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C Poremba

Publications and source records attributed to C Poremba.

At least 19 recordsLinked to original sources
PubMed2006

[Transient elastography for diagnosing liver cirrhosis].

BACKGROUND AND OBJECTIVE: Detection of liver cirrhosis has numerous implications because of the potential sequelae of cirrhosis. Transient elastography (Fibroscan), was evaluated as a novel, non-invasive means of assessing cirrhosis by measuring liver stiffness. METHODS: 147 consecutive patients with different forms of liver disease and histologically determined stages of liver fibrosis were prospectively studied by transient elastography. 48 patients had liver cirrhosis. RESULTS: The number of transient elastographic measurements per patient was 12+/-4 (range 6 - 30). Valid elastography measurements were available for 135 out of 147 patients (92 %). The results of transient elastography correlated positively with the histological score of liver fibrosis (r = 0.8; 95 % CI: 0.72 - 0.85; p < 0.001). Areas under the receiver operating characteristic curve (AUROC) were 0.91 for > or = F3 fibrosis (95 % CI: 0.85 - 0.96) and 0.94 for cirrhosis (95 % CI: 0.90 - 0.98). Using a cut-off value of 13 kPa for detection of liver cirrhosis a sensitivity of 90 %, a specificity of 82 %, a positive predictive value of 71 % and a negative predictive value of 95 % were obtained. CONCLUSIONS: Measuring liver stiffness by transient elastography proved to be an easy method to assess liver cirrhosis. In combination with clinical signs, ultrasound and biochemical markers noninvasive diagnosis of liver cirrhosis will be further improved.

Adolescent↗
PubMed2006

Suppression of KCMF1 by constitutive high CD99 expression is involved in the migratory ability of Ewing's sarcoma cells.

High CD99 expression levels and rearrangements of the EWS gene with ETS transcription factor genes characterize the Ewing's sarcoma family of tumors (ESFT). CD99 is a cell surface glycoprotein whose engagement has been implicated in cell proliferation as well as upregulation and transport of several transmembrane proteins in hematopoietic cells. In ESFT, antibody ligation of CD99 induces fast homotypic cell aggregation and cell death although its functional role in these processes remains largely unknown. Here, using an RNAi approach, we studied for the first time the consequences of modulated CD99 expression in six different ESFT cell lines, representing the most frequent variant forms of EWS gene rearrangement. CD99 suppression resulted in growth inhibition and reduced migration of ESFT cells. Among genes whose expression changes in response to CD99 modulation, the potassium-channel modulatory factor KCMF1 was consistently upregulated. In a series of 22 primary ESFT, KCMF1 expression levels inversely correlated with CD99 abundancy. Cells forced to express ectopic KCMF1 showed a similar reduction in migratory ability as CD99 silenced ESFT cells. Our results suggest that in ESFT, high CD99 expression levels contribute to the malignant properties of ESFT by promoting growth and migration of tumor cells and identify KCMF1 as a potential metastasis suppressor gene downregulated by high constitutive CD99 expression in ESFT.

12E7 Antigen↗
PubMed2005

Endosonographic and histopathological staging of extrahepatic bile duct cancer: time to leave the present TNM-classification?

