Frédéric Prat

A randomized trial of endoscopic drainage methods for inoperable malignant strictures of the common bile duct

BACKGROUND Although metallic stents remain patent longer than plastic stents, the optimal palliation of inoperable malignant biliary strictures remains controversial because of the high cost of metallic stents and short patient survival. METHODS A total of 101 patients (mean age 72.5+/-12.9 years) with malignant strictures of the common bile duct were included in this study, after three exclusions for technical failure (n = 3) and one for noncompliance with study design. The etiology of the strictures included pancreatic cancer (65), cholangiocarcinoma (21), ampullary tumor (3), and metastatic lymph nodes (12). Patients were randomized to receive either an 11.5F polyethylene stent to be exchanged in case of dysfunction (group 1, n = 33), an 11.5F stent to be exchanged every 3 months (group 2, n = 34), or a self-expanding metallic Wallstent (group 3, n = 34). RESULTS Endoscopic procedures were successful (including complete relief of jaundice) in 97.1 % of cases. Procedure-related morbidity was 11.9%, and mortality was 2.9%. Bilirubinemia after 48 hours (37.2%+/-21.7% decrease from the preoperative level) did not differ between groups. Patients were followed for a mean of 166 days (median 143, range 0 to 596 days). Overall survivals were not different between groups, but complication-free survival for groups 2 and 3 was longer than that of group 1 (p < 0.05). Cumulated hospital days were 7.4+/-1.5, 10.6+/-1.7, and 5.5+/-1.4 (groups 1, 2, and 3, respectively) (p < 0.05; analysis of variance). Cost analysis showed that metallic stents were advantageous in patients surviving more than 6 months, whereas a plastic stent was advantageous in patients surviving 6 months or less. CONCLUSIONS Metallic stents and plastic stents exchanged every 3 months are valuable alternatives for increasing complication-free survival in patients with malignant strictures of the common bile duct. Metal stents are advantageous in patients with the longest life expectancy.

Predictive factors for survival of patients with inoperable malignant distal biliary strictures: a practical management guideline.

Background—Stenting is the treatment of choice for inoperable malignant strictures of the common bile duct. Criteria for the choice of stents (plastic versus metallic) remain controversial because predicting survival is difficult. Aims—To define prognostic factors in order to improve the cost effectiveness of endoscopic palliation. Patients—One hundred and one patients were included in a prospective trial. Seven prognostic variables for survival were analysed (age, sex, bilirubinaemia, weight loss, presence of liver metastases, and tumour histology and size). All patients were followed until death or at least one year after inclusion. By the end of the study, 81 (80.2%) patients had died. Results—In univariate analysis, the variables associated with survival were weight loss (p<0.05) and tumour size (p<0.01). By multivariate analysis, tumour size was the only independent prognostic factor (p<0.05). A threshold of 30 mm at diagnosis distinguished two survival profiles: the median survival of patients with a tumour greater than 30 mm was 3.2 months, whereas it was 6.6 months for patients with a tumour less than 30 mm (p<0.001). Conclusions—A practical strategy could be based on tumour size at diagnosis: a metal stent should be systematically chosen for patients with an inoperable tumour smaller than 30 mm, while larger tumours are efficiently palliated by a plastic stent.

Ultrasound applicator for heating an ultrasound absorbent medium

An ultrasound applicator for heating, via an internal path, an ultrasound absorbent medium, includes an application head having a longitudinal axis and including at least one ultrasonic transducer having a planar emission face and an opposite face, a leakproof membrane which overlays and is spaced from the emission face, and which is transparent to ultrasound, and means for preventing propagation of ultrasound from the opposite face; means for remotely connecting the transducer to an electricity generator; and means for providing ultrasound coupling with the membrane. The planar emission face emits ultrasound waves through the membrane and in a direction that is substantially perpendicular to the emission face, such that the waves emitted are substantially planar and do not diverge in the vicinity of the transducer and the application head.

Prediction of drainage effectiveness during endoscopic stenting of malignant hilar strictures: the role of liver volume assessment.

