The choice of calcineurin inhibitor does not influence centrilobular necrosis after orthotopic liver transplantation.
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Biopsy↗
Biomedical subjects
L M Petrovic
Publications and source records attributed to L M Petrovic.
Activation of hepatic stellate cells in liver tissue of patients with fulminant liver failure after treatment with bioartificial liver.
We studied the explanted livers from 12 patients with fulminant hepatic failure who were treated with a bioartificial liver and subsequently underwent orthotopic liver transplantation and from 18 patients who underwent orthotopic liver transplantation without previous treatment. Ten normal livers were used as controls. In addition to morphologic evaluation, an immunohistochemical analysis was performed with the monoclonal antibodies for alpha-smooth muscle actin and proliferation marker Ki-67. The expression of these markers was graded semiquantitatively from 0 to 3+ in a blinded fashion. The zonal distribution of activated hepatic stellate cells was also evaluated. In all cases, the hepatic stellate cells were activated and expressed alpha-smooth muscle actin. In all patients with submassive or massive liver cell necrosis, the distribution of activated hepatic stellate cells was predominantly in zone 1 of the acinus (periportal area). In contrast, in cases with early nodular regeneration and no significant fibrosis, the activated hepatic stellate cells were distributed throughout the liver parenchyma, involving zones 2 and 3 of the acinus. Expression of the proliferation marker Ki-67 was graded 3+ in all patients treated with the bioartificial liver who had orthotopic liver transplantation and 2+ in patients who underwent orthotopic liver transplantation only.
Actins↗
Recurrent hepatitis C virus infection after orthotopic liver transplantation.
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Disease Progression↗
Posttransplant lymphoproliferative disease, monoclonal, Epstein-Barr virus related.
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Epstein-Barr Virus Infections↗
Inflammatory pseudotumor of the liver as the first manifestation of Crohn's disease.
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Adult↗
Successful treatment of Whipple disease diagnosed 36 years after symptom onset.
Whipple disease is a rare infectious disorder with multiorgan manifestations and a widely varied clinical presentation. Involvement of the small intestine with resultant malabsorption is a classic finding, although extraintestinal manifestations such as fever and arthralgias may precede gastrointestinal symptoms by many years. We describe a 63-year-old man in whom Whipple disease was diagnosed 22 years after his initial presentation (36 years after symptom onset) with lymphadenopathy, when a biopsy yielded nonnecrotizing granulomas. His recent symptoms included persistent fatigue, weight loss, fever, and arthralgias. Endoscopic biopsy specimens from the distal duodenum showed features consistent with Whipple disease, and Tropheryma whippelii DNA was detected in both the small bowel biopsy specimen and the blood specimen by polymerase chain reaction and DNA probe hybridization. His symptoms resolved with long-term co-trimoxazole therapy. We discuss the protean manifestations of Whipple disease, the difficulties in clinical diagnosis, and the recent advances in the molecular diagnosis of this disorder.
Anti-Infective Agents↗
Primary liposarcoma of the liver: a case report and review of literature.
Liposarcoma is a rare mesenchymal malignant tumor, which usually originates in the retroperitoneum and the extremities. Seven cases of primary liposarcoma of the liver have been previously reported. We present the eighth case, which occurred in an adult female patient. Primary liposarcoma of the liver, although extremely rare, must be considered in the differential diagnosis of a hepatic mass that develops in a noncirrhotic liver, especially in patients who are potential candidates for orthotopic liver transplantation. Liposarcoma is an absolute contraindication for liver transplantation.
Contraindications↗
Metastatic pancreatic adenocarcinoma to the heart diagnosed antemortem.
Pancreatic tumors frequently metastasize widely, though it is rare to diagnose pancreatic cardiac metastases in the antemortem state. We report an unusual case of metastatic pancreatic adenocarcinoma to the right atrium. Transesophageal echocardiography showed that the tumor was attached to the superior aspect of the right atrium, prolapsing through and obstructing the tricuspid valve in diastole and retracting back into the right atrium during systole. The tumor was excised, and histologic examination confirmed the presence of moderately differentiated adenocarcinoma with a papillary architectural pattern and with desmoplastic stroma, features comparable to the original primary pancreatic neoplasm.
