The aberrant DNA methylation plays a critical role in a number of different malignancies, including melanoma. DNA methylation is catalyzed by DNA methyltransferases (DNMTs), involved in methylation maintenance (DNMT1) and de novo DNA methylation (DNMT3A and DNMT3B). The current study investigated the association of genetic variants in the DNMT1 and DNMT3B with the clinicopathologic features and the clinical course of melanoma patients. In the present study, DNMT1 (rs2228612, rs2228611, and rs2114724) and DNMT3B (rs406193 and rs2424932) polymorphisms were examined in 123 melanoma patients. Single nucleotide polymorphisms were assessed using TaqMan SNPs Genotyping Assays according to the manufacturer's protocols. The carriers of the variant genotype of DNMT1 rs2228612 had poorer overall survival and recurrence-free survival, (P=0.000 and 0.000, respectively), and an increased risk for adverse outcome [hazard ratio (HR)=6.620, 95% confidence interval (CI): 2.214-19.791, P=0.001]. DNMT1 rs2228612 was also associated with ulceration (P=0.045), nodal status (P=0.030), progression (P=0. 007), and stage of disease (P=0.003). Univariate analysis indicated that tumor-infiltrating lymphocytes could be a marker of good prognosis in melanoma patients (HR=0.323, 95% CI: 0.127-0.855, P=0.025), whereas the genotype distribution of the DNMT3B rs406193 polymorphism correlated significantly with the presence of tumor-infiltrating lymphocytes (P=0.012). The multivariate analysis showed that the DNMT1 rs2228612 polymorphism (HR=12.126, 95% CI: 2.345-62.715, P=0.003) is an independent predictor of poor overall survival in melanoma patients. As expected, disease progression was also found to be an independent prognostic factor in melanoma patients (HR=37.888, 95% CI: 3.615-397.062, P=0.002). DNMT1 rs2228612 was found to be an independent predictor of poor overall survival in melanoma patients. DNMTs polymorphisms could serve as a potential target for novel therapeutic approaches.

Background/Aim. Colorectal cancer (CRC) represents one of the most common cancers worldwide. CRC is frequently diagnosed at advanced stages with poor prognosis, indicating the need for new diagnostic and prognostic markers. The aim of this study was to determine systemic and fecal values of galectin- 1 (gal-1) and ratios between gal-1 and proinflammatory cytokines: tumor necrosis factor-alpha (TNF-?), interleukin-1 beta (IL-1?) and interferon gamma (IFN-?), in the patients with CRC and the relationship with clinicopathological aspects of the disease. Methods. The blood samples and feces liquid fraction of 58 patients with CRC were analyzed. The serum and fecal levels of TNF-?, IL-1? and IFN-? and gal-1 were measured using sensitive enzyme-linked immunosorbent assay (ELISA) kits. Results. The fecal level of gal-1 was increased in the CRC patients with higher nuclear grade and poor tumor tissue differentiation. The gal-1/TNF-? ratio in the serum and feces had a higher trend in the patients with the advanced tumor-nodemetastasis (TNM) stage as well as the detectable lymphatic and blood vessel invasion. The gal-1/TNF-? and gal-1/IFN-? ratios were increased in the serum of patients with presence of lung/liver metastasis or peritoneal carcinomatosis, while the enhanced gal-1/IL-1 ratio was detected only in the serum of patients with lung metastasis. A positive correlation between the gal-1 value in feces and histological differentiation of tumor and biomarkers alpha-fetoprotein (AFP) and cancer antigen- 19-9 (CA 19-9), respectively, was also observed. The fecal values of gal-1 higher than 13,708.29 pg/g presented a highly sensitive and specific marker for histological differentiation of tumor tissue. Conclusion. We believe that the predomination of gal-1 over pro-inflammatory cytokines TNF-?, IL-1? and IFN- ? in the patients with advanced and progressive CRC may implicate on an immunomodulatory role of gal-1 in the limiting ongoing proinflammatory processes. The fecal values of gal-1 can be used as a valuable marker for the severity of CRC.

