Biomedical subjects

Philippe Compagnon

Publications and source records attributed to Philippe Compagnon.

8 recordsLinked to original sources

PubMed2006

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↗

PubMed2005

[Liver transplantation for hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is the most frequent primitive cancer of the liver. It mostly develops on cirrhotic livers. Orthotopic liver transplantation is the only treatment that definitively addresses both the metachronous occurrence risk of HCC and the underlying disease. Under Milan criteria, i.e. less than 3 nodules of 3 cm max in diameter, or 1 nodule of 5 cm maximum, OLT has been shown effective and provides with survival rates almost equal to those obtained with HCC free cirrhotic patients. In Rennes, 195 patients with early HCC on cirrhotic livers have been transplanted from January 1995 to June 2005. Global and disease free 8 years patient survival rates were 73 and 70%, respectively. These results were significantly altered when the recipient was female, the cirrhosis due to C virus and the patient of B blood group. Despite these excellent results, the principal limit to the application of transplantation for HCC remains the long period of time patients have to wait for a graft. During this period of time, growth of the tumour may drop the patient out of Milan criteria and subsequently from the waiting list. The role of chemoembolisation, liver resection and thermal ablation while the patient is waiting for a graft remains debatable.

Carcinoma, Hepatocellular↗

PubMed2005

Resection of hepatocellular carcinoma in noncirrhotic liver: analysis of risk factors for survival.

BACKGROUND: The aim of this study was to identify factors predictive of survival after curative resection of hepatocellular carcinoma (HCC) in noncirrhotic liver. STUDY DESIGN: Eighty-four patients underwent resection of HCC in noncirrhotic liver between January 1998 and December 2003. Univariate and multivariable analyses were used to retrospectively identify factors associated with overall survival and disease-free survival when resection was curative for the primary tumor. RESULTS: Overall 1-, 3-, and 5-year survival rates were 77.8%, 55.0%, and 44.4%, respectively, and 84.0%, 62.0%, and 50.0% when resection was curative for the primary tumor. HCC recurred in 27 patients (39.1%). Recurrence was intrahepatic in 14 patients (51.9%), extrahepatic in 3 patients (11.1%), and both intra- and extrahepatic in the remaining 10 patients (37.0%). In multivariable analysis, three independent factors were associated with poorer overall survival and recurrence-free survival, namely multiple tumors, macroscopic vascular invasion, and nonuse of adjuvant iodine-131-iodized oil. CONCLUSIONS: Aggressive operation is an effective treatment for HCC in noncirrhotic patients, whatever the degree of liver fibrosis. Multiple tumors and macroscopic vascular invasion are poor prognostic factors. Postoperative iodine-131-iodized oil injection appears to prevent recurrence and improve overall survival, although this needs to be confirmed in a prospective randomized trial.

Adult↗

PubMed2005

UW solution for hypothermic machine perfusion of warm ischemic kidneys.

BACKGROUND: Donation of kidneys from non-heart beating donors (NHBD) is increasingly being used to expand the donor pool. Warm ischemic injury of these kidneys suffered at harvest results in DGF at transplantation. In this study, we used hypothermic continuous machine perfusion preservation to mitigate this injury using two available solutions. METHODS: Dog kidneys (beagles) were exposed to 0, 60, or 75 min of in situ warm ischemia (37 degrees C), followed by 24 to 72 hr preservation by machine perfusion with Belzer MPS solution or the UW-solution (Viaspan). Auto-transplantation was performed with immediate contralateral nephrectomy. Survival and renal function (serum creatinine) were evaluated for up to 10 days posttransplant. RESULTS: Both solutions were equally effective for 72 hr machine perfusion preservation of dog kidneys giving 100% survival with only minor renal injury. Both solutions were also equally effective for preservation of kidneys exposed to 60 min of warm ischemia. However, only the UW solution gave reliable preservation (86% survival vs. 25% survival) in kidneys exposed to 75 min of warm ischemia and 24 hr machine perfusion. CONCLUSION: UW solution used with continuous hypothermic machine perfusion preservation can rescue canine kidneys from severe warm ischemic injury.

Adenosine↗

PubMed2005

Ischemic preconditioning and liver tolerance to warm or cold ischemia: experimental studies in large animals.

BACKGROUND: In the rodent, ischemic preconditioning (IPC) has been shown to improve the tolerance of the liver to ischemia-reperfusion under normothermic or hypothermic conditions. The aim of the present study was to test this hypothesis in a dog model, which may be more relevant to the human. METHODS: Beagle dogs were used in two distinct animal models of hepatic warm ischemia and orthotopic liver transplantation (hypothermic ischemia). IPC consisted of 10 minutes of ischemia followed by 10 minutes of reperfusion. In the first model, livers were exposed to 55 minutes prolonged warm ischemia and reperfused for 3 days (n = 6). In the second model, livers were retrieved and preserved for 48 hours at 4 degrees C in University of Wisconsin solution, transplanted, and reperfused without immunosuppression for 7 days (n = 5). In each model, nonpreconditioned animals served as controls (n = 5 in each group). Also, isolated dog hepatocytes were subjected to warm and cold storage ischemia-reperfusion to model the animal transplant studies using IPC. RESULTS: In the first model (warm ischemia), IPC significantly decreased serum aminotransferase activity at 6 and 24 hours post-reperfusion. After 1 hour of reperfusion, preconditioned livers contained more adenosine triphosphate and produced more bile and less myeloperoxidase activity (neutrophils) relative to controls. In the second model (hypothermic preservation), IPC was not protective. Finally, IPC significantly attenuated hepatocyte cell death after cold storage and warm reperfusion in vitro. CONCLUSIONS: IPC is effective in large animals for protecting the liver against warm ischemia-reperfusion injury but not injury associated with cold ischemia and reperfusion (preservation injury). However, the IPC effect observed in isolated hepatocytes suggests that preconditioning for preservation is theoretically possible.