Adenocarcinoma↗
Overview of hepatitis B and transplantation in the hepatitis B patient.
Hepatitis B is a disease that infects 300,000 people in the United States each year, resulting in 15,000-30,000 cases of chronic hepatitis. Outcomes include death; development of chronic carrier state, chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Hepatitis B surface antigen (HBsAg) carriers, especially those with cirrhosis, are at high risk for development of hepatocellular carcinoma. Histologically, chronic carriers of HBsAg may have a range of degree of tissue changes, ranging from normal, to varying degrees of portal or lobular inflammation, to significant cell injury with widespread necrosis, fibrosis and cirrhosis. Current histological grading systems reflect both graded inflammation and stage of fibrosis.
Carcinoma, Hepatocellular↗
Uterine pleomorphic rhabdomyosarcoma in a patient receiving tamoxifen therapy.
INTRODUCTION: Tamoxifen has been used as adjuvant therapy for the treatment of breast cancer. Its use has been associated with the development of proliferative endometrial lesions such as polyps, hyperplasia, and carcinoma. Mesenchymal tumors including malignant mixed mullerian tumors, endometrial stromal sarcomas, adenosarcomas, and leiomyosarcomas have been more recently described with tamoxifen use. CASE REPORT: This report describes the first case of a pure uterine rhabdomyosarcoma in a patient receiving tamoxifen therapy. DISCUSSION: Although uterine rhabdomyosarcomas are rare tumors and may arise de novo, we discuss the possible role of tamoxifen in the development of these mesenchymal tumors.
Antineoplastic Agents, Hormonal↗
Novel human malignancy-associated gene (MAG) expressed in various tumors and in some tumor preexisting conditions.
We have identified a novel human malignancy-associated gene (MAG) expressed in various malignant tumors including glioblastomas and hepatocellular carcinomas (HCCs) and in tumor preexisting conditions such as hepatitis C virus- and hepatitis B virus-induced liver cirrhosis. The expression of MAG was characterized using reverse transcription-PCR (RT-PCR), rapid amplification of cDNA ends PCR, RNA dot blotting, RNase protection assay, and Northern blot analysis. Rapid amplification of cDNA ends PCR yielded a 536-bp MAG fragment in HCC, macroregenerative liver nodules with dysplasia, and liver cirrhosis but not in normal liver or placenta. By RT-PCR, MAG expression was not found in 12 different normal tissues but found in 46 of 51 (90%) premalignant and malignant tissues of various sites. Embryonic liver and brain were positive for MAG expression together with tumors from the same organs, but the corresponding normal adult tissues were negative. By RNase protection assay, MAG mRNA was expressed in the HepG2 liver tumor cell line and in an ovarian carcinoma but not in normal liver. The estimated transcript size from Northern blot analysis was 8.8 kb. This novel gene may play a role in the progression of premalignant conditions and in the development of HCC and other cancers.
Adult↗
The application of image analysis and neural network technology to the study of large-cell liver-cell dysplasia and hepatocellular carcinoma.
Liver cell dysplasia (LCD) is considered a preneoplastic lesion, whose characterization and differentiation from hepatocellular carcinoma (HCC) and from the reactive changes seen in cirrhosis has been controversial. We studied 12 cases of LCD (large cell type) with image analysis techniques (IA) and compared the findings with those of HCC (n = 40), and a spectrum of non-neoplastic hepatic lesions including normal liver and cirrhosis (n = 49). A minimum of 200 Feulgen-stained nuclei were measured from each lesion with the CAS 200 image analysis system. The data were collected with the aid of CellSheet software. Thirty-four variables were measured, including geometric, textural, and photometric nuclear features and DNA ploidy. The data were analyzed with multivariate statistics and a backpropagation neural network (NN). Stepwise statistical analysis selected 22 variables that were statistically significant in the three groups with P values <.05. Various NN architectures were developed using these variables. The best NN architecture included a sigmoidal transfer function, 14 input, 16 hidden, and 3 output neurons. It trained to completion after 8,887 runs using 90% of the lesions. This NN yielded a 100% cross-validation rate for unknown cases. These data support the concept of LCD (large cell type) as a lesion that can be objectively distinguished from HCC and non-neoplastic liver. Our study also demonstrates the potential usefulness of IA for the evaluation of difficult histopathological problems.
