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D Cherqui

Publications and source records attributed to D Cherqui.

At least 37 records · Page 2Linked to original sources
PubMed1999

Inhibitor against coagulation factor V after liver transplantation.

A new case of anti-factor V inhibitor is described in a 46-year-old man, who received a liver transplantation for hepatocellular carcinoma, without exposure to bovine thrombin or fibrin glue during the operative course. The inhibition occurred on the 14th postoperative day, while the patient was being treated with oxacillin, azathioprine, and a new immunosuppressive drug, FK506. The inhibition was of short duration (3 days), and no bleeding complication occurred despite a very low plasmatic level of factor V activity and antigen (<5%). Plasma samples drawn after cessation of FK506 disclosed a dose-dependent inhibitory activity when alcoholic solutions of FK506 were exogeneously added; this suggests a possible role of the FK506 drug in the occurrence of this anti-factor V inhibitor.

Carcinoma, Hepatocellular↗
PubMed1999

Specific vascular complications of orthotopic liver transplantation with preservation of the retrohepatic vena cava: review of 1361 cases.

OBJECTIVE: The objective of this study was to describe the complications specifically related to orthotopic liver transplantation (OLT) with preservation of the inferior vena cava and to their therapeutic management. This preservation technique has considerably influenced the surgical phases of liver transplantation, increasing hepatectomy time and modifying the number of vascular anastomoses. METHODS: Our retrospective multicentric study, based on data from 1361 adult patients that had undergone orthotopic liver transplantation with preservation of the inferior vena cava in France between 1991 and 1997, analyzed the concomitant surgical complications. Type of cavo-caval anastomosis performed (piggyback, end-to-side, or side-to-side), use of a temporary portacaval anastomosis, technique-related complications, and mortality, were investigated. RESULTS: Cavo-caval anastomosis was side-to-side in 50.6% of cases (n=689), piggyback in 42.7% (n=582), and end-to-side in 6.6% (n=90). In total, 882 temporary portacaval anastomosis were carried out. Fifty-five patients presented with one or more complications related to the preservation of the inferior vena cava technique; i.e., overall morbidity was 4.1% (55/1361). Overall mortality was 0.7% (10/1361). Mortality rate for patients who presented with surgical complication was 18%. A total of 64 complications were recorded: 57 (89%) were in the perioperative or immediate postoperative period and 7 (11%) were postoperative. CONCLUSIONS: These retrospective, descriptive results show significant advantages in favor of side-to-side anastomosis in terms of vascular complications. Certain factors should be evaluated specifically at pretransplant assessment to prevent certain serious complications; principally, these are anatomic factors of the recipient (inferior vena cava included in segment I, anatomic abnormalities of the inferior vena cava) and graft size. Depending on these factors, surgeons must be able to adapt the orthotopic liver transplantation, either before or during orthotopic liver transplantation, preferring the standard technique.

Anastomosis, Surgical↗
PubMed1999

Increased incidence of oropharyngeal squamous cell carcinomas after liver transplantation for alcoholic cirrhosis.

BACKGROUND: THE aim of this study was to describe the features of posttransplantation tumors observed in a series of liver transplant recipients with special reference to patients receiving a transplant for alcoholic cirrhosis. METHODS: Among 171 consecutive liver transplant recipients, 90 patients who had received a first liver allograft for cirrhosis were studied. After liver transplantation, detection of de novo malignancies was prospectively undertaken and the characteristics of the patients in whom tumors occurred were compared with those in whom tumors did not develop. RESULTS: With a follow-up of 45.2+/-21.2 months, 11 tumors were observed in 90 patients (overall incidence of 12.2%). The incidence of tumors was higher in patients receiving a transplant for alcoholic cirrhosis than in patients receiving a transplant for nonalcoholic cirrhosis (26.7% vs. 5.0%, P<0.01). Squamous cell carcinoma (SCC) of the oropharynx or esophagus and posttransplant lymphoproliferative disorders were mainly observed. SCC (uvula in two cases, tongue in one case, esophagus in one case, pharynx in one case) occurred exclusively in patients transplanted for alcoholic cirrhosis (16.7% vs. 0%, P=0.001). The incidence of posttransplant lymphoproliferative disorders was similar in alcoholics and nonalcoholics (6.7% vs. 5%, NS). Survival was not influenced by the occurrence of SCC. CONCLUSION: The incidence of oropharyngeal SCC could be high in patients receiving a transplant for alcoholic cirrhosis. This could be due to an additional effect of posttransplantation immunosuppression in patients exposed to alcohol and tobacco before transplant. Careful posttransplantation screening of oropharyngeal SCC is warranted after liver transplantation for alcoholic cirrhosis.

