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G Cathomas

Publications and source records attributed to G Cathomas.

At least 37 records · Page 2Linked to original sources

[Liver transplantation and tumors: risk and chance].

Liver transplantation is the established therapy of choice for endstages of acute and chronic liver diseases of various aetiologies. The place of liver transplantation in the treatment of malignant liver disease, in particular hepatocellular carcinoma, remains, however, debated: liver transplantation for hepatocellular carcinoma achieves 5-year survival similar to that for other indications, and 5-year disease-free survival better than that following "curative" resection, provided certain criteria are fulfilled (one node max. 5 cm in diameter or max. 3 nodes each of max. 3 cm in diameter). This must be weighed against the uncertainties of preoperative staging and the shortage of donor organs. In contrast, cholangiocarcinoma has a poor prognosis after liver transplantation with 3- and 5-year survival rates below 20%. Only small, incidental, peripheral, intrahepatic cholangiocarcinomas in patients with primary sclerosing cholangitis seem to be an exception to this rule. Liver metastases indicate generalised tumour spread, and thus are not an indication for liver transplantation. Liver transplantation may be justified for liver metastases of neuroendocrine gastrointestinal tumours, provided the primary has been curatively resected and there is no extrahepatic spread. Finally, liver-transplanted (immunosuppressed) patients are at increased risk to develop malignant tumours. This includes in particular epithelial skin tumours, (EBV-associated lymphoproliferative diseases and (HHV8-induced) Kaposi's sarcoma.

Contraindications↗

Human herpes virus 8: a new virus discloses its face.

The human herpes virus 8 (HHV8) or Kaposi's sarcoma-associated herpes virus (KSHV) is present in all Kaposi's sarcoma, and the detection of the virus using polymerase chain reaction or in situ hybridization is a highly sensitive and specific diagnostic test for the diagnosis of this neoplasm. HHV8 is furthermore invariably present in primary effusion lymphoma (PEL) and has also been detected in patients with acquired immunodeficiency syndrome (AIDS)-associated multicentric Castleman's disease (MCD) as well as, to a lesser extent, in non-AIDS MCD. In contrast to Kaposi's sarcoma, in which the tumor cells show primarily latent HHV8 infection, a higher rate of lytically infected cells can be observed in MCD. Epidemiological surveys indicate that the seroprevalence for HHV8 parallels the risk of developing Kaposi's sarcoma--5-10% in the general population of the Western world but ranging up to 20-70% in homosexual human immunodeficiency virus (HIV)-infected patients, and the infection precedes the development of Kaposis's sarcoma. Finally, HHV8 has been reported in a number of other diseases, especially in multiple myeloma. However, the highly controversial role of HHV8 in these lesions has to be clarified. Based on the data available today, HHV8 can be assigned as a new human virus, associated with tumors.

Herpesviridae Infections↗

A spectrum of histopathologic findings in autoimmune liver disease.

We retrospectively studied 42 liver biopsy specimens from 39 patients who met serologic and histologic criteria of autoimmune liver diseases. We found 10 cases of overlap syndrome (OLS), 10 autoimmune cholangitis (AIC), 10 primary biliary cirrhosis (PBC), and 9 autoimmune hepatitis (AIH) type 1. The following results were obtained: (1) Granulomas and biliary duct lesions were more prominent in PBC and AIC than in OLS and AIH. (2) Bile duct loss was not observed in AIH cases. (3) Features of hepatocellular damage such as piecemeal necrosis, spotty lobular necrosis, and confluent necrosis, were much more prevalent in OLS and AIH than in PBC and AIC. (4) HLA-DR antigen expression by hepatocytes was more frequent in AIH and OLS, whereas the expression of the same antigen by the bile duct epithelium was more frequent in PBC and AIC. We conclude there is a morphologic spectrum in autoimmune liver diseases, in which PBC forms one end of the spectrum, AIH the other, OLS the middle but closer clinically and histologically to AIH than to PBC, and AIC, which seems to be an antimitochondrial antibody-negative subtype of PBC.

Adult↗

Beta-catenin mutations are frequent in human hepatocellular carcinomas associated with hepatitis C virus infection.

Hepatocellular carcinoma (HCC) is one of the most common fatal cancers worldwide. Hepatitis B virus and hepatitis C virus infections, exposure to aflatoxin, and excessive intake of alcohol have been identified as major risk factors. However, the molecular mechanisms underlying their development are still poorly understood. Recently, beta-catenin, one of the key components of the Wnt signaling pathway, has been found to be mutated in about 20% of HCCs, suggesting a role of the Wnt pathway in their development. In this study, we examined beta-catenin and APC mutations in 22 HCCs associated with HCV infection, using single-strand conformation polymorphism (SSCP) followed by direct DNA sequencing. beta-Catenin mutations were found in nine (41%) cases, but no APC mutations were found. beta-Catenin immunohistochemistry revealed nuclear accumulation of beta-catenin protein in all nine tumors with a beta-catenin mutation and two additional tumors without a mutation. These results suggest that activation of the Wnt signaling pathway by beta-catenin mutation contributes significantly to the hepatocellular carcinogenesis associated with HCV infection.

