RESUMEN
AIM: The dose-response relationship between doxorubicin and superabsorbent drug-eluting microspheres has not been established. In this study, we investigated the relationships between dose and delivery parameters as they pertain to toxicity and response in surgically resectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Twenty-five patients with resectable HCC were randomly assigned and divided into four groups, each receiving either bland, 25 mg, 50 mg or 75 mg of doxorubicin loaded Super Absorbent Polymer microspheres, with 24 patients undergoing surgical resection. Response Evaluation and Criteria in Solid Tumors (RECIST) 1.0 and European Association for the Study of the Liver (EASL)-based volumetric response was performed at one month and surgical resection of the reference tumor was performed at two months. Adverse events were collected at regular intervals. RESULTS: Fifty-six percent of patients demonstrated complete response according to EASL criteria as opposed to 0% according to RECIST (v1.0) criteria. Residual tumor was identified in all groups (0 mg: 35%±28.5%; 25 mg: 42%±30.4%; 50 mg: 3.6%±3.3%; and 75 mg: 49.29%±32.6%. A total of 112 adverse events of grades 1-3 occurred (average 5.1 per patient), with no grade 4 or 5. No difference was noted between bland embolic and drug-loaded groups. Subset analysis did demonstrate a significantly increased degree of necrosis in the 50 mg-loaded group (p=0.018). Strong correlation existed between arterial phase Computer Tomography EASL-based response and histopathology (r=0.81; p<0.0001). All groups had residual tumor. CONCLUSION: Histology correlates strongly with one-month post-procedural imaging and response optimized at 50 mg of loading per vial. Adverse events were a reflection of embolization, with no relationship between loading dose or administered dose of doxorubicin.
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Antibióticos Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Doxorrubicina/administración & dosificación , Neoplasias Hepáticas/terapia , Anciano , Antibióticos Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Relación Dosis-Respuesta a Droga , Doxorrubicina/efectos adversos , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Masculino , Microesferas , Persona de Mediana EdadRESUMEN
Hepatic artery thrombosis (HAT) is relatively infrequent, but possibly a devastating complication of orthotopic liver transplantation (OLT). It often requires urgent retransplantation. Two main forms of HAT are recognized as early and late HAT (diagnosis within or after 30 days following LT). Early HAT typically results in graft failure. Late HAT features biliary obstruction, cholangitis, and hepatic abscess formation. We report here the case of a patient of Wilson's disease who presented twelve years post-liver transplant symptoms typical of acute HAT and hepatic infarction. On diagnostic imaging, celiac axis and hepatic artery were thrombosed, resulting in ischemic necrosis of the left hepatic lobe. The resulting sepsis and transient hepatic insufficiency were managed conservatively, and repeat OLT was avoided. The patient remains stable more than one year later. To the best of our knowledge this case report is unique in the literature for the unusually long interval between OLT and late acute HAT, as well as celiac and portal vein occlusion. The acute presentation of sub massive hepatic necrosis is also uncharacteristic of late HAT and more typical of acute HAT. This report describes our experience in managing this and a literature review of the topic.
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Arteria Celíaca , Arteria Hepática , Infarto/etiología , Trasplante de Hígado , Hígado/irrigación sanguínea , Vena Porta , Trombosis/complicaciones , Adulto , Humanos , Infarto/diagnóstico , Hígado/diagnóstico por imagen , Masculino , Trombosis/diagnóstico , Tomografía Computarizada por Rayos XRESUMEN
Prophylaxis against recurrent hepatitis B virus (HBV) infection with hepatitis B immune globulin (HBIG), in combination with antiviral agents such as lamivudine, has allowed transplantation for this condition to become feasible and accepted. Current protocols allow for HBIG administration either intravenously or intramuscularly. To date, there has been no reported experience with the subcutaneous route of post-transplant HBIG delivery. We report our experience of a 60-yr-old man for whom liver transplantation was performed for chronic HBV. HBIG was administered intramuscularly during the anhepatic phase of surgery. The finding of a portal vein thrombosis requiring repeated thrombectomy necessitated chronic anticoagulation. Post-operatively, HBIG was administered subcutaneously, in four separate injections, for a daily dose of 2170 IU along with continued lamivudine dosing. Hepatitis B surface antibody (anti-HBs) titres reached a serum concentration of >500 IU/L by seven d post-transplant and approximately 1000 IU/L by nine d post-transplant. Five months post-transplant, with continued combination of subcutaneous HBIG and lamivudine, there has been no recurrent HBV infection and anti-HBs titres have been at target levels. Our experience suggests that subcutaneous delivery of HBIG may be a feasible consideration when intramuscular/intravenous dosing is not possible.