Carcinoma, Squamous Cell↗
PubMed1999

Role of hepatitis C virus in lymphoproliferative disorders after liver transplantation.

It has been suggested that hepatitis C virus (HCV) infection could be associated with B-cell clonal expansion. The aim of this study was to analyze the relationship between lymphoproliferative disorders and HCV infection in liver transplant recipients. We studied 157 patients receiving a liver transplant between January 1989 and May 1997 with a follow-up longer than 3 months. The incidence of posttransplant lymphoproliferative disorders (PTLDs) was analyzed with reference to the indication for liver transplantation, the induction and maintenance immunosuppression, the incidence of acute rejection episodes, and Epstein-Barr virus (EBV) infection. Six PTLDs occurred after a median posttransplant follow-up of 7 months (3.8%). Four of the 6 PTLDs occurred among the 38 patients transplanted for HCV-related cirrhosis, and 2 PTLDs occurred in the 119 patients receiving a liver transplant for non-HCV liver diseases (10.5% vs. 1.7%, respectively; P =.03). The 4-year probability of PTLD was significantly higher in patients receiving a liver transplant for HCV-related cirrhosis than non-HCV liver diseases (12.3% vs. 2.2%, respectively; P =.015). Patients receiving a liver transplant for HCV-related cirrhosis were more likely to receive antithymocyte globulins (ATG). However, in patients treated with ATG, the 4-year probability of PTLD was higher among those patients receiving a liver transplant for HCV-related cirrhosis than for non-HCV liver diseases (27.1% vs. 6.4%, respectively; P =.08). EBV gene products were detected in tumor tissues in 3 of 4 patients with HCV-associated PTLD. Our data suggest that, in addition to EBV infection, 2 mutually nonexclusive factors, i.e., the use of ATG and HCV infection, could play a role in the occurrence of PTLD after a liver transplant for HCV-related cirrhosis.

Adult↗
PubMed1999

[Selective use of vascular clamps in major hepatectomy].

OBJECTIVE: To report the results of a selective use of vascular occlusions in major hepatectomies according to the size and location of the hepatic lesion. BACKGROUND: Total vascular exclusion (TVE) and portal triad clamping (PTC) ensure efficient hemostatic effect but lead to warm ischemia of the liver. Lobar vascular occlusion (LVO) avoids warm ischemia of the remnant liver but could result in increased blood loss. PATIENTS AND METHODS: Sixty consecutive major hepatectomies were studied. TVE was applied in 22 patients with large lesions (= 10 cm) or lesions with connections to the major hepatic veins or inferior vena cava. PTC (n = 15) and LVO (n = 23) were applied in remaining cases. RESULTS: Clamping method was efficient in 87%, 93% and 100% for LVO, PTC and TVE, respectively. Median blood transfusions were 0.3 and 2 units for LVO, PTC and TVE, respectively. Postoperative aminotransferase peak value was significantly lower after LVO than after PTC or TVE, while those peaks were not statistically different with these latter two methods. Postoperative prothrombin time fall value was identical in the three groups. Mortality was 3.3% (2/60) and was not influenced by the type of clamping, but both deaths and most complications occurred in patients with abnormal underlying liver parenchyma. CONCLUSION: Provided that adequate techniques are used, the need for blood transfusions is more dependent on the characteristics of the resected tumor than on the type of clamping used. Total vascular exclusion does not create more ischemic injury to the liver than portal triad clamping and it should be recommended for the resection of large or strategically located tumors. Other tumors can be resected in more than 80% of the cases with LVO, thus avoiding ischemia to the remnant liver. With the control of hemorrhage, pathology of underlying liver parenchyma has emerged as the main prognostic factor in major liver resections.

