Hereditary hemorrhagic telangiectasias with liver involvement and high cardiac output.
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Aortography↗
Biomedical subjects
H Bismuth
Publications and source records attributed to H Bismuth.
Prospective phase II trial of iriontecan, 5-fluorouracil, and leucovorin in combination as salvage therapy for advanced colorectal cancer.
Irinotecan (CPT11) has established activity in the treatment of advanced colorectal cancer without cross-resistance with established 5-fluorouracil/folinic acid-based therapy. This phase II study was conducted to establish the efficacy and tolerance of combination treatment with irinotecan and 5-fluorouracil as salvage treatment for this disease. Open phase II trial of CPT11 180 mg/m2 on day 1, leucovorin 200 mg/m2 on days 1 and 2, and 5-fluorouracil 400 mg/m2 loading dose followed by 600 mg/m2 infusion on days 1 and 2. Treatment was continued until progression or limiting toxicity. Responders could proceed to surgical resection of residual disease. Thirty-nine patients from 2 institutions received a total of 287 cycles of therapy (median 7 cycles/patient). Eight patients achieved an objective response (7 for liver metastasis and 1 for lung metastasis), and an additional 12 obtained stabilization of disease or minor responses (MR); of these patients, 8 with liver metastasis (7 partial response and 1 MR) underwent hepatic resection of metastases and all them obtained a complete response. The median duration of response was 14 months, and the median survival was 11 months. Hematologic toxicity (neutropenia) was the most common serious side effect (29% of patients in 2% of cycles), but significant fever developed in only 4 patients. Grade III diarrhea was experienced in at least 1 cycle by 10% of patients. The results of this schedule compare favorably with previously reported experience of a phase I study designed to establish the dose of CPT11. Efficacy in this poor prognosis group of patients is very encouraging, and the schedule is well tolerated by even previously treated patients.
Adult↗
Phase I-II study of irinotecan in combination with mitomycin C in patients with advanced gastrointestinal cancer.
This phase I-II study was conducted to determine the maximum tolerated dose and optimal schedule of a combination of irinotecan (CPT 11) and mitomycin C (MMC) in a population of previously treated patients with gastrointestinal malignancies. Four cohorts of patients were recruited with MMC given at 8 mg/m2 for the first 3 levels together with irinotecan at 300 mg/m2, 325 mg/m2, and 350 mg/m2; the fourth dose level was given with MMC at 10 mg/m2 and irinotecan at 325 mg/m2. All treatment was repeated at 21-day intervals. The dose-limiting toxicity was hematologic (thrombocytopenia at level 4), and the recommended doses for subsequent phase II studies are MMC 8 mg/m2 with irinotecan 325 mg/m2. Evidence of efficacy was seen at all dose levels examined and justifies further exploration of this combination in a less heavily pretreated patient population.
Adult↗
Split-liver transplantation for two adult recipients: feasibility and long-term outcomes.
OBJECTIVE: To identify the outcomes and risks of split-liver transplantation (SLT) for two adult recipients to determine the feasibility of more widespread use of this procedure to increase the graft pool for adults. SUMMARY BACKGROUND DATA: The shortage of cadaver liver grafts for adults is increasing. Using livers from donors defined as optimal, the authors have been developing techniques for SLT for two adult recipients at their center. METHODS: From July 1993 to December 1999, 34 adults have undergone SLT with grafts from optimal donors prepared by ex situ split (n = 30) or in situ split (n = 4), and 88 adults received optimal whole-liver grafts that were not split. Four split-grafts were transplanted at other centers. The outcomes of transplantation with right and left split-liver grafts were compared with those of whole-liver transplants. The main end points were patient and graft survival at 1 and 2 years and the incidence and types of complications. RESULTS: For whole-liver, right and left split-liver grafts, respectively, patient survival rates were 88%, 74%, and 88% at 1 year and 85%, 74%, and 64% at 2 years. Graft survival rates were 88%, 74%, and 75% at 1 year and 85%, 74%, and 43% at 2 years. Patient survival was adversely affected by graft steatosis and recipients inpatient status before transplantation. Graft survival was adversely affected by steatosis and a graft-to-recipient body weight ratio of less than 1%. Primary nonfunction occurred in three left split-liver grafts. The rates of arterial (6%) and biliary (22%) complications were similar to published data from conventional transplantation for an adult and a child. SLT for two adults increased the number of recipients by 62% compared with whole-liver transplantation and was logistically possible in 16 of the 104 (15%) optimal cadaver donors. CONCLUSIONS: Split-liver transplantation for two adults is technically feasible. Outcomes and complication rates can be improved by rigid selection criteria for donors and recipients, particularly for the smaller left graft, and possibly also by in situ splitting in cadaver donors. Wider use will require changes in the procedures for graft allocation and coordination between centers experienced in the techniques.