Background/Aim. Ulcerative colitis (UC) is a chronic, relapsing inflammatory disease affecting the distal colon and rectum with complex pathogenesis and diagnosis, indicating the need for new diagnostic and prognostic markers. The aim of this study was to determine the fecal values of TNF- ?, IL-17, IL-10 and soluble protein ST2 (sST2) in the patients with UC and their relationship with clinicopathological aspects. Methods. The samples of stool of 80 patients with UC were analyzed. Concentrations of TNF-?, IL-17, IL-10 and sST2 were measured by ELISA. Results. Concentrations of TNF-?, IL-17 and sST2 were significantly increased in the feces of patients with the higher endoscopic, clinical and total Mayo score, as well as in the patients with an intense crypt destruction, erosion of the mucous membranes, architectural changes, neutrophil infiltration and eosinophil infiltration. The local value of anti-inflammatory cytokine IL-10 in liquid fraction of feces was increased in the patients with an advanced endoscopic stage of UC. The moderate positive correlation between the fecal sST2/IL-17 and the clinical and histological parameters of disease severity and also the strong correlation between sST2 and IL-17 was also observed in the feces of patients with UC. The analysis of receiver operating characteristic (ROC) curves showed that the optimal cut-off value for sST2 of 624.0 pg/g allows the discrimination of clinical stages of UC. Conclusion. The increased fecal value of sST2 in the UC patients with a higher endoscopic, clinical and histological stage of disease may be considered as a sign of the disease severity. The fecal values of sST2 can be used as a valuable marker for UC severity.

Introduction. Primary breast angiosarcoma is a very rare tumor and accounts for 0.04% of all breast malignant tumors and most commonly occur in young women. Kasabach-Merritt syndrome (KMS) is described as consumption coagulopathy with thrombocytopenia, and without adequate therapy almost certainly leads to a very fast lethal outcome. Case report. We present a rare case of 60-year-old postmenopausal woman with metastatic primary angiosarcoma of the breast associated with a picture like Kasabach-Merritt's syndrome (thrombocytopenia and anemia without the coagulation factor disorder with massive bleeding in the tumor). Conclusion. Primary breast angiosarcoma in postmenopausal women is a very rare tumor, and may be associated with anemia and thrombocytopenia without other laboratory parameters for Kasabach-Merritt's syndrome. Anemia and thrombocytopenia are refractory to standard treatment protocols, and also significantly reduces the quality of life of these patients. The literature contains only a few cases of Passociated with thrombocytopenia or with KMS and there are no clear defined protocols for the treatment of these patients, which requires the presentation of as many cases as possible.

Colorectal cancer (CRC) represents one of the most common cancers. It is frequently diagnosed at advanced stages, indicating on need for new diagnostic markers. The aim of this study was to determine systemic and fecal values of IL-17 and IL-33 in patients with CRC and the relationship with clinicopathological aspects of disease. The blood samples and feces liquid fraction of 50 patients with CRC were analyzed. Serum and fecal levels of IL-33 and IL-17 were measured using sensitive enzyme-linked immunosorbent assay (ELISA) kits. Fecal levels of Il-33 and IL-17 were increased in CRC patients with poor tumor tissue differentiation. Serum IL-33 and fecal IL-17 were increased in patients with presence of lung/liver metastasis or peritoneal carcinomatosis, respectively, while enhanced fecal IL-33 was detected only in patients with peritoneal carcinomatosis. Positive correlation between IL-33 and IL-17 values in sera and feces, respectively was also observed. We believe that increased local values of IL-33 and IL-17, reflected trough higher fecal concentration, in CRC patients with poor tumor tissue differentiation and with presence of lung/liver metastasis or peritoneal carcinomatosis may be considered as a sign of the tumor’s malignant progression and, consequently, of a poor prognosis for patients.

