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We studied the long-term effect of ileal transposition (IT) metabolic surgery on the hepatokines: retinol-binding protein-4 (RBP4), α-2-HS-glycoprotein (aHSG/fetuin-A), and fibroblast growth factor 21 (FGF21), C-reactive protein (CRP) plasma levels, glucose metabolism, body weight, liver histology, as well as total lipids concentration in muscle, liver, and fat tissue of obese Zucker (Crl:ZUC(ORL)-Leprfa) rats. 14 adult males were randomly submitted either to IT or SHAM (control) surgery. Pre-operative hepatokines plasma levels were not significantly different in rats submitted to IT or SHAM protocol. Three months after the procedures the plasma levels of RBP4, aHSG, FGF21, and CRP were significantly lower in IT-operated animals when compared to SHAM-operated group. Three and 12 weeks after the IT and SHAM surgery, the AUCOGTT were significantly lower than AUCOGTT before the surgery. HOMA-IR was lower in rats after IT surgery in comparison to the SHAM-operated rats. Muscle and liver total lipids concentration was reduced after the IT procedure when compared to pre-IT conditions. IT had a significant reductive impact on the body weight in comparison to SHAM surgery in the 4th, 6th, 8th, and 10th week after the surgery. We conclude that IT reduces hepatokines’ plasma concentrations, muscle and liver total lipids concentration but not the inflammatory processes in the liver of Zucker (Crl:ZUC(ORL)-Leprfa) rats.

Aim of the study Chronic hepatitis C (CHC) is a viral disease with metabolic disturbances involved in its pathogenesis. Adipokines may influence the inflammatory response and contribute to development of metabolic abnormalities in CHC. Visfatin exerts immunomodulatory and insulin-mimetic effects. The aim was to measure visfatin serum concentrations and its mRNA hepatic expression in non-obese CHC patients and to assess the relationships with metabolic and histological parameters. Material and methods In a group of 63 non-obese CHC patients (29 M/34 F) infected with genotype 1b aged 46.6 ±14.6 years, body mass index (BMI) 24.8 ±3.0 kg/m2, serum visfatin levels and its mRNA hepatic expression were examined and the subsequent associations with metabolic and histopathological features were assessed. Results Serum visfatin levels were significantly higher in CHC patients compared to controls (22.7 ±5.7 vs. 17.8 ±1.5 ng/ml, p < 0.001). There was no difference in serum visfatin and its mRNA hepatic expression regardless of sex, BMI, insulin sensitivity and lipids concentrations. There was no mutual correlation between serum visfatin and visfatin mRNA hepatic expression. Hepatic visfatin mRNA levels but not visfatin serum levels were higher in patients with steatosis (1.35 ±0.75 vs. 0.98 ±0.34, p = 0.009). Conclusions Serum visfatin levels may reflect its involvement in chronic inflammatory processes accompanying HCV infection. Increased visfatin mRNA hepatic expression in patients with steatosis seems to be a compensatory mechanism enabling hepatocytes to survive metabolic abnormalities resulting from virus-related lipid droplet deposition prerequisite to HCV replication.

Background The epithelial–mesenchymal transition (EMT) is a highly coordinated process observed during embryonic development and adult tissue repair. It is characterized by the loss of cell–cell adhesion and apicobasal polarity, and the transition to a cell type with a spindle-like phenotype able to migrate through the basal membranes. Methods This review article includes available date from peer-reviewed publications associated with the role of Notch signaling and Snail1 transcription factor in activation and regulation of EMT. Results Growing evidences in the past few years demonstrated a significant role of Notch in EMT activation. It is not surprising because this pathway is the nexus of a unique and versatile signaling network, that regulates and is regulated by a variety of cellular mechanisms highly dependent on the biological context—especially tissue microenvironment. This compartment sends signals promoting and regulating EMT, which usually acts as a transcriptional repressors. Among them, Snail1 has been shown to be crucial for cellular movement during cancer progression and metastasis. In cancer patients, increased level of Snail1 is usually connected with poor clinical outcome, probably due to downregulation of E-cadherin expression. Moreover, the continuous expression of E-cadherin during developmental EMT in Snail1-deficient mouse embryos clearly supports the idea that its ranscriptional repression is mostly related to Snail1 activity. Conclusion Cooperation of Notch signaling and Snail1 plays very significant role in such pathologies as wound healing and cancer development. Nevertheless, they are also involved in tissue embryonic development.

Background. The proper use of new medical tests in clinical practice requires the establishment of their value and range of diagnostic usefulness. While whole-exome sequencing (WES) has already entered the medical practice, recognizing its diagnostic usefulness in multifactorial diseases has not yet been achieved. Aims. The objective of this study was to establish usability of WES in determining genetic background of chronic cholestatic liver disease (CLD) in young patients. Methods. WES was performed on six young patients (between 17 and 22 years old) with advanced fibrosis or cirrhosis due to CLD and their immediate families. Sequencing was performed on an Ion Proton sequencer. Results. On average, 19,673 variants were identified, of which from 7 to 14 variants of an individual were nonsynonymous, homozygous, recessively inherited, and considered in silico as pathogenic. Although monogenic cause of CLD has not been determined, several heterozygous rare variants and polymorphisms were uncovered in genes previously known to be associated with CLD, including ATP8B1, ABCB11, RXRA, and ABCC4, indicative of multifactorial genetic background. Conclusions. WES is a potentially useful diagnostic tool in determining genetic background of multifactorial diseases, but its main limitation results from the lack of opportunities for direct linkage between the uncovered genetic variants and molecular mechanisms of disease.

