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Biomedical subjects

Carole Meyer

Publications and source records attributed to Carole Meyer.

11 recordsLinked to original sources

Role of immunosuppression and tumor differentiation in predicting recurrence after liver transplantation for hepatocellular carcinoma: a multicenter study of 412 patients.

AIM: To assess pre-orthotopic liver transplantation (OLT) factors that could be evaluated pre-operatively or controlled post-operatively associated with hepatocellular carcinoma (HCC) recurrence and disease-free survival after liver transplantation (LT). METHODS: Four hundred and twelve patients transplanted for HCC between 1988 and 1998 in 14 French centers, who survived the postoperative period were studied. Kaplan Meier estimates were calculated for 24 variables potentially associated with recurrence of HCC. Uni- and multivariate analyses were conducted to identify independent predictors of recurrence. RESULTS: Overall 5-year disease-free survival was 57.1%. By univariate analysis, variables associated with disease-free survival were: presence of cirrhosis (P = 0.001), etiology of liver disease (P = 0.03), alpha fetoprotein level (< 200, 200 to 2000, or > 2000; P < 0.0001), gamma-GT activity (N, N to 2N or > 2N; P = 0.02), the number of nodules (1, 2-3 or > or = 4; P = 0.02), maximal diameter of the largest nodule (< 3 cm, 3 to 5 cm or > 5 cm; P < 0.0001), the sum of the diameter of the nodules (< 3 cm, 3 to 5 cm, 5 to 10 cm or > 10 cm; P < 0.0001), bi-lobar location (P = 0.01), preoperative portal thrombosis (P < 0.0001), peri-operative treatment of the tumor (P = 0.002) and chemoembolization (P = 0.03), tumor differentiation (P = 0.01), initial type of calcineurin inhibitor (P = 0.003), the use of antilymphocyte antibodies (P = 0.02), rejection episodes (P = 0.003) and period of LT (P < 0.0001). By multivariate analysis, 6 variables were independently associated with HCC recurrence: maximal diameter of the largest nodule (P < 0.0001), time of LT (P < 0.0001), tumor differentiation (P < 0.0001), use of anti-lymphocyte antibody (ATG) or anti-CD3 antibody (OKT3) (P = 0.005), preoperative portal thrombosis (P = 0.06) and the number of nodules (P = 0.06). CONCLUSION: This study identifies immunosuppression, through the use of ATG or OKT3, as a predictive factor of tumor recurrence, and confirms the prognostic value of tumor differentiation.

Analysis of Variance↗

Long-term survival in post-transplant lymphoproliferative disorders with a dose-adjusted ACVBP regimen.

Post-transplant lymphoproliferative disorders (PTLD) are severe complications after solid organ transplantation with no consensus on best treatment practice. Chemotherapy is a therapeutic option with a high response and a significant relapse rate leading to a low long-term tolerance rate. Currently, most centres use anthracycline-based drug combinations, such as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). We assessed the efficacy and safety of a dose-adjusted ACVBP (doxorubicin reduced to 50 mg/m(2), cyclophosphamide adjusted to renal function, vindesine, bleomycin, prednisone) regimen in patients failing to respond to a reduction in immunosuppressive therapy. Favourable responses were observed in 24 (73%) of the 33 treated patients. Fourteen (42%) patients died, mostly from PTLD progression. Actuarial survival was 60% at 5 years and 55% at 10 years. Survival prognostic factors were: number of involved sites (P = 0.007), clinical stage III/IV (P = 0.004), bulky tumour (P < 0.0001), B symptoms (P = 0.03), decreased serum albumin (P = 0.03) and poor performance status (P = 0.06). Both the international and the PTLD prognostic index were predictive for survival (P = 0.001 and P = 0.002, respectively). Overall 128 cycles were given. Grade 3 or 4 neutropenia was recorded after 26 (20%) chemotherapy cycles in 19 (58%) patients. Forty-one (32%) infections were recorded in 26 (79%) patients. This study demonstrated that an individual dose-adjustment of ACVBP regimen was manageable in PTLD patients and favourably impacted on long-term survival.

