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Pierre-Alain Clavien

Publications and source records attributed to Pierre-Alain Clavien.

86 records · Page 5Linked to original sources
PubMed2002

Orthotopic liver transplant patients require less postoperative morphine than do patients undergoing hepatic resection.

STUDY OBJECTIVE: To compare postoperative morphine use, analgesic efficacy, and side effect profiles in patients following orthotopic liver transplantation (OLTx) and liver resection (LR). DESIGN: Retrospective study. SETTING: Liver transplant and liver resection surgery at a university hospital. PATIENTS: 25 ASA physical status I, II, III, and IV patients undergoing OLTx or liver resection. MEASUREMENTS AND MAIN RESULTS: Morphine use was significantly decreased in the OLTx patients at 6,12, 24, 48, and 72 hours following commencement of patient-controlled analgesia. After commencement of patient-controlled analgesia, pain scores were significantly reduced in the OLTx group compared with those in the liver resection group at 6 and 12 hours. CONCLUSIONS: Orthotopic liver transplant patients experienced less pain and used less morphine postoperatively than did liver resection patients.

Adult↗
PubMed2002

Tumor necrosis factor alpha, but not Fas, mediates hepatocellular apoptosis in the murine ischemic liver.

BACKGROUND & AIMS: Apoptosis of hepatocytes is a central feature of ischemic injury in the liver. The aim of this study was to identify extracellular inducers of apoptosis in the murine ischemic liver. METHODS: Involvement of tumor necrosis factor (TNF)-alpha and Fas signaling was evaluated using various knockout mice (TNF-receptor 1 [TNF-R1]-/-, Fas[lpr]-/-, and Fas ligand[gld]-/-) and wild-type mice pretreated with pentoxifylline, an inhibitor of TNF-alpha synthesis. RESULTS: Expression of TNF-alpha was increased after ischemia and reperfusion in wild-type mice and TNF-R1-deficient mice when compared with sham-operated animals. Pentoxifylline prevented up-regulation of TNF-alpha expression. Inhibition of TNF-alpha resulted in significant decrease of serum aspartate aminotransferase levels and prolonged animal survival. Markers of apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining, cytochrome C release, and caspase 3 activity) were consistently decreased, and animal survival was prolonged after blocking TNF-alpha. In contrast, inhibition of Fas signaling did not alter parameters of tissue injury or apoptosis, and animal survival remained unchanged. CONCLUSIONS: We identify TNF-alpha as a crucial inducer of apoptotic cell death in the ischemic liver. A role for Fas could not be identified. These findings may lead to novel strategies to prevent ischemic injury of the liver.

Animals↗
PubMed2002

Cold ischemia decreases liver regeneration after partial liver transplantation in the rat: A TNF-alpha/IL-6-dependent mechanism.

New strategies of partial liver transplantation such as cadaveric split or living related liver transplantation have been developed to overcome organ shortage. Thus, studies on the ability of small partial grafts to regenerate to normal size while maintaining adequate function have become important. Here, we evaluated the effects of cold preservation on hepatocyte proliferation and function in a novel model of partial liver transplantation in rats. Lewis rats subjected to 70% liver resection (control) were compared with rats that underwent total hepatectomy and 30% partial liver transplantation (recipient). Livers were preserved at 4 degrees C for 30 minutes, 10 hours, or 16 hours in University of Wisconsin solution. Seventy percent liver resection was associated with 100% survival, whereas 30-minute, 10-hour, and 16-hour preservation before 30% transplantation resulted in 80%, 40%, and 20% animal survival, respectively. Prolonged time of cold preservation (10 and 16 hours) was associated with a dramatic decrease of all markers of regeneration (P <.05). Tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) levels were also significantly decreased in recipient rats compared with the control group. Finally, pretreatment of recipients with recombinant IL-6 (rIL-6) normalized all markers of regeneration and significantly improved survival in the 10-hour group (90% vs. 40%; P <.05). In conclusion, sustained periods of cold preservation significantly impaired TNF-alpha and IL-6 production, the regenerative ability of the liver, and animal survival. rIL-6 reversed impaired regeneration in the 10-hour cold ischemia group and suggests a primary role of nonparenchymal cells in modulating hepatocyte proliferation in the ischemic liver.

