Background and Aims: Hepatic steatosis seems to be a risk factor for poor response to interferon and ribavirin therapy in patients with chronic hepatitis C. The aim of this study was to determine presence of hepatic steatosis in chronic hepatitis C and its influence on early virological response in patients treated with combined antiviral therapy (pegylated interferon and ribavirin). Methods: We studied 96 patients treated at Gastroenterohepatology Department, in the period of four years (2005-2009). There were 71 males and 25 females enrolled in this study. 72 patients had genotype 1, 5 patients had genotype 2, 17 patients had genotype 3 and 2 patients had genotype 4. Liver histology was evaluated in order to establish presence of inflammation, fibrosis and steatosis. HCV RNA levels in sera were measured by real time PCR. Early virological response (EVR) was defined as negative serum HCV RNA at week 12. In order to measure the effect influence of steatosis on early response to therapy, as well as genotype and response to therapy, we calculated relative risk and the corresponding p-value after 12 and 48 weeks. Results: The overall rate of EVR was 70%. The rate was significantly lower in the group with steatosis, regardless of the presence of micro or macrosteatosis, amounting to 60%. Serum cholesterol level was significantly higher in females than in males (7.4±0.7 vs. 5.1±0.3 mg/mL). The values of relative risks (and p-values) for effect of steatosis on the response are RRS12=8.4615 (2.87E-05), and RRS48=0.9844 (0.7399), while the values for the effect of genotype to therapy were RRG12=1.3378 (0.7543), and RRG48=3.5862 (0.2709). Conclusions: Our findings suggested that hepatic steatosis may have a strong influence on interferon therapy response in the sence that it is eight times more probable to not respond in the presence of steatosis. The presence of steatosis was highly associated with progressive disease and failure to achieve the EVR; therefore it can be a predictor of poor response to antiviral therapy.

Early detection and treatment of preneoplastic lesions represents an obvious option to reduce morbidity and mortality from lung malignancies. Until now, radiological detection, sputum cytology, and autofluorescence have shown limited effectiveness as screening methods. Novel technologies such as Narrow Band Imaging (NBI) are showing promising results, but new studies are still needed to evaluate their use as screening methods. Together with early detection, adequate methods of lesion treatment, such as argon plasma coagulation, are needed. This case report concerns a 45-year-old man who was referred for bronchoscopy after his annual checkup. Using NBI technology, a preneoplastic lesion was identified, and treated using argon plasma coagulation. Our experience has shown us that both NBI screening and argon plasma coagulation are very promising, easily implemented, methods.

Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a natural inhibitor of matrix metalloproteinases (MMPs). Aim of this study was to assess the immunohistochemical expression of TIMP-1 in invasive breast carcinomas, and to examine its association with classical clinico-pathological parameters, oestrogen receptor, progesterone receptor and Her-2/neu protein expression. Immunohistochemistry was used to determine the expression of TIMP-1 on 38 paraffin-embedded breast tissue specimens - 18 with invasive ductal carcinoma, 10 with invasive lobular carcinoma, and 10 specimens from patients with fibrocystic breast disease. TIMP-1 protein was immunodetected in the carcinoma cells, fibroblasts and inflammatory cells of the stroma in 92,9%, 65,8%, and 65,8% of cases, respectively. TIMP-1 protein expression in carcinoma cells showed positive correlation with TIMP-1 protein expression in peritumoural fibroblasts (p=0,010). Positive peritumoural fibroblast TIMP-1 expression was associated with histological tumour type with higher frequency in ductal carcinomas (p=0,023). Negative association was found between TIMP-1 protein expression in carcinoma cells and HER-2/neu nuclear staining (p=0,005). TIMP-1 may be particularly useful as a predictive marker in breast carcinoma when evaluated along with HER-2/neu protein being a promising indicator of favourable prognosis in breast carcinoma.

