François-Xavier Caroli-Bosc

Endoscopic bilateral metal stent placement for malignant hilar stenoses: identification of optimal technique ☆

BACKGROUND The aim of this study was to identify factors that facilitate bilateral insertion of metal stents in malignant hilar stenoses, for which plastic stents often result in incomplete drainage and subsequent cholangitis. METHODS Between January 1994 and April 1998, we collected 45 cases of advanced (Bismuth stage II or higher) hilar malignant stenoses. The insertion technique was progressively modified and the success rate in the early period (1994 to 1995) was compared with that of a later period (1996) and the most recent period (1997 to 1998). RESULTS Overall success rate was 73.3% (33 of 45). The success rates for the three periods were 50%, 67%, and 88% (p = 0.008), respectively. Cholangitis occurred in 3 of the patients with unilateral stents compared with 1 with bilateral stents. CONCLUSION We have described a technique for endoscopic insertion of bilateral metallic stents for malignant hilar stenoses that results in high (>88%) and reproducible success rates.

A prospective study of pancreatic disease in patients with alcoholic cirrhosis: comparative diagnostic value of ERCP and EUS and long-term significance of isolated parenchymal abnormalities

BACKGROUND The prevalence of pancreatic disease in patients with alcohol-related liver cirrhosis is uncertain. We assessed the prevalence of pancreatic abnormalities in patients with alcoholic cirrhosis, and we compared endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) for the detection of chronic pancreatitis and other pancreatic lesions. In addition, we assessed the long-term significance of isolated pancreatic parenchymal abnormalities detected at EUS. METHODS EUS and ERCP were performed in each patient. Subjects with minimal parenchymal changes at initial EUS underwent clinical follow-up and subsequent EUS and/or ERCP to document the occurrence, absence, or progression of these changes. RESULTS Seventy-two patients with alcoholic cirrhosis were recruited. Chronic pancreatitis was diagnosed in 14 patients (19%) by both methods independently. Isolated parenchymal lesions were observed in 18 patients by EUS alone. After a mean follow-up of 22 months the EUS appearance was unchanged. Ten of the 18 patients underwent follow-up ERCP and this was normal in all cases. CONCLUSIONS This study demonstrated that (1) 19% of patients with alcoholic cirrhosis have chronic pancreatitis, (2) an additional 25% have isolated pancreatic parenchymal changes at EUS, and (3) these parenchymal abnormalities do not progress during follow-up.

A study of the effect of age on pancreatic duct morphology

BACKGROUND Interpretation of endoscopic pancreatograms is difficult in elderly patients. Age-related parenchymal changes and associated ductographic changes are ill-defined, and it is sometimes difficult to distinguish these from pathologic processes. METHODS To define age-related pancreatogram changes, all endoscopic retrograde pancreatograms performed in patients older than 70 years of age over a 6-year period were analyzed and compared with those of a control group (younger than 50 years of age). RESULTS Of the 136 elderly subjects included in the study, 31 (22.8%) were found to have definite pathology. Comparing the remaining 105 subjects with the control group, the mean main pancreatic duct diameter (in millimeters) was larger in the head (5.3 vs. 3.3), body (3.7 vs. 2.3), and tail (2.6 vs. 1.6) (p < 0.05). The duct diameter also increased significantly in each of the age cohorts (70 to 79, 80 to 89, and 90 to 99 years). Only 33 of 105 (31.4%) of the elderly patients had duct diameters within defined normal limits. In the majority (63.3%), dilatation was global but in a minority it was confined to the head and/or body. In 21 subjects the ductal diameter was greater than 2 standard deviations above normal, and in 5 subjects it was greater than 3 standard deviations above normal. Dilatation of secondary ducts was also observed. CONCLUSION The majority of elderly patients who do not have pancreatic pathology have a dilated pancreatic duct by comparison with younger patients. Patient age must be considered when interpreting endoscopic pancreatograms.