Background: Chemical pleurodesis is generally accepted palliative dyspnea therapy and preventive of re-accumulation of pleural fluid in patients with malignant pleural effusions. Aim: Comparative analyses of efficiency of chemical pleurodesis between Video Assisted Thoracoscopic Surgery (VATS) and standard thoracostomy. Methods: From 01.01.2016-01.01.2017 at the Clinic for Thoracic Surgery of University Clinical Center (UCC) Sarajevo retrospective analysis was performed. Studied patients underwent VATS pleurodesis (G1) and standard thoracostomy pleurodesis (G2), with 60 in each group, respecting defined inclusion and exclusion criteria. Pleurodesis success was examined radiologically over the next three months. Results: Average age of all patients was 63.97±8.75 years. Gender related, 45% were men and 55% were women (F/M=1.47:1). Average hospitalization was 7.22±1.37 (G1: 6.68±1.16; G2: 7.44±1.40; Mann-Whitney U-test: p=0.0016) days. Average thoracic drainage duration was 5.45±1.69, (G1: 4.28±1.15,G2: 6.05±1.58; Mann-Whitney U-test p<0.0001) days. Pleurodesis success after first month was 98.30% in G1, 91.60% in G2 (G1 vs. G2; p=0.2089); after second month was 98.30% in G1, 78.30% in G2 (G1 vs. G2; p=0.0011) and after three months was 91.60% in G1, 63.30% in G2(G1 vs. G2; p=0.0006). Average dyspnea degree (0-5) after the pleurodesis was 0.050±0.22 in G1 and 0.62±0.76 in G2 (Mann-Whitney U-test; p=0.0001). Complication were noticed in 9.2% patients, in G1 3.3%, 15.0% in G2. Conclusion: Difference in pleurodesis efficiency between the G1 and G2 was established after second month and was even more evident after third month in favor of G1. Results show the significant statistical improvement of the degree of dyspnea in G1 as opposite to the G2.

Abstract Ulcerative colitis (UC) represents chronic inflammation of the large intestine. Immune response plays an important role in disease genesis and progression. Activated leukocytes secrete several cytokines that actively regulate the inflammatory response in UC. The aim of this study was to determine levels of cytokines IL-17, IL-27, IFN-γ and TGF-β in patients with UC and to test them as biomarkers for disease. The blood samples of 24 patients with ulcerative colitis without previous treatment and 37 healthy individuals were analyzed. Serum levels of IL-17, IL-27, IFN-γ and TGF-β were measured using sensitive enzyme-linked immunosorbent assay (ELISA) kits. Serum levels of IL-17, IL-27, IFN-γ and TGF-β were increased in patients with UC, compared to healthy controls (p=0.022; p=0.001; p=0.001; and p=0.002; respectively). Ratios of cytokines IL-27/IL-17, IFN-γ/TGF-β and IL-17/TGF-β were significantly higher in group of patients with UC (p=0.002; p=0.002; p=0.003; respectively). Serum value of TGF-β higher than 20 pg/ml presents a highly sensitive and specific marker for UC. We believe that increased production and predominance of immunosupressive TGF-β may represent compensatory mechanism for ongoing pro-inflammatory processes in UC.

Background and Objectives The aim of the study was to determine systemic and fecal values of galectin-3 and pro- and anti-inflammatory cytokines in patients with CRC and the relationship with clinicopathological aspects. Methods Concentrations of galectin-3, TNF-α, TGF-β, IL-10, and IL-1β were analyzed in samples of blood and stool of 60 patients with CRC. Results Systemic concentration of TNF-α was significantly lower in patients with severe diseases (advanced TNM stage, nuclear grade, and poor histological differentiation) as in patients with more progressive CRC (lymph and blood vessel invasion, presence of metastasis). Fecal values of anti-inflammatory cytokines TGF-β and IL-10 were increased in patients with severe stadium of CRC. Fecal concentration of Gal-3 was enhanced in CRC patients with higher nuclear grade, poor tumor tissue differentiation, advanced TNM stage, and metastatic disease. Gal-3/TNF-α ratio in sera and feces had a higher trend in patients with severe and advanced diseases. Positive correlation between fecal Gal-3 and disease severity, tumor progression, and biomarkers AFP and CEA, respectively, was also observed. Conclusions Predomination of Gal-3 in patients with advanced diseases may implicate on its role in limiting ongoing proinflammatory processes. The fecal values of Gal-3 can be used as a valuable marker for CRC severity and progression.