Tissue inhibitor of metalloproteinase- (TIMP-) is a natural inhibitor of matrix metalloproteinases (MMPs). Aim of this study was to assess the immunohistochemical expression of TIMP- in invasive breast carcinomas, and to examine its association with classical clinico-pathological parameters, oestrogen receptor, progesterone receptor and Her-/neu protein expression. Immunohistochemistry was used to determine the expression of TIMP- on  paraffi n-embedded breast tissue specimens  with invasive ductal carcinoma,  with invasive lobular carcinoma, and  specimens from patients with fi brocystic breast disease. TIMP- protein was immunodetected in the carcinoma cells, fi broblasts and infl ammatory cells of the stroma in ,, ,, and , of cases, respectively. TIMP- protein expression in carcinoma cells showed positive correlation with TIMP- protein expression in peritumoural fi broblasts (p=,). Positive peritumoural fi broblast TIMP- expression was associated with histological tumour type with higher frequency in ductal carcinomas (p=,). Negative association was found between TIMP- protein expression in carcinoma cells and HER-/neu nuclear staining (p=,). TIMP- may be particularly useful as a predictive marker in breast carcinoma when evaluated along with HER-/neu protein being a promising indicator of favourable prognosis in breast carcinoma.

We report a case of exceedingly rare cutaneous neoplasm with histological features of malignancy and uncertain biological potential. The nodular, darkly pigmented facial tumor with central exulceration, size 12 x 10 x 7 mm, of the skin 61-year-old man preauricular left was completely exised. Histologically tumor consists of atypical squamous cells, which express signs of moderate to significant pleomorphism, mitotically active, with foci forming of parakeratotic horn cysts ("pearls"). Characteristically tumor also consists of large number of atypical melanocytes with multifocal pattern, inserted between atypical squamous cells, and which contain large amount of dark brown pigment melanin. Immunohistochemically, squamous cells stain positively with keratin (CK116), melanocytes were stained with S -100 protein, HMB 45, and vimentin, but failed to stain with CK 116. To our knowledge this is the sixth reported case in world literature. The follow-up time of four years no evidence of recurrence or metastasis, similar all reported cases, but it is too short period in estimation to guarantee a benign course. However, it appears that this group of neoplasm may have different prognosis from pure squamous carcinoma or malignant melanoma.

The aim of the study was to define the distribution of p53, bcl-2 and Ki-67 proteins in the inflammatory-regenerative and dysplastic lesions of the colon mucosa. The relationship between the presentation of p53, bcl-2 and Ki-67 proteins and the intensity of the inflammatory-regenerative and dysplastic lesions in the colon flat mucosa was investigated as well. Biopsy specimens from 270 patients were examined: 74 were classified as inflammatory-regenerative and 196 as dysplastic lesions (108 mild, 58 moderate, and 30 severe dysplasia). The expression of all three proteins was assessed on the basis of location, quantity, and intensity of immunostaining, by counting antigen positive cells, in comparison with normal mucosa and adenocarcinoma. p53 protein appears only in sporadic cases (6.6%) of severe dysplasia. Bcl-2 expression appears significantly (p<0.005) more often in cases of mild dysplasia (61.1%) compared to inflammatory-regenerative mucosa (14.8%). In cases of mild dysplasia, bcl-2 positive cells were spreading from the lower third to the middle third of the crypts. Bcl-2 expression was maintained through the stadiums of moderate and severe dysplasia (75.8%), where antigen positive cells were found all along the crypts. A significant increase (p<0.005) in the expression of nuclear protein Ki-67 was noticed in the stadiums of moderate (labelling index =26.3) compared to mild dysplasia (labelling index=16.7), and severe (labelling index=36.7) compared to moderate dysplasia, where the zone of cellular proliferation was widen along the whole crypt length. In the process of the development of epithelial dysplasia in the flat mucosa of colon a degree of the gene p53 alteration is low and appears only in sporadic cases of severe dysplasia. Mutation of the bcl-2 gene is involved in the genesis of the lesion but not in its progression to carcinoma. Increased expression of Ki-67 protein speaks in favour of an increased cellular proliferation which, together with the above mentioned mechanisms, is involved in the process of occurrence and progression of epithelial dysplasia in the flat mucosa of colon.

