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Biomedical subjects

P Calès

Publications and source records attributed to P Calès.

At least 19 recordsLinked to original sources

[Prevention of esophageal varix rupture].

PRIMARY PREVENTION: Preventive measures against esophageal varicose vein bleeding are needed for grade 2 risk resulting from the presence of large varix. Medical or endoscopic methods can be used. USEFUL DRUGS: With beta-blockers the incidence of a first bleeding episode is significantly reduced and mortality is almost significantly reduced. Three controlled trials have demonstrated that a nitrate derivative beta-blocker combination improves the efficacy of beta-blockers in terms of reduced bleeding. Nitrates can be prescribed alone in case of a contraindication for beta-blockers but the efficacy is poorly demonstrated. SCLEROTHERAPY: Both incidence of first bleeding episode and mortality are significantly reduced after sclerotherapy. Variable results have however been reported and sclerotherapy is probably only effective in high-risk patients; the consensus conference has not recommended its use. On the contrary, endoscopic ligature is probably useful since 5 preliminary studies have demonstrated a significant effect on first bleeding and mortality. Its relative contribution compared with propranolol remains to be demonstrated. RECOMMENDATIONS: The first intention therapy should rely on beta-blockers or nitrates in case of a contraindication or adverse effect. Endoscopic ligature can be discussed in high-risk patients. The beta-blocker-nitrate combination and the beta-blocker-endoscopic treatment combination cannot be recommended at the present time. SECONDARY PREVENTION: Meta-analyses have shown that beta-blockers or sclerotherapy significantly reduce the incidence of recurrent bleeding and mortality. Sclerotherapy significantly reduces the risk of recurrent bleeding compared with beta-blockers although there is no difference in mortality and the incidence of complications is significantly greater with sclerotherapy. Associating the two methods can significantly reduce recurrent bleeding but has no effect on mortality. Elastic ligature is significantly more effective in terms of recurrent bleeding and mortality or complication rate. Transjugular intrahepatic portosystemic shunt (TIPS) significantly reduces the incidence of recurrent bleeding but has no effect on mortality and the risk of hepatic encephalopathy is increased. PRACTICAL ATTITUDE: Elastic ligature can be proposed as a first intention treatment. Sclerotherapy is useful to eradicate varix after size reduction by ligature and to prevent recurrence. In case of failure, a TIPS or surgical shunt can be discussed. Liver transplantation would be indicated in high-risk patients keeping in mind that digestive tract bleeding is a supplementary argument favoring transplantation. RECOMMENDATIONS: The international consensus group (CFEHTP) recommends elastic ligature or beta-blockers, endoscopic treatment being preferred. TIPS or surgical shunt may be discussed in case of failure.

Adrenergic beta-Antagonists↗

Early administration of vapreotide for variceal bleeding in patients with cirrhosis.

BACKGROUND: In patients with cirrhosis, pharmacologic or endoscopic treatment may control variceal bleeding. However, the effects of early administration of a somatostatin analogue followed by endoscopic treatment are unknown. METHODS: We studied the effects of treatment with vapreotide, a somatostatin analogue, begun before endoscopic treatment in 227 patients with cirrhosis who were hospitalized for acute upper gastrointestinal bleeding. The patients were randomly assigned to receive vapreotide (a 50-microg intravenous bolus followed by an infusion at a rate of 50 microg per hour for five days) or placebo within a mean (+/-SD) of 2.3+/-1.5 hours after admission. All the patients received endoscopic treatment a mean of 2.6+/-3.3 hours after the infusion was begun. After the exclusion of 31 patients whose bleeding was not caused by portal hypertension, there were 98 patients in each group. RESULTS: At the time of endoscopy, active bleeding was evident in 28 of 91 patients in the vapreotide group (31 percent), as compared with 43 of 93 patients in the placebo group (46 percent) (P=0.03). During the five-day infusion, the primary objective--survival and control of bleeding--was achieved in 65 of 98 patients in the vapreotide group (66 percent) as compared with 49 of 98 patients in the placebo group (50 percent) (P=0.02). The patients in the vapreotide group received significantly fewer blood transfusions (2.0+/-2.2 vs. 2.8+/-2.8 units, P=0.04). Overall mortality rates at 42 days were not significantly different in the two groups. CONCLUSIONS: In patients with cirrhosis and variceal bleeding, the combination of vapreotide and endoscopic treatment is more effective than endoscopic treatment alone as a method of controlling acute bleeding. However, the use of combination therapy does not affect mortality rates at 42 days.