Animals↗
PubMed2002

Improved treatment response with basiliximab immunoprophylaxis after liver transplantation: results from a double-blind randomized placebo-controlled trial.

Basiliximab, a high-affinity chimeric monoclonal antibody, is effective in reducing acute rejection episodes in renal allograft recipients. We assessed the ability of this antibody to similarly improve the outcome in liver transplant recipients. Adult recipients of a primary cadaveric liver transplant were randomized to treatment, stratified by hepatitis C virus (HCV) seropositivity. Patients were administered 40 mg of basiliximab (n = 188) or placebo (n = 193) as two 20-mg bolus injections days 0 and 4, plus cyclosporine and steroids. Primary efficacy variables were biopsy-confirmed acute rejection and its composite end point, including death or graft loss, and were assessed at 6 and 12 months and by HCV cohort. Because of differential efficacy responses between HCV-positive and HCV-negative cohorts, an additional analysis incorporating HCV recurrence as a component of treatment failure, termed problem-free transplant, was introduced. Safety and tolerability were monitored over the 12 months of the study. All 381 patients were assessable, and no meaningful differences in background characteristics were apparent between treatment groups. Biopsy-confirmed acute rejection rates 6 months after transplantation were 35.1% in the basiliximab group versus 43.5% in the placebo group. For death, graft loss, or first biopsy-confirmed acute rejection, rates were 44.1% versus 52.8%, respectively. The reduction in rejection episodes was concentrated in the HCV-negative cohort (14.5% relative to placebo; P =.034), with a much smaller difference (2.9%) in the HCV-positive cohort. For HCV-positive patients, problem-free transplant was shown at 12 months in 26.6% of the basiliximab group versus 11.6% in the placebo group (P =.020) and for all patients at 12 months in 39.7% of the basiliximab group versus 30.1% in the placebo group (P =.035). The incidence of infection and other adverse events was similar across the two treatment groups. There were 56 deaths (25 deaths, basiliximab group; 31 deaths, placebo group) over the 12-month study. The intravenous bolus injection was well tolerated. Immunoprophylaxis with 40 mg of basiliximab, in combination with cyclosporine and steroids, reduces the incidence of acute rejection episodes with no clinically relevant safety or tolerability concerns. The influence of HCV recurrence on efficacy results can be accounted for in future trials by using the concept of problem-free transplant, incorporating recurrence as a component of treatment failure.

Adult↗
PubMed2002

Downstaging of hepatocellular carcinoma and liver metastases from colorectal cancer by selective intra-arterial chemotherapy.

BACKGROUND: Although resection is the sole chance of cure in patients with hepatocellular carcinoma (HCC) or metastatic colorectal cancer to the liver, most patients are not candidates for surgery at the time of diagnosis. Strategies aiming at downstaging large or multifocal tumors to enable curative resection are appealing. The aim of this study was to evaluate the effects of neoadjuvant selective intra-arterial chemotherapy in noncirrhotic patients with unresectable HCC or metastatic colorectal cancer to the liver in the absence of extrahepatic disease. METHODS: Selective chemotherapy was provided by using a subcutaneous pump device via a catheter placed in the gastroduodenal artery. Chemotherapy regimen included floxuridine (0.2 mg/kg/day for 14 days) in each patient with additional boluses of cisplatin and doxorubicin on day 1 of each cycle in the presence of HCC. Patients were evaluated at 3, 6, 9, and 12 months for possible curative resection. Complete follow-up was available for each patient. RESULTS: Twenty-eight patients with unresectable liver tumors (5 HCC and 23 metastatic colorectal cancer) were included in this study. There were no surgical complications related to pump insertion, and local chemotherapy was started within 1 week of surgery in each patient. The median follow-up in survivors was 31 months (range, 30 months to 5 years). Chemotherapy was well tolerated in 18 (64%) patients. Chemotherapy was discontinued in 4 patients because of abnormal liver function test results, and 2 of them required a biliary stent to relieve a biliary stricture. In 9 patients downstaging enabled curative resection (3 HCC, 6 colorectal metastasis). Seven of these patients were alive and tumor free at the completion of the study, with at least 2 years of follow-up. The actuarial survival rates at 3 years for HCC and colorectal metastases were 60% and 50%, respectively. CONCLUSIONS: About one third of patients with unresectable liver tumors can be successfully treated by neoadjuvant intra-arterial chemotherapy followed by curative resection. This strategy appears particularly promising in patients with large HCC. This approach should be investigated further.