OBJECTIVES: The discrepancy between high rates of sensitivity, specificity, and accuracy for intraductal ultrasonography (IDUS) in extrahepatic bile duct carcinoma and the failure to depict different wall layers as defined by the TNM classification have not yet been elucidated sufficiently. METHODS: In a prospective study, endosonographic images were correlated with histomorphology including immunohistochemistry. Using IDUS, we examined fresh resection specimens of patients who had undergone pancreato-duodenectomy. For histological analysis, the formalin-fixed and paraffin-embedded specimens were stained by hematoxylin-eosin, elastica-van-Gieson, and immunohistochemically by smooth muscle-actin. To confirm our hypothesis, further cases from the archives were analyzed histopathologically and immunohistochemically. RESULTS: The various wall layers of the extrahepatic bile duct as described by the International Union Against Cancer are neither histomorphologically nor immunohistochemically consistently demonstrable. Especially, a clear differentiation between tumor invasion beyond the wall of the bile duct (T2) and invasion of the pancreas (T3) by histopathological means is often not possible. Endosonographic images using high-resolution miniprobes similarly confirm the difficulty in imaging various layers in the bile duct wall. CONCLUSIONS: Most adaptations made by the sixth edition of the TNM classification accommodate to the endosonographic and most of the histopathological findings as demonstrated in our study. In contrast to the new edition, however, our findings suggest to combine T2- and T3-staged tumors into one single class leading to clarification, and improved reproducibility of histopathological staging.

Aged↗
PubMed2004

[Molecular pathology in hereditary colorectal cancer. Recommendations of the Collaborative German Study Group on hereditary colorectal cancer funded by the German Cancer Aid (Deutsche Krebshilfe)].

Although twin studies indicate that inherited genetic factors contribute to about 35% of colorectal cancers (CRC), the exact genetic background has currently been elucidated in only 5-10% of cases. These comprise several hereditary cancer predisposition syndromes that present with a high number of syn- or metachronous neoplasms within an affected person and/or family. Many of these tumors exhibit typical histopathological changes. In general, one should discriminate between cancer syndromes associated with adenomatous and non-adenomatous (i.e., hamartomatous) polyps, the latter being quite rare. The patient's age often serves as a substantial hint to hereditary cancer. The next step of diagnostic work-up includes analysis of microsatellite instability (MSI) together with immunohistochemical detection of a loss of expression in one of the most frequently affected mismatch repair genes (MSH2, MSH6; MLH1, PMS2). Finally, the molecular demonstration of a gene mutation in the blood or germline is the most expensive and tedious procedure. This requires a signed informed consent from the patient after appropriate genetic counseling.

Colonic Neoplasms↗
PubMed2003

Papillary mesothelioma of the peritoneum in the absence of asbestos exposure.

BACKGROUND: Malignant mesothelioma of the peritoneum is a very rare neoplasm, commonly associated with asbestos exposure and often rapidly fatal. Well Differentiated Papillary Mesothelioma of the Peritoneum (WDPMP) is regarded as a less aggressive variety of the tumor. Progressive ascites is often the only clinical manifestation of the disease and differentiation of WDPMP from benign mesothelial hyperplasia or adenocarcinoma is difficult. PATIENTS AND METHODS: Here we report the case of a 45-year-old patient who presented with ascites but without evidence of portal hypertension, liver disease or abdominal malignancy. On diagnostic laparoscopy small tumor nodules were found to cover the parietal peritoneum and the greater omentum and histopathologically corresponded to papillary mesothelial hyperplasia with minimal nuclear atypia. Histochemically biopsies were positive for Calretinin, Cytokeratins and Epithelial Membrane Antigen (EMA). Based on these findings the diagnosis of WDPMP was made and the patient was closely followed without primary cytostatic therapy. CONCLUSIONS: Progressive ascites was the only clinical symptom in this patient, while liver disease, portal hypertension and gastrointestinal malignancies were ruled out by clinical, laboratory and imaging techniques. Laparoscopic biopsy revealed WDPMP to be the underlying disease. Immunocytochemistry is required to establish the diagnosis of this rare malignant disorder which is even more uncommon in the absence of a history of asbestos exposure. Due to the indolent course of WDPMP therapy should only be initiated when signs of rapid tumor progression become apparent.

Asbestosis↗
PubMed2003

Secretory carcinoma of the breast: a genetically defined carcinoma entity.