Blood Transfusion↗

Prospective study on the application of the Baveno II Consensus Conference criteria in patients with cirrhosis and gastrointestinal bleeding.

BACKGROUND/AIMS: This study aimed to evaluate the Baveno II criteria defining key events in variceal bleeding. METHODS: These criteria were applied to 196 patients with cirrhosis admitted for upper gastrointestinal bleeding due to portal hypertension and enrolled in a trial. Blood pressure, heart rate, hematocrit and clinical signs of upper digestive tract hemorrhage were recorded for 5 days. The blind overall clinical judgment of hemodynamic stability was recorded separately by the Steering Committee. RESULTS: The evaluation of several hemodynamic criteria was left to the judgment of the clinician. The first time point for the control of bleeding, fixed at 6 h after admission, was impractical since 13% of the patients had not yet received specific treatment. The independent judgment did not agree in 38% of 82 cases without control of bleeding. In 15% of cases this was due to tachycardia. Calculation of several judgment criteria was not defined in the Baveno II criteria: survival without bleeding at 5 days, transfusion rate, and length of hospital stay. CONCLUSIONS: Although the Baveno II criteria have improved the definitions of key events, the criteria are hampered by limits such as false positive criteria of failure to control bleeding. We make several proposals for improvement.

Blood Transfusion↗

Spleno-renal shunt blood flow is an accurate index of collateral circulation in different models of portal hypertension and after pharmacological changes in rats.

BACKGROUND/AIMS: Recently, we developed a new method to measure collateral blood flow in rats: splenorenal shunt (SRS) blood flow (BF). The aims were to evaluate the reproducibility of SRSBF measurement in different models of portal hypertension, and to investigate the ability of SRSBF to disclose pharmacological changes. METHODS: Hemodynamics were determined in anesthetized rats with secondary biliary, CCl4 or DMNA cirrhosis and portal vein ligation (PVL) under baseline and pharmacological (octreotide, vapreotide) conditions. The main measurements performed were: SRSBF by the transit time ultrasound (TTU) method and % portosystemic shunts (PSS) by the microsphere method. RESULTS: SRSBF was 6 to 10 times higher in portal hypertensive rats and was similar in the different models of cirrhosis but was higher in portal vein ligated rats than in cirrhotic rats (1.1+/-0.7 vs 0.6+/-0.7 ml x min(-1) x 100 g(-1), p=0.01). SRSBF was correlated with mesenteric %PSS (r=0.61, p<0.01), splenic %PSS (r=0.54, p<0.05), portal pressure (r= 0.32, p<0.05) and the area of liver fibrosis (r=0.33, p<0.05). Octreotide significantly decreased SRSBF (-23+/-20%, p<0.01 vs placebo: -6+/-8%, NS). Vapreotide significantly decreased SRSBF but not mesenteric or splenic %PSS compared to placebo. The variations in SRSBF (-26+/-32%) and in splenic %PSS (0+/-15%) with vapreotide were significantly different (p<0.05) and not correlated (r=-0.1, NS). CONCLUSIONS: Determination of SRSBF by TTU is an accurate way to measure collateral blood flow in different models of intra- and extra-hepatic portal hypertension in rats. Its sensitivity provides accurate measurement of pharmacological changes, unlike the traditional estimation of %PSS by the microsphere method.

Animals↗

Multicenter randomized controlled trial of terlipressin versus sclerotherapy in the treatment of acute variceal bleeding: the TEST study.