Role of Fibrates and HMG-CoA Reductase Inhibitors in Gallstone Formation

Fibrate derivatives and HMG-CoA reductase inhibitors modify homeostasis of cholesterol. The aim of this study was to assess in an unselected population whether these hypolipidemic drugs are risk factors for cholelithiasis or, conversely, are protective agents. Both sexes, all socioeconomic categories, pregnant women, and cholecystectomized subjects were included. Clinical data collection and gallbladder ultrasonography were both carried out in a double-blind fashion. Fibrate derivatives were predominantly fenofibrate, HMG-CoA reductase inhibitors were simvastatin and pravastatin. On univariate analysis, age (>50 years), sex, and use of fibrates were found to be significantly related to the presence of cholelithiasis. Age, sex, and fibrate treatment remained independently correlated with the presence of gallstones on multivariate analysis. With fibrates, the relative risk for lithiasis was 1.7 (P = 0.04). The HMG-CoA reductase inhibitors were not associated with a protective effect on univariate analysis. Of the lipid-lowering drugs, only fibrate derivatives were found to increase the risk of gallstone formation.

Prevalence of Cholelithiasis (Results of an Epidemiologic Investigation in Vidauban, Southeast France)

Cholelithiasis leads to 80,000 cholecystectomiesbeing performed every year in France, but its prevalenceis still unknown. The aim of this study was to assessthe prevalence and risk factors of cholelithiasis in a random population of 1027 women and 727men over the age of 30 in a small town in the southeastof France. Detailed clinical history, dietaryinvestigation, and gallbladder ultrasound were collected for each subject and assessed by univariateanalysis. A regression model was used in themultivariate analysis to detect the relative risk ofcholelithiasis. Cholelithiasis was found in 130individuals (global prevalence 13.9%). The relative riskfor lithiasis was higher in women compared to men(1.89). Age (P < 0.0001) and body mass index (BMI)>25 (P = 0.013) were also significant risk factors. Neither pregnancy nor oral contraceptive useproved to be risk factors. Typical biliary colic painwas the only symptom significantly associated withcholelithiasis (P < 0.0001). These results show that the prevalence of gallstones in France issimilar to that in Denmark and Italy.

Endoscopic insertion of biliary stents in 18 patients with metallic duodenal stents who developed secondary malignant obstructive jaundice

AIM The aim of this work was to evaluate the feasibility of endoscopic insertion of biliary stents in patients with duodenal stents who develop secondary malignant obstructive jaundice. PATIENTS AND METHODS The study population included 133 patients with unresectable malignant duodenal obstruction. In 106 patients a biliary stent was inserted before or at the same time as the duodenal stent. Malignant biliary obstruction appeared secondarily in 18 patients; fifteen of these patients already had a biliary stent. We present our experience of biliary stent insertion in these 18 patients with metallic duodenal stents. RESULTS Biliary obstruction was successfully alleviated in 17 out of 18 patients (94%) without complication. Insertion of a new biliary stent failed in one patient because the mesh of the duodenal stent passed over the metallic biliary stent already in place. Mean duration of endoscopic insertion was 95 minutes (range: 60 - 180). All patients remained free of biliary complications to death (57 days, range: 30 - 120). CONCLUSION Our report shows that endoscopic insertion of a biliary stent is feasible in patients who have metallic duodenal stents. Technical difficulties exist especially if the mesh of the duodenal stent passes over the papilla.

Cholelithiasis and Dietary Risk Factors (An Epidemiologic Investigation in Vidauban, Southeast France)

Dietary risk factors have been implicated in thedevelopment of cholelithiasis. The aim of this study wasto determine in a homogeneous French population whethera particular type of diet may be lithogenic. Seventy-six subjects over 30 years of age (26men, 50 women) with cholelithiasis detected byultrasound were selected from a population sample of 830subjects by drawing lots using the polling list. These were matched by 76 control subjects withoutcholelithiasis randomly selected from the samepopulation. Univariate analysis was significant for ahigh calorie diet >2500 kcal/day (OR = 3.62, P =0.0065), a diet rich in carbohydrates with a consumption≥55 g/day (OR = 2.98, P = 0.0067), and a diet rich intotal lipids (OR = 4,97, P = 0.023) or saturated fattyacids (OR = 3.06, P = 0.0146). An alcohol consumption equivalent to 20-40 g/day was protective (P =0.018). Multivariate analysis confirmed these results.Our study suggests that a change in dietary habits bylimiting excess calories, saturated fats and carbohydrates could reduce the incidence ofcholelithiasis.