Adult↗
Auxiliary partial orthotopic versus standard orthotopic whole liver transplantation for acute liver failure: a reappraisal from a single center by a case-control study.
OBJECTIVE: To reappraise the results of auxiliary partial orthotopic liver transplantation (APOLT) compared with those of standard whole-liver transplantation (OLT) in terms of postoperative death and complications, including neurologic sequelae. SUMMARY BACKGROUND DATA: Compared with OLT, APOLT preserves the possibility for the native liver to recover, and to stop immunosuppression. METHODS: In a consecutive series of 49 patients transplanted for fulminant or subfulminant hepatitis, 37 received OLT and 12 received APOLT. APOLT was done when logistics allowed simultaneous performance of graft preparation and the native liver partial hepatectomy to revascularize the graft as soon as possible. Each patient undergoing APOLT (12 patients) was matched to two patients undergoing OLT (24 patients) according to age, grade of coma, etiology, and fulminant or subfulminant type of hepatitis. All grafts in the study population were retrieved from optimal donors. RESULTS: Before surgery, both groups were comparable in all aspects. In-hospital death occurred in 4 of 12 patients undergoing APOLT compared with 6 of 24 patients undergoing OLT. Patients receiving APOLT had 1 +/- 1.3 technical complications compared with 0.3 +/- 0.5 for OLT patients. Bacteriemia was significantly more frequent after APOLT than after OLT. The need for retransplantation was significantly higher in the APOLT patients (3/12 vs. 0/24). Brain death from brain edema or neurologic sequelae was significantly more frequent after APOLT (4/12 vs. 2/24). One-year patient survival was comparable in both groups (66% vs. 66%), and there was a trend toward lower 1-year retransplantation-free survival rates in the APOLT group (39% vs. 66%). Only 2 of 12 (17%) patients had full success with APOLT (i.e., patient survival, liver regeneration, withdrawal of immunosuppression, and graft removal). One of these two patients had neurologic sequelae. CONCLUSIONS: Using optimal grafts, APOLT and OLT have similar patient survival rates. However, the complication rate is higher with APOLT. On an intent-to-treat basis, the efficacy of the APOLT procedure is low. This analysis suggests that the indications for an APOLT procedure should be reconsidered in the light of the risks of technical complications and neurologic sequelae.
Adolescent↗
Influence of liver hepatitis C virus RNA and hepatitis C virus genotype on FAS-mediated apoptosis after liver transplantation for hepatitis C.
BACKGROUND: Recurrent hepatitis C virus (HCV) infection after liver transplantation is characterized by a high level of intrahepatic HCV replication and more severe liver damage in case of genotype 1b infection. We investigated the involvement of apoptosis in recurrent HCV liver disease, and its possible links with histological findings, HCV genotype, liver HCV RNA level, and liver Fas mRNA level. METHODS: We studied 61 liver graft biopsy specimens from 25 patients transplanted for HCV-related cirrhosis. DNA fragmentation was determined semi-quantitatively by in situ end labeling. HCV RNA and liver Fas mRNA were determined in parallel by quantitative polymerase chain reaction, with ribosomal 28S RNA as internal standard. RESULTS: Apoptotic lesions were predominantly portal (nonhepatocytic) or lobular (hepatocytic). Both were correlated with serum aminotransferase levels. The degree of portal apoptosis correlated with acute rejection (P<0.001), although lobular apoptosis was associated with lobular hepatitis (P<0.02), and HCV genotype 1b (P=0.04). In multivariate analysis, liver Fas mRNA level independently correlated with HCV-related chronic active hepatitis (P=0.04), age (P=0.01), and liver HCV RNA level (P=0.0007). CONCLUSIONS: After liver transplantation, 1) apoptosis is involved in HCV-related liver damage; 2) HCV type 1b may induce more severe apoptotic lesions than other genotypes; and 3) Fas transcription may be up-regulated by intrahepatic HCV replication.