Failure to control bleeding and early rebleeding account for the high mortality associated with variceal hemorrhage in cirrhosis. We compared endoscopic sclerotherapy to terlipressin, a drug that effectively controls acute bleeding while reducing in-hospital mortality. This multicenter randomized controlled trial included 219 cirrhotic patients admitted for endoscopy-proven acute variceal bleeding and randomized to receive repeated injections of terlipressin during 6 days (n = 105) or emergency sclerotherapy (n = 114). Success was defined as obtaining control of bleeding (24-hour bleeding-free period during the first 48 hours) and lack of early rebleeding (any further bleeding from initial control to 5 days later) and survival during the study. Both groups were similar at inclusion. Failure rate for terlipressin was 33% and 32% for sclerotherapy (not significant [NS]). Early rebleeding was responsible for 43% and 44% of failures, respectively. This high efficacy was observed in both Child-Pugh class A + B and Child-Pugh class C patients. Both treatments were similar regarding transfusion requirements, in-hospital stay, and 6-week mortality (26 vs. 19 patients). Side effects appeared in 20% of patients receiving terlipressin and in 30% of those on sclerotherapy (P =.06); being serious in 4% and 7%, respectively (NS). In conclusion, terlipressin and sclerotherapy are equally highly effective therapies achieving the initial control of variceal bleeding and preventing early rebleeding. Both treatments are safe, but terlipressin is better tolerated. Therefore, terlipressin may represent a first-line treatment in acute variceal bleeding until the administration of elective therapy, especially in hospitals where a skilled endoscopist is not available 24 hours a day.

Acute Disease↗

Gastric mucosal surface in cirrhosis evaluated by magnifying endoscopy and scanning electronic microscopy.

BACKGROUND AND STUDY AIMS: Gastric mucosa may have several tiny patterns in portal hypertension. In this prospective study, we used magnifying endoscopy and scanning electron microscopy (SEM) to better characterize the morphology of gastric mucosa in patients with cirrhosis, and we evaluated the diagnostic accuracy of magnifying endoscopy. PATIENTS AND METHODS: Videotapes of gastric mucosal patterns from 39 cirrhotic patients and 20 control patients were blindly evaluated by the same observer using magnifying endoscopy (magnification x 25) and conventional endoscopy. SEM was performed in 12 other patients. The basic anatomical entities of the gastric architecture on conventional endoscopy were the gastric area in control patients and the mosaic pattern in patients with cirrhosis. RESULTS: With regard to the prevalence of endoscopic patterns in the antrum, the mosaic pattern was more frequent in cirrhotic patients. In the body, the mosaic pattern, white spots, and red marks were significantly more frequent in cirrhotic patients, whereas gastric areas were more frequent in control patients. Concerning the contributions of the techniques, significantly more gastric areas were identified by magnifying endoscopy than by conventional endoscopy. However, in multivariate analysis, only conventional endoscopy with esophageal varices had significant independent diagnostic accuracy for cirrhosis, and magnifying endoscopy of mucosal signs did not add any significant information. SEM did not improve discrimination between control and cirrhotic patients. CONCLUSIONS: Magnifying endoscopy provides more details of the mucosa, thus improving the delineation of gastric mucosal morphology. However, magnifying endoscopy has little clinical value in cirrhosis since it does not improve on the accuracy of conventional endoscopy for the diagnosis of cirrhosis.

Adult↗

Late recurrence of a hepatic angiomyolipoma.

Angiomyolipomas are benign mesenchymal tumours, mostly of renal origin. Hepatic angiomyolipomas are rare, and radiological and pathological diagnoses may be difficult We report on the first case of hepatic angiomyolipoma recurrence known to us, 6 years after surgical treatment of the initial tumour. Moreover, this hepatic recurrence was associated with renal angiomyolipoma without any stigmata of tuberous sclerosis.

Adolescent↗

[The Hepatitis Network in Maine-et-Loire city hospitals: six year follow-up of patients and physicians. Hepatitis Network of Maine-et-Loire].