Adult↗
PubMed2002

Evidence-based pancreatic head resection for pancreatic cancer and chronic pancreatitis.

OBJECTIVE: To review the current status of pancreatoduodenectomy for pancreatic cancer and chronic pancreatitis using evidence-based methodology. SUMMARY BACKGROUND DATA: Despite improved results of pancreatoduodenectomy over the recent years, the reputation of the Whipple procedure and its main modifications has remained poor. In addition, the current status of newer modifications of standard pancreatoduodenectomy is still under debate. METHODS: Medline search and manual cross-referencing were performed to identify all relevant articles for classification and analysis according to their quality of evidence. The search was limited to articles published between 1990 and 2001. RESULTS: The mortality rate of pancreatoduodenectomy has declined to less than 5% for chronic pancreatitis and 3% to 8% for pancreatic cancer. In contrast, overall morbidity rates remain high, ranging between 20% and 70%. Delayed gastric emptying represents almost half of all complications. The overall 5-year survival rate for patients with pancreatic cancer remains poor, ranging between 5% and 15%, with a median survival of 13 to 17 months. Mortality and morbidity are not related to the type of pancreatoduodenectomy; however, patients with pancreatic cancer tend to be at increased risk for complications. Extended lymph node dissection and portal vein resection can be performed with similar mortality and morbidity rates as standard procedures, but without apparent survival benefits in the long term. Major relief of pain is achieved in 70% to 100% of patients with chronic pancreatitis. CONCLUSIONS: Pancreatoduodenectomy and its main modifications are safe and effective treatment modalities, especially in experienced centers with a high patient volume. For chronic pancreatitis, surgical resection provides major relief of pain and thus increased quality of life. Overall survival for patients with pancreatic cancer is determined predominantly by the pathology within the resected specimen.

Adenocarcinoma↗
PubMed2002

The role of F-18 FDG positron emission tomography in preoperative assessment of the liver in patients being considered for curative resection of hepatic metastases from colorectal cancer.

PURPOSE: The authors' goal was to determine the sensitivity and specificity of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying patients with hepatic metastases from colorectal cancer and the accuracy of PET for determining the number and distribution of lesions within the liver. Intraoperative sonography and surgical inspection and palpation were used as the reference standard. METHODS: Twenty-three patients being evaluated for surgical resection of hepatic metastases from colorectal carcinoma underwent FDG PET before operation. Findings of the PET studies were reviewed in a blinded, retrospective manner, with the results compared with the findings of intraoperative sonography and surgical exploration. Lesions of all sizes were considered in the analysis. RESULTS: The FDG-PET results were positive in 21 of the 22 patients ultimately found to have metastatic disease to the liver, and they were negative in the single patient without metastases. Therefore, for identification of patients with hepatic metastatic disease, PET has a sensitivity of 95% and a specificity of 100%. In all, 48 metastatic lesions were identified in these patients, of which 38 (79%) were identified on PET images. The probability of lesion detection by PET was directly correlated with lesion size (P < 0.01). The assessment of lobar disease distribution in the liver was discordant between PET and surgery in 3 of 23 (13%) patients. CONCLUSIONS: In patients being evaluated for potential curative resection of hepatic metastases from colorectal cancer, FDG PET is accurate for the identification of the presence or absence of metastatic disease to the liver. However, detection of individual lesions depends on their size, and determination of lesion number and distribution within the liver is more accurately accomplished with intraoperative sonography.