Apoptosis↗
Normalised intrinsic mortality risk in liver transplantation: European Liver Transplant Registry study.
BACKGROUND: No model exists for liver transplantation to estimate the mortality risk in a given patient, and no standard by which to assess performance in different centres. We investigated the intrinsic mortality risk in the absence of known mortality risk factors. METHODS: We identified mortality risk factors and risk ratios quantified in data from the European Liver Transplant Registry (22,089 patients at 102 centres in 18 countries) registered from 1988 to 1997. To develop a model of the intrinsic risk and the risk ratios for specific factors, univariate and multivariate analyses were done separately for the overall population, for adults, and for children younger than 15 years, and the number of deaths were estimated. We validated the model by comparing mortality in patients without risk factors with the model-adjusted mortality in patients with risk factors. FINDINGS: Overall 5-year and 8-year actuarial survival was 66% (95% CI 65-66) and 61% (60-62). 65% of deaths occurred within 6 months. Retransplantation, transplantation for cancer, acute liver failure, fewer than 20 split-liver grafts per year, and a centre workload of fewer than 25 transplants per year were the main risk factors of 12 identified factors. 1-year and 5-year death rates among adults with no risk factors were similar to model estimates (15 [13-16] vs 14% [13-15], and 22 (20-24) vs 23% [21-24]). Corresponding data for paediatric transplants were 9% (7-12) compared with 11% (9-12) and 13% (10-17) compared with 14% (11-16). The reduction of mortality risk in high-volume centres was even greater in patients without risk factors (48 vs 23%, p<0.001). INTERPRETATION: The normalised intrinsic mortality risk can be combined with the relative risk ratios of known risk factors to better estimate the mortality risk of a given procedure in a given patient. Centres can assess performance by removing potential bias of donor and recipient selection.
Adolescent↗
Transplantation of three adult patients with one cadaveric graft: wait or innovate.
Graft shortage continues to prolong waiting times for adults requiring liver transplantation. Living related donor transplantation is possible for only a small minority of adults. The techniques for in situ splitting of the liver used for right and left hepatectomies in living donors were adapted to a combined split-liver-domino procedure to obtain right and left hemiliver grafts from a patient undergoing total hepatectomy with liver transplantation for a metabolic disorder. The two grafts were adequate in size and function for transplantation to two adults with low priority for regular cadaver grafts. More frequent use of split-liver techniques in cadaver donors could considerably reduce the graft shortage and waiting time for adult liver recipients.
Adult↗
Results after nonsurgical local treatment of primary liver malignancies.
Although it is generally agreed that surgical resection is the only curative treatment for liver malignancy, this is not possible in all cases. In situ methods for destruction of liver tumors are now available. We describe recently developed methods, with an up-date based on the literature and our own experience. Under ultrasound guidance chemical agents such as ethanol, hot saline, and acetic acid may be injected into the tumor, or thermally mediated techniques involving cryotherapy, microwaves, radiofrequency, or interstitial laser photocoagulation may be applied. Also, various ways of delivering radiotherapy to primary liver cancer have been developed. Although there are few randomized studies to compare these local, nonsurgical techniques, they have been shown to improve survival and in some cases to render tumors resectable. The long-term results will show the real benefits of these newer treatments, particularly in high-risk patients.
Acetic Acid↗
Hepatitis and solid organ transplantation.
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Antiviral Agents↗
Hepatobiliary surgery.