Secretory carcinomas (SBC) are characterized by their characteristic histomorphology and more favorable prognosis compared to invasive ductal carcinoma of usual type (IDC). On this basis, 13 SBCs are evaluated by molecular and immunohistochemical (IH) methods. 13 SBCs and 4 IDCs were analyzed for ETV6-NTRK3 gene fusion by reverse transcriptase-polymerase chain reaction (RT-PCR) and by Fluorescence in situ Hybridization (FISH). 8 of 13 microdissected SBCs with evaluable DNA were evaluated for genetic alterations (GA) by comparative genomic hybridization (CGH). IH included estrogen-receptor (ER), progesterone-receptor (PR), Her-2/neu and Ki-67 (MIB-1) in all 13 cases. Molecular and immunohistochemical results in SBCs were compared with previous data regarding immunohistochemical and molecular characteristics of IDCs. 12 of 13 (92 %) SBC cases, but not IDCs expressed the ETV6-NTRK3 fusion gene which encodes a chimeric tyrosine kinase. Retroviral transfer of ETV6-NTRK3 (EN) into murine mammary epithelial cells resulted in transformed cells that readily formed epithelial tumors in nude mice. CGH revealed an average of 2.0 GAs (range 0-6), including recurrent gains of chromosome 8q and 1q and losses of 22q. Four SBCs were positive for ER and 2 were positive for PR. The mean MIB-1-labeling index was 11.4% (range: <1-34%). Her-2/ neu protein overexpression was detected in 1 case (score 3+). Compared to previous findings in IDCs, SBCs are characterized by the recurrent expression of ETV6-NTRK3 fusion gene, a relatively low number of GAs, low proliferative rate, infrequent Her-2/ neu protein overexpression and a lower rate of steroid hormone receptor expression. These results support the hypothesis that SBCs have immunohistochemical and genetic features that specifically distinguish them from IDCs.

3T3 Cells↗
PubMed2002

High-dose interferon alpha-2a with ribavirin and amantadine in naïve chronic hepatitis C patients--results of a randomized, prospective, pilot study.

BACKGROUND: Hepatitis C viral kinetic studies have demonstrated the increased anti-viral effect of higher than standard dosages of interferon and of daily treatment schedules. AIM: To compare, in a prospective, randomized, controlled trial, the efficacy and safety of high-dose interferon-alpha therapy vs. standard-dosage interferon-alpha therapy, in a triple therapy combination with ribavirin and amantadine. METHODS: Previously untreated patients with chronic hepatitis C were randomized to the standard interferon-alpha group (n = 15), receiving thrice weekly 6 MU interferon-alpha for 12 weeks, followed by 3 MU interferon-alpha for 36 weeks, or the high-dose interferon-alpha group (n = 15), receiving daily 9 MU interferon-alpha for 4 weeks, followed by 6 MU (weeks 5-8), 3 MU (weeks 9-12) and 1.5 MU (weeks 13-48) interferon-alpha. All patients were given ribavirin (1000-1200 mg) and amantadine (200 mg) daily for 48 weeks. RESULTS: At the end of treatment and after the 24-week follow-up period, serum hepatitis C virus RNA was undetectable in eight (53%) and six (40%) patients treated with standard-dosage interferon-alpha, respectively, compared with 11 (73%) and 10 (67%) treated with high-dose interferon-alpha, respectively (not significant). The safety profile of both treatment regimens was similar. Severe adverse events leading to withdrawal from the study occurred in one patient (7%) in each group, and in both groups one patient (7%) was lost during therapy for unknown reasons. CONCLUSIONS: The findings suggest that, although the difference between the response rates of standard and high-dose interferon-alpha regimens (within a triple anti-viral therapy combination) did not reach statistical significance, there was a clear trend towards a higher response with high-dose interferon-alpha therapy and an equal safety profile.

Adult↗
PubMed2002

Population-based genetic alterations in Ewing's tumors from Japanese and European Caucasian patients.