Introduction. Primary appendiceal adenocarcinoma is a very rare malignancy which accounts for 0.1% of all appendectomy specimens. In both patients presented in this paper, appendectomy was performed due to suspected acute complicated appendicitis. Case Reports. The first patient, a 77-year-old man, presented with a low grade colonic-type pT3 adenocarcinoma of the appendix, diagnosed by histopathological examination of the resected appendix delivered in a fixative. A month after appendectomy, the patient underwent right hemicolectomy of a tumor at the edge of the resection. Due to a cardiovascular disease, adjuvant chemotherapy was not indicated. The second patient, a 74-year-old female, presented with a low grade mucinous adenocarcinoma of the appendix with subserous infiltration, diagnosed by histopathological analysis of the resected appendix. Eight months after appendectomy, the patient developed a recurrent tumor in the cecal area. After radical surgical excision of the recurrent tumor, the patient received adjuvant chemotherapy. Both patients had a 5-year survival without relapse. Conclusion. Preoperative diagnosis of appendiceal adenocarcinoma is a challenge due to overlapping symptoms of complicated acute appendicitis. Our results suggest that in elderly patients with symptoms of complicated acute appendicitis, appendectomy should be done with intraoperative histopathological frozen section consultation. In advanced stages of adenocarcinoma, right hemicolectomy is a better choice than appendectomy.

Introduction: Hospital-acquired infections (HAI) and surgical site infections (SSI) are a global public health problem. The aim of the study was to determine the incidence of SSIs at the Surgical Clinics of the University Clinical Centre Banja Luka and to identify risk factors for the development of SSIs. Methods: In order to determine the frequency of SSIs through the incidence compared to the patients operated at the Surgical Clinics of the University Clinical Centre Banja Luka, we conducted a prospective cohort study which encompassed 11.216 operated patients, in the period from November 11th, 2014 to September 30th, 2015. In order to identify risk factors for the development of SSIs, a nested case-control study of risk factors for SSIs was conducted. The study group consisted of patients who were diagnosed with SSIs in the period of monitoring, while the control group was consisted of patients without SSIs who corresponded with the study group in age and sex. Results: The highest values of incidence of SSIs were observed at the Department of Anesthesia and Intensive Care (2.65%), Department of Orthopaedic Surgery (2.48%) and the Department of Vascular Surgery (2.15%), and the lowest ones at the Department of Urology (0.59%). Among the cases of SSIs, deep infections of the surgical site were the most represented (82.7%). Multivariate logistic regression was used to identify the following independent risk factors: length of pore-operative stay in hospital (p=0.000; OR=1.062; 95% CI=1.037-1.087), reintervention (p=0.000; OR=22.409; 95% CI=6.361-79.071) and cotrticosteroids (p=0.023; OR=4.141; 95%CI=1.221-14.047). Conclusion: The incidence of SSIs at the Surgical Clinics of the University Clinical Centre Banja Luka is at the level of hospitals in developed countries. There are a number of risk factors for SSIs, which may be prevented.