The transformation of liver and biliary tract surgery into a full speciality began with the application of functional anatomy to segmental surgery in the 1950's, reinforced by ultrasound and new imaging techniques. The spectrum of gall-stone disease encountered by the hepatobiliary surgeon has changed with the laparoscopic approach to cholecystectomy. There is increased need for conservation techniques to repair the bile duct injuries that arise more often in the laparoscopic approach to cholecystectomy. These and other surgical interventions on the bile ducts should be selected as a function of risk versus benefit in relation to the patient's requirements and the institutional expertise. Bile duct cancers, including hilar cholangiocarcinoma, and gallbladder cancers have a dismal reputation, but evidence is accumulating for better survivals from aggressive approaches performed by specialist hepatobiliary surgeons. Hepatic surgery has increased in safety and effectiveness, largely due to the segmental approach, but also to experience with techniques for vascular control and exclusion used in liver transplantation. Techniques such as portal vein embolisation, which induces hypertrophy of the future remnant liver, percutaneous local tumour destruction using cryotherapy or radiofrequency tumour coagulation and more effective chemotherapy are beginning to increase the number of patients who can undergo curative resection. In liver transplantation, segmental surgery has been applied to graft reduction and to split liver grafts, and is opening new perspectives for living donor transplantation. Today the limitation to survival in primary and metastatic liver cancer lies not in the surgical technique but in the difficulty of dealing with microscopic and extrahepatic disease. Progress in these fields will enable the hepatobiliary surgeon to further extend the possibilities for proposing curative resections.
Bile Duct Neoplasms↗
Caval inflow to the graft: a successful way to overcome diffuse portal system thrombosis in liver transplantation.
Portal vein thrombosis was considered to be a major contraindication to liver transplantation before the introduction of vessel grafts from the recipient's area of confluence of the splenic and superior mesenteric veins, behind the neck of the pancreas, to the graft's portal vein. Refinement in surgical technique has given rise to a large number of possibilities to overcome portal vein thrombosis in OLT recipients, ranging from portal vein thrombectomy to several different venous graft jump reconstructions. All these reconstructions require the presence of a patent vein of the portal system. When neither splanchnic veins nor sufficiently large venous collaterals are available, liver transplantation has been considered impossible. Salvage solutions include arterialization of the portal vein with the associated risk of liver damage in the longterm, a combined liver and bowel transplantation has been proposed but not yet reported (and in any case the results of combined liver and bowel transplants are not as good as those of liver transplantation alone) and finally the use of blood inflow from the inferior vena cava as first reported by Tzakis and coworkers. Portal flow from the inferior vena cava may be performed as a last resort. Although the consequences of severe pretransplantation portal hypertension remain and should be treated before, during, and after transplantation, liver function is normal in the short and midterm. With this new procedure, diffuse portal vein thrombosis is no longer an absolute contraindication to liver transplantation. But this needs to be confirmed in light of further experience and longterm followup.
Anastomosis, Surgical↗
Transjugular intrahepatic portosystemic shunt (TIPS) for severe veno-occlusive disease of the liver following bone marrow transplantation.
Severe veno-occlusive disease (VOD) of the liver is a leading cause of mortality after bone marrow transplantation (BMT). Vascular and parenchymal injuries account for acute portal hypertension and liver failure is frequently present. We describe the results of transjugular intrahepatic portosystemic shunt (TIPS) for the management of VOD after BMT. TIPS was performed in 10 patients with histologically proven severe VOD. Portal hypertension was controlled by TIPS in all patients (mean hepatic venous pressure gradient before, 20 +/- 11 vs 6 +/- 5 mm Hg after TIPS, P < 0.01) without technical complications. Five patients with rapidly worsening VOD died within 10 days of TIPS without any improvement. The five remaining patients with less advanced disease showed improvement in various clinical and biological parameters. Four patients subsequently died. The lone survivor continues to do well with resolution of VOD 6 months after TIPS. TIPS can be performed safely and controls portal hypertension in VOD after BMT. Arguments from the present series and from eight previously reported cases favour earlier application of TIPS to obtain improved overall survival. Bone Marrow Transplantation (2000) 25, 987-992.
Adolescent↗
Hepatocellular carcinoma with lymphoid stroma: a tumour with good prognosis after liver transplantation.