BACKGROUND The optimal endoscopic approach to the drainage of malignant hilar strictures remains controversial, especially with regard to the extent of desirable drainage and unilateral or bilateral stenting. OBJECTIVE To identify useful criteria for predicting successful endoscopic drainage. DESIGN AND SETTING Retrospective 2-center study in the greater Paris area in France. PATIENTS A total of 107 patients who had undergone endoscopic stenting for hilar tumors Bismuth type II, III, or IV and a set of contemporaneous cross-sectional imaging data available. INTERVENTIONS The relative volumetry of the 3 main hepatic sectors (left, right anterior, and right posterior) was assessed on CT scans. The liver volume drained was estimated and classified into 1 of 3 classes: less than 30%, 30% to 50%, and more than 50% of the total liver volume. MAIN OUTCOME MEASUREMENTS The primary outcome was effective drainage, defined as a decrease in the bilirubin level of more than 50% at 30 days after drainage. Secondary outcomes were early cholangitis rate and survival. RESULTS The main factor associated with drainage effectiveness was a liver volume drained of more than 50% (odds ratio 4.5, P = .001), especially in Bismuth III strictures. Intubating an atrophic sector (<30%) was useless and increased the risk of cholangitis (odds ratio 3.04, P = .01). A drainage > 50% was associated with a longer median survival (119 vs 59 days, P = .005). LIMITATIONS Heterogeneous population and volume assessment methodology to improve in further prospective studies. CONCLUSION Draining more than 50% of the liver volume, which frequently requires bilateral stent placement, seems to be an important predictor of drainage effectiveness in malignant, especially Bismuth III, hilar strictures. A pre-ERCP assessment of hepatic volume distribution on cross-sectional imaging may optimize endoscopic procedures.

Prediction of common bile duct stones by noninvasive tests

OBJECTIVE To define accurate and useful predictors of common bile duct stones (CBDS). SUMMARY BACKGROUND DATA The ability to predict CBDS with noninvasive tests can avoid unnecessary, costly, or risky procedures. METHODS All patients referred for examination for CBDS by endoscopic ultrasonography (EUS) from 1993-1996 were prospectively entered in a database. In a first sample selected randomly from the whole population, predictors of CBDS were determined by univariate analysis and logistic regression. Predictors were subsequently tested in that sample and in the rest of the population. A separate analysis was done for patients planned for cholecystectomy. RESULTS Eight hundred and eighty patients (328 men, 552 women), aged 57.8 +/- 17 years (range 16-94), were included. The prevalence of CBDS was 18.8%. Age, serum levels of bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase (GGT), and alkaline phosphatase, and the existence of jaundice and fever, a dilated bile duct, and a pathologic gallbladder were found to be associated with CBDS. Logistic regression was undertaken separately for patients younger than 70 years (predictors: GGT >7 x normal; pathologic gallbladder; dilated bile duct) and older than 70 years (predictors: GGT >7 x normal; fever > 38 degrees C; dilated bile duct). Odds ratios were 3 to 6.7. The model was satisfactorily applicable to the second sample; age <70 years: chi2 = 3.3 (NS); age >70 years: chi2 = 3.8 (NS). In patients younger than age 70 and planned for cholecystectomy, the combination of the level of GGT and dilated bile duct predicted CBDS accurately. CONCLUSIONS A simple screening of patients at risk for CBDS can be achieved with three predictive criteria adapted for the patients age.

Nifedipine for prevention of post-ERCP pancreatitis: A prospective, double-blind randomized study