Water-soluble polymer-drug conjugates were obtained and analyzed towards their potential use as prodrugs for two hydrophobic antipsoriatic agents, including methotrexate (MTX) and acitretin (AC). The conjugation efficacy of MTX decreased with a decreasing molar ratio of N,N-dimethylaminoethyl methacrylate (DMAEMA) repeating units in the polymethacrylic chains. Cytotoxicity of positively charged (from +5 to +10 mV) nano- and microparticles (3–1500 nm in DMEM at 37 °C) were estimated by in vitro MTT and Annexin-V apoptosis assays on Me45, NHDF, HaCaT and BEAS-2B cell lines. Further, cell cycle analysis revealed arrest in G0/G1 phase in melanoma cells, while neither apoptosis induction nor cell cycle arrest occurred in normal epidermal and epithelial cells. Tested conjugates displayed a novel cytostatic effect in Me45 cells and a pro-apoptotic effect in HaCaT cells. Epithelial BEAS-2B cells were the most sensitive to the tested conjugates and responded via induction of necrosis. Cell line models allowed for characterization of the biologically relevant potential action of pro-drugs. Additionally, a skin in vitro evaluation assay provided the first known evidence of side-effect reduction with pro-drug use. Histological examinations confirmed the lack of negative effects of conjugates on the skin and showed no irritating properties.

Background: Lichen sclerosus (LS) is an immune-mediated chronic dermatosis of perimenopausal women. Inflammatory infiltration has been suggested as a potential cause of LS changes in epidermis and dermis. Photodynamic therapy (PDT) is a specific noninvasive treatment based on detection and subsequent selective destruction of LS-affected tissues that are marked by a photosensitizer. Immunomodulatory and cytotoxic effects of PDT are responsible for inducing several immunologic reactions which leads to inflammatory condition improvement. The aim of the study was to determine the efficacy of photodynamic therapy for genital LS in correlation to protein expression involved in inflammatory infiltration – CD3, CD4, CD8, CD57, Granzyme B and Fascin. Material and methods: A group of patients has been treated for active LS disease, diagnosis was histologically confirmed in skin biopsies. The skin biopsies were taken and analyzed with antibodies: CD3, CD4, CD8, CD57, Granzyme B and Fascin before and after PDT treatment. Results: The study shows the efficacy of PDT in LS treatment including changes to CD3, CD4, CD57, Fascin, Granzyme B and the lymphocytic infiltration in skin sections. The proliferation index of CD4 did not differ before and after PDT. Conclusions: The PDT is a very effective therapeutic method in LS treatment.

Inflammatory bowel disease (IBD) is characterized by a chronic inflammation accompanied by procoagulation settings. However, tissue hemostasis in IBD patients was only incidentally reported. Accordingly, the current study characterizes changes in tissue hemostasis components in a colon inflammatory setting. Serial cryostat sections of endoscopic mucosal biopsy specimens taken from 26 consecutive IBD patients diagnosed de novo and normal colon resection specimens taken from 6 patients were immunohistochemically stained with monoclonal anti-human tissue factor (TF), tissue factor pathway inhibitor (TFPI), thrombomodulin (TM), as well as CD3 and CD68 positive cells. The hemostatic components studied differed significantly from the control subjects. Up-regulation predominated in the case of TF while down-regulation was mainly found in TM and TFPI in IBD. In the control sections, TF was observed in a few fibroblast-shaped cells in the lamina propria, while in the majority of IBD sections, TF positively stained small microvessels, infiltrating mononuclear cells and fibroblast-shaped cells tightly surrounding the colon crypts. Thrombomodulin intensively stained the endothelium of the small capillary vessels in the control, whereas such staining mainly accompanied infiltrating mononuclear cells of the IBD subjects. Tissue factor pathway inhibitor positively stained the endothelium of the small capillary vessels in the control group, whereas in the IBD group endothelial cells presented only weak TFPI staining. The mean number of CD3-positive lymphocytes in IBD was 23.3 ± 14.3, but the mean number of CD68-positive cells was 114.5 ± 55.8. In the control sections, it was 4.1 ± 2.4 and 39.6 ± 17.9, respectively. There was no relationship between CD3 and CD68 (+) cells and the hemostasis markers studied. The results of the current study indicate a shift of tissue hemostasis toward the procoagulant state irrespective of the severity of inflammatory infiltration. In addition, TF distribution in the colon sections of IBD patients may indicate a role in the restoration of the barrier function in injured intestinal mucosa.

Vaspin was found to modulate insulin resistance (IR) and to inhibit proinflammatory and profibrogenic agents. The aim of the study was to evaluate vaspin serum concentration prior to and after antiviral treatment and to assess its relationship with morphological alterations, IR and response to antiviral therapy. The study encompassed 75 non-obese, non-diabetic chronic hepatitis C (CHC) patients, 30 of whom underwent antiviral treatment. Serum vaspin levels decreased in CHC patients and was positively associated with fibrosis stage (r = 0.44, p = 0.001). Serum vaspin was significantly higher in patients with septal fibrosis/cirrhosis or periportal fibrosis compared to those with portal fibrosis or without fibrosis (F3-4 vs. F2 vs. F1 vs. F0, p = 0.012). A marked increase in the serum vaspin level occurred in patients with periportal or more advanced fibrosis (F0-1 vs. F2-4, p < 0.001). Serum vaspin levels were also positively related to steatosis grade (r = 0.32, p = 0.03). Antiviral therapy did not change serum vaspin levels, irrespective of its efficiency. Our study showed that the serum vaspin level is decreased in CHC patients with non-advanced fibrosis, but the virus seems to have no direct effect on this finding. Progressive fibrosis is associated with rise of the vaspin level and this adipokine may serve as a predictor of advanced liver fibrosis.