Hepatitis C virus infection (HCV), one of the greatest causes of liver disease, is a frequent complication in patients with end-stage renal disease (ESRD) on dialysis. ESRD is defined as decreased glomerular filtration and also accompanied by impaired function of the immune system. Galectin-3 is a β-galactoside-binding lectin, involved in various biological processes including pathogenesis of chronic renal disease. The aim of our study was to estimate disease severity in ESRD HCV+ patients and analyze the serum concentrations of IL-1β, IL-4, IL-23, and IL-6; anti-HCV antibodies; and galectin-3. Also, we attempted to determine potential correlation between galectin-3 level and parameters of disease severity ALT and AST. Our results showed decreased levels of ALT and AST (p = 0.00), demonstrating less liver destruction in ESRD HCV+ patients in comparison to HCV+ patients. Increased levels of IL-6 (p = 0.03) implicate a hepatoprotective role of IL-6 in these patients. Also, level of galectin-3 (p = 0.00) in the serum of ESRD HCV+ patients was higher than that of HCV+ patients. This alteration was accompanied with negative correlation between galectin-3 and AST and ALT, respectively (p = 0.029; p = 0.033). The presence of increased systemic levels of IL-6 and Gal-3 in ESRD HCV+ patients may be an attempt to counteract or limit ongoing proinflammatory processes and to downregulate chronic inflammation, suggesting the new aspects of HCV infection in ESRD patients.

BACKGROUND Kidney size may differ between healthy members of Balkan endemic nephropathy (BEN) and non-BEN families. The present study was designed to elucidate this, in comparison with values for BEN patients. METHODS A total of 71 BEN patients (34 males, 64.4 ± 12.0 years), 74 healthy BEN family members (39 males, 49.1 ± 12.2 years), and 59 non-BEN family members (19 males, 49.2 ± 12.3 years) were involved. We measured the longest craniocaudal length and minimal parenchymal thickness on each kidney of all examined subjects using ultrasound. RESULTS No significant difference was found between the kidney length of healthy subjects from BEN (11.0 ± 0.8 cm) and non-BEN families (10.9 ± 0.8 cm), but kidneys were significantly longer than in BEN patients (9.9 ± 1.3 cm). Minimal parenchymal thickness was similar in all three groups. When subjects from each group were divided according to estimated glomerular filtration rate (eGFR), kidney length of the healthy groups was significantly longer than in BEN patients both in stage 1 (p =0.039) and stage 2 (p =0.044) of chronic kidney disease. The parental history of BEN was not associated with kidney dimensions, eGFR, or urinary excretion of albumin and alpha1-microglobulin. CONCLUSION Kidneys of BEN patients were significantly shorter than in healthy members of both BEN and non-BEN families, but no difference was found in kidney length and parenchymal thickness between healthy members of BEN and non-BEN families. No significant association was found between parental history of BEN and kidney size and function either in BEN patients or in healthy members from BEN families. Hippokratia 2015; 19 (4): 304-308.

Background/Aims: The aim of this study was to find out the prevalence of the most frequent risk factors for chronic kidney disease (CKD) and the prevalence of urinary abnormalities in adult inhabitants of three Balkan endemic nephropathy (BEN) villages near Bijeljina, Bosnia and Herzegovina. Methods: The survey consisted of an interview, blood pressure measurement, and urine dipstick test for proteinuria, hematuria, and glycosuria. Results: The study involved 1625 (739 males, aged 51 ± 16 years) subjects: 319 (19.6%) with positive family history for BEN, 585 (36%) with hypertension, 604 (37.2%) above 60 years, 146 (9%) with diabetes, and 566 (34.8%) with none of these risk factors. Proteinuria was present in 6.2–7.1% of the subjects with risk factors for CKD but in 3.4% of those without risk factors. Systolic blood pressure and BEN in brother/sister were found to be significant variables associated with proteinuria, but female gender and history of kidney disease with hematuria. Conclusion: In addition to a family burden for BEN, other risk factors for CKD were highly prevalent in BEN villages of the Bijeljina municipality. The frequency of proteinuria was higher in the at-risk group than in the group without risk factors and increased with the number of risk factors.