BACKGROUND Pancreatitis is the most common complication of ERCP. Calcium channel inhibitors have been shown to prevent the development of experimental pancreatitis. The aim of this randomized, placebo-controlled trial was to determine whether the calcium channel blocker nifedipine prevents post-ERCP pancreatitis. METHODS Patients referred for ERCP were enrolled. Those being treated with a calcium channel inhibitor and those with acute or chronic pancreatitis were excluded. Nifedipine or placebo was administered orally less than 3 hours before and within 6 hours after ERCP. The main outcome measure was the number of cases of post-ERCP pancreatitis; a secondary outcome was the rate of post-ERCP pain (without pancreatitis) that persisted for 12 or more hours. RESULTS One hundred fifty-five patients (70 women, 85 men; mean [SD] age 65.8 [18.2] years; range, 23-97 years) were enrolled and randomized to receive nifedipine (76 patients) or placebo (79 patients). The two groups were comparable. Procedures performed were retrograde diagnostic cholangiopancreatography alone (n = 33), biliary sphincterotomy (n = 31), stone extraction (n = 39), stent placement (n = 37), sphincteroplasty (n = 5), and other (n = 3). ERCP was unsuccessful in 5 patients. A single case of severe pancreatitis was observed (placebo group). The rate of post-ERCP pancreatitis was not different between groups (nifedipine, 10 patients, 13.2%; placebo, 14 patients, 17.7%; p = 0.4). The frequency of post-ERCP pain was not different between the groups. The only independent predictor of post-ERCP pancreatitis was difficult cannulation in both groups (OR = 3.78: 95% CI [1.25, 11.45]). CONCLUSION This study failed to demonstrate a significant effect of nifedipine in the prevention of post-ERCP pancreatitis. A multicenter trial with greater statistical power would be needed to demonstrate a benefit for this drug.

CHARACTERIZATION OF EXTRACORPOREAL ABLATION OF NORMAL AND TUMOR-BEARING LIVER TISSUE BY HIGH INTENSITY FOCUSED ULTRASOUND

Treatment parameters of extracorporeal high intensity focused ultrasound (HIFU) were analysed in normal and tumor-bearing rabbit liver. HIFU was generated with a 1 MHz transducer and energy was provided by a 7.5 kW power amplifier. In vivo experiments were conducted on 74 New Zealand rabbits. Normal rabbits and rabbits bearing an intrahepatic VX2 tumor were used. In group 1, spatial peak temporal peak (SPTP) intensities ranging from 1470 to 5500 W cm-2 and exposure times from 0.5 to 5 s were tested at a constant depth in the liver; in group 2, the output power was adjusted as a function of the target depth in order to keep constant the focal in situ intensity in the liver; in group 3 (liver tumors), the focal in situ intensity was 1365 W cm-2 in eight rabbits and 500 W cm-2 in nine. In groups 1, 2 and 3, rabbits were sacrificed 48 h after the treatment. Groups 4 and 5 were designated for analysis of the lesion in the normal liver 4 weeks after treatment at 1000 W cm-2 and 3000 W cm-2 SPTP intensities, respectively. In normal rabbits, the lesion volume increased with exposure time at constant intensity; there was a negative correlation between intensity and exposure time (group 1). When the output power was adjusted as a function of the path length, the lesion size was nearly constant (group 2). In VX2 rabbits, tumor destruction rates were significantly higher in rabbits treated at 500 W cm-2 than in rabbits treated at 1365 W cm-2 (p < 0.05; group 3). As in the normal liver, the lesion volume increased with the exposure time at constant intensity. HIFU lesions treated at 1000 w cm-2 (SPTP) healed as thin fibrous scars, and no severe complication occurred (group 4); at 3000 W cm-2 (SPTP), scars were larger and perforation of a neighbouring organ was seen in 7 of 11 rabbits (group 5).

Temporary placement of partially covered self-expandable metal stents for anastomotic biliary strictures after liver transplantation: a prospective, multicenter study

BACKGROUND Management of anastomotic biliary strictures after liver transplantation deserves optimization. OBJECTIVE To evaluate placement and removal of partially covered self-expandable metal stents (PCSEMSs) in this setting. DESIGN Prospective, multicenter, uncontrolled study. SETTING Three French academic hospitals with liver transplantation units and tertiary referral endoscopy centers. PATIENTS Twenty-two patients (18 men, 4 women, aged 49.7 ± 12 years) with anastomotic biliary stricture. Seventeen (77.3%) presented stricture recurrence after plastic stenting. INTERVENTIONS PCSEMSs were placed across the stricture for 2 months and then removed. Patients were followed by clinical examination and liver function tests 1, 3, 6, 9, and 12 months after PCSEMS removal. MAIN OUTCOME MEASUREMENT The ability to remove PCSEMS. RESULTS PCSEMS placement was successful in all patients, after sphincterotomy in 21 patients. Stent-related complications included minor pancreatitis (3 patients), transient pain (1 patient), and cholangitis (1 patient). Stent removal was achieved in all patients but 2 whose stents had migrated distally. Partial stent dislocation was noted in 5 patients (upward in 4, downward in 1). Complications associated with stent removal were minor, including self-contained hemorrhage (1 patient) and fever (1 patient). The stricture persisted at the end of treatment in 3 patients (13.6%), all of whom had stent migration or dislocation. Recurrence of anastomotic stricture after initial success occurred in 9 of 19 patients (47.4%) within 3.5 ± 2.1 months. Sustained stricture resolution was observed in 10 of 19 patients (52.6%), 45.6% from an intent-to-treat perspective. LIMITATIONS Uncontrolled study with limited follow-up. CONCLUSIONS Temporary placement and removal of PCSEMSs in anastomotic biliary strictures after liver transplantation is feasible, although sometimes demanding. Stent migration may impair final outcome.