Visfatin is a new adipokine involved in several processes. The data concerning visfatin in chronic hepatitis C (CHC) is small. To assess visfatin serum concentration and to study its association with biochemical and morphological features in CHC. Seventy nonobese patients with CHC (Group 1) confirmed by the presence of serum hepatitis C virus (HCV)-RNA and 20 healthy volunteers (Group 2), similar in age and BMI with normal fasting glucose and lipid profile were included. Visfatin was significantly increased in Group 1 compared with Group 2 (55.6 +/- 23.1 vs 23.7 +/- 3.8 ng/mL; P < 0.001). Visfatin was negatively associated with necro-inflammatory activity grade (r = -0.36; P = 0.007). The lowest levels were found in patients with the most advanced inflammation: grades 3-4 - 46.8 +/- 17.1, grade 2 - 52.6 +/- 18.4 and grade 1 - 75.2 +/- 27.6 ng/mL; P = 0.017. A significant difference was also shown comparing patients with minimal inflammatory activity to the rest of the cohort (P = 0.009). Visfatin receiver operating characteristic curve analysis for different necro-inflammatory activity - grade 1 vs grades 3-4 with area under the curve 0.81 indicated a good discriminant power for differentiation of moderate/severe inflammation, with the cut-off set at 57.6 ng/mL (sensitivity 75%, specificity 90%, positive predictive value 0.90, negative predictive value 0.75). Serum visfatin concentration increases significantly in CHC patients. These findings suggest that visfatin is important in the pathogenesis of the inflammatory process in CHC. Visfatin may play a dual role as a pro-inflammatory or/and protective factor. The measurement of visfatin serum concentration may serve as an additional tool in distinguishing more advanced grades of the necro-inflammatory activity.

Introduction:Lichen sclerosus (LS) is a chronic skin and mucosa inflammatory disease. It affects mainly the female anogenital area especially in postmenopausal period. The main symptoms include pruritus, burning, pain, sometimes urinary problems, or difficulties in defecation. Usually, porcelain-white plaques are seen in the skin and mucosa. The etiology and pathogenesis of LS are still uncertain. There are some research studies on possible genetic predisposition, yet autoimmune, hormonal, or infectious factors are not excluded. The typical treatment of LS is mainly pharmacological, although the alternative treatment method used in LS is photodynamic therapy (PDT), which is noninvasive technique based on selective destruction of lesions. Our study is focused on molecule markers of vascularisation (CD34), nervous cell function (myelin basic protein [MBP]), keratinocyte function (CD44), and proliferation index (Ki67) in cases treated with photodynamic method.Materials and Methods:A group of 100 patients treated in our department was included in the study. All 100 women had LS on the basis of clinical and histological criteria. All the subjects underwent PDT. In all cases, skin biopsies were taken before and after treatment, and samples were analyzed with CD34, CD44, MBP, and Ki67 antibodies using immunohistochemical staining.Results:The study shows the high efficacy of PDT in LS treatment including beneficial changes to CD34, CD44, and MBP immunostained molecules. The Ki67 proliferation index did not change significantly. A significant increase of CD34 (microvessel density), MBP, and CD44 expression was confirmed in the histological images and in the partial or full remission of clinical objective and subjective symptoms.Conclusions:The PDT is a very effective therapeutic method in LS treatment.

Summary Immunohistochemical assessment of proliferation marker – Ki67 in nasal polyps tissue and in healthy nasal mucosa was performed. There was no statistically significant difference between percentage of Ki67 positive cells in nasal polyps and nasal mucosa. These cells were observed mainly in epithelial layer and few in subepithelial layer. In examined group Ki67 expression was higher in planoepithelial metaplasia. Assessment of cells proliferation processes could be sensitive and early indicator of neoplasmatic transformation. Examined subgroup in which Ki67 expression was also higher, was subgroup with eosinophilic infiltrations. Cells proliferation processes in nasal polyps tissue are very important occurrence and require further examinations.

Objective: The aim of this study was to evaluate prognostic importance of cell ploidy and proliferation activity in non-small cell lung cancers. Survivals were compared according to the following factors: sex, age, histology, grading, DNA ploidy, tumour size, T factor, N factor and operative procedure. Methods: In a group of 191 patients in whom cytofluorometric examinations had been performed on archival tumour specimens, postoperative recurrences were observed. Results: Postoperative recurrence was observed in 64 (64.6%) of 99 patients with aneuploid tumours and in 35 (38.0%) of 92 with diploid tumours (P , 0:001). Overall survival (OS) rates for the group of 92 patients operated for diploid non-small cell lung cancer (NSCLC) at 5 and 10 years were 62 and 51.1%, whereas of other 99, operated for aneuploid tumours 33.3 and 25.9%, respectively (P , 0:001). In the former group of patients disease-free survival (DFS) rates at 5 and 10 years were 58.7 and 51.4% but in the latter 29.3 and 26%, respectively (P ¼ 0:00014). Significant differences dependent on cell ploidy were also observed in OS and DFS rates of patients operated respectively for SCLC (P ¼ 0:0029; P ¼ 0:00318) and adenocarcinoma (AC; P ¼ 0:0241; P ¼ 0:02109). In general, the mean percentage of S-phase cells in non-small cell lung cancers was 14.0% (SD ¼ 13.1) in patients who survived 5 years, and 22.4% (SD ¼ 15.7) in those who had a recurrence or died (P , 0:001). Conclusions: In our opinion the most important finding of our work is that determination of cell ploidy in NSCLC provides a valuable supplement to the TNM stage when evaluating late results of the surgical treatment. However, the paper demonstrates that aneuploidy, although unfavourable, is not an independent prognostic factor in the group of patients with NSCLC and in the subgroups – both with squamous cell carcinoma and adenocarcinoma. Our results show also that the percentage of S-phase cells is an independent, unfavourable prognostic factor in patients treated surgically for non-small cell lung cancer and in the subgroup with squamous cell lung carcinoma. q 2003 Elsevier Science B.V. All rights reserved.