Adolescent↗

Early decrease in circulating dendritic cells number after liver transplantation could favor hepatitis C virus recurrence.

Cirrhosis and hepatocarcinoma related to hepatitis C virus (HCV) lead to more than 30% of liver transplantations. Host- and virus-related mechanisms, involved in the recurrence of HCV infection of the liver graft, are not yet well known. A weak CD4+ T-cell response was shown to be involved in the outcome of re-infection but whether dendritic cell numbers are modified in patients transplanted for HCV-related disease has never been evaluated. Eight transplanted patients for HCV-related disease and eight non-HCV-infected transplanted controls were included. Blood plasmacytoid dendritic cells and myeloid dendritic cells were quantified before transplantation, at day 7 and 1 month after transplantation. Plasma interferon (IFN)-alpha and interleukin (IL)-12 were concomitantly measured. The results showed a significant decrease in the relative (P < 0.0001) and absolute (P = 0.0002) values of blood plasmacytoid dendritic cells at day 7 after transplantation when compared to the values obtained before transplantation, increasing again 1 month later, in both HCV-infected patients and controls. The same tendency was observed for myeloid dendritic cell relative values (P = 0.0004) and plasma IL-12 (P < 0.05). IFN-alpha appeared to be less often detectable for HCV-infected patients. These results obtained on dendritic cell numbers could explain partially the early and systematic recurrence of HCV infection on the liver graft and contribute to better adapted therapeutic strategies.

Cell Count↗

Impact of UCSF criteria according to pre- and post-OLT tumor features: analysis of 479 patients listed for HCC with a short waiting time.

Orthotopic liver transplantation (OLT) indication for hepatocellular carcinoma (HCC) is currently based on the Milan criteria. The University of California, San Francisco (UCSF) recently proposed an expansion of the selection criteria according to tumors characteristics on the explanted liver. This study: 1) assessed the validity of these criteria in an independent large series and 2) tested for the usefulness of these criteria when applied to pre-OLT tumor evaluation. Between 1985 and 1998, 479 patients were listed for liver transplantation (LT) for HCC and 467 were transplanted. According to pre-OLT (imaging at date of listing) or post-OLT (explanted liver) tumor characteristics, patients were retrospectively classified according to both the Milan and UCSF criteria. The 5-yr survival statistics were assessed by the Kaplan-Meier method and compared by the log-rank test. Pre-OLT UCSF criteria were analyzed according to an intention-to-treat principle. Based on the pre-OLT evaluation, 279 patients were Milan+, 44 patients were UCSF+ but Milan- (subgroup of patients that might benefit from the expansion), and 145 patients were UCSF- and Milan-. With a short median waiting time of 4 months, 5-yr survival was 60.1 +/- 3.0%, 45.6 +/- 7.8%, and 34.7 +/- 4.0%, respectively (P < 0.001). The 5-yr survival was arithmetically lower in UCSF+ Milan- patients compared to Milan+ but this difference was not significant (P = 0.10). Based on pathological features of the explanted liver, 5-yr survival was 70.4 +/- 3.4%, 63.6 +/- 7.8%, and 34.1 +/- 3.1%, in Milan+ patients (n = 184), UCSF+ Milan- patients (n = 39), and UCSF- Milan- patients (n = 238), respectively (P < 0.001). However, the 5-yr survival did not differ between Milan+ and UCSF+ Milan- patients (P = 0.33). In conclusion, these results show that when applied to pre-OLT evaluation, the UCSF criteria are associated with a 5-yr survival below 50%. Their applicability is therefore limited, despite similar survival rates compared to the Milan criteria, when the explanted liver is taken into account.

California↗

Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma.

