biliary (40–210 μU · ml^-1) concentrations of insulin. Bile flow was stimulated even at plasma insulin concentrations similar to those seen postprandially. It is concluded that insulin-induced choleresis to a great extent can be explained by direct, hepatic actions of the hormone, but a delayed release of glucagon may be of importance for the terminal phase of insulin choleresis. The results also demonstrate that insulin crosses the liver by an intercellular pathway. This mode of transport could be of importance for its action on bile production.     

Effect of Gemfibrozil Administration on Biliary Lipid Secretion in Hyperlipidemic Patients

Gemfibrozil, like clofibrate, is effective in lowering both serum cholesterol and triglycerides and in increasing high-density lipoproteins. The information available about its effects on biliary lipids is still limited, and conflicting results have been reported. In this study we evaluated the effect of gemfibrozil (1.2g/day) and clofibrate (2.0g/day), in a single-blind crossover design for 6 weeks with a 4-week washout period, on the biliary cholesterol saturation index (SI) in stimulated hepatic bile and on the hepatic secretion rate of biliary lipids in patients with hyper-lipidemia. Clofibrate increased cholesterol SI (from 1.70 ± 0.14 to 2.05 ± 0.24), whereas gemfibrozil decreased it (from 1.70 ± 0.14 to 1.54 ± 0.16). The results were not statistically significant. The hepatic secretion rate of cholesterol was significantly (p < 0.04) increased by clofibrate therapy, whereas it was significantly (p < 0.04) decreased after gemfibrozil; a significant (p < 0.04) decrease in the hepatic secretion rate of bile acids, bile acid pool size, and bile acid fecal excretion (p < 0.04) was also found after gemfibrozil administration. Gemfibrozil interferes extensively with bile acid metabolism, but it does not increase biliary cholesterol secretion, as clofibrate does. These results suggest that gemfibrozil does not seem to increase the risk of gallstone formation in patients with hyperlipidemia.     

Nonparallel patterns of circadian pancreatic and biliary secretions in fasting rats

We compared the circadian patterns of pancreatic and biliary secretions in fasting rats. For this purpose, indwelling plastic catheters were placed in 10 male Wistar rats (300-320 g) for the collection of biliary and pancreatic secretions. After small samples were taken for analysis, pancreatic and biliary secretions were recirculated into the duodenum by an additional connecting system. The rats were adapted to an inverse night-day cycle by artificial light during the night (8 pm-8am) and by darkroom housing at daytime (8 am -8 pm ). During a 24-h fasting period, samples of bile (100 μL) and pancreatic juice (20 μL) were taken every hour for determination of the following parameters: pancreatic and biliary flow rate, protein, amylase, lipase, trypsin, and bile acid output. Peak pancreatic flow rate (1.96 ± 0.05 mL/h-kg) was achieved toward the end of the dark period at 7 pm. A significant increase of pancreatic secretion could be achieved merely by turning the lights off, a significant decrease by turning the lights on. Similar circadian patterns were found for pancreatic protein, amylase, and lipase output with peak secretions at 7 PM. An increase of nearly 5x was found between minimal (15.64 ± 0.65 mg/h-kg) and maximal (72.43 ± 2.83 mg/h-kg) pan-creatic protein output. The amplitude was highest for amylase; peak amylase output (13740 ± 832 U/h-kg) was about 18-fold above minimal output (758 ± 44.3 U/h-kg). Conversely, the peak of trypsin concentration in pancreatic juice (1095 ± 17.8 U/mL) occurred during the light period when flow rates were lowest. Circadian patterns of biliary vol flow rate and bile acid output were also present, with peak secretions after 4 and 5 h of the dark phase, respectively (9.22 ± 0.31 mL/h-kg; 440 ± 9,53 μmol/h-kg). No acute alterations in biliary secretion resulted from turning the lights on or off. We conclude that pancreatic and biliary secretions are nonparallel in fasting rats and that distinct mechanisms are likely to be involved in the regulation of these different circadian patterns.     

The effect of bilirubin on biliary lipid secretion: Analysis by horseradish peroxidase associated intrahepatic vesicular transport system

The mechanism of biliary lipid secretion is still controverial and there is no definite information regarding how bilirubin inhibits biliary phospholipid and cholesterol secretions without affecting bile salt secretion. In this study, the effects of biliribin on intrahepatic vesicular transport and biliary lipid secretion were examined using bile-fistula rats. Horseradish peroxidase (HRP) was used as a tracer of intrahepatic vesicular transport. Bilirubin (5mg/100g BW) and/or HRP (5mg/100gBW) were injected through the mesenteric vein. Bile flow, biliary bile acid, biliary phospholipid and cholesterol outputs were examined in saline, HRP and HRP+bilirubin groups, respectively. Bile flow and biliary bile acid output were not affected by bilirubin administration. Biliary phospholipid and cholesterol as well as biliary HRP outputs were inhibited just after bilirubin administration, 42.8±6.1 SD% 47.7±5.1 SD%, and 33.4±3.8 SD%, respectively. These results suggested the participation of intrahepatic vesicular transport system in the inhibition of biliary lipid secretion by bilirubin and in its secretory mechanism. This study was partially funded by Uehara Life Science Foundation.     

Effects of somatostatin on hepatic bile formation

Somatostatin is a peptide that has anticholeretic properties in the dog. The purpose of the present work was to investigate if somatostatin is an anticholeretic agent in humans also. The effects of intravenous infusion of somatostatin on hepatic bile flow and biliary electrolytes and secretion of biliary lipids were studied in 7 patients with complete biliary drainage who had been operated on for choledocholithiasis. Somatostatin, 250 microgram/h, was found to decrease the hepatic bile secretion by approximately 30%. The peptide also reduced the outputs of bile acids, cholesterol, and phospholipids and the outputs of sodium, potassium, and chloride. The concentrations of the biliary lipids were not significantly changed. Somatostatin inhibited the erythritol clearance in the 2 patients studied by approximately 25%. The present study thus provides evidence that somatostatin inhibits bile formation in humans. It appears as if the reduction in bile production is mainly due to decreased canalicular bile flow. It is possible that this effect of somatostatin is attributable to inhibition of bile acid synthesis or of transport-secretion of bile acids, or both.     

Bile lipid composition and bile acid pool size in diabetes

Since the prevalence of gallstones is higher in diabetics than in controls and since cholelithiasis is often associated with supersaturated bile, we measured bile lipid composition and bile acid pool size in 8 patients with juvenile diabetes, 16 with maturity-onset diabetes, and 10 control subjects. Bile lipid composition was expressed as “saturation index.” In the maturity-onset diabetics the saturation index (1.60:±0.45SDM) was significantly higher (P<0.005) than that in the controls (0.82±0.20) and in patients with juvenile diabetes (0.75±0.24). The absolute values for biliary bile acid concentration were significantly lower (P<0.01) in the maturity-onset diabetics than in the other two groups. There were no differences in either the proportion of the individual biliary bile acids or the size of the bile acid pool between the three groups. The results suggest that the incidence of cholelithiasis in diabetes is associated with the secretion of a supersaturated bile only in the maturity-onset subgroup.