Association of HOTAIR, MIR155HG, TERC, miR-155, -196a2, and -146a Genes Polymorphisms with Papillary Thyroid Cancer Susceptibility and Prognosis.

Polymorphisms in long non-coding RNA and microRNA genes may play a significant role in the susceptibility and progression of papillary thyroid carcinoma (PTC). The current study investigates the polymorphisms HOTAIR rs920778, MIR155HG rs1893650, TERC rs10936599, miR-155 rs767649, miR-196a2 rs11614913 and miR-146a rs2910164 in 102 PTC patients and 106 age- and sex-matched controls of the Caucasian Serbian population, using real-time PCR. We observed differences in genotype distributions of the HOTAIR rs920778 (p = 0.016) and MIR155HG rs1893650 (p = 0.0002) polymorphisms between PTC patients and controls. HOTAIR rs920778 was associated with increased PTC susceptibility (adjusted OR = 1.497, p = 0.021), with the TT variant genotype increasing the risk compared to the CC genotype (OR = 2.466, p = 0.012) and C allele carriers (CC + CT) (OR = 1.585, p = 0.006). The HOTAIR rs920778 TT genotype was associated with lymph node metastasis (p = 0.022), tumor recurrence (p = 0.016), and progression-free survival (p = 0.010) compared to C allele carriers. Multivariate Cox regression revealed that ATA risk (HR = 14.210, p = 0.000004) and HOTAIR rs920778 (HR = 2.811, p = 0.010) emerged as independent prognostic factors in PTC. A novel polymorphism, MIR155HG rs1893650, was negatively correlated with susceptibility to PTC, with TC heterozygotes exerting a protective effect (OR = 0.268, p = 0.0001). These results suggest that the polymorphisms HOTAIR rs920778 and MIR155HG rs1893650 could be potential prognostic and risk biomarkers in papillary thyroid carcinomas.

Peripheral Versus Intraparenchymal Papillary Thyroid Microcarcinoma: Different Morphologies and PD-L1 Expression.

Peripheral localisation of papillary thyroid microcarcinoma (PTMC), in comparison with intraparenchymal PTMC (i-PTMC) is related to some clinicopathological features related with biological aggressiveness, including lymph node metastasis (LNM). The expression of PD-L1 in tumour cell has been associated with increased tumour survival, progression, and potentially an aggressive clinical course. This study evaluates the relation between clinicopathological features of PTMC, including tumour localisation, with PD-L1 immunoexpression. The study included 99 patients with the histological diagnosis of PTMC (≥ 5 mm). PD-L1 protein expression was assessed by immunohistochemistry. PTMCs were divided into the four following groups: G1- peripherally localised PTMC (p-PTMC) with PD-L1 expression; G2-p-PTMC without PD-L1 expression; G3-i-PTMC with PD-L1 expression and G4-i-PTMC without PD-L1 expression. G1 was the most frequent (n = 46; 46.5%), followed by G4 (n = 25; 25.3%) and similar distribution of G3 (n = 15; 15.2%) and G2 (n = 13; 13.1%). In comparison with other groups, G1 was significantly associated with classical morphology, invasive growth, lymphatic invasion (LI), vascular invasion (VI), psammoma bodies, intratumoral fibrosis, PD-L1 positive tumour-infiltrating lymphocytes, and multinuclear giant cells (MGCs). G4 more commonly exhibited follicular morphology, expansive/circumscribed growth, and absence of the following: intratumoural fibrosis, LI, VI, psammoma bodies, PD-L1 positive tumour-infiltrating lymphocytes, and MGCs. LNMs were significantly more frequent in G1 in comparison with the other groups (p = 0.000). In conclusion, morphology and tumour microenvironment of p-PTMC with PD-L1 expression is different from i-PTMC without PD-L1 expression. The differences between these two groups of PTMC include clinicopathological features related with biological aggressiveness such as the occurrence of LNM.