Blood Loss, Surgical↗
PubMed1999

Nuclear accumulation of mutated beta-catenin in hepatocellular carcinoma is associated with increased cell proliferation.

Inappropriate activation of the Wnt pathway resulting from beta-catenin gene alterations has recently been implicated in the development of hepatocellular carcinoma (HCC). To explore the in vivo effects of mutated beta-catenin, HCC specimens from 32 patients carrying one or several tumors were screened for somatic mutations in exon 3 of the beta-catenin gene, and the expression and subcellular localization of beta-catenin was studied by immunohistochemistry. Missense mutations or interstitial deletions in beta-catenin exon 3 were detected in 12 of 35 (34%) HCC samples. After immunostaining, most tumors exhibited increased membranous and/or cytoplasmic expression of beta-catenin compared with adjacent nontumoral liver. Strong nuclear accumulation of beta-catenin was observed either focally or uniformly in 15 of 35 (43%) tumor specimens, but not in cirrhotic nodules or dysplastic liver cells in adjacent liver. Aberrant nuclear expression of beta-catenin was significantly associated with the presence of mutations in the beta-catenin gene (P < 0.005). Moreover, nuclear beta-catenin staining correlated significantly with increased Ki-67 proliferative index in tumor (P < 0.001) and seemed to be associated with poor outcome in patients with HCC. In conclusion, our data indicate that activation of the Wnt/beta-catenin pathway in HCC results mainly from somatic mutations in the beta-catenin gene and may promote tumor progression by stimulating tumor cell proliferation.

Adult↗
PubMed1999

Evaluation of efficacy of liver transplantation in alcoholic cirrhosis using matched and simulated controls: 5-year survival. Multi-centre group.

BACKGROUND/AIMS: Alcoholic cirrhosis is the most common cause of liver transplantation in US males. The limited number of donor livers calls for "prioritisation", favouring those patients who will benefit most. The aim was to assess the efficacy of liver transplantation in patients with alcoholic cirrhosis. METHODS: We compared the survival of 169 transplanted patients with two conservatively treated control groups, one of 169 patients matched for prognostic factors (age, cirrhosis severity, bleeding history) and one of 169 simulated patients. RESULTS: The probability of survival to 5 years in the transplanted group was 66% (95% confidence interval 58-74%) vs. 52% (44-60; p = 0.03) in the matched group and 54% (51-57; p = 0.01) in the simulated controls. Transplantation was associated with survival (relative risk = 1.51; p = 0.02), independently of risk score (risk = 2.07; p<0.001), indication, period of inclusion, centre experience, and alcohol abstinence. Patients with severe disease (Pugh C11-15) benefited most in terms of 5-year survival: 58% (44-72) vs. 31% (17-45; p = 0.008) in the matched and 35% (30-40; p<0.001) in the simulated control groups. For patients at lower risk there was no significant difference. CONCLUSIONS: Liver transplantation increases the 5-year survival of patients with severe alcoholic cirrhosis. In patients at lower risk, efficacy of transplantation should be confirmed by longer follow-up or by randomised trial.

Case-Control Studies↗
PubMed1999

Low HCV replication levels in end-stage hepatitis C virus-related liver disease.