Adult↗
PubMed2002

New treatments with curative intent for metastatic colorectal liver cancer.

Although surgical resection is the mainstay of therapy in metastatic colorectal liver cancer, < 10 - 15% of patients are suitable for resection. In addition, recurrence rates after resection may reach 75% in the first 2 years, of which 50% involve local recurrences in the liver. This has provided an impetus for the development of neoadjuvant and adjuvant protocols in the treatment of this malignancy, techniques concentrating on improving the residual liver functional reserve, as well as local tumour ablative therapies using radiofrequency and cryotherapy. A multimodal interdisciplinary approach is a pre-requisite when treating secondary liver tumours from colorectal cancer and should be concentrated in centres of reference. The development of such innovative modalities as preoperative downstaging in the absence of extrahepatic tumour disease, local tumour control and new adjuvant therapies has expanded the patient population thus providing the opportunity to treat patients with large or advanced stage colorectal liver tumours. The following is a review of some of the approaches currently being evaluated in the treatment of colorectal liver metastases.

Antineoplastic Agents↗
PubMedDate not supplied

Protection of the liver during hepatic surgery.

Very few areas in medicine have seen as many controversies as the evaluation and treatment of patients with liver diseases. Many novel therapies, often marketed before conclusive demonstration of their efficacy, have been developed to enable selective destruction of liver tumors to minimize the risk of liver failure associated with major surgery. Whether these techniques are effective and result in lesser complications often remains speculative. Persisting challenges in selecting the optimal therapy are the evaluation of the risk of surgery in patients with normal or diseased liver and the preparation for surgery. A panel of hepato-biliary surgeons experienced in the management of complex cases convened at the annual meeting of the American Hepato-Pancreato-Biliary Association in Boston, MA, to address the rapidly evolving field of protective strategies for hepatic surgery.

Embolization, Therapeutic↗
PubMedDate not supplied

Cryosurgery after chemoembolization for hepatocellular carcinoma in patients with cirrhosis.

Most cirrhotic patients with hepatocellular carcinoma (HCC) are not candidates for resection. Transarterial chemoembolization (TACE) may ablate a significant portion of the tumor but has a high rate of recurrence. Cryosurgery may permit successful ablation of hepatic tumors but can be complicated by postoperative hemorrhage and is also associated with a significant risk of recurrence. The combination of the two techniques might be beneficial. We evaluated in a prospective study the safety and efficacy of this combination in cirrhotic patients with unresectable HCC. Fifteen patients were included in this study. All but one patient underwent one or several sessions of TACE before cryosurgery. Cryoablation was successfully performed in each patient. The patient who did not undergo preoperative TACE required reoperation for hemorrhage. Another patient with Child-Pugh class B cirrhosis died postoperatively of hepatic and multiorgan failure. At a mean follow-up of 2.5 years, three patients had recurrence of disease, and 13 of 15 patients were alive with the longest survival time being 5 years. The actuarial survival rate at 5 years was 79%. Cryosurgery after TACE is feasible in cirrhotic livers with HCC and can increase the cure rate in large tumors. TACE may reduce the risk of hemorrhage after cryosurgery but can increase the risk of hepatic failure in patients with poor hepatic function.

Adult↗
PubMedDate not supplied

Liver ischemia: apoptosis as a central mechanism of injury.

Injuries due to cold and warm (normothermic) ischemia remain an important source of morbidity and mortality in liver surgery and transplantation. While the mechanisms of injury are complex, involving apoptotic and necrotic types of cell death, accumulating evidence points to a central role for various apoptotic pathways in mediating cell death following ischemia. A number of antiapoptotic strategies have been shown to confer a high degree of protection, including improved animal survival following long ischemic insult. The future may lie in the identification of practical and effective antiapoptotic strategies to enhance tolerance to ischemic injury.

Animals↗