Antioxidant enzymes (AOEs), including superoxide dismutase isoenzymes (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) along with glutathione reductase (GR), reduced glutathione (GSH) and glutathione transferase (GST), are thought to be necessary for life process in all oxygen-metabolizing cells by removing reactive oxygen species (ROS). The biological significance of AOEs in transformed cells is still unclear, but their capacity to survive may be affected by changes in cellular process such as proliferation, invasiveness, migration, apoptosis and drug resistance. This review summaries the significance of antioxidant enzymes in cancer cell progression mainly in an in vitro context.

There is sufficient evidence that blood group related Lewis antigens are tumor-associated molecules. We have conducted immunohistochemical analysis of the expression of Lewis antigens in breast cancer tissue as an indicator of the degree of malignancy and as a prognostic factor. The studies were performed by examining 43 female patients diagnosed with invasive ductal carcinoma of the breast. Postoperative specimens were stained immunohistochemically using a panel of monoclonal antibodies (MAbs) specific for tumor-associated antigens: sialosyl LewisA, LewisA, LewisB, Lewisx, and LewisY. The aims of the study were to compare the appearance of metastases, degree of cancer stage (pTNM), and its histologic differentiation with the expression of Lewis phenotype. The evaluation of antigen expression was performed quantitatively and independently by two pathologists. Statistical significance was defined by Mann-Whitney test. The presented analysis of Lewis antigens showed higher expression of LeB and LeA (p = 0.03) in patients in stage N2 than in stage N1. The expression of LeB and LeY was higher in patients in stage T4 than in stage T1 (p = 0.02). No differences were observed for histologic differentiation. These data suggest that the expression of sialosyl-LeA and LeB antigens in breast cancer may predict metastases to lymph nodes.

Squamous cell carcinomas of the head and neck show frequent and complex chromosome aberrations, but little is known about the changes that occur during the metastatic process. To compare the accumulation of changes in primary and metastatic tumors we analyzed 19 pairs of primary larynx cancer tumors and their metastases. The most frequent changes were found at 3p, 3q, 5p, 9, and 13. Losses at 13, 8p, and 9q were more frequent in metastases than in primary tumors.

Angiogenesis can be described as a formation of new vessels from the existing microvasculature and is a process of great importance to the tumor development. Parathyroid tissue can trigger spontaneous induction of angiogenesis in vitro and in vivo models in a vascular endothelial growth factor (VEGF)–dependent manner. Autotransplantated parathyroid tissue after thyroidectomy is able to form new vasculature and produce parathormone, maintaining calcium homeostasis. A great amount of factors contributes to the process of new vessel formation in primary hyperparathyroidism, such as VEGF, transforming growth factor β, and angiopoietins. Studies demonstrated that markers for angiogenesis can be useful in distinguishing between parathyroid hyperplasia and neoplasia, due to the increased angiogenesis in parathyroid proliferative lesions compared with parathyroid adenomas. These factors include, inter alia, VEGF, VEGFR2, CD105, and fibroblast growth factor-2. Although these differences appear promising in the differential diagnosis, there is an overlap between benign and malignant parathyroid lesions and there is no definite cutoff value. Loss of heterozygosity and comparative genomic hybridization studies revealed chromosomal regions frequently altered in parathyroid tumorigenesis at 9p21, 1p21-22, 1p35-36, and 11q13. Therefore, immunohistochemistry and genetic testing should be an additional diagnostic marker in combination with the traditional criteria. A better understanding of angiogenesis in primary hyperparathyroidism could result in more precise assessment of diagnosis and more effective treatment, especially in those cases, in which the commonly used parameters are insufficient.

Introduction. Chemerin seems to be involved in pathogenesis of chronic hepatitis C (CHC). Hepatic expressions of chemerin and its receptor, chemokine receptor-like 1 (CMKLR1), in CHC have not been studied so far.Aim. To evaluatechemerinandCMKLR1hepatic expression together with serumchemerinconcentration in CHC patients and to assess their relationship with metabolic and histopathological abnormalities.Methods. The study included 63 nonobese CHC patients. Transcription ofchemerinandCMKLR1was assessed by quantitative real-time PCR, while serum chemerin was assessed by enzyme-linked immunosorbent assay.Results. Expression ofchemerinandCMKLR1was present in the liver of all CHC patients regardless of sex or age. This expression was not associated with necroinflammatory activity and steatosis grade, fibrosis stage, and metabolic abnormalities. There was a negative association between serum chemerin andchemerinhepatic expression (r= (−0.41),P= 0.006).Conclusion. The study for the first time confirmed a marked expression ofchemerinandCMKLR1in the liver of CHC patients. The study was performed using the homogenates of human liver tissue, so it is not possible to define whether hepatocytes or other cell types which are abundantly represented in the liver constitute the main source ofchemerinandCMKLR1mRNA.