BACKGROUND/AIMS: The relationship between HCV RNA levels and the severity of HCV-related liver disease has been addressed in a few studies, which has led to conflicting results. To clarify this point, we studied serum HCV RNA levels in patients with HCV liver disease at various stages, using a second-generation branched DNA (bDNA) assay. METHODS: One hundred and forty-eight patients with chronic HCV infection were classified into 3 groups: group A included 92 patients with chronic active hepatitis (CAH) without cirrhosis; group B included 30 patients with CAH and compensated cirrhosis; group C included 26 patients with end-stage cirrhosis. In all patients, serum HCV RNA was sought by qualitative PCR and quantified using second-generation bDNA assay. HCV RNA was also quantified after liver transplantation in 22 patients from group C. HCV genotype was determined in all patients. RESULTS: HCV RNA was detected by PCR in 100%, l00% and 92% of the patients from groups A, B and C, respectively (NS). The proportion of patients with HCV RNA levels higher than the cut-off of bDNA assay was significantly lower in patients from group C than in patients from groups A and B (50% vs 94% and 93% respectively, p<0.0001). The mean HCV viremia was lower in group C than in groups A and B (1.35+/-0.24 MEq/ml vs 5.00+/-6.04 MEq/ml and 5.85+/-7.70 MEq/ml, respectively, p<0.0001). This difference was independent of HCV genotype. In the patients from group C, post-transplant HCV RNA levels were significantly higher than pretransplant HCV RNA levels (14.90+/-26.40 vs 1.35+/-0.24 MEq/ml, p=0.0065). CONCLUSIONS: HCV RNA levels do not appear to differ significantly among patients with CAH with or without compensated cirrhosis. In contrast, HCV RNA levels seem to be significantly lower in patients with end-stage HCV-related liver cirrhosis. In these patients, high levels of replication are restored after liver transplantation, suggesting that low pretransplant viral loads are not due to the intrinsic characteristics of the infective viral strains, but rather to the severity of liver disease.

Adult↗
PubMed1999

Hepatic vascular exclusion with preservation of the caval flow for liver resections.

OBJECTIVE: To report the technique and results of an alternative method of vascular clamping during liver resections. BACKGROUND: Most liver resections require vascular clamping to avoid excessive blood loss. Portal triad clamping is often sufficient, but it does not suppress backflow bleeding, which can be prevented only by hepatic vascular exclusion. The latter method adds clamping of the inferior vena cava, which results in hypotension, requiring invasive anesthetic management. There is growing evidence that intermittent clamping is better tolerated than continuous clamping, especially in the presence of underlying liver disease. METHODS: Hepatic vascular exclusion with preservation of the caval flow (HVEPC) involved conventional inflow clamping associated with outflow control by clamping the major hepatic veins, thus avoiding caval occlusion. HVEPC was used in 40 patients undergoing major or complex liver resection, including 16 with underlying liver disease. HVEPC was total (clamping of the porta hepatis and all major hepatic veins) in 20 cases and partial (clamping of the porta hepatis and the hepatic veins of the resected territory) in 20. Clamping was continuous in 22 cases and intermittent in 18. Resections included 12 hemihepatectomies, 12 extended hepatectomies, 3 central hepatectomies, and 13 uni- or bisegmentectomies. RESULTS: Hemodynamic tolerance of clamping was excellent in all cases, without the need for therapeutic adjustment. Median red cell transfusion requirements were 0 units, and 28 patients (70%) did not receive any transfusions during the hospital stay. There were no deaths, and the morbidity rate was 17.5%. Median hospital stay was 10 days. CONCLUSION: HVEPC is a safe and effective procedure applicable to liver tumors without invasion to the inferior vena cava. It offers the advantages of conventional hepatic vascular exclusion without its hemodynamic drawbacks, and it can be applied intermittently or partially.

Constriction↗
PubMed1999

[Auxiliary hepatic transplantation in iproniazid-induced subfulminant hepatitis. Should iproniazid still be sold in France?].

We report a new case of subfulminant hepatitis due to iproniazid, a MAO-inhibitor antidepressant, in a 27-year-old man. An auxiliary liver transplantation was performed. Liver function returned to normal and the patient was discharged from the hospital. However, the patient's native liver did not regenerate, and immunosuppressive therapy had to be maintained. Iproniazid hepatotoxicity is characterized by jaundice in 1% of cases, with a fulminant or subfulminant course in 20% of icteric patients. Although iproniazid is no longer sold in most countries, it is still commercialized in France. Because of the frequency and severity of hepatic injury, commercialization of iproniazid in France should no longer be authorized.

Adult↗
PubMed1998

Surgery vs endoscopy as primary treatment in symptomatic patients with suspected common bile duct stones: a multicenter randomized trial. French Associations for Surgical Research.