EWSR1 rearrangement in papillary thyroid microcarcinoma is related to classic morphology and the presence of small-cell phenotype.

The EWSR1 rearrangements with unknown genes were detected in a high percentage of classic variants of papillary thyroid carcinoma. The small-cell carcinoma of the thyroid with Ewing family tumor elements (CEFTE) typically presents with EWSR1-FLI1 rearrangement suggesting the possible role of EWSR-FLI1 translocation in the loss of thyroid differentiation and acquisition of a small-cell phenotype. In order to determine the frequency and association of EWSR1 rearrangements, particularly the EWSR1-FLI1 fusion with clinicopathological features of papillary thyroid microcarcinoma (m-PTC) and the presence of small cells, we analyzed a series of 99 m-PTCs using the fluorescence in situ hybridization method.  Ninety cases (90.9%) of m-PTC were positive for small cells. This group of m-PTC has shown more often invasive growth, lymphatics invasion, and moderate/extended intratumoral fibrosis. Three cases out of 99 were inconclusive for EWSR1 rearrangement. Eighty-nine (92.7%) and twenty-seven (28.1%) out of 96 m-PTC cases were positive for EWSR1 rearrangement and EWSR1-FLI1 fusion, respectively. m-PTC with classical architectural pattern presented more frequently with EWSR1 rearrangement relative to m-PTC with other patterns (p = 0.005). Other clinicopathological features were not related to the presence of EWSR1 rearrangement or EWSR1-FLI1 fusion. The percentage of small cells present significantly correlated with the percentage of cells positive for EWSR1-FLI1 fusion (p = 0.05) and EWSR1 rearrangement (p <0.001). EWSR1-FLI1 fusion is not rare in m-PTC and it is associated with the acquisition of small-cell phenotype. The EWSR1 gene rearrangement is a frequent event in m-PTC and is related to the classical pattern of m-PTC.

Significance of nuclear factor - kappa beta activation on prostate needle biopsy samples in the evaluation of Gleason score 6 prostatic carcinoma indolence.

Background The goal of our study was to find out whether the immunohistochemical expression of nuclear factor-kappa beta (NF-κB) p65 in biopsy samples with Gleason score 3 + 3 = 6 (GS 6) can be a negative predictive factor for Prostate cancer (PCa) indolence. Patients and methods Study was conducted on a retrospective cohort of 123 PCa patients with initial total PSA ≤ 10 ng/ml, number of needle biopsy specimens ≥ 8, GS 6 on biopsy and T1/T2 estimated clinical stage who underwent laparoscopic radical prostatectomy and whose archived formalin-fixed and paraffin-embedded (FFPE) prostate needle biopsy specimens were used for additional immunohistochemistry staining for detection of NF-κB p65. Both cytoplasmic and nuclear NF-κB p65 expression in biopsy cores with PCa were correlated with postoperative pathological stage, positive surgical margins, GS and biochemical progression of disease. Results After follow-up of 66 months, biochemical progression (PSA ≥ 0.2 ng/ml) occurred in 6 (5.1%) patients, 3 (50%) with GS 6 and 3 (50%) with GS 7 after radical prostatectomy. Both cytoplasmic and nuclear NF-κB p65 expressions were not significantly associated with pathological stage, positive surgical margin and postoperative GS. Patients with positive cytoplasmic NF-kB reaction had significantly more frequent biochemical progression than those with negative cytoplasmic NF-kB reaction with PSA 0.2 ng/ml as cutoff point (p = 0.015) and a trend towards more biochemical progression with PSA ≥ 0.05 ng/ml as cutoff point (p = 0.068). Conclusions Cytoplasmic expression of NF-κB is associated with more biochemical progression and might be an independent prognostic factor for recurrence-free survival (RFS), but further studies including larger patient cohorts are needed to confirm these initial results.

Tissue and urinary KIM-1 relate to tumor characteristics in patients with clear renal cell carcinoma.