A 72 year-old woman with primary hyperparathyroidism was operated for parathyroid crisis. PTH serum level was 808 pg/mL. During the operation, only two superior parathyroid glands were found. One was normal, and hypertrophy was revealed in the other. After the surgical procedure, PTH serum level was 726.5 pg/mL. Helical computer tomography examination showed a heterogeneous mass in the anterior mediastinum. The tumour was removed via a sternotomy approach. Histopathological examination revealed parathyroid carcinoma. PTH level dropped to 5.74 pg/mL. Cytofluorometric examination revealed diploidy (DI = 1) in both the hypertrophic and the unchanged upper glands, whereas parathyroid cancer was aneuploid. After the initial operation, the woman was discharged from the hospital on the 27th postoperative day. One year after surgical procedures, she is well. She has to take calcium.

It is unclear whether angiogenesis merely represents a homeostatic mechanism aimed at ensuring an adequate oxygen supply or one that exerts an additional pathogenic role leading to liver damage in chronic hepatitis. Chronic hepatitis C (CHC) patients present a proangiogenic profile of angiogenic markers. Adipokines not only regulate adipose tissue and glucose metabolism, but also influence inflammation, fibrogenic process and production of proangiogenic factors. On the basis of this evidence we aimed to assess the number of new blood vessels in lobules and portal tracts in the liver and evaluate the relationship between angiogenesis intensity and serum adipokine concentrations in CHC. Our study showed a positive association between serum vaspin and angiogenesis intensity in portal tracts and lobules in CHC patients (r = 0.41, p = 0.04; r = 0.46, p = 0.03; respectively). Serum visfatin was found to be negatively related to angiogenesis in portal tracts and lobules but only in females (r = -0.76, p = 0.03; r= -0.95, p0.001; respectively). In conclusion, the role of some adipokines in liver angiogenesis seems to be different in females than in males. Serum vaspin concentration seems to reflect intensity of liver angiogenesis in CHC. Further studies are necessary to better determine the role of adipokines in new blood vessel formation in CHC.

The most common histopathological classification of chronic hepatitis was determined by descriptive terms, which included a subjective factor of histopathological description. It might have caused a lot of interpretative discrepancies among diagnosticians dealing with chronic liver inflammation. These difficulties led sometimes to inappropriate treatment protocol, such as the use of interferon, or caused discrepancies in the morphological rating of treatment efficiency. The first attempt of rating liver specimens in an objective way was Histological Activity Index (HAI), reported in 1981 by Knodell et al. Subsequently, many locally used modifications have been created (Lindh, Scheuer, Batts&Ludwig, Ishak, Gabriel, METAVIR). It made chronic hepatitis classification much more objective and helped in statistical analysis of research results. New diagnostic criteria of chronic liver diseases prepared in 1984 by the World Congress of Gastroenterology and International Association for the Study of the Liver (IASL) prompted authors to update previously used classifications (International Working Party, 1994). The purpose of this study is to optimize the clinical data necessary in proper diagnosis, taking into account the new criteria of inflammatory activity, process of fibrosis and steatosis.

The skeletal system is the third most frequent (after lungs and liver) seat of metastases, and metastatic tumours are the most common bone malignancies. The diagnostic work-up of spinal metastases begins with the identification of the primary neoplastic site. Histological analysis confirms the final diagnosis. The work-up of bony metastases poses considerable difficulty and requires the collaboration of a number of specialists. Historical paraffin-embedded tissue samples were subjected to a routine procedure for the preparation of histology specimens. All specimens were independently reassessed by two diagnosticians. The samples of metastatic tumours of 57 patients whose primary tumour sites had not been identified were subjected to an immunohistochemical analysis based on monoclonal antibodies and assays for antigens associated with tumours most often producing bony metastases, i.e.:: PSA, thyreoglobulin, villin, cytokeratin 7, cytokeratin 8, cytokeratin 17, cytokeratin 18, cytokeratin 19, cytokeratin 20, CD 38, oestrogen and progesterone and Vimentin, LCA, HMB-45 and S-100. The monoclonal antibodies and assays were shown to be useful aids for the identification of the histology and location of the primary tumour in patients in whom routine histological assessments had failed to determine the histological type of tumour. In many cases, effective immunohistochemical work-up can contribute to halting the progression of the tumour by enabling qualification for appropriate surgical and oncological treatment.

The relationship between steatosis and angiogenesis in chronic hepatitis C (CHC) is unclear.The aim was to explain whether liver steatosis presence and its extent are associated with the number of new-formed blood vessels in lobules and portal tracts in CHC. 72 CHC patients infected with viral genotype 1b, 35 of whom had steatosis were evaluated. Monoclonal antibody anti-CD34 was used to identify new-formed blood vessels.Patients with steatosis had a significantly more advanced stage of fibrosis (p = 0.002) and higher inflammatory activity grade (p = 0.062). CD34 expression in portal tracts (CD34pt), lobules and fibrous septa (CD34lfs) and total (CD34) were significantly higher in patients with steatosis (p = 0.034; p = 0.021; p = 0.023, respectively). CD34, CD34pt and CD34lfs differed significantly between patients with various steatosis grade (p = 0.006; p = 0.009; p = 0.013, respectively). CD34 and CD34pt differed significantly between each steatosis grade whereas CD34lfs between grade 1 and 3. Fibrosis stage and inflammatory grade were positively associated with steatosis extent (p = 0.015; p = 0.003, respectively).Our observations suggest that extensive steatosis of liver parenchyma in CHC patients is associated with formation of new blood vessels in lobules and portal tracts. Understanding the relationship between steatosis, fibrosis and angiogenesis is therefore of great importance for the introduction of new therapeutic approaches and in the evaluation of CHC progression.