Adenomatous Polyposis Coli Protein↗

Gastric pouch acid secretion in response to physiologic digestive function.

OBJECTIVES: To evaluate acid secretion and histologic features of the gastric segment used for bladder replacement in bladder cancer. METHODS: Nine patients were investigated a mean of 36 months after gastric pouch surgery with modified shamfeeding and feeding. We determined urinary acidity, urinary pH, serum gastrin, and serum pancreatic polypeptide values and tried to find a relationship between feeding and acid secretion in the gastric pouch. In 6 patients, biopsy and histopathologic examination were performed. RESULTS: In 8 patients, urinary acidity increased after feeding following the rise of gastrin; in 1 patient no increase of gastrin or acidity was observed. In 7 patients, urinary acidity did not change after modified shamfeeding, indicating vagal denervation after surgery. This group showed a minimal urinary pH of above 4 after feeding. On the other hand, in 2 patients an increased acid secretion was observed after modified shamfeeding, indicating the possible presence of residual vagal innervation. In this group, the acid secretion in the pouch was higher, reaching the minimal pH level earlier after feeding. Histopathologic examination showed no major structural changes of gastric mucosa. CONCLUSIONS: Most patients are vagally denervated after gastric pouch surgery, and the gastric segment continues its original gastrointestinal function by a hormonal pathway. Our data indicate, however, that in some patients, the gastric pouch keeps a residual vagal innervation. We therefore suggest that nerve fibers present in the blood supply of the gastric segment be interrupted to avoid the complications associated with increased acid secretion of the gastric pouch.

Aged↗

Langerhans cell histiocytosis of the stomach with atypical morphological features.

We report the unique case of a 52-year-old patient with atypical morphological features of gastric Langerhans cell histiocytosis. The man was admitted because of increasing upper abdominal pain and weight loss. The upper gastrointestinal endoscopy showed a submucous, hemispherical tumor of the stomach wall along the lesser curvature. The tumor was completely removed and the patient was discharged 11 days later. Two months later, he died at home. The cause of death is unknown, because the autopsy was denied by the relatives. Macroscopically, the stomach showed a 4.5 x 2.5 cm large, spherical tumor of the lesser curvature of the corpus, which infiltrated the perigastric omenta and lymph nodes, the distal pancreas and the glissonian liver capsule. The vast majority of neoplastic cells were intensely positive for S-100 and CD1a. Typical Birbeck granules could be identified in almost all cells. Cell nuclei analyzed by flow cytometry showed an aneuploid peak, a feature typically associated with malignant disease.

Cytoplasmic Granules↗

Cytomegalovirus (CMV)-specific T cell immunity after renal transplantation mediates protection from CMV disease by limiting the systemic virus load.

The role of cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CTLs) and T helper cells (Th) in controlling CMV infection, as detected by antigenemia assay and polymerase chain reaction (PCR) in blood leukocytes, and CMV disease was investigated in 20 renal transplant recipients. Within 3 months after transplant, CMV-specific CTL and Th responses were demonstrable in 11 (55%) and 15 (75%) patients, respectively; CMV infection was detected by antigenemia and PCR in 19 (95%) patients each. During the month of first CMV detection, there was an inverse correlation between CTL response and antigenemia at >/=20 positive cells/105 leukocytes (P=.007) but no association with lower antigenemia levels or PCR positivity. CMV disease developed in 7 (35%) patients and was associated with high-level antigenemia but was inversely correlated with detection of CTLs (P=.04). After renal transplantation, CMV-specific CTLs limit the systemic virus load as reflected by antigenemia levels and thereby mediate protection from CMV disease.

Adult↗

Transmission of human herpesvirus 8 infection from renal-transplant donors to recipients.

BACKGROUND: Human herpesvirus 8 (HHV-8) has been detected in all forms of Kaposi's sarcoma, including transplantation-associated Kaposi's sarcoma. To investigate the possibility of transmission of HHV-8 through allografts, we measured the seroprevalence of HHV-8 before and after renal transplantation. METHODS: Using an enzyme-linked immunosorbent assay with the recombinant HHV-8 protein orf 65.2, we analyzed serum samples from 220 renal-transplant recipients for the presence of antibodies to HHV-8 on the day of transplantation and one year later. Positive results were confirmed by an indirect immunofluorescence assay that detects antibodies to latent antigen and by Western blotting. Follow-up lasted at least four years. RESULTS: The seroprevalence of HHV-8 in graft recipients increased from 6.4 percent on the day of transplantation to 17.7 percent one year after transplantation. Seroconversion occurred within the first year after transplantation in 25 patients, and Kaposi's sarcoma developed in 2 of them within 26 months after transplantation. Sequential serum samples were obtained from 10 of the patients with seroconversion, and in 8 of these patients, IgM antibodies to HHV-8 appeared within three months after transplantation. In the case of six patients who seroconverted, serum samples from the donors were available, and five (83 percent) tested positive for HHV-8. In a control group of eight patients who were seronegative at the time of transplantation and who received allografts from HHV-8-negative donors, none seroconverted within the year after transplantation. CONCLUSIONS: HHV-8 is transmitted through renal allografts and is a risk factor for transplantation-associated Kaposi's sarcoma.