BACKGROUND: The incidence of Ewing's tumors (ETs) is lower in Asians or African-Americans than in Caucasians. PATIENTS AND METHODS: Japanese ETs were available for analysis of chromosomal aberrations by comparative genomic hybridization (n = 16) and for expression of chimeric EWS transcripts by reverse-transcriptase polymerase chain reaction (n = 11). These results in Japanese patients were compared with those of 62 ETs in European Caucasian patients registered in the European Intergroup Cooperative Ewing's Sarcoma Study. RESULTS: Japanese patients with ET had lower overall survival (P = 0.0446) and relapse-free survival (P = 0.0371) compared with European Caucasian patients. Ten of 11 Japanese ETs and 31 of 62 European Caucasian ETs had type I (EWS exon 7 to FLI1 exon 6) fusion transcripts. In Japanese ETs, the median numbers of chromosomal aberrations were 2.0 and 6.0 in 11 primary tumors and five relapsed tumors, respectively. In European Caucasian ETs, the median number of changes were 2.5 and 5.0 in 52 primary and 10 relapsed tumors, respectively. Frequent gains were 8q (38%), 8p (31%) and 12q (25%) in Japanese ETs and 8q (52%), 8p (48%) and 12q (19%) in European Caucasian ETs. Frequent losses were 19q (44%), 19p (38%) and 17p (25%) in Japanese ETs and 16q (21%), 19q (18%) and 17p (15%) in European Caucasian ETs. The incidence of losses of 19p (P = 0.0215) and 19q (P = 0.0277) were significantly higher in Japanese ETs than in European Caucasian ETs. An amplification (1p33-p34) was observed in only one Japanese ET. CONCLUSIONS: Japanese patients with ET in this study had a worse prognosis than European Caucasian patients. In molecular genetic analyses, Japanese ETs had a higher frequency of loss of chromosome 19 than European Caucasian ETs. Different genetic aberrations may explain the different incidences and prognoses of ET between Caucasian and Japanese patients.

Adolescent↗
PubMed2002

Endoscopic transpapillary biopsies and intraductal ultrasonography in the diagnostics of bile duct strictures: a prospective study.

BACKGROUND: In bile duct strictures, examination of wall layers by intraductal ultrasonography (IDUS) performed during endoscopic retrograde cholangiopancreatography (ERCP) may be diagnostically useful. METHODS: In the present study 60 patients with bile duct strictures of unknown aetiology were examined preoperatively by ERCP, including transpapillary biopsies and IDUS. Histopathological correlation was available for all patients undergoing these procedures. RESULTS: Postoperative diagnosis revealed 30 pancreatic carcinomas, 17 bile duct cancers, three gall bladder cancers, and 10 benign bile duct strictures. Using endoscopic transpapillary forceps biopsies (ETP), a correct preoperative diagnosis was achieved in 36 of 60 patients (60% of cases). Among the 50 malignant tumours, preoperative diagnosis by ETP revealed a sensitivity of 52% and a specificity of 100%. ERCP supplemented by IDUS allowed for correct preoperative diagnosis in 83% of cases (50 of 60 patients), which was significantly higher than the accuracy of ETP (p=0.008). By combining ETP with IDUS, a correct preoperative diagnosis was made in 59 of 60 patients resulting in an accuracy rate of 98%. CONCLUSIONS: Because of its low accuracy, exclusive use of ETP is not a reliable diagnostic tool for a definitive preoperative diagnosis of bile duct strictures. By combining IDUS and ETP with ERCP however, preoperative diagnostic accuracy can be improved substantially.

Adolescent↗
PubMed2001

Alternative lengthening of telomeres is associated with chromosomal instability in osteosarcomas.