The objective of this prospective follow-up trial was to ascertain whether the urinary kidney injury molecule-1 (uKIM-1) associates with tumor tissue (tKIM-1) expression and with the pathological characteristics of clear renal cell carcinoma (cRCC) in radically nephrectomized (RN) and/or in partially nephrectomized (PN) patients with cRCC, pre- and postoperatively. This clinical study included 40 patients subjected to RN/PN (cRCC group) and 30 healthy volunteers (control group). Urinary KIM-1 was determined by ELISA TIM-1/KIM-1 kit and normalized by urinary creatinine. Immunohistochemical staining (monoclonal anti-human anti-TIM-1/KIM-1/HAVCR antibody) was used for semiquantitative analysis of the tKIM-1 expression and expressed as a score (% KIM-1 positively stained tubules). Both markers were interpreted in terms of the tumor characteristics comprising tumor size, Fuhrman grade, pathological (pT) stage, tumor/nodes/metastasis (TNM) stage, lymphovascular invasion and type of surgery RN/PN. Preoperative uKIM-1 was significantly higher in the cRCC group compared to controls, such as uKIM-1 was statistically higher in RN than in PN patients. Postoperatively, uKIM-1 decreased to control values. Expression of tKIM-1 was documented in all nephrectomized patients. Significant associations were achieved between uKIM-1 and tKIM-1 and with considered tumor characteristics, especially with tumor size and grade. Based on the accomplished associations, we found uKIM-1 as a highly sensitive marker for cRCC diagnosis. The clinical trial registration number: 1110-2012.

Pheochromocytoma of the urinary bladder--A case report.

INTRODUCTION: Pheochromocytoma of the urinary bladder is a rare tumor and presents less than 0.06% of all urinary bladder tumors. CASE REPORT: We presented a 49-year-old female patient with a history of daily paroxysmal hypertension accompanied with flushing of the face and upper chest, palpitations and excessive sweating prior to micturition. Ultrasonography reported a 3 cm bladder wall tumor. The 131I-metaiodobenzylguanidine (131I-MIBG) scan showed a pathological isotope accumulation in the projection of the bladder. The patient underwent a partial cystectomy. One year following the operation the patient was normotensive and without recurrence. CONCLUSION: The most efficient treatment option for bladder pheochromocytoma is surgical resection. The most important fact in the diagnostics is suspicion on this rare condition.

Urinary KIM-1 and AQP-1 in patients with clear renal cell carcinoma: Potential noninvasive biomarkers.

BACKGROUND/AIM: Kidney injury molecule-1 (KIM-1) and aquaporin-1 (AQP-1) are potential early urinary biomarkers of clear renal cell carcinoma (cRCC). The aim of this study was to ascertain relationship between the urine concentrations KIM-1 and AQP-1 with tumor size, grade, pT stage and type of operation (radical or partial nephrectomy) in patients with cRCC. METHODS: Urinary concentrations of urinary KIM-1 (uKIM-1) and urinary AQP-1 (uAQP-1) were determined by commercially available ELISA kits. The analysis included 40 patients undergoing partial or radical nephrectomy for cRCC and 40 age- and sex-matched healthy adult volunteers. RESULTS: The median preoperative concentrations of KIM-1 in the cRCC group [0.724 ? 1.120 ng/mg urinary creatinine (Ucr)] were significantly greater compared with controls (healthy volunteers) (0.210 +/- 0.082 ng/mgUcr) (p = 0.0227). Postoperatively, uKIM-1 concentration decreased significantly to control values (0.177 +/- 0.099 ng/mgUcr vs 0.210 + 0.082 ng/mgUcr, respectively). The size, grade and stage of tumor were correlated positively with preoperative uKIM-1 concentrations. Contrary to these results, concentrations of uAQP-1 in the cRCC group were significantly lower (0.111 +/- 0.092 ng/mgUcr) compared with the control group (0.202 +/- 0.078 ng/mgUcr) (p = 0.0014). Postoperatively, the concentrations of uAQP-1 increased progressively up to control values, approximately. We find no significant correlation between preoperative uAQP-1 concentrations and tumor size, grade and stage. CONCLUSION: uKIM-1 was found to be a reliable diagnostic marker of cRCC, based on its significantly increased values before and decreased values after the nephrectomy.