The actual impact of transarterial chemoembolization before liver transplantation (LT) for hepatocellular carcinoma (HCC) on patient survival and HCC recurrence is not known. Between 1985 and 1998, 479 patients with HCC in 14 French centers were evaluated for LT. Among these 479 patients, this case-control study included 100 patients who received transarterial chemoembolization before LT (TACE group) and 100 control patients who did not receive chemoembolization (no-TACE group). Patients and controls were matched for the pre-LT tumor characteristics, the period of transplantation, the time spent on the waiting list, and pre- and posttransplantation treatments. Kaplan-Meier estimates were calculated 5 years after LT and were compared with the log-rank test. The mean waiting time before LT was 4.2 +/- 3.2 months in the TACE group and 4.3 +/- 4.4 months in the no-TACE group. The median number of TACE procedures was 1 (range: 1-12). Demographic data, median alpha-fetoprotein level (21.6 ng/mL and 22.0 ng/mL, respectively), and pre- and post-LT morphologic characteristics of the tumors did not differ in the TACE and no-TACE groups. Overall 5-year survival was 59.4% with TACE and 59.3% without TACE (ns). Survival rates did not differ significantly between the two groups with respect to the time on the waiting list, the tumor diameter, or the type of TACE (selective or nonselective). In the TACE group, 30 patients had tumor necrosis > or =80% on the liver explant with a 5-year survival rate of 63.2%, compared with 54.2% among their matched controls (P = 0.9). In conclusion, with a mean waiting period of 4.2 months and 1 TACE procedure, pre-LT TACE does not influence post-LT overall survival and disease-free survival.

Carcinoma, Hepatocellular↗

Impact of graft mass on the clinical outcome of kidney transplants.

The effect of nephronic mass reduction of kidney transplants has not been analyzed specifically in a large cohort. Transplant injuries in cadaver kidney graft may have led to an underestimation of the magnitude of this factor. The aim of this study was to analyze the consequences of kidney mass reduction on transplantation outcome. The weights of 1142 kidney grafts were collected prospectively immediately before grafting. Donors and recipients <15 yr of age, simultaneous kidney/pancreas grafts, and technical failures before day 7 were excluded from the analysis. The analysis was performed on Cockroft-calculated creatinine clearance and proteinuria in 964 patients for whom all of the necessary information was available. This study reports that the smallest kidneys transplanted into the largest recipients (donor kidney weight/recipient body weight [DKW/RBW] <2 g/kg, n = 88) increased their clearance by 2.38 ml/min every month for 6 mo (P < 0.0001) and by 0.27 ml/min thereafter (P < 0.0001). Conversely, creatinine clearance did not change for the largest kidneys transplanted into the smallest recipients (DKW/RBW ratios >/=4 g/kg). Next, using a Cox model analysis, it was shown that the risk of having a proteinuria >0.5 g/kg was significantly increased for the low DKW/RBW ratios <2 g/kg with 50% of patients having a proteinuria, compared with DKW/RBW ratios >/=4 g/kg (P < 0.001). In cadaver transplant recipients, graft mass has a rapid impact on graft filtration rate and proteinuria. Avoiding major kidney/recipient inadequacy should have a significant influence on long-term transplant function.

Adolescent↗

Recovery from a variegate porphyria by a liver transplantation.

The porphyrias are a group of inherited or acquired enzymatic defects of heme biosynthesis. Each type of porphyria has a characteristic pattern of overproduction and accumulation of heme precursors based on the location of dysfunctional enzyme in the heme synthetic pathway. Variegate porphyria, one of the acute hepatic porphyrias, is characterized by a partial reduction in protoporphyrinogen oxidase, the seventh enzyme of the heme biosynthetic pathway. A case of liver transplantation is described with a recovery from a variegate porphyria. Acute porphyria is commonly worsened by a wide variety of medications. We describe a step-by-step perioperative management protocol.

Humans↗

Coingestion of cyclooxygenase inhibitors can worsen severe paracetamol poisoning by middle-sized and small arteries vasoconstriction.