Adipocytokine profile seems to play a distinct role in the pathogenesis of chronic hepatitis C (CHC). Chemerin and vaspin are recently described adipocytokines with various suggested functions and potential to modulate inflammatory response and insulin resistance (IR). We assessed chemerin, vaspin and leptin serum concentration and studied their association with IR laboratory and morphological features in patients with hepatitis C. The study included 40 patients with hepatitis C and 20 healthy volunteers, similar in age and body mass index (43.6 +/- 11.6 vs 40.9 +/- 11.8 years and 25.0 +/- 4.1 vs 23.9 +/- 3.3 kg/m(2), respectively). Patients had to have a normal lipid profile, and diabetes was an exclusion criteria. Serum chemerin and leptin levels and IR were significantly higher in patients with hepatitis C when compared to the controls (P = 0.02, P = 0.02 and P = 0.02, respectively), whereas vaspin level was significantly decreased (P = 0.01). Serum chemerin was negatively associated with necro-inflammatory grade (r = (-0.49), P = 0.01). The lowest levels of serum chemerin were found in patients with moderate/severe inflammation (P = 0.03). Serum leptin tended to be up-regulated in patients with minimal inflammatory activity. Serum vaspin was higher, although not significantly, when fibrosis was more advanced. IR was positively associated with fibrosis stage (r = 0.33, P = 0.03). Serum chemerin and leptin were related to each other (r = 0.45, P = 0.02).Our findings support a complex interaction between the analysed adipokines and pathogenesis of inflammatory process in CHC. The role of chemerin and vaspin in pathogenesis of inflammatory response should be further investigated.

Aim: To analyze the relationship between pretreatment clinical or histological features and the levels of soluble platelet-endothelial cell adhesion molecule-1 (sPECAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), to determine their serum concentration in responders and nonresponders, to evaluate the behavior under antiviral therapy, to explain their relationship in response to therapy and to assess the association between these two molecules in chronic hepatitis C (CHC). Methods: The study analyzed 65 CHC patients, including 50 patients (Group 1) with marked fibrosis treated with peginterferon plus ribavirin, 15 patients without fibrosis (Group 2) and 13 healthy volunteers (the control group, Group 3). sPECAM-1 and sVCAM-1 levels were assessed by an immunoenzymatic method (ELISA) before and after therapy. Results: sVCAM-1 and sPECAM-1 serum concentrations increased significantly in CHC patients (p Conclusions: Hepatitis C virus (HCV) infection results in upregulation of sPECAM-1 and sVCAM-1. sPECAM-1 levels are related to necroinflammatory activity and may also identify patients with advanced fibrosis. The sPECAM-1 value was decreased by therapy but its measurement cannot predict therapy outcome and confirm HCV persistence. sPECAM-1 may influence VCAM-1 expression.

The skeletal system is the third most frequent (after lungs and liver) seat of metastases, and metastatic tumours are the most common type of bone malignancies. The aim of the study was to evaluate the influence of the type of neoplasm and method of treatment on the survival of patients with malignant spinal tumours.A retrospective analysis of 452 patients operated on between 2000 and 2004 in the Orthopaedic Surgery Hospital in Piekary Slaskie revealed a group of 203 patients whose histopathologic examination confirmed the presence of neoplastic foci in the spine. Data concerning the type of surgery and tumour location in 139 patients with the most frequent malignant spinal tumors were analyzed. The other information concerning subsequent treatment was analyzed in the Maria Skłodowska-Curie Oncology Centre and Institute in Gliwice. Patient deaths were verified in the Regional Administrative Office in Katowice.The most common types of neoplasms producing spinal metastases (in patients who underwent surgery) were: breast cancer, prostatic adenocarcinoma and kidney cancer. Multiple myeloma was the most frequent diagnosis among primary bone neoplasms. The survival of patients with multiple myeloma was statistically longer than the survival of patients with renal, breast and prostatic cancer metastases. It appears that, in the absence of contraindications, the best treatment for patients with spinal metastases is locally radical surgery combined with radiation therapy (a single teleradiotherapy session of 8 Gy). This treatment resulted in a statistically significant prolongation of life of the patients.The length of survival of patients with malignant spinal metastases is influenced by the type of neoplasm and locally radical surgery combined with palliative radiation therapy.

Dermatofibrosarcoma protuberans (DFSP) is a locally malignant neoplasm derived from fibrous tissue. Similar picture of such lesions to malignant tumors as well as to benign changes creates a risk of too gentle treatment and consequently of recurrence and malignant transformation of the lesions with possible remote metastases. Therefore accurate diagnosis and aggressive surgical treatment can prevent the recurrence of the tumor. Authors of the study present case report of 49-year-old woman with DFSP of vulvar area.

The data on the association between angiogenesis and mast cell density in cervical tumors and pretumoral conditions are scanty. The aims of the study were as follows: (1) to assess microvessel density and mast cell density in cervical lesions as well as in normal cervix samples and (2) to study the correlation between these variables. A hundred and one cervical samples were submitted to histopathological evaluation. Four study groups were distinguished: normal cervix samples, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and invasive squamous cell carcinomas. The immunohistochemistry was performed using anti-CD34, Anti-Human Mast Cell Tryptase, and Anti-Human Mast Cell Chymase antibodies. The microvessels and mast cells in the corresponding areas of tissue samples were counted by three observers using a multi-headed microscope. Microvessel density and density of mast cells that contain tryptase increased from normal samples through intraepithelial lesions to invasive carcinoma. The density of mast cells containing chymase was significantly higher in invasive carcinomas than in normal samples. In the entire study population, but not in the separated study groups, significant correlations between microvessel density and mast cell density were found. A specific mechanism of this interaction still needs to be evaluated.