OBJECTIVE: To compare surgical treatment (ST) with endoscopic management (EM) in patients with suspected common bile duct stones. PATIENTS: Two hundred twenty eligible patients originating from 18 surgery units. Patients enrolled in this multicenter randomized study had clinical symptoms that included jaundice, mild pancreatitis (Ranson score < or = 2), or mild acute cholangitis; biliary colic (with increased alkaline phosphatase levels); and common bile duct stones or a common bile duct diameter of 1 cm or larger on ultrasonography. METHODS: Two hundred two patients were randomly assigned to either ST (n=105) or EM (n=97) during a 5-year period. Both groups were comparable with respect to age, sex, American Society of Anesthesiologists score, and clinical presentation. MAIN OUTCOME MEASURES: The rates of early postoperative additional procedures necessary to deal with the impossibility to perform the initial procedure, complications, and retained stones after ST or EM. Subsidiary endpoints were intention-to-treat analyses of mortality and of major complications and the duration of hospital stay. RESULTS: Surgical treatment was associated with a significantly (P<.001) lower rate of 1 or 2 additional procedures (8% vs 29%) due to a significantly lower rate of the impossibility to perform the initial procedure (0% vs 5%) (P<.05), major complications (4% vs 13%) (P<.05), and retained stones (6% vs 16%) (P<.04). Minor complications occurred more often in patients having ST (4%) than in those having EM (0%) (P<.01). Cholecystectomy was performed routinely in 102 patients having ST and electively in 36 patients having EM. There was 1 death in each group initially. On an intention-to-treat analysis, 3 deaths (3.1%) occurred after EM and 1 (0.9%) after ST; this difference was not statistically significant (P=.56). Major complications occurred in 4% of patients having ST compared with 1 1% of patients having EM (P<.002). The median duration of hospital stay was 16 days in patients having ST and 12 days in those having EM; this difference was not statistically significant (P=.09). CONCLUSION: Whether an additional cholecystectomy is performed routinely or electively, the high risk of additional procedures after EM precludes its use as the optimal therapy in patients with symptomatic common bile duct stones, except in those with severe cholangitis.

Aged↗
PubMed1998

Role of adjuvant treatment in liver transplantation for advanced hepatocellular carcinoma.

The results of liver transplantation for advanced hepatocellular carcinoma have been disappointing because of high recurrence rates, leading to low long-term survival; this indication remains controversial in an era of organ shortage. To continue to offer this treatment possibility, efforts were made to reduce recurrence and improve survival. The first approach is to maintain a strict selection policy excluding patients with extraheptic disease. The second approach is to test the efficacy of perioperative adjuvant therapies in patients selected for transplantation. The reasons for recurrence include: (1) undetected preoperative micrometastases, (2) intraoperative dissemination by surgical manipulation, and (3) acceleration of tumor growth by immunosuppression. Preoperative treatment, which may include systemic chemotherapy or arterial chemoembolization, seems necessary to limit tumor progression during the waiting period. Systemic chemotherapy has been tested pre-, intra-, and postoperatively. It is considered essential postoperatively and should be used as soon as possible after surgery (i.e., in the 1st postoperative week). Several teams have performed pilot studies that included rather limited numbers of patients, and the results were compared with those for historic controls. Published results show that chemoembolization creates tumor necrosis in most instances. This is efficient in limiting tumor progression but the effect on recurrence and survival is unknown. All authors who used postoperative chemotherapy reported improved survival over controls, with 50%-60% 3-year survival and up to 50% 5-year survival. However, recent results suggest that late recurrence may occur. Chemotherapy was usually well tolerated, although leukopenia, sometimes severe, was observed in most patients. The use of granulocyte colony-stimulating factor seems useful to overcome this problem. Perioperative adjuvant treatments seem to prolong survival in patients undergoing liver transplantation for advanced hepatocellular carcinoma, but delayed recurrence remains possible. Further studies are necessary; these should ideally be multicentric, prospective, and randomized.

