Hepatocellular carcinomas in native livers from patients treated with orthotopic liver transplantation: Biologic and therapeutic implications

The gross and histopathologic characteristics of 212 nonfibrolamellar hepatocellular carcinomas (HCCs) discovered in native livers removed at the time of liver transplantation were correlated with features of invasive growth and tumor-free survival. The results show that most HCCs begin as small well-differentiated tumors that have an increased proliferation rate and induce neovascularization, compared with the surrounding liver. But at this stage, they maintain a near-normal apoptosis/mitosis ratio and uncommonly show vascular invasion. As tumors enlarge, foci of dedifferentiation appear within the neoplastic nodules, which have a higher proliferation rate and show more pleomorphism than surrounding better-differentiated areas. Vascular invasion, which is the strongest predictor of disease recurrence, correlates significantly with tumor number and size, tumor giant cells and necrosis, the predominant and worst degree of differentiation, and the apoptosis/mitosis ratio. In the absence of macroscopic or large vessel invasion, largest tumor size (P <.006), apoptosis/mitosis ratio (P <.03), and number of tumors (P <.04) were independent predictors of tumor-free survival and none of 24 patients with tumors having an apoptosis/mitosis ratio greater than 7.2 had recurrence. A minority of HCCs (< 15%) quickly develop aggressive features (moderate or poor differentiation, low apoptosis/mitosis ratio, and vascular invasion) while still small, similar to flat carcinomas of the bladder and colon. In conclusion, hepatic carcinogenesis in humans is a multistep and multifocal process. As in experimental animal studies, aggressive biologic behavior (vascular invasion and recurrence) correlates significantly with profound alterations in the apoptosis/mitosis ratio and with architectural and cytologic alterations that suggest a progressive accumulation of multiple genetic abnormalities

Assessment of proteolytic degradation of the basement membrane: a fragment of type IV collagen as a biochemical marker for liver fibrosis

<p>Abstract</p> <p>Background</p> <p>Collagen deposition and an altered matrix metalloproteinase (MMP) expression profile are hallmarks of fibrosis. Type IV collagen is the most abundant structural basement membrane component of tissue, which increases 14-fold during fibrogenesis in the liver. Proteolytic degradation of collagens by proteases produces small fragments, so-called neoepitopes, which are released systemically. Technologies investigating MMP-generated fragments of collagens may provide more useful information than traditional serological assays that crudely measure total protein. In the present study, we developed an ELISA for the quantification of a neoepitope generated by MMP degradation of type IV collagen and evaluated the association of this neoepitope with liver fibrosis in two animal models.</p> <p>Methods</p> <p>Type IV collagen was degraded <it>in vitro </it>by a variety of proteases. Mass spectrometric analysis revealed more than 200 different degradation fragments. A specific peptide sequence, 1438'GTPSVDHGFL'1447 (CO4-MMP), in the α1 chain of type IV collagen generated by MMP-9 was selected for ELISA development. ELISA was used to determine serum levels of the CO4-MMP neoepitope in two rat models of liver fibrosis: inhalation of carbon tetrachloride (CCl₄) and bile duct ligation (BDL). The levels were correlated to histological findings using Sirius red staining.</p> <p>Results</p> <p>A technically robust assay was produced that is specific to the type IV degradation fragment, GTPSVDHGFL. CO4-MMP serum levels increased significantly in all BDL groups compared to baseline, with a maximum increase of 248% seen two weeks after BDL. There were no changes in CO4-MMP levels in sham-operated rats. In the CCl₄model, levels of CO4-MMP were significantly elevated at weeks 12, 16 and 20 compared to baseline levels, with a maximum increase of 88% after 20 weeks. CO4-MMP levels correlated to Sirius red staining results.</p> <p>Conclusion</p> <p>This ELISA is the first assay developed for assessment of proteolytic degraded type IV collagen, which, by enabling quantification of basement membrane degradation, could be relevant in investigating various fibrogenic pathologies. The CO4-MMP degradation fragment was highly associated with liver fibrosis in the two animal models studied.</p

Investigation of Antithrombotic Drug Effects on Preventing Thrombosis Emerging in Gluteus Maximus Flaps before Anastomosis