OBJECTIVES: To evaluate 6 years of a city-hospital hepatitis network. The network was set up in 3 steps: 1988: intrahospital network, 1991: city-hospital network, 1997: compliance with government regulations. METHODS: The whole activity from 1991 to 1997 was evaluated and special attention was paid to patient files and participating physicians. RESULTS: From June 1991 to December 1997 (6.5 years), 759 patient files were registered which corresponds to 531 patients (male 57%) with a mean age of 44 +/- 16 years (+/- standard deviation). Four hundred and twenty one patients (79%) had hepatitis C, 95 (18%) hepatitis B and 15 (3%) co-infection; 83% of patients had had a liver biopsy confirming cirrhosis in 21.5%. The annual number of files registered increased continuously. This was more a result of recruiting known patients than new patients, after the network had been in place for several years, mainly with hepatitis B virus (known patients in 1997: hepatitis B virus: 53% vs 33% for hepatitis C virus, P<0.05). Treatment protocols (73%) were more frequent for hepatitis C virus patients than for hepatitis B (73% vs 59%, P<0.01). Therapeutic trial proposals (37%) increased from 21% in 1991 to 59% in 1997, P<0.01. Participation in monthly meetings by academic hepato-gastroenterologists increased slightly while that of regional hospital hepato-gastroenterologists increased markedly and that of private hepato-gastroenterologists remained stable. The annual proportion of files submitted by academic hepato-gastroenterologists decreased in parallel to the increase in submission of patient files by other hepato-gastroenterologists. CONCLUSIONS: During 6 years of activity, the network grew with an increase in the annual number of patient files, growing participation in therapeutic trials as well as in monthly meetings by practitioners.

Adult↗

Hepatic hyper-vitaminosis A: importance of retinyl ester level determination.

We report the case of a 32-year-old man with portal hypertension without cirrhosis due to chronic vitamin A intoxication. Portal hypertension revealed by oesophageal varice rupture progressively worsened and ascites occurred 5 years after the patient stopped vitamin A intake. Initially, serum retinyl palmitate concentration was increased whereas serum retinol concentration was normal. There was no hepatic fibrosis on light microscopic examination of liver biopsy specimens. Five years after the patient stopped excessive vitamin A intake, serum retinol and retinol-binding protein concentrations were below the normal range even though there was an increased hepatic retinyl ester content. This was attributed to the late development of peri-sinusoidal fibrosis. This case mainly shows the importance of retinyl ester level determination: serum retinyl palmitate should be measured immediately after intoxication and hepatic retinyl esters should be measured initially and particularly later. Indeed, later serum and hepatic retinol levels in chronic hyper-vitaminosis A may be normal and lead to under-estimation of liver vitamin A overload.

Adult↗

Long-term administration of PGE1 increases liver fibrosis and collateral blood flow in bile-duct-ligated rats.

BACKGROUND/AIMS: The aim of this study was to assess the effect of early and chronic administration of a prostaglandin E1 analogue (misoprostol) in the prevention of liver fibrosis and portal hypertension. METHODS: Liver fibrosis was induced by bile duct ligation. Controls had a sham operation. Bile-duct-ligated rats were divided into two groups: placebo (vehicle only) and misoprostol (10 microg/d by gavage) for 4 weeks after surgery. Liver fibrosis was assessed by the area of fibrosis (image analysis), liver hydroxyproline content and serum hyaluronate. Systemic and splanchnic hemodynamics were evaluated including spleno-renal shunt blood flow by the transit-time ultrasound technique. RESULTS: Mean arterial pressure was significantly lower in the misoprostol group (p<0.01). There was an unexpected increase in fibrosis parameters in the misoprostol group compared to the placebo group, e.g. area of fibrosis: 9.5+/-4.0 vs 15.0+/-8.1% (p<0.05). Spleno-renal shunt blood flow was significantly higher in the misoprostol group than in the placebo group (4.6+/-3.7 vs 2.2+/-2.0 ml/min, p<0.05) while portal pressure was unchanged. CONCLUSIONS: The early and chronic administration of misoprostol enhances porto-collateral circulation blood flow and the development of liver fibrosis in bile-duct-ligated rats.

Animals↗

Ultrasonographic diagnosis of hepatic fibrosis or cirrhosis.