Data regarding the assessment of angiogenesis in liver tissue in chronic hepatitis C (CHC) are rare. The study was performed to explain the association between the histopathological features and the number of new blood vessels in lobules and portal tracts in CHC. The second aim of the study was to define the localization of sprouting and pattern of formation of new vessels by estimating CD 34 antigen expression in the liver. The study involved 74 patients with CHC, infected with viral genotype 1b before antiviral therapy. The number of new-formatted blood vessels was positively associated with fibrosis stage and inflammatory activity grade in the liver biopsy from CHC patients. The relationship was evident in the portal tract, fibrous septa and periportal zones of lobules. The results suggest that inflammatory hepatocyte injury may promote neo-angiogenesis.

Percutaneous kidney biopsy is a widely applied diagnostic procedure providing with kidney tissue for microscopy.The assessment of diagnostic value of kidney tissue specimens gained by percutaneous biopsy and the assessment of that method's safety.119 percutaneous kidney biopsies performed on patients of Pediatric Clinic in Zabrze from 1998 through 2007 were analysed.Histopathological diagnosis was assessed in 107 cases (90%). The other 12 specimens (10%) were described by the pathomorphologist as non-diagnostic. In analysed group of patients serious complications were noted in 5 cases (4.2%): massive haematuria (in 2 cases), massive bleeding in perirenal space (in 3 cases including 1 resulting in nephrectomy).Percutaneous kidney biopsy is a valuable diagnostic procedure. Because of possible complications it is very important to comply with indications and contraindications established for that procedure.

Immunohistochemical assessment of proliferation marker--Ki67 in nasal polyps tissue and in healthy nasal mucosa was performed. There was no statistical significance difference between percentage of Ki67 positive cells in nasal polyps and nasal mucosa. These cells were observed mainly in epithelial layer and few in subepithelial layer. In examined group Ki67 expression was higher in planoepithelial metaplasia. Assessment of cells proliferation processes could be sensitive and early indicator of neoplasmatic transformation. Examined subgroup in witch Ki67 expression was also higher, was subgroup with eosinophilic infiltrations. Cells proliferation processes in nasal polyps tissue are very important occurrence and require further examinations.

The purpose of the experiment was to estimate an influence of portal blood arterialization in animals with tetrachloromethane-induced acute hepatic failure.Thirty-five pigs were divided into four groups: three groups of 10 and a control group of 5 animals. On day 1 of the experiment an intraperitoneal dose of 477 mg CCl4//kg body wt. in a suspension of corn oil was given to the trial groups to induce an acute hepatic failure. On day 3 after the intoxication all animals were operated on. Aortovenous splenic anastomosis without splenectomy, aorto-venous splenic anastomosis with splenectomy, and splenectomy procedure alone, were performed in groups I, II, and III, respectively. In the control group only laparotomy was performed. Histopathologic estimation of hematoxylin- and eosin-stained specimens and immunohistochemical analysis of regenerating hepatocytes by applying monoclonal serum for CK19, CD56, CD117 were carried out.Liver biopsies demonstrated no quantitative differences concerning the surface of damaged lobules between groups I, II, and III. The phenomenon of parenchyma regeneration was observed in both groups (with and without splenectomy procedure performed). Small stem cells could be observed mainly in the central part of lobules. The immunohistochemical analysis showed that part of the regenerating cells had CD56 and CD117 antigens' receptors, demonstrating no expression of antigen CK19. In the third group of animals (splenectomy without blood arterialization) neither the phenomenon of parenchyma regeneration nor the presence of cells of hepatoblast phenotype were observed.The arterialization of portal blood in pigs with acute hepatic failure triggered off the regeneration of damaged parenchyma through the colonization of impaired areas of lobules by small stem cells. The lack of the receptor for antigen CK19 could mean that the cells do not originate in bile duct epithelium.

The aim of this study was to evaluate correlations between DNA ploidy type, the immunostaining of cyclin D1, bcl-2 and the intensity of lymphocytic infiltration of the tumor microenvironment in relation to the histopathological G differentiation and pTNM classification. Thirty two patients were treated surgically for laryngeal cancer with total or partial laryngectomy in the Department of Otolaryngology Zabrze. The percentage of bcl-2 immunostaining was showed in 53% of the cases and was found to correlate with G differentiation and the patients' age. Cyclin D1 antigen stained positively in 24 cases (75%). Expression of cyclin D1 correlated with cancer stage. Cyclin D1 negative stain was found in T4-stage. DNA ploidy was examined in 19 cases. Aneuploidy was found in 5 cases only, while the rest were diploid. DNA ploidy value correlated with cyclin D1 expression. All paraffin sections were found to contain lymphocytic infiltrations of CD43 and CD45RO phenotype in the tumor front. Some cases showed high intensity of lymphocytic infiltrations of CD45RO phenotype. The intensity of CD43 lymphocytic infiltrations in the tumor front was related to the expression of cyclin D1 and bcl-2.

The authors present the connection between the hepatitis type B and C with connective tissue diseases, mainly with vasculitis. They underline the role of immunological complexes deposited in the blood vessels as a main pathomechanism of vasculitis. They describe the etiopathogenic role of the viruses of hepatitis B and C in the vasculitis. The authors present also the problem of extrahepatic symptoms during the hepatitis B and C and the therapeutical difficulties with they patients.

Idiopathic adult ductopenia is a rare disease characterized by chronic cholestasis related to an unexplained loss of the interlobular bile ducts. We report on a 43-year-old woman, whose clinical course of cholestatic disease was indolent and non-progressive, and laboratory abnormalities occurred intermittently. Histological examination of liver specimen showed absence of interlobular bile ducts, intensive proliferation of peripheral bile ductules and only minimal inflammatory portal response. Given the presence of microscopic non-specific chronic proctitis, hypothyroidism and antinuclear antibodies in serum we hypothesize that idiopathic adult ductopenia could be a variant of primary sclerosing cholangitis affecting exclusively small bile ducts.