The aim of this study was to investigate expression of cyclin D1, bcl-2, p53, Ki-67 and HER-2 proteins in 14 cases of non-small cell lung cancer and to establish their correlation to classical clinico-pathological findings, and alleged prognostic value to estimate biological potential of tumor. Retrospective pilot study of the surgically treated non-small cell lung cancer biopsy specimen, paraffin embedded, used immunohistochemical method to demonstrate expression of cyclin D1, bcl-2, p53, Ki-67 and HER-2. Protein quantification was performed by the semi-quantitative method. Achieved results were correlated with classical clinico-pathological parameters, like tumor size, histological type, differentiation level, presence of vascular invasion and metastasis in regional lymph nodes. Out of 14 cases of non-small cell lung cancer, squamous cell carcinoma was found in 7 patients, giant cell carcinoma in 3, adenocarcinoma in 2, and 1 case of pleomorphic and mucoepidermoid carcinoma. Expression of cyclin D1 was not found, while expression of HER-2 and bcl-2 protein was established in one cases each. p53 expression was noted in 8 cases (57,1%). Statistically positive significant correlation (p<0,05) was found among: presence of lymphovascular invasion to tumor tissue and appearance of nodal metastasis; proliferation Ki-67 index and level of tumor differentiation, i.e. size of tumor. Other investigated parameters showed no significant statistically dependence. p53 expression was not correlated to any of the investigated parameters what might imply the possibility that there is an independent pathway of this protein expression. Negative expression of bcl-2 protein points out to possibility that it is not included into process of tumor apoptosis, as well as that proteins cyclin D1 and HER-2 are not included into processes of the tumor genesis. Since the proliferative activity of the tumor, measured by the expression of Ki-67, is correlated to the gradus and size of the tumor mass, Ki-67 protein can be of a prognostic value to determine biological potential of non-small cell lung cancer.

Gastrointestinal stromal tumors (GIST) are neoplasm of mesenchymal origin that usually begins in cells of the wall of the gastrointestinal tract. It can be benign or malignant. In this report, we have presented a case of malignant GIST with uncommon site of metastasis. This is of interest because of three reasons. Firstly, metastases to the testis are extremely rare. However, metastases to distally localized organs are not commonly associated with GIST, and finally, to our knowledge this is the first case of malignant GIST metastasis to the testis reported in the world.

The aim of the study was to verify the presence of mutated tumor suppresser gene p53 in intestinal mucosa with histologically confirmed premalignant lesions and gastric carcinoma, and assess its prognostic value. The paper presents prospective study that included 50 patients with gastric adeno-carcinoma of intestinal type that were treated at Gastroenterohepatology Clinic, and 50 patients with histologically confirmed chronic atrophic H. pylori positive gastritis. In the mucosa biopsy samples, we analyzed presence, frequency and severity of inflammatory-regenerative, metaplastic and dysplastic changes. We typed intestinal metaplasia immunohistochemically and confirmed the presence of p53 onco-protein in antigen positive gastric carcinoma cells, and evaluated its prognostic value. Our results suggest that H. pylori acts as an initiator of inflammatory processes in gastric mucosa, which are followed by emergence of precancerous lesions. p53 is expressed late in carcinogenesis (14%) and as such, may be considered as an indicator of transformation of premalignant into malignant lesion.

The effects of nonsteroidal mycotoxin zearalenone on the lymphoid tissue of thymus in a sense of investigating the subacute toxicity Wistar-albino rats have been examined in the course of the study. We analyzed 42 rats' specimens of both gender, treated with three dosage levels: 0,5; 2 and 4 mg/kg of body weight, after oral submission of the compound, and observed during three different time intervals: 10, 20 and 30 days. Microscopically was semiquantitatively determined lymphophagocytosis (apoptosis) and cortical thymic cellularity. It was percepted statistically significant growth of lymphophagocytosis compared to a dosage (p<0,01), as well as combination of dosage and interval (p<0,001), while gender had no statistically significant influence on tested parameter (p>0,05). Changes in cortical thyme cellularity were not percepted. Effects of applied doses of zearalenone on the lymphoid tissue of thymus were very mild and in correlation with estrogenicity. They are probably the result of interaction with estrogenic receptors.

The aim of our study was to determine the genotypes of viral hepatitis C. We examined 54 patients with chronic hepatitis C who were treated at Gastroenterohepatology Department University of Sarajevo. We also monitored effects of therapeutical results in same group of patients. Polymerasa chain reaction (PCR) was used to quantified the number of HCV-RNA copies in 1 ml of blood. Genotype of virus was determined as well. We created therapeutical protocols based on genotype and quantity of virus that contained pegilated interferon alpha2a(40) kD and ribavirin. The result of our investigation presented that the highest number of patients, 25 had genotype 1a; 13 patients had genotype lb; 11 patients had genotype 3; 4 patients had genotype 4 and 1 patients with genotype 2a. At the end of therapy, 42 patients were HCV-RNA PCR negative; 7 female and 35 male. Four women with genotype 1a, responded on therapy; two with genotype 1b and one with genotype 3. Within the male group of patients (35 patients), 16 patients had a genotype 1a, 3 patients had a genotype 1b, 11 patients had a genotype 3, 4 patients had genotype 4 and one patient had genotype 2a. Patients who did not respond on therapy or were HCV-RNA-PCR positive at the end of therapy were genotype 1a and 1b. According to result of our investigation, genotype 1 is the most frequent among our patients, and the most severe damages in liver parenchyma are associated with genotype 1a and 1b. Genotype 1b also had less respond on therapy.