Gallbladder Volume in Adults and Its Relationship to Age, Sex, Body Mass Index, Body Surface Area and Gallstones

Background/Aims: The role of a large gallbladder volume with regard to a predisposition for gallstones is unknown. It is possible that an increase in gallbladder volume could result in impaired gallbladder motility and bile stasis. We looked for factors affecting gallbladder volume in a random population in the southeast of France. Methods: To assess the relationship between gallbladder volume and gallstones, 528 subjects over the age of 30 were studied (72 with lithiasis). Age, sex, body mass index, body surface area and gallbladder volume were collected for each subject. A linear regression analysis was performed to look for significant variables. Results: The overall adjusted prevalence of cholelithiasis was 13.9% in our population. On linear regression analysis, two variables (age and surface area) were found to be independently correlated with gallbladder volume. Gallbladder volume was significantly increased in subjects over 50 years (p < 0.001). There was a positive correlation between gallbladder volume and body surface area (r = 0.33, p < 0.001). In this study, the presence or absence of gallstones did not significantly affect the gallbladder volume. Conclusions: We report that there is dilatation of the gallbladder with age and with an increase in body surface area. Whether this could represent risk factors for the occurrence of gallstone remains uncertain.

Relationship between cystic duct diameter and the presence of cholelithiasis

We sought to measure cystic duct diameter in patients without biliary calculi and in those with cholelithiasis or choledocholithiasis. Using endoscopic retrograde cholangiopancreatography (ERCP), we visualized the cystic duct in 168 patients referred to our unit. These patients were distributed into three groups based on findings at ERCP: Group I (N=57), no calculi in the gallbladder or common bile duct; group II (N=27), stones found in the gallbladder but absent from the common bile duct; and group III (N=34), stones present in the common bile duct with or without gallbladder stones. The diameter of the cystic duct was measured at its widest and narrowest dimensions. The largest diameter measured was greater in group III (7.72±2.29 mm) than in groups I (2.63±0.67 mm) and II (4.59±1.13 mm) (P<0.001). The same differences were found in measurement of the smallest diameter (5.00±0.99 mm, 3.10±0.62 mm, and 1.83±0.53 mm, for groups III, II, and I, respectively) (P<0.001). Maximal and minimal cystic duct diameter show a progressive increase at each level of disease. This increase in cystic duct size may facilitate the migration of gallstone fragments after lithotripsy and facilitate the instrumentation of the cystic duct during ERCP and laparoscopic cholecystectomy.

Ursodeoxycholic acid modulates cyclosporin A oral absorption in liver transplant recipients

Abstract— The aim was to study the ursodeoxycholic acid (UDC) effect on the cyclosporin A (CsA) pharmacokinetics after oral administration of the microemulsion formulation Neoral® (CsA‐ME) in liver transplant recipients, and test the potential protective effect of this bile acid on liver and renal CsA‐ME‐induced toxicity. At entry into the study, 12 patients who underwent orthotopic liver transplantation received CsA‐ME, for at least 6 months. They then received a cotreatment CsA‐ME plus UDC (13.8 mg.kg−1.day−1) for three months. Blood concentrations of CsA were measured using a monoclonal antibody specific for the parent compound. The kinetic data were analysed by a mathematical model incorporating a time dependent rate coefficient for CsA intestinal absorption, before and after UDC treatment. Changes in serum markers of hepatic and renal injury were assessed. Individual serum bile acids were determined by chromatography. Serum levels of UDC increased from 3 to about 45 % of total serum bile acids after UDC treatment. The estimated model parameters indicate that UDC administration modulates CsA intestinal absorption. In the nine non‐cholestatic patients, UDC reduced the absorption rate and the bioavailability of CsA without modifying the elimination rate constant of CsA and the CsA pre‐drug levels. In contrast, in the three cholestatic patients, the bioavailability tended to be higher and the absorption rate faster when CsA was combined with UDC. UDC significantly decreased elevated γ‐glutamyl transferase and creatinine serum levels and induced some clinical improvements such as disappearance of headaches in four patients. In conclusion, a 3‐month UDC treatment modifies CsA intestinal absorption without affecting CsA elimination rate constant. On the other hand, UDC supplementation appears to improve CsA tolerability.