Carcinoma, Hepatocellular↗
Hepatic angiomyolipoma: two case reports of caudate-based lesions and review of the literature.
Two case reports of hepatic angiomyolipoma, both originating in the caudate lobe, are reported with a review of the literature. The liver is the second most common site of angiomyolipoma, an uncommon benign tumor of mixed mesenchymal origin. It is commonly diagnosed following abdominal pain or as an asymptomatic mass discovered on abdominal ultrasound or computed tomography scan. Of 74 cases reported, the lesions ranged from 0.3 to 36 cm in diameter and are noted between the first and eighth decade, with predominant female predilection. The right lobe is the most common site, with lesions arising in the caudate lobe comprising only five cases. The natural history of the hepatic lesion is unknown. Malignant invasion or metastatic disease has not been documented. Hepatic and renal angiomyolipoma can occur concurrently (13 of 60 cases), although the majority are not biopsy proven. Multicentric hepatic disease occurs. The correlation between tuberous sclerosis and hepatic angiomyolipoma is not confirmed histologically and occurs rarely. These lesions have a characteristic radiographic appearance due to high fat content. Histologically, angiomyolipoma are characterized by an admixture of adipose tissue, blood vessels, and smooth muscle cells. These lesions cannot reliably be differentiated from a malignant lesion based on clinical history, radiologic examination, and/or pathologic interpretation. If clinical suspicion for malignancy is low, then careful observation with serial radiologic follow-up is performed. The treatment for a symptomatic or suspicious lesion is resection, if feasible. Liver transplantation may be considered for large or centrally located lesions not amenable to resection.
Adult↗
Comparison of histopathology in acute allograft rejection and recurrent hepatitis C infection after liver transplantation.
Recurrent hepatitis C infection after orthotopic liver transplantation (OLT) is frequent and may occur as early as a few weeks postoperatively. Early histopathological features of recurrent hepatitis C virus (HCV) infection may be modified by immunosuppressive therapy and can be difficult to differentiate from acute allograft rejection (AAR). Thus, we retrospectively compared histopathological features of liver biopsy specimens from two carefully selected patient groups: one with unequivocal recurrent hepatitis C, the other with unequivocal AAR. Index biopsy specimens obtained at the time of the appearance of liver test abnormalities after OLT and all serial liver biopsy specimens (2 to 13 per patient) were assessed under code and scored semiquantitatively for 44 histopathological variables. The index biopsy specimens from patients with recurrent HCV infection and AAR index biopsies (AAR-Ib) differed significantly (P < .05) for 11 features (10 features were statistically associated with AAR and 1 with early recurrence of HCV infection). Statistically significant features associated with AAR included bile duct injury with overlapping nuclei, lymphocytic infiltrates and necrosis, endothelialitis, portal inflammatory infiltrates containing eosinophils and polymorphonuclear leukocytes, hepatocyte mitoses, and zone 3 canalicular cholestasis. In contrast, the only statistically significant feature associated with early recurrent HCV was sinusoidal dilatation. Stepwise discriminant analysis showed that the presence of eosinophils in the portal inflammatory infiltrate, bile duct necrosis, and bile duct lymphocytic infiltrates were independently associated with AAR. However, serial biopsy specimens from patients with recurrent HCV infection showed statistically significant progression in scores for portal inflammation, portal lymphoid aggregates, and lobular inflammation. We conclude that (1) multiple histopathological features are associated with AAR; (2) early recurrent HCV infection is characterized by elevated alanine aminotransferase levels, positive HCV RNA by polymerase chain reaction (PCR), and absence of diagnostic histopathological features; and (3) serial biopsies are needed to demonstrate progression of histopathological features of recurrent hepatitis C.