Solitary extramedullary plasmacytoma of the duodenum and pancreas: A case report and review of the literature.

Introduction: The extramedullary plasmacytomas (EMPs) are rare tumors of plasma cell disorders which are rarely found in the duodenum. We presented a case of solitary EMPs involving the duodenum and pancreas successfully treated by surgical resection after failure of chemotherapy. Case Report: A 55-year-old female with previously diagnosed solitary EMP of the duodenum was admitted to our institution after failure of three cycles of vincristine, adriablastine, dexamethasone (VAD) chemotherapy regimen with an upper gastrointestinal obstruction. On admission computed tomography of the abdomen showed tumor in the region of the second part of duodenum and uncinate process of the pancreas with a complete duodenal obstruction. Intraoperatively a tumor formation was in the region of the second duodenal part, originated from the wall of duodenum with the total diameter of 7 x 5 cm, covering the entire circumference of duodenal wall leaded to a narrowing of duodenal lumen to the thigh gap with an upper gastrointestinal obstruction. Infiltration in the head of the pancreas and uncinate process were also found. The Whipple's procedure was performed but postoperative course was complicated by rapidly refilling chylous ascites which was resolved 4 days after the surgery. Conclusion: Each patient with gastrointestinal EMPs should be considered separately and in timely manner, thus adequate treatment could provide local disease control.

Neobladder "Belgrade pouch": Metabolic consideration.

Background/Aim: The ileal neobladder should be a lowpressure reservoir with acceptable volume and relatively small resorptive surface. A larger inner surface of the ileal pouch is associated with the high resorption of urine metabolites through intestinal mucosa and systemic metabolic disturbances, while a too small pouch results in a higher frequency of voiding and incontinency. The aim of this study was to investigate it is possible to create a neobladder from a shorter ileal segment compared to standard surgical techniques, and reduce metabolic complications. Methods: This prospective study included 77 male patients, scheduled for radical cystectomy and orthotopic neobladder derivation. The patients were divided into two groups: the standard pouch (SP) group of 37 patients scheduled for standard orthotopic neobladder, using a 50−70 cm long terminal ileum segment; the "Belgrade pouch" (BP) group of 40 patients scheduled for original, orthotopic urinary reservoir, using a 25−35 cm long terminal ileum segment. We measured neobladder capacity, acidosis, base excess and bicarbonate concentration in the postoperative month 3rd, 6th, 12th and 15th. Results: At the end of the study, the patients from the SP group had much higher neobladder capacity than the natural bladder − 750 mL (range 514−2,050 mL); in contrast, the patients from the BP group had average capacity of 438 mL (range 205−653 mL) (p < 0.001). At the end of the study, there were more patients with acidosis (37.8% : 2.5%), base excess (35.1% : 7.5%) and low bicarbonate level (40.5% : 20.0%) in the SP group, than in the BP group, respectively (p < 0.001). Conclusion: "Belgrade pouch", make from 25−35 cm long terminal ileum segment may obtain adequate capacity and lower rate of metabolic disturbances than standard, high capacity orthotopic neobladders.

Correlation of local and systemic expression of survivin with histopathological parameters of cutaneous melanoma.