Aim of this study was to investigate the effects of thromboprophylactic agents at pre-anastomotic period of thrombosis in gluteus maximus muscle flaps. Forty five male Sprague-Dawley rats that have 289 g average weight were randomly diveded into 9 experiment groups and, each group was consisted of five rats. The first group was a control (sham) and not treated with antithrombotic agents. The other groups were consisted of rats treated with SC heparin, SC LMWH, oral aspirin and the combinations of these groups with IV heparin, and only treated with IV heparin and flaps of these groups were washed with % 10 heparin solution. For the ninth group, we didn\'t give any thromboprophylactic agents but washed flaps with % 10 heparin solution. The presence of fibrinogen, vWf and the thrombomoduline were investigated in the flap tissues. A diffuse thrombosis was evaluated in the sham group. There was found the lowest thrombosis findings in SC heparin group. A mild to moderate degree of thrombosis was seen in the SC LMWH, oral aspirin or IV heparin injected group. In this animal model, preoperative SC heparin treatment has significant thrombroprophylactic effect when used alone but not in combination. [Med-Science 2012; 1(2.000): 90-102

Varicella-Zoster Virus-Induced Hepatitis in a Liver Transplant Recipient: A Case Report

PMID = 3098140

Varicella-Zoster Virus-Induced Hepatitis in a Liver Transplant Recipient: A Case Report

Infections after solid organ transplantation are a major cause of mortality and morbidity. Varicella-zoster virus (VZV) infection after solid organ transplantation is rare. Here we present a case presenting with acute hepatitis and shingles after a liver transplantation (LT). A 36-year-old male patient underwent a liver transplantation; 7 months later his liver function tests increased. An examination and test results revealed that he had VZV-induced hepatitis. After VZV treatment, his test results returned to normal levels. Hepatic involvement of VZV infection is rare, but it may be fatal in immunocompromised individuals. Early diagnosis and early initiation of antiviral therapy is important in the control of hepatitis and rare hepatotropic viruses in immunocompromised individuals

Comparison of conventional cytology and SurePath in split thyroid fine needle aspiration materials

Objective: The aim of the present study was to compare the cytomorphological features and cytopathological diagnoses in thyroid aspiration materials prepared by SurePath (R) (SP) and conventional cytology (CC)

Metástase cerebral de carcinoma hepatocelular após transplante de fígado

AIM: We report the case of a patient with hepatocellular carcinoma submitted to liver transplantation, who subsequently manifested tumor recurrence initially as brain metastasis. CASE DESCRIPTION: A 48-year-old male cirrhotic patient with hepatitis C infection, and two focal hepatic lesions, had a cytologic and histologic diagnosis of hepatocellular carcinoma. Before transplant, he was submitted to adjuvant treatment with a combination of arterial embolization and intratumoral ethanol injection. In the 3rd month post-liver transplantation, the patient developed headache, nausea and vomiting, without any neurological impairment. Brain computed tomography and magnetic resonance imaging identified an expansive hypervascular lesion with internal bleeding. Evaluation of the surgical explant revealed macroscopic invasion of portal vessels. CONCLUSION: Brain metastasis of a hepatocellular carcinoma after liver transplantation may occur. This metastasis may have occurred before or soon after the transplant. Patients with hepatocellular carcinoma, awaiting liver transplant, should be screened for cerebral metastasis. Vascular invasion may indicate hematogenic dissemination of the tumor. _________________________________________________________________________________________ ABSTRACT: OBJETIVO: Relatar o caso de paciente com carcinoma hepatocelular submetido a transplante de fígado, que subseqüentemente manifestou recurrência tumoral em cérebro após o transplante. DESCRIÇÃO DO CASO: Homem de 48 anos de idade, com cirrose hepática secundária à infecção pelo vírus da hepatite C, com duas lesões focais hepáticas diagnosticadas como carcinoma hepatocelular pela citologia e histologia. Antes do transplante, foi submetido a tratamento coadjuvante com embolização da artéria hepática e injeção intra-tumoral de etanol. No terceiro mês pós-transplante, o paciente apresentou cefaléia, náuseas e vômitos, sem déficit neurológico focal. Tomografia computadorizada e ressonância magnética de crânio identificaram lesão expansiva hipervascular com sangramento interno. Avaliação da peça cirúrgica do transplante de fígado evidenciou invasão tumoral macroscópica da veia porta. CONCLUSÃO: A metástase cerebral de carcinoma hepatocelular após transplante de fígado pode ocorrer antes ou logo após a cirurgia. Pacientes, em lista para transplante de fígado, devem ser investigados para presença de metástase cerebral. Invasão vascular pode indicar disseminação tumoral hematogênica