Acute Disease↗
Lack of hepatocyte growth factor receptor (c-met) gene expression in fulminant hepatic failure livers before transplantation.
To gain insight into liver regeneration mechanisms in fulminant hepatic failure, we compared gene expression of hepatocyte growth factor, its receptor c-met, c-myc, and albumin in human normal (4 cases) and fulminant (14 cases) livers by reverse transcription-polymerase chain reaction. In normal livers, hepatocyte growth factor gene was not expressed, whereas c-met, c-myc and albumin genes were always expressed. In fulminant hepatic failure, hepatocyte growth factor gene was expressed in 1 of 14 cases, c-met in none of 14 cases, c-myc in 10 of 14 cases, and albumin in 3 of 14 cases. By immunofluorescence, c-met protein was revealed in normal but not in fulminant hepatic failure liver tissue. Liver tissue is unlikely to account for high hepatocyte growth factor plasma levels typical for fulminant hepatic failure. Lack of its receptor (c-met) expression may explain a poor response of fulminant hepatic failure livers to exogenous hepatocyte growth factor that normally promotes liver growth and regeneration.
Actins↗
Expression of HGF, its receptor c-met, c-myc, and albumin in cirrhotic and neoplastic human liver tissue.
Hepatocellular carcinoma (HCC) is a common type of cancer, with approximately 260,000 new cases each year, and liver cirrhosis is generally considered a major predisposing factor for HCC. However, specific changes of gene expression in liver cirrhosis and HCC remain obscure. The expression of genes for hepatocyte growth factor (HGF), its receptor c-met proto-oncogene, c-myc proto-oncogene, and albumin was analyzed. Gene expression was studied by PCR in seven normal human livers, nine cases of hepatitis C cirrhosis, 12 cases of alcoholic cirrhosis, two cases of liver adenoma, and 12 cases of HCC. HGF and c-met protein were revealed by immunofluorescent staining. HGF mRNA was not expressed in normal livers but was detected in adenomas, in 80% of HCC, and in some cirrhoses. Paraffin-embedded and fresh-frozen tissue samples yielded similar results. Immunohistochemical data correlated with PCR results regarding the overexpression of the HGF/c-met system in HCC. Albumin gene expression was decreased in HCC vs normal livers, consistent with altered function of tumor hepatocytes. The elevated expression of the HGF/c-met system in HCC may play a role in tumor development and/or progression. Tissue localization studies of HGF and its receptor c-met protein support the existence of both autocrine and paracrine mechanisms of action of HGF in HCC vs only a paracrine mechanism in normal liver.
Adenoma, Liver Cell↗
Hepatobiliary and pancreatic mucinous cystadenocarcinomas with mesenchymal stroma: analysis of estrogen receptors/progesterone receptors and expression of tumor-associated antigens.
Hepatobiliary and pancreatic mucinous cystadenocarcinomas with mesenchymal stroma are relatively rare neoplasms that occur preponderantly in women, suggesting a role for unidentified sex-specific factor(s) in the pathogenesis of these tumors. We used paraffin tissue immunohistochemical analysis with an appropriate panel of monoclonal antibodies to look for estrogen and progesterone receptors in two cases of hepatobiliary mucinous cystadenocarcinoma with mesenchymal stroma and one case of pancreatic mucinous cystadenocarcinoma. In all three of these cases, the nuclei of tumor stroma and, in the hepatic tumors, the nuclei of tumor epithelium, reacted with both antibodies. These data strongly suggest that a relationship to hormonal functions exists for these tumors. Because of the rarity of these tumors we also investigated the expression of a variety of oncoprotein antigens, epithelial antigens, and cytoskeletal antigens. The oncoprotein antigens, p53 and c-erbB-2, were focally expressed in hepatic and pancreatic tumor epithelium; bcl-2 was focally expressed in hepatic tumor epithelium. Keratin was strongly expressed in most epithelial cells. In addition, epithelial membrane antigen, carcinoembryonic antigen, and chromogranin were focally expressed in epithelial cells. Actin and vimentin were strongly expressed in most stromal cells but not in epithelial cells, and desmin expression was similar but less widespread.
Adult↗