BACKGROUND/AIMS: Evaluation of the degree of hepatic fibrosis is especially important in patients with chronic liver disease. Our aim was to study the diagnostic accuracy of abdominal ultrasonography for cirrhosis or fibrosis. METHODS: Twenty-three clinical (n=12) and Doppler ultrasonic (n=11) variables were recorded in 243 patients with chronic (alcoholic and viral) liver disease under conditions close to those of clinical practice. Fibrosis was classified into six grades by two pathologists. Diagnostic accuracy was evaluated by discriminant analysis, first globally using all variables, then by stepwise analysis. RESULTS: A) Diagnosis of cirrhosis: 1) whole group (n=243): diagnostic accuracy was globally 84%, and 84% with two variables: spleen length, portal velocity; 2) compensated chronic liver disease (n=191): diagnostic accuracy was globally 85%, and 82% with two variables: liver surface, liver length (right kidney); 3) alcoholic compensated chronic liver disease (n=109): diagnostic accuracy was globally 86%, and 88% with two variables: spleen length, liver length (middle clavicle); 4) viral compensated chronic liver disease (n= 83): diagnostic accuracy was globally 86% and 86% with one variable: liver surface. By subtracting the proportion of patients who could not be investigated due to anatomical limitations, the highest calculated univariate diagnostic accuracy decreased by 7%. B) Diagnosis of fibrosis: diagnostic accuracy was globally 84% for extensive fibrosis. CONCLUSIONS: Cirrhosis can be correctly diagnosed in 82-88% of patients with chronic liver disease using a few ultrasonographic signs. However, the diagnostic accuracy of ultrasound is decreased by the anatomical limitations of this technique.

Adult↗

Non-invasive diagnosis of esophageal varices in chronic liver diseases.

BACKGROUND/AIMS: The primary prevention of bleeding from esophageal varices is a major therapeutic issue requiring early screening of esophageal varices. Our aim was to study the diagnostic accuracy of non-endoscopic means for the diagnosis of esophageal varices. METHODS: Sixty-three clinical, biochemical, endoscopic and Doppler ultrasound variables were prospectively recorded in 207 consecutive patients with chronic liver disease. Diagnostic accuracy was evaluated by discriminant analysis, first globally using all variables with diagnostic accuracy > or = 65% in univariate analysis, then by stepwise regression. RESULTS: A) whole group (n=207), 1) diagnosis of esophageal varices: diagnostic accuracy was globally 81%, and 81% with 1 variable: irregular liver surface at ultrasound, 2) Diagnosis of large esophageal varices (grades 2+3): diagnostic accuracy was globally 80%, and 79% with 2 variables: prothrombin index, gamma-globulins. B) patients with cirrhosis (n=116), 1) diagnosis of esophageal varices: diagnostic accuracy was globally 71%, and 72% with 2 variables: platelet count, prothrombin index, 2) diagnosis of large esophageal varices (grades 2+3): diagnostic accuracy was globally 71%, and 72% with 3 variables: platelet count, prothrombin index, spider naevi. The ROC curve showed that the best threshold for the diagnostic accuracy of platelet count was 160 G/l providing a sensitivity of 80% and a specificity of 58%. Platelet count > or = 260 G/l has a negative predictive value > or = 91%. CONCLUSIONS: Using a few non-endoscopic criteria, esophageal varices can be correctly diagnosed in 81% of patients with chronic liver disease and in 71% of patients with cirrhosis. These results show that the non-invasive screening of patients who are candidates for the primary prevention of variceal bleeding is possible, but should be improved before being used in a clinical setting.

Analysis of Variance↗

[Budd-Chiari syndrome due to membranous obstruction of the inferior vena cava of congenital origin. Ten-year follow-up after radiologic treatment].

We report a case of Budd-Chiari syndrome due to membranous obstruction of the inferior vena cava with a congenital malformation composed of a left inferior vena cava at the sub-renal level with an azygo-caval continuation without a retrohepatic segment of the inferior vena cava. To our knowledge, this is the first report of this association. The congenital venous malformation suggests a congenital etiology to the inferior vena cava membrane. The membranous obstruction was treated by percutaneous transluminal angioplasty. During the 10-year follow-up, there was no recurrence of the membranous obstruction as seen with Doppler ultrasound and magnetic resonance imaging.

Adult↗