Biliary obstruction caused by portal cavernoma: a study of 8 cases

BACKGROUND/AIMS Biliary obstruction secondary to portal cavernoma is a rare and little-known entity. From 1985 to 1994, we observed eight cases of portal cavernoma compressing the biliary tract. We report here the features of biliary involvement in these cases of portal cavernoma including the circumstances of diagnosis, biliary tract morphology, liver pathology and the efficiency of various treatments. METHODS AND RESULTS The causes of portal vein obstruction were portal vein thrombosis in one case, peritonitis in another, omphalitis in two cases, portal vein catheterization in one case and unknown in two cases. The portal cavernoma was revealed through esophageal varices ruptures in four patients. The mean time from portal cavernoma diagnosis to biliary involvement was 8 years (range 0-21). Six patients had acute cholangitis, one of whom revealed portal vein obstruction. All the patients had abnormal liver function tests. Imaging techniques (transparietal abdominal ultrasonography and abdominal computed tomography scan [n = 8], endosonography [n = 5] and endoscopic retrograde cholangiography [n = 7]) showed in all cases an extraluminal obstacle, laminating the common bile duct. Pathologic examination of the liver showed secondary biliary cirrhosis in one patient, periportal and perisinusoidal fibrosis in another and no abnormalities in three other cases. Three patients were treated by endoscopic sphincterotomy but cholangitis persisted in two cases, leading to death in one. One patient who underwent a splenorenal shunt was symptom-free 60 months after surgery. Balloon endoscopic dilatation of the common bile duct, performed in one case, led to normalization of liver biological tests. The patients with abnormal liver pathology were treated by propranolol and ursodesoxycholic acid. No complication had occurred after 6 and 24 months of follow-up. CONCLUSIONS In conclusion, eliminating biliary obstruction seems to be essential in providing the best change of survival for patients when biliary obstruction becomes symptomatic. In cases of abnormal liver pathology, associating propranolol with ursodesoxycholic acid would seem to be useful.

Design and preliminary results of an ultrasound applicator for interstitial thermal coagulation

The extracorporeal high-intensity focused ultrasound (HIFU) techniques are not still transposable for tumors of the digestive tract because of their locations. This study was designed to evaluate the feasibility of interstitial applicators (3.8 mm O.D.) to comply with this therapeutic lack and to demonstrate the possibility of producing coagulation necrosis by a specially designed probe and with a short exposure time (20 s). The active surface of the applicators consists of plane water-cooled PZT transducers working at 10 or 5 MHz. They were evaluated in terms of acoustic power emitted as a function of the frequency, and applied electrical input (electroacoustic efficiency of 75% at their working frequency) and in vitro and in vivo pig liver tissue destruction. The in vitro and in vivo necroses depth from the applicator surface ranged from 8 to 20 mm. This showed the advantage of a nondivergent source: the pressure decay is only due to the tissue absorption in the Fresnel zone. The lesions dimensions are slightly dependent on perfusion: 8 +/- 2 mm deep in vitro for a 10.7-MHz transducer working at 14 W/cm2 against 10 mm in vivo. Operating at 5 MHz makes it possible to increase the therapeutic heating depth. For example, at a similar close-to-transducer temperature, the 5-MHz applicator induced, at a depth of 10 mm, a temperature elevation of 27 degrees C against 15 degrees C for that working at 10 MHz.