Adaptation, Physiological↗

PubMed2005

A single solution for multiple organ procurement and preservation.

Two or three different solutions may be used to preserve thoracic and abdominal organs during a single procurement. The aim of this prospective, multi-center, noncomparative study was to evaluate the safety and efficacy of Celsior (study solution, solution S) as a flushing and cold storage solution for both thoracic and abdominal organs. Between August 1999 and July 2000, 72 consecutive multiple-organ procurements were performed using solution S as the sole solution for flushing out and cold-storing thoracic and abdominal grafts. Two hundred and sixty-four grafts were implanted into 245 recipients (131 kidneys, 9 kidney-pancreases, 69 livers, 34 hearts and 6 heart-lungs). The mean cold ischemia time was 21 h for kidneys (26%>24 h); 11 h 26 min for pancreases, 9 h 16 min for livers (23%>12 h), and 2 h 58 min for hearts and lungs. No cardiac failure or arrhythmia occurred on graft reperfusion. Fourteen percent of kidney recipients had delayed graft function. The mean serum creatinine level at 3 months was 123 +/- 41 micromol/l. All pancreas recipients were insulin-free at 3 months. Primary graft nonfunction occurred in one liver recipient. Complete hepatic artery thrombosis occurred in six liver recipients during the first month; four of these patients had a risk factor for thrombosis. All but three of the heart recipients were in sinus rhythm on day 1, and 65% were extubated on day 1. Inotropic drugs were necessary during the first 72 h in 25% of heart recipients. Twelve-month patient and graft survival rates were, respectively, 100% and 96% (kidney), 100% and 89% (pancreas), 88% and 83% (liver), 77.5% (heart) and 67% (heart-lung). These results suggest that Celsior, a ready-to-use solution, is safe and effective for multiple organ procurement and preservation.

Adolescent↗

PubMed2002

Brain death does not affect hepatic allograft function and survival after orthotopic transplantation in a canine model.

BACKGROUND: Brain death has been shown to decrease graft function and survival in rodent models. The aim of this study was to evaluate how brain death affects graft viability in the donor and liver tolerance to cold preservation as assessed by survival in a canine transplant model. METHODS: Beagle dogs were used for the study. Non-brain dead (BD) donors served as controls. Brain death was induced by sudden inflation of a subdural balloon catheter with continuous monitoring of arterial blood pressure and electroencephalographic activity. Sixteen hours after confirmation of brain death, liver grafts were retrieved. All livers were flushed in situ and preserved for 24 hr in cold University of Wisconsin solution before transplantation. Recipient survival rates, serum hepatic enzyme levels, coagulation, and metabolic parameters of the recipients were analyzed. RESULTS: No significant changes were observed in serum aminotransferases (alanine and aspartate transaminases) and lactate dehydrogenase levels in the BD donor. After preservation, control (n=6) and BD livers (n=5) showed full functional recovery after transplant with 100% survival in both groups at day 7. There was no significant difference in peak serum alanine, aspartate transaminases, and lactate dehydrogenase after transplantation in recipients who received a liver from BD donor compared to control group. BD livers were functionally as capable as control livers in correcting metabolic acidosis during the first 24 hr posttransplantation. Coagulation profiles (index normalized ratio, activated partial thromboplastin time) after reperfusion were similar between groups. CONCLUSION: In contrast to previous reports in rodent models, our study shows that brain death does not cause significant liver dysfunction in the donor before organ removal. Donor brain death and prolonged liver graft preservation do not interact significantly to impair liver function and survival after transplantation.

Adenosine↗

PubMed2002

Ischemic preconditioning in a rodent hepatocyte model of liver hypothermic preservation injury.

Ischemic preconditioning (IPC) is a phenomenon of protection in various tissues from normothermic ischemic injury by previous exposure to short cycles of ischemia-reperfusion. The ability of IPC to protect hepatocytes from a model of hypothermic transplant preservation injury was tested in this study. Rat hepatocytes were subjected to 30min of warm ischemia (37 degrees C) followed by 24 or 48h of hypothermic (4 degrees C) storage in UW solution and subsequent re-oxygenation at normothermia for 1h. Studies were performed with untreated control cells and cells treated with IPC (10min anoxia followed by 10min re-oxygenation, 1 cycle). Hepatocytes exposed to IPC prior to warm ischemia released significantly less LDH and had higher ATP concentrations, relative to untreated ischemic hepatocytes. IPC significantly reduced LDH release after 24h of cold storage before reperfusion and after 48h of cold storage and after 60min of warm re-oxygenation, relative to the corresponding untreated hepatocytes. ATP levels were also significantly higher when IPC was used prior to the warm and cold ischemia-re-oxygenation protocols. In parallel studies, IPC increased new protein synthesis and lactate after cold storage and reperfusion compared to untreated cells but no differences in the patterns of protein banding were detected on electrophoresis between the groups. In conclusion, IPC significantly improves hepatocyte viability and energy metabolism in a model of hypothermic preservation injury preceded by normothermic ischemia. These protective effects on viability may be related to enhanced protein and ATP synthesis at reperfusion.

Adenosine↗