The aim of the study was to ascertain the existence of intestinal metaplasia in gastric mucosa of patients with gastric carcinoma coupled with H. pylori positive chronic atrophic gastritis and possible connection of IM with the development of gastric carcinoma. The paper presents prospective study that included 50 patients with gastric carcinoma and 50 patients with chronic atrophic H. pylori positive gastritis. All the patients were subjected to gastroscopy as well as biopsy targeted at antrum, lesser curvature and corpus and at the area 1-2 cm removed from tumor lesion. Biopsy samples were sliced by microtome and stained. We analyzed presence, frequency and severity of inflammatory-regenerative, metaplastic and dysplastic changes in the mucosa and evaluated their prognostic value. We typed IM immunohistochemically. This study confirmed responsibility of H. pylori for inflammatory events in gastric mucosa in patients with gastric carcinoma. According to our findings incomplete IM of types IIa and IIb as precancerous lesion is responsible for the development of gastric carcinoma and is associated with chronic atrophic gastritis grade I and II (92% of subjects, p=0.0097, h=1, p=0.01). Thus, the finding of incomplete intestinal metaplasia may be used as an indicator for early gastric carcinoma detection. Patients with patho-histologically verified incomplete intestinal metaplasia associated with active chronic atrophic gastritis of levels I and II represent risk group for the development of gastric carcinoma of intestinal type.

The aim of the study was to ascertain presence of Helicobacter pylori in gastric carcinoma as a responsible promoter of inflammatory-regenerative changes, which lead to pathological differentiation and transformation of normal epithelial cells into intestinal type and, in progression, cause epithelial dysplasia that develops into early gastric carcinoma. The paper presents prospective study that includes clinical, pathohistological and microbiological aspects of carcinogenesis initiation in gastric mucosa. The subjects are patients treated at Gastroenterohepatology Clinic divided into two groups. One group included 50 patients with gastric carcinoma while the control group included 50 patients with chronic atrophic H. pylori positive gastritis. All the patients were subjected to endoscopy as well as biopsy targeted at antrum, lesser curvature and corpus and at the region 1-2 cm removed from tumor lesion. We used HUT test to verify H. pylori presence in biopsy samples. We analyzed the samples for presence, frequency and severity of inflammatory-regenerative, metaplastic and dysplastic changes in gastric mucosa and evaluated their meaning for the prognosis. Our study confirmed Helicobaster pylori responsibility for inflammatory events in gastric mucosa in patients with gastric carcinoma. Slight and mild epithelial dysplasia with chronic atrophic gastritis grade I and II coupled with intestinal metaplasia may be considered an indicator for early detection of carcinoma. Such patients represent risk group for gastric carcinoma development.

AIM OF THE STUDY To investigate the correlation between the expression of HER-2 membrane protein and basic pathohistological parameters in cases of infiltrative breast cancer. MATERIAL AND METHODS Sixty-nine cases of lobular infiltrative breast cancer were investigated. Mastectomy with a dissection of axillary's lymph nodes was performed in all cases. Upon standard procedure of formalin fixation, embedding in paraffin and examination of slides stained with hematoxillin-eosin, a semiquantitaive method of evaluation of immunohistochemical expression of the HER-2 protein has been performed in all tissue samples of the tumor. RESULTS Majority of patients (91,3 %) were above 41 year-of-age. In the majority of cases (44,9 %) cancer's diameter ranged from 20-50 mm (pT2), with a moderate degree of differentiation (46,4 %), no signs of vascular invasion (50,7 %) and no metastases in axillary's lymph nodes (65,2 %). Evaluation of immunohistochemical expression of the HER-2 protein revealed that only the degree of tumor differentiation has been in statistically significant (p=0, 037) correlation with the intensity of the HER-2 protein expression. CONCLUSION In cases of lobular infiltrative breast cancer, oncogenic effect of the HER-2 protein was associated with the degree of cellular differentiation, while it was not in correlation with other pathological parameters of poorer prognosis, such as the size of tumor, presence of vascular invasion and occurrence of metastases in regional lymph nodes.