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Hepatitis B/prevención & control , Hepatitis B/cirugía , Inmunoglobulinas/uso terapéutico , Lamivudine/uso terapéutico , Fallo Hepático Agudo/cirugía , Trasplante de Hígado/inmunología , Antivirales/uso terapéutico , Hepatitis B/tratamiento farmacológico , Hepatitis B/inmunología , Humanos , Inmunización Pasiva , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , RecurrenciaRESUMEN
BACKGROUND: Every centre has contraindications to liver transplantation and declares patients unsuitable for medical or nonmedical reasons. To date, there has been no published review of any centre's experience. METHODS: A retrospective chart review was completed from 1997 to 2001, inclusive of all patients referred for liver transplant to the British Columbia Transplant Society who were declared unsuitable for transplantation, as well as the reasons for unsuitability. RESULTS: One hundred fifty patients were considered to be unsuitable for transplantation. During this period, 167 transplants were performed and 737 patients were referred for candidacy. Data were missing on three patients; analysis was performed on the remaining 147. Patients' ages ranged from 15 to 72 years, and 33.3% were female. The most common primary liver disease was hepatitis C (n=53, 35%), followed by alcoholic liver disease (n=35, 24%) and autoimmune liver diseases (n=23, 16%). Medical contraindications constituted 74 patients (49.0%) and the most common reasons for unsuitability were no need of a liver transplant (29 patients [39%]), exclusion due to hepatoma or extrahepatic malignancy (20 patients [27%]) and multisystem failure (12 patients [16%]). Nonmedical contraindications constituted 73 patients. Failure to meet minimal alcohol criteria comprised the largest group (n=39, 53.4%) followed by inadequate social support (n=12, 16.4%), failure to follow up medical assessment (n=10, 13.7%) and drug abuse (n=6, 8.2%). CONCLUSIONS: Although many patients were declined for transplantation, the proportion is relatively small compared with the number of referred patients. Nonmedical reasons, including failure to meet alcohol criteria and lack of social support, remain a significant reason for unsuitability in British Columbia. Community intervention before transplant referral is recommended.
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Hepatopatías/cirugía , Trasplante de Hígado , Selección de Paciente , Adolescente , Adulto , Anciano , Colombia Británica , Comorbilidad , Contraindicaciones , Femenino , Hepatitis C/cirugía , Humanos , Hepatopatías Alcohólicas/epidemiología , Hepatopatías Alcohólicas/cirugía , Masculino , Persona de Mediana Edad , Apoyo SocialRESUMEN
With today's donor organ shortage, enhanced efforts must be made to utilize organs that previously would have been declined. We report a 26-year-old man with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection who received a liver transplant from an HBsAg-positive donor. HBV viremia (6,281,185 copies/ml) was seen early posttransplant despite lamivudine prophylaxis, but became negative with addition of adefovir. Virologic analysis revealed predominantly donor HBV strain immediately posttransplant. At 5 months there was an elevation of liver enzymes accompanied by histologic evidence of hepatitis. At this time, HCV-RNA was positive but HBV DNA was undetectable. Treatment with pegylated interferon and ribavirin resulted in sustained clearance of HCV RNA. Two years posttransplant, the patient has normal liver biochemistry and HCV and HBV viral load are undetectable with persistence of HBsAg. Our experience suggests that with effective antiviral therapy, the use of HBsAg seropositive donors is feasible in selected circumstances.