Telomere maintenance is regarded as a key mechanism in overcoming cellular senescence in tumor cells and in most cases is achieved by the activation of telomerase. However there is at least one alternative mechanism of telomere lengthening (ALT) which is characterized by heterogeneous and elongated telomeres in the absence of telomerase activity (TA). We evaluated the prevalence of TA, gene expression of telomerase subunits and ALT in relation to telomere morphology and function in matrix producing bone tumors and in osteosarcoma cell lines and present evidence of a direct association of ALT with telomere dysfunction and chromosomal instability. Telomere fluorescence in situ hybridization (T-FISH) in ALT cells revealed elongated and shortened telomeres, partly in unusual configurations and loci, dicentric marker chromosomes and signal-free chromosome ends. Free ends give rise to end-to-end associations and may induce breakage-fusion-bridge cycles resulting in an increased number of complex chromosomal rearrangements, as detected by multiplex-FISH (M-FISH). We propose that ALT cannot be seen as an equivalent to telomerase activity in telomere maintenance. Its association with telomere dysfunction and chromosomal instability may have major implications for tumor progression.

Adult↗
PubMed2001

Monoclonality in normal epithelium and in hyperplastic and neoplastic lesions of the breast.

The clonal nature of neoplastic lesions such as invasive breast cancer and ductal carcinoma in situ (DCIS) has been widely proven by several proliferative, genetic or other malignancy-associated markers. The aim of this study is to clarify whether benign hyperplastic lesions such as ductal hyperplasia of usual type (DH) and papilloma can be distinguished from neoplastic lesions such as DCIS by X-chromosome inactivation analysis. Clonal analysis was performed using a polymerase chain reaction-based assay for non-random X-chromosome inactivation of the human androgen receptor gene (HUMARA). Formalin-fixed and paraffin-embedded archival tissue of ten DCIS, sixteen DH, nine papillomas, and seven normal terminal ductal lobular units (TDLUs) was laser-microdissected to avoid contamination with surrounding tissue. All of the cases analysed revealed a monoclonal origin. Furthermore, in one of these cases, opposite X chromosomes were inactivated within the same breast. X-linked inactivation analysis clearly demonstrates that, at least in the breast, monoclonality is not restricted to neoplastic processes. The data support the hypothesis that the mammary gland is organized into distinct stem cell-derived monoclonal patches and that TDLUs are monoclonal in origin. Any proliferative lesion arising within such a pre-existing clonal patch should therefore be clonal, irrespective of whether it originates from one or more patch cells. Thus, X-chromosome inactivation analysis cannot be considered a valid method for distinguishing between neoplastic and hyperplastic breast lesions.

Breast↗
PubMed2001

Genetic imbalances revealed by comparative genomic hybridization in Ewing tumors.

Ewing tumors are characterized by reciprocal translocations involving the EWS gene on 22q12 fused to ETS transcription-factor family members. Little is known about further aberrations contributing to tumor development and progression. Sixty-two frozen tumors with known EWS rearrangements (52 primary tumors, 10 relapses) of ET patients registered in the EICESS protocol were analyzed by comparative genomic hybridization (CGH). The median number of changes in 52 primary and 10 relapsed cases was 2.5 and 5.0 per tumor (P = 0.153). Frequent abnormalities included gains of chromosomes 8, 12, 20, and 1q and losses of 16q and 19q. Neither number nor type of aberration was associated with histology, tumor size, disease stage, tumor localization, or histologic tumor response to chemotherapy. Among the 52 primary tumors, 26 with Type I fusion (EWS exon 7 to FLI1 exon 6) and 26 with other fusion types had a median of 2.0 and 3.0 aberrations per tumor, respectively (P = 0.031). Combinations of gains of chromosomes 8 and 12, gains of chromosome 20, and either gains of 8q or 18q and losses of 16q and 17p frequently occurred. The cumulative overall survival (OAS) was different between 35 patients with <5 aberrations and 13 patients with > or =5 aberrations (P = 0.009). Univariate analysis showed that patients with gains of 1q, 2q, 12, and 20 or losses of 16q and 17p had significantly lower OAS than those without aberrations. By multivariate analysis, loss of 16q (relative risk [RR] = 5.3; P = 0.0006) was an independent prognostic factor.