AIMS: Carcinomas with lymphoid stroma arising in non-liver-organs have a better prognosis than other carcinomas and may be associated with Epstein-Barr virus. We determined the frequency, characteristics and prognosis of hepatocellular carcinomas with lymphoid stroma. METHODS AND RESULTS: Histology of the livers of 162 patients with hepatocellular carcinoma, who underwent an orthotopic liver transplantation, was reviewed independently by three pathologists. Hepatocellular carcinoma with lymphoid stroma was diagnosed when all tumour samples contained more lymphocytes than tumour cells. Epstein-Barr virus was detected by in-situ hybridization and by polymerase chain reaction. Five patients (3.6%) were classified as hepatocellular carcinomas with lymphoid stroma. All patients were males. Cirrhosis was present in four/five patients. Serum alpha-fetoprotein levels were normal. Inter-observer histological reproducibility was good. Tumour cells did not contain Epstein-Barr virus. The five patients were alive without tumour at three years, although two of them had adverse prognostic factors at the time of transplantation (more than one tumour with a diameter > or = 40 mm). Only one patient had tumour recurrence, but he survived 7.6 years post-transplantation. The 5-year survival of patients with hepatocellular carcinoma with lymphoid stroma was better than that of the patients with other types of hepatocellular carcinomas (P = 0.04). CONCLUSIONS: Hepatocellular carcinoma with lymphoid stroma should be considered as a distinct clinicopathological and prognostic entity.
Carcinoma, Hepatocellular↗
A la carte interferon for hepatitis C?
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Antiviral Agents↗
Revisiting liver transplantation for patients with hilar cholangiocarcinoma: the Mayo Clinic proposal.
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Cholangiocarcinoma↗
The course and prognostic factors of familial amyloid polyneuropathy after liver transplantation.
Familial amyloid polyneuropathy (FAP) associated with mutations of the transthyretin (TTR) gene is the most common type of FAP, a devastating disease causing death within 10 years after the first symptoms. Because most of the amyloidogenic mutated TTR is secreted by the liver, transplantation is widely used to treat these patients, but long-term quantitative evaluation of the effects of liver transplantation on the progression of the neuropathy are not available. We have treated 45 patients with symptomatic TTR-FAP, including 43 with the Met30 TTR gene mutation, and report on the results of periodic evaluation of markers of neuropathy in 25 of them, who have been followed for more than 2 years after liver transplantation (mean follow-up 4 years). The overall survival rates at 1 and 5 years were 82 and 60%, respectively. Urinary incontinence and a low Norris score at liver transplantation were associated with poorer outcome. The motor score stabilized in seven of 11 patients (64%) with mild sensorimotor neuropathy (walking unaided) and in two of the eight patients (25%) with severe sensorimotor deficit (walking with aid) at liver transplantation. In five other patients, deterioration of motor deficit occurred only within the first year after liver transplantation, but was progressive after this interval in two patients. None of the six patients with pure sensory neuropathy developed motor loss and superficial sensory loss remained unchanged. Two years after liver transplantation, the rate of myelinated axon loss in nerve biopsy specimens was markedly lower in seven transplanted patients (0.9/mm(2) of endoneurial area/month) than in non-transplanted patients (70/mm(2) of endoneurial area/month). Symptoms of dysautonomia and quantitated cardiocirculatory autonomic tests remained unchanged. In all patients, serum mutated TTR decreased to 2.5% of pre-liver transplantation values and remained at this level during follow-up. We presently recommend liver transplantation in FAP patients at onset of first symptoms and exclusion of those with a Norris score below 55 and/or with urinary incontinence.
Action Potentials↗
Resection of nonresectable liver metastases from colorectal cancer after percutaneous portal vein embolization.
OBJECTIVE: To assess the influence of preoperative portal vein embolization (PVE) on the long-term outcome of liver resection for colorectal metastases. SUMMARY BACKGROUND DATA: Preoperative PVE of the liver induces hypertrophy of the remnant liver and increases the safety of hepatectomy. METHODS: Thirty patients underwent preoperative PVE and 88 patients did not before resection of four or more liver segments. PVE was performed when the estimated rate of remnant functional liver parenchyma (ERRFLP) assessed by CT scan volumetry was less than 40%. RESULTS: PVE was feasible in all patients. There were no deaths. The complication rate was 3%. The post-PVE ERRFLP was significantly increased compared with the pre-PVE value. Liver resection was performed after PVE in 19 patients (63%), with surgical death and complication rates of 4% and 7% respectively. PVE increased the number of resections of more than four segments by 19% (17/88). Actuarial survival rates after hepatectomy with or without previous PVE were comparable: 81%, 67%, and 40% versus 88%, 61%, and 38% at 1, 3, and 5 years respectively. CONCLUSIONS: PVE allows more patients with previously unresectable liver tumors to benefit from resection. Long-term survival is comparable to that after resection without PVE.
Aged↗