The mechanism of multistage carcinogenesis initiated by environmental carcinogens produces clonal evolution of initiated cells to the stage of metastasis. However, the simultaneous co-existence of various cell clones is not excluded. The analysis of chromosome alterations appears to be the best method to assess the clonal composition of a tumor.Laryngeal tumor specimens and their corresponding metastases to the adjacent lymph nodes (20 pairs) were analysed by comparative genome hybridization (CGH).The profile of gains and losses of DNA copy number was found to be fairly similar in the primary tumor location and in its metastasis. In this study the most frequent losses were found on 3p, 5q, 9p, 13p, and 13q, while gains occurred in 1q, 3q, 5p and 11q. The gains and losses were found more frequently in metastasis than in primary tumor, except for the loss of 3p and the gain of 5p. The biological function of the latter chromosome alterations seems to be limited to tumor growth, rather than metastasis formation.A comparison of the profiles of chromosome alterations in primary tumor locations and metastases indicate that the progression of laryngeal cancer is connected with the clonal evolution of tumor cells.

The aim of this study was to evaluate semiquantitative and qualitative analysis of lymphocytic infiltrations in a neoplasm microenvironment in patients with laryngeal cancers and the correlation analysis between the intensitivity degree and composition of lymphocytic infiltration in foreseeing a survival time and probability of the appearance of lymph node metastases. Postoperative specimens from 43 patients (Upper Silesia region) operated on for laryngeal cancer in the 2nd ENT Department, Silesian Medical University in Zabrze between 1985 and 1995 all had unfavorable courses due to tumor recurrences. The patients’ ages ranged from 39 to 79 years (mean 57 years). Tissue specimens were subjected to routine processing. The degree of pathological changes was ascertained and immunohistochemical preparations of laryngeal tissue were prepared according to generally accepted methods. The following primary monoclonal antibodies were used: CD 3, CD 20, CD 43, CD 45 RO, CD 56. The distribution analysis of the intensity of the phenotype CD 43 evaluated the lymphocytic infiltration in relation to differentiation of the whole study group. The intensity of CD 43 cell infiltration increased in the group of patients with lymph node metastases. In patients with stage IV disease, a relationship was found between survival time and intensity of cell infiltrations with CD 43 and CD 45 RO lymphocytes. The influence of these two lymphocyte phenotypes in the patient subgroups – one after total laryngectomy with confirmed lymph node metastases and the other group without lymph node metastases – showed their prognostic value. Our analysis of lymphocytic infiltration, mostly of CD 43 cells, in the neoplasm microenvironment indicated a prognostic value for determining a shorter survival time and the possibility of lymph node metastases in patients with recurrences of cancer.

injury in hepatitis C and non-alcoholic steatohepatitis patients. The safety, tolerability, and pharmacokinetics (PK) of single and multiple oral dose administration of GS-9450 in healthy volunteers were studied. Gender and food effects were also evaluated. Methods: Two Phase I, randomized, double-blind, placebo-controlled studies were conducted to evaluate the PK of GS-9450 following single and multiple dose administration. Single ascending oral doses of 0, 5, 10, 20, 40, 80 and 120mg of GS-9450 were administered to 48 healthy male volunteers. Volunteers in the 40mg cohort who received the single dose in a fasted state also received GS-9450 after a high fat breakfast. Six female volunteers received GS-9450, 40mg, to evaluate the effect of gender on GS-9450 PK. In the second study, 24 volunteers received multiple daily doses of 0, 40, 80 and 120mg of GS-9450 over 15 days. Results: GS-9450 reached peak plasma concentrations (Cmax) at 0.5−3 hours (hrs) post-dose. GS-9450 was eliminated with median elimination half-lives (T1/2) of approximately 10 to 16 hrs across all dose levels. Systemic exposure to GS-9450 increased in a dose-proportional manner over the range of single and multiple doses. Only 2−4% of the dose was excreted unchanged as GS-9450 in urine consistent with metabolism of GS-9450 in the liver. Neither food nor gender had a significant effect on the PK of GS-9450. GS-9450 was well tolerated without serious or severe adverse events (AEs). The most frequently reported AE was headache. There was no clear relationship between dose and incidence, frequency, onset or duration of treatment-related AEs, which were transient and mild in nature. One male volunteer discontinued dosing due to development of a rash of mild severity. No clinically significant changes in laboratory data, vital signs, and ECG values were observed. Conclusions: The half-life of GS-9450 supports once-daily dosing and no evidence was found for a significant gender or food effect on GS-9450 PK. GS-9450 was well tolerated by healthy male and female volunteers.

The objective of this study was to examine the relationship between TGF-beta expression in steatotic liver and the stage and yearly progression rate of fibrosis in chronic hepatitis C (CHC) patients.We examined 44 CHC fatty liver patients, using 76 non-steatotic CHC patients as controls. The stage of hepatic fibrosis was assessed on a score scale. TGF-beta expression was determined with the use of monoclonal serum and the ABC three-step method.We demonstrated a positive correlation of steatosis with the stage of fibrosis (P0.05). No relationship of thiskind was found with the yearly progression rate of fibrosis (P0.09). In steatotic biopsies, TGF-beta expression index in portal spaces and lobules was found to be higher as compared to TGF-beta expression in biopsies without steatosis (P0.05).In CHC patients steatosis induces the development of fibrosis by elevating the hepatic expression of TGF-beta.