Adolescent↗

High human herpesvirus 8 seroprevalence in the homosexual population in Switzerland.

The seroprevalence of human herpesvirus 8 (HHV-8) in the Swiss population was investigated. By enzyme-linked immunosorbent assay, sera reactive to the recombinant HHV-8 antigen orf 65.2 were found in 24% of human immunodeficiency virus (HIV)-positive patients without and in 92% of HIV-positive patients with Kaposi's sarcoma. Surprisingly, 20% of homosexual HIV-negative men, versus only 7% of heterosexual HIV-negative individuals and 5% of blood donors, had antibodies to HHV-8.

AIDS-Related Opportunistic Infections↗

Diagnosis of pulmonary Kaposi's sarcoma by detection of human herpes virus 8 in bronchoalveolar lavage.

Human herpes virus 8 (HHV8) DNA has recently been detected in sarcoma tissue of patients with Kaposi's sarcoma. HHV8 DNA could also be found in bronchoalveolar lavage (BAL) fluid of patients with tracheobronchial Kaposi's sarcoma. To determine the specificity, sensitivity and predictive values of HHV8 DNA detection in the BAL for the diagnosis of pulmonary Kaposi's sarcoma, 100 consecutive BAL were prospectively analyzed for the presence of HHV8 DNA using a nested PCR assay. In addition, 19 BAL samples of 14 AIDS patients with cutaneous or visceral Kaposi's sarcoma were retrospectively investigated. The prospective group consisted of 79 BAL performed in immunocompromised and of 21 BAL in nonimmunocompromised patients. Four patients of the prospectively analyzed group undergoing six BAL showed tracheobronchial Kaposi's sarcoma at five bronchoscopies. All of the five BAL samples performed in these patients with endoscopically visible Kaposi's sarcoma were positive for HHV8 DNA. Following chemotherapy and antiretroviral treatment tracheobronchial Kaposi's sarcoma was no longer detectable at a subsequent bronchoscopy and HHV8 DNA in BAL became negative in one patient. One BAL sample of a HIV-positive patient with no evidence of Kaposi's sarcoma was HHV8 DNA-positive. The sensitivity, specificity, positive and negative predictive values of HHV8 detection for the diagnosis of tracheobronchial Kaposi's sarcoma were 100%, 98.9%, 83.3%, and 100%, respectively. Twelve of 19 BAL samples of the retrospective group were HHV8 DNA-positive. In this group, 10 patients undergoing a total of 14 BAL suffered from pulmonary Kaposi's sarcoma. HHV8 DNA was documented in 10 of these 14 BAL samples. In three BAL of this group HHV8 DNA was positive, but pulmonary Kaposi's sarcoma was diagnosed at a later stage. In conclusion, the detection of HHV8 DNA in BAL is restricted to patients with Kaposi's sarcoma and is highly sensitive and specific for pulmonary involvement of Kaposi's sarcoma.

Adult↗

Distribution of human herpesvirus 8 DNA in tumorous and nontumorous tissue of patients with acquired immunodeficiency syndrome with and without Kaposi's sarcoma.

Human herpesvirus 8 (HHV-8) DNA is present in virtually all Kaposi's sarcomas (KSs). Conflicting results, however, exist with respect to the presence of HHV-8 in nontumorous tissue samples. To define the specificity and predictive value of HHV-8 DNA detection in KS, we analyzed autopsy-derived tissue samples from patients with acquired immunodeficiency syndrome (AIDS) with and without KS for the presence of HHV-8 DNA, using single-step and nested polymerase chain reaction. Semiquantitative analysis of HHV-8 DNA was performed by endpoint dilution assays. HHV-8 DNA was detected in 41 (100%) tumor tissue samples of KSs. According to nested polymerase chain reaction results, HHV-8 DNA was also present in 16 (32%) of 50 nontumorous specimens of patients with AIDS patients with KS and in 3 (2.7%) of 113 specimens of patients with AIDS without KS; it was absent in 26 autopsy tissues and 15 transurethral resected prostatic specimens of patients without AIDS. By use of a second, unrelated primer set, the presence of HHV-8 DNA was confirmed in 12 (63.2%) of 19 nontumorous samples and detected in another 6 (17.7%) of 34 samples tested. Significantly higher titers of HHV-8 DNA were found in tumorous than in nontumorous tissues samples (1.9 x 10(4) vs. 1.2 x 10(2); P < .05). Specificity and positive predictive values for the diagnosis of KS by detecting HHV-8 DNA in a given tissue sample were 56 and 65.1% in patients with manifest KS and 97.4 and 100% in patients without previously known KS. An increased specificity and a positive predictive value were observed when the presence of KS anywhere in a given patient was considered (92.9 and 77.8%, respectively). In conclusion, the detection of HHV-8 DNA is a sensitive test for the diagnosis of KS. Its specificity, however, might be lower because HHV-8 can be detected in histologically unaffected tissue of patients with KS.

Acquired Immunodeficiency Syndrome↗