Carcinoma, Hepatocellular↗
PubMed1998

Myofibroblasts and hepatocellular carcinoma: an in vivo and in vitro study.

BACKGROUND/AIMS: The number of perisinusoidal myofibroblasts has been shown to be increased in hepatocellular carcinoma, as compared to cirrhosis. This increase might suggest a cooperative relationship between tumour cells and myofibroblasts. To assess this relationship, we undertook: (a) an immunohistochemical study to confirm the existence of an increased number of perisinusoidal myofibroblasts in human hepatocellular carcinoma, as compared to cirrhosis with or without liver cell dysplasia, (b) an in vitro study testing the role of normal or tumoral human hepatocytes in myofibroblast proliferation. METHODS: Forty explanted cirrhotic livers, including 14 with hepatocellular carcinoma and 24 with liver cell dysplasia, were studied. Myofibroblasts were detected by immunohistochemistry using an antibody directed against alpha-smooth muscle actin. Hepatic myofibroblasts in culture were obtained by outgrowth from human liver explants. RESULTS: There was a progressive increase in the number of perisinusoidal myofibroblasts, from cirrhotic nodules without dysplasia to liver cell dysplasia and hepatocellular carcinoma. Conditioned medium from isolated normal human hepatocytes had only minor mitogenic effects on myofibroblasts, as assessed by measuring DNA synthesis and cell growth. In contrast, conditioned medium from a human hepatoma cell line (HepG2 cells) markedly stimulated the proliferation of human myofibroblasts. This mitogenic activity was stored in HepG2 cells and secreted in the extracellular medium rather than being simply released following cell lysis. CONCLUSIONS: These results suggest that the increased number of myofibroblasts in hepatocellular carcinoma might be due to a paracrine mechanism involving soluble mitogenic factor(s) secreted by tumour cells.

Actins↗
PubMed1998

Safety of selective vascular clamping for major hepatectomies.

BACKGROUND: Although hepatic vascular clampings are widely used during major hepatic resections, they may not always be necessary. Selective vascular clamping, which only controls the afferent blood flow of the resected liver, could be a valuable alternative, provided that blood loss is not increased because the opposite liver remains perfused. STUDY DESIGN: The aim of the study was to assess the safety of selective vascular clamping in 43 patients who underwent 36 right hepatectomies and 7 left hepatectomies for lesions located peripherally within the liver. Blood transfusions, hepatic tests, morbidity, mortality, and hospital stay were evaluated. RESULTS: Selective vascular clamping was efficient in 34 of the 43 attempts (79%), but bleeding from the contralateral liver required conversion to portal triad damping in 9 patients (21%). Median blood transfusions were 0 units (range 0 to 4 U), and 28 patients (65%) did not require transfusions. Postoperative laboratory tests showed that larger changes occurred at day 1 and tended to return to preoperative values at the end of the first postoperative week. Median time of hospitalization was 10 days (range 7 to 28 days). Postoperative course was uneventful in 35 patients (81%). Nonlethal complications occurred in 7 patients (16.3%). One patient (2%) with massive hepatic steatosis died of liver failure after right hepatectomy. CONCLUSIONS: Selective vascular clamping is a safe alternative to total inflow occlusion for major hepatectomies applicable in 80% of selected patients with peripheral liver tumors.

Adult↗
PubMed1997

[Hepatic transplantation for cirrhosis].

Cirrhosis accounts for 60% of liver transplantations that are performed. The main causes are chronic viral hepatitis B and C, and alcoholism. However, all patients with severe cirrhosis are potential candidates for liver transplantation, regardless of the cause. Liver transplantation is indicated when the patient's life expectancy is one year or less. The main criterion for transplantation is severe liver failure (Child-Pugh's stage C). Transplantation is also proposed in patients with intractable ascites, and in patients with spontaneous encephalopathy. Isolated portal hypertension is not an indication for transplantation. Liver transplantation in hepatocellular carcinoma is still a matter of debate. The results of liver transplantation are very satisfactory with survival rates of 70% at 5 years and patient rehabilitation is usually excellent.

Adult↗