Adolescent↗
PubMed2001

Ductal invasive G2 and G3 carcinomas of the breast are the end stages of at least two different lines of genetic evolution.

Ductal invasive grade (G) 2 and G3 carcinomas represent the majority of invasive breast cancers. Previous morphological and cytogenetic studies have provided evidence that ductal invasive G2 carcinoma may originate from at least two different genetic pathways. The aim of this study was to evaluate further the heterogeneity of G2 breast cancer in comparison with G3 cancers by cytogenetic and quantitative analysis. To this end, 35 cases of ductal invasive G2 and 42 cases of ductal invasive G3 carcinomas were investigated by means of comparative genomic hybridization (CGH) and these findings were correlated with DNA ploidy status, mitotic activity index (MAI), mean nuclear area (MNA), volume per lumen (VPL), and clinico-pathological parameters. The findings of this study demonstrate that ductal invasive G2 carcinomas, in contrast to ductal invasive G3 carcinomas, have to be interpreted as the morphological end stage resulting from two different cytogenetic and morphological pathways; the loss of 16q material is the cytogenetic key event in the evolution of a subgroup of this entity. By correlating genetic alterations with DNA ploidy status, an extended morphology-based cytogenetic progression model is presented, with early and late genetic alterations in the pathogenesis of breast cancer. The correlation with MAI gives rise to the hypothesis that these different genetic pathways significantly differ in their proliferation rate. Further studies will be required to elucidate which genes contribute to an altered proliferation rate in these subgroups and to the associated prognosis.

Breast Neoplasms↗
PubMed2001

Ductal epithelial proliferations of the breast: a biological continuum? Comparative genomic hybridization and high-molecular-weight cytokeratin expression patterns.

According to current concepts, benign proliferative breast disease (BPBD) is a direct precursor of breast cancer, in a spectrum ranging from ductal hyperplasia to overtly invasive carcinoma. In this study, comparative genomic hybridization (CGH) was used to screen ductal hyperplasia and other BPBD lesions and ductal carcinoma in situ (DCIS) for common genomic abnormalities, to test the relationship between these hyperplastic and neoplastic lesions. Immunohistochemistry for cytokeratin 5/6 was used as a diagnostic adjunct to distinguish ductal hyperplasia from DCIS. A total of 42 cases of BPBD comprising ductal hyperplasia of the usual type (n=14), papilloma (n=22), tubular adenoma (n=3), and adenosis (n=3), as well as 52 cases of DCIS, were studied. All cases of BPBD consistently displayed the presence of a subpopulation of cytokeratin 5/6-expressing basal-type cells within the proliferative lesion, whereas all of the non-high-grade and most of the high-grade DCIS lesions lacked cytokeratin 5/6-positive cells. Whereas gross genomic alterations, as determined by CGH, were undetectable in BPBD, distinct genetic changes characterized all cases of DCIS, with one exception. These results confirm the usefulness of cytokeratin 5/6 immunohistology in the diagnosis of BPBD and neoplastic breast lesions and support the view that BPBD and DCIS are not closely related entities and that BPBD is not an obligate direct precursor of DCIS.

Adenoma↗
PubMed2001

Reassignment of the EPB4.1 gene to 1p36 and assessment of its involvement in neuroblastomas.

