André Cosme de Oliveira

Sorafenib in Advanced Hepatocellular Carcinoma

BACKGROUND No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma. METHODS In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Secondary outcomes included the time to radiologic progression and safety. RESULTS At the second planned interim analysis, 321 deaths had occurred, and the study was stopped. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P<0.001). There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs. 4.9 months, respectively, P=0.77). The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P<0.001). Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a complete response. Diarrhea, weight loss, hand-foot skin reaction, and hypophosphatemia were more frequent in the sorafenib group. CONCLUSIONS In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo. (ClinicalTrials.gov number, NCT00105443.)

Intrahepatic Glissonian Approach for Laparoscopic Right Trisectionectomy

A 22-year-old woman with a giant angiomyolipoma was referred for surgical treatment. The patient was placedin aleft semilateral decubitus position with the surgeon between the patient’s legs. Five trocars (three 12 and two 5mm) were used. The pneumoperitoneum is established at a pressure of 12mm Hg. Round and falciform ligaments are taken down close to the abdominal wall in order to facilitate left-liver fixation at the end of the procedure. The falciform and coronary ligaments are divided by using laparoscopic coagulation shears (Harmonic Scalpel LCS; Ethicon Endo-Surgery Industries, Cincinnati, OH)toexpose thesuprahepaticinferiorvenacava. After cholecystectomy, the right hepatic artery is ligated, resulting in an ischemic delineation of the right liver. Due to previous right-portal-vein embolization in this patient, the hepatic pedicle was not fully dissected. The right liver is then fully mobilized, and the inferior vena cava is dissected. A large inferior right hepatic vein arising from segment 6 is ligated and divided between metallic clips. Another accessory right hepatic vein from segment 7 (middle-right hepatic vein) is divided with a vascular endoscopic stapler. The right hepatic vein is finally encircled, and downward retraction permits the safe application of a vascular endoscopic stapler. The stapler is fired, leaving three lines of metallic clips. With this maneuver, the anterior surface of the retrohepatic vena cava is completely exposed. The main trunk, including the middle and left hepatic veins, is now the only venous drainage of the liver. It is encircled and traction or temporary clamping permits complete outflow control of the liver, minimizing bleeding during liver transection. At this time, the intrahepatic access to the main right Glissonian pedicle is achieved with two small incisions: An incision is performed on the right portion of the caudate lobe and another anterior incisionismadeinfrontofthehilum.Anendoscopicvascular

Treatment Options in the Management of Thrombocytopenia in Patients Infected with HCV

) inpatients with chronic hepatitis has been associated with twofactors: the first is hypersplenism resulting from splenomegalyin portal hypertension [1]. The spleen continuouslysequesters one-third of circulating platelets, so thatsplenomegaly increases the fraction of platelets trapped inthe splenic sinusoids, especially when resulting from passivecongestion or an increase in venous portal pressure [1].Hypersplenism seems to be the most common cause ofthrombocytopenia associated with liver cirrhosis and portalhypertension.The second mechanism is related to the decreasedproduction of thrombopoietin, a hormone produced byhepatocytes, which regulates the development of themegakaryocyte. In cirrhosis, due to the reduction in the massof functioning hepatocytes, there can be a reduction ofthrombopoiesis in the bone marrow, leading tothrombocytopenia in the peripheral blood [1].In some situations, patients who are otherwise eligible forHCV treatment with interferon and ribavirin cannot be sotreated because their platelets counts are low, whichjeopardizes the treatment [2,3].Nevertheless, hepatitis C patients treated with interferon andribavirin also present a drop in the platelet count as a sideeffect [2,3].There is as yet no treatment consensus in the literature forthe management of these patients. We therefore present somerelated studies that address the management of these patients,in the pre-treatment and intra-treatment phases.Patients receiving interferon alpha or peginterferon alphacan present a 30-50% reduction in the baseline platelet count,and a dose reduction is necessary in approximately 4% of thepatients [2,3]. We should consider possible reduction of thedose when platelet counts drop to < 50,000/mm

Characterization of Malignant Portal Vein Thrombosis with Contrast-Enhanced Ultrasonography

We prospectively evaluated the effectiveness of contrast-enhanced ultrasonography (CEUS) for differentiation of benign versus malignant portal vein thrombosis (PVT). We studied a total of 43 patients with chronic liver disease, hepatocellular carcinoma-suggestive nodules and confirmed PVT, in whom the nature of the PVT was confirmed by follow-up imaging (US, computed tomography and/or magnetic resonance imaging) performed up to 6 mo after CEUS. PVT was assessed by US, Doppler US and CEUS with respect to vessel wall disruption and/or invasion, color Doppler vascularization, pulsed Doppler vascularization pattern and CEUS enhancement and vascularization pattern, and thrombi were classified as benign or malignant based on these findings. Follow-up studies revealed malignant PVT in 22 of the 43 patients (51%) and benign PVT in 21 patients (49%). CEUS findings were consistent with follow-up studies in 41 of the 43 patients (95%), with κ = 0.903 (p < 0.0001), sensitivity = 91% and specificity = 100%, indicating that CEUS can be confidently used to differentiate benign from malignant portal vein thrombosis in the setting of chronic liver disease.

Parâmetros dopplervelocimétricos na avaliação da perviedade da anastomose portossistêmica intra-hepática transjugular (TIPS): estudo prospectivo

OBJETIVO: Estudar as alteracoes hemodinâmicas consideradas normais apos a realizacao da anastomose portossistemica intra-hepatica transjugular (TIPS) e a eficacia dos parâmetros sugestivos de estenose do TIPS com o ultra-som Doppler. MATERIAIS E METODOS: Dezesseis pacientes foram avaliados de maneira prospectiva, no periodo de dezembro de 2001 a marco de 2003. As avaliacoes foram realizadas 24-48 horas apos o TIPS e a seguir em intervalos regulares de 30 dias, tres meses, seis meses e um ano, com ultra-som modo B, Doppler pulsado, Doppler colorido e de amplitude em diferentes pontos da protese relacionados ao TIPS. A angiografia foi realizada apenas para a confirmacao dos resultados e terapeutica pertinente. RESULTADOS: Ate o momento apenas os achados de fluxo continuo no terco proximal da protese e o gradiente de velocidade entre dois pontos da protese apresentaram significância estatistica para o diagnostico de estenose do TIPS (p < 0,001), mas outros diferentes criterios tambem estiveram presentes, porem sem significância estatistica. CONCLUSAO: O ultra-som Doppler e uma ferramenta eficaz no diagnostico da perviedade e das complicacoes secundarias a realizacao do TIPS, sobretudo da estenose. No entanto, e necessaria casuistica maior, a fim de determinar um conjunto de parâmetros que facilite o seguimento destes pacientes, reservando a angiografia apenas para o tratamento pertinente.