OBJECTIVE: We report fatal cases of multifocal ischemic injuries occurring in patients awaiting liver transplantation after severe concomitant paracetamol and cyclooygenase inhibitors self-poisoning. DESIGN AND SETTING: Case report in an intensive care unit. PATIENTS: In addition to signs of acute liver failure with a systemic inflammatory response syndrome, these three previously healthy young women demonstrated cutaneous vasoconstriction. One patient displayed a sudden ST-segment elevation with ventricular fibrillation. INTERVENTIONS: Angiography, plasma endothelin concentrations measurements, and autopsy. RESULTS: Radiography showed diffuse vasospasm on mesenteric and renal arteries, transiently reversed by vasodilators. We measured tenfold higher plasma endothelin concentrations than in healthy controls. Autopsy revealed no atherosis (including coronary arteries); organs showed multifocal ischemic injuries without thrombosis. CONCLUSIONS: Such injuries subsequent to dramatic vasoconstriction suggest that cyclooygenase inhibition has specific deleterious vascular side effects once systemic inflammatory response syndrome is in progress during paracetamol poisoning.

Acetaminophen↗

Small hepatocellular carcinoma in Child A cirrhotic patients: hepatic resection versus transplantation.

Hepatic resection (HR) is the treatment of choice for small hepatocellular carcinoma (HCC) in a noncirrhotic liver, whereas liver transplantation (LT) offers better results in patients with impaired hepatic function (Child B and C). However, it is still debated whether HR or LT is the best strategy for patients with Child A cirrhosis. We conducted a retrospective study on 37 consecutive patients with Child A cirrhosis and small HCC, treated between 1991 and 1999. Seventeen of these patients, who underwent LT, were compared with 20 patients who underwent HR, and prognostic factors for survival and tumor recurrence were analyzed. The primary endpoints were the intention-to-treat, 3- and 5-year survival, and 3- and 5-year recurrence-free survival. Three- and 5-year patient survival rate both were significantly (P =.04) higher in the LT group (87% and 71%, respectively) than in the HR group (67 and 36% respectively). Similarly, the 3- and 5- year recurrence-free survival rates were 87% and 80% for the LT group, and 52% and 40% for the HR group (P =.03). Absence of microscopic vascular invasion was the only other prognostic factor correlated with significantly better recurrence-free survival (P =.02). Therefore, we concluded that in patients with Child A cirrhosis and small HCC, liver transplantation resulted in better overall and disease-free survival than HR.

Aged↗

Auxiliary partial orthotopic liver transplantation (APOLT) in the treatment of acute liver failure.

BACKGROUND: Auxiliary partial orthotopic liver transplantation (APOLT) has been developed in order to benefit from the efficacy of orthotopic liver transplantation (OLT) in the treatment of fulminant hepatic failure (FHF), but to avoid the negative counterpart of OLT which is to eliminate the possibility of native liver (NL) regeneration and which consequently implies a life-long immunosuppression. METHODS: In our institution we performed 16 consecutive APOLTs in 15 patients between October 1992 and December 1999. Patients' mean age was 30 years (range 0.5-65 years). The causes of FHF were viral (HAV = 3; HBV = 3), drugs (n = 4), or others (n = 5). None of the patients had a history of chronic liver disease. The decision to transplant was taken when the patients met well-defined criteria. All but one of the patients were in a coma. RESULTS: Five patients died, 10 patients are alive (66.7%). Regeneration of the NL occurred in 11 of the 15 patients (73.3%) and in 8 of the 10 survivors. Six of these 8 patients have permanently stopped immunosuppressive therapy. These results can be favorably compared with those of OLT for FHF. In the European Transplant Registry, the survival rate is 57% at 5 years (2612 patients receiving OLT for FHF between 1988 and 1998). In our experience the survival rate is 59% at 5 years (42 patients receiving OLT for FHF between 1987 and 1999). CONCLUSIONS: APOLT is feasible in both adults and children; it rapidly restored liver function and reversed encephalopathy. Right APOLT seems more advisable since the right liver provides more functional hepatocytes; however, left APOLT harvested in an adult appears sufficient for a child. APOLT should be proposed only to patients with high chances of liver regeneration: age of recipient, etiology of liver failure, interval between onset of jaundice and occurrence of encephalopathy, and quality of liver graft are early prognostic indicators. Better results have been observed with younger patients (less than 40 years old) presenting with FHF (rather than subfulminant hepatic failure (SHF)) and due to HAV, HBV, or paracetamol.

Adolescent↗