OBJECTIVES: EPB4.1 has been previously mapped to human chromosome 1p33-p34.2. In contradiction to this chromosomal location, we have mapped EPB4.1-1p36 by using fluorescence in situ hybridization and radiation hybrid mapping. In neuroblastomas, deletions of the telomeric end of chromosome 1 (1p36) are the most common genetic aberration. METHODS: We investigated whether genetic aberrations of EPB4.1 can be detected in some neuroblastomas by analyzing 72 tumours for EPB4.1 mutation, expression, and alternative splicing pattern. Furthermore, EPB4.1 protein from a neuroblastoma cell line was studied for its subcellular localization. RESULTS: Sequence changes could be detected in 14 out of 72 neuroblastomas, including missense, silent, and intronic changes. Duplex RT-PCR analysis revealed a subset of 11 tumours expressing significantly low levels of EPB4.1. Significant EPB4.1 sequence changes that were detected included an exon 4 G/A missense mutation (amino acid: V/I) that was shown to be associated with absence of wild-type EPB4.1 expression (3 tumours), an exon 8 G/A missense mutation (V/M) (1 tumour), and an intronic sequence change that was shown to be associated with the presence of an aberrant transcript (1 tumour). Splicing pattern analysis revealed that all EPB4.1 transcripts from tumours exclude exon 3, a splicing pattern for generating the 135 kDa isoform. EPB4.1 cDNA cloned from a neuroblastoma cell line produced a 135-kDa protein with a cytoplasm/membrane localization. CONCLUSIONS: Out of 72 neuroblastomas we have identified 11 tumours with impaired EPB4.1 expression and 5 tumours with significant sequence changes. We also found that the 135 kDa isoform is the main EPB4.1 product in neuroblastoma. EPB4.1 cDNA from a neuroblastoma cell line produced a 135-kDa protein and displayed a cytoplasm/membrane localization in transfected cells.

Alternative Splicing↗
PubMed2001

Caspase activation correlates with the degree of inflammatory liver injury in chronic hepatitis C virus infection.

Hepatitis C virus (HCV) infection is a major cause of liver disease characterized by inflammation, cell damage, and fibrotic reactions of hepatocytes. Apoptosis has been implicated in the pathogenesis, although it is unclear whether proteases of the caspase family as the central executioners of apoptosis are involved and how caspase activation contributes to liver injury. In the present study, we measured the activation of effector caspases in liver biopsy specimens of patients with chronic HCV infection. The activation of caspase-3, caspase-7, and cleavage of poly(ADP-ribose)polymerase (PARP), a specific caspase substrate, were measured by immunohistochemistry and Western blot analysis by using antibodies that selectively detect the active truncated, but not the inactive precursor forms of the caspases and PARP. We found that caspase activation was considerably elevated in liver lobules of HCV patients in comparison to normal controls. Interestingly, the immunoreactive cells did yet not reveal an overt apoptotic morphology. The extent of caspase activation correlated significantly with the disease grade, i.e., necroinflammatory activity. In contrast, no correlation was observed with other surrogate markers such as serum transaminases and viral load. In biopsy specimens with low activity (grade 0) 7.7% of the hepatocytes revealed caspase-3 activation, whereas 20.9% of the cells stained positively in grade 3. Thus, our results suggest that caspase activation is involved in HCV-associated liver injury. Moreover, measurement of caspase activity may represent a reliable marker for the early detection of liver damage, which may open up new diagnostic and therapeutic strategies in HCV infection.

Adult↗
PubMed2001

Common bile duct obstruction due to candidiasis.

Biliary obstruction with its wide range of potential causes (e.g. neoplastic lesions, gallstones and inflammatory processes) is a common disease in gastroenterology. Although infections with Candida and other fungal species have increasingly been recognized in patients with certain predispositions, fungal involvement of the biliary tract is extremely rare. We report the case of a male patient with a past history of long-time mechanical ventilation and who was referred to our department with cholangitis. Endoscopic retrograde cholangio-pancreatography (ERCP) of the septic patient revealed a high-degree stenosis of the distal common bile duct with a prestenotic dilation which was strongly suspicious of an underlying malignancy. Control ERCP revealed a beads-like deformation of the intra- and extrahepatic bile duct system which was compatible with chronic secondary sclerosing cholangitis. Examining the bile duct system with a balloon catheter, a long tubular. filamentous structure with several branches at its sides could be extracted and was assessed histologically to be a Candida conglomerate. Candida colonization of the bile duct was confirmed by microbiological analysis of aspirated bile.

Aged↗