Background/Aim: Survivin is a multifunctional protein abundantly expressed in tumors of various types, including melanoma. There are still sparse data regarding relationship of melanoma cell survivin expression with accepted histopathological characteristics as well as serum concentration. The aim of this study was to investigate the association of local tumor survivin expression (primary tumor and metastatic lesions) and serum concentration with clinical and histopathological parameters in melanoma patients. Methods: The level of survivin expression was determined immunocytochemically in tumor tissue and with ELISA test in the serum of 84 melanoma patients diagnosed from 2009 to 2013 at the Institute for Pathology and Forensic Medicine and Institute for Medical Research at Military Medical Academy, Belgrade, Serbia. Results: The intensity of survivin expression was significantly higher in the patients whose tumor had ulceration, higher mitotic index, higher Clark and Breslow stage, that made vascular invasion or spread through lymphatic vessels in primary tumor, and was significantly higher in the patients with metastatic disease. Survivin expression and the number of survivin positive cells in metastatic lesions were significantly associated with the duration of disease free interval (DFI). The patients with high expression score had almost double shorter DFI comparing to those with weak local survivin expression and a small number of survivin+cells (9 ± 7 vs 19 ± 13 months, respectively). The degree of tumor infiltrating lymphocytes presence in tumor tissue was significantly associated with serum survivin concentration, with lowest average level detected in samples of patients with the highest degree of infiltration. Serum survivin concentrations were highest in samples of melanoma patients with IA American Joint Commission on Cancer (AJCC) clinical stage, pT1a histological stage, patients whose tumors were still in horizontal growth phase, without signs of lympho-hematological disease spreading, with the highest number of mitoses and the smallest Clark index. Conclusion: Survivin expression in tumor tissue and its serum concetration significantly correlate with clinical and histopathological parameters. Serum levels could be important in initial follow-up as indicators of those patients that would have aggressive local tumor growth and spreading. Survivin determination in tumor tissue is of great significance in estimation of DFI.

Pseudomesotheliomatous carcinoma of the lung.

Introduction: Pseudomesotheliomatous lung carcinoma is a special, rare entity characterized by large pleural growth and minor invasion of lung tissue. Clinically, radiologically, macroscopically and even histologically this tumor can be misdiagnosed as malignant pleural carcinoma. Case report: We represent a 64-year-old male patient, former smoker. Due to difficulties in the form of dry cough, feeling of dis-comfort and pain in the right hemithorax, fatigue, heavy breathing, sweating, fever up to 39.6°C the patient was treated as with combined antibiotic therapy (macrolides, cephalosporins and penicillin), but without improving of his condition. Chest radiography showed a shadow of pleural effusion by the height of the front end of the third right rib. Chest MSCT showed the extremely thickened pleura apically and to the posterior along the upper right lobe in addition to existence of massive pleural effusion. Subpleural condensation of parenchyma ranging about 30 mm was described in the upper right lobe. Cytological analysis of the pleural effusion showed the presence of malignant cells impossible to differentiate whether they were metastasis of adenocarcinoma or malignant pleural mesothelioma. By histochemical and immunohistohemical analyses of a pleural sample, pseudomesotheliomataus lung adenocarcinoma was diagnosed. Conclusion: Pseudomesotheliomataus carcinoma of the lungs can be a diagnostic problem. Its diagnosis is based on recognition of histopathological characteristics which enable its discernment from the epithelial variant of malignant pleural mesothelioma.

Acquired cystic disease and renal cell carcinoma in hemodialysis patients--A case report on three patients.

INTRODUCTION: Renal cell carcinoma (RCC) is derived from renal tubular epithelial cells and represents approximately 3.8% of all malignancies in adults. The incidence of renal cell carcinoma has been growing steadily and ranging from 0.6 to 14.7 for every 100,000 inhabitants. Patients with end-stage renal disease and acquired cystic kidney disease are at increased risk of developing RCC while undergoing dialysis treatment or after renal transplantation. CASE REPORT: We presented 3 patients undergoing hemodialysis, with acquired cystic kidney disease accompanied by the development of RCC. In all the patients tumor was asymptomatic and discovered through ultrasound screening in 2 patients and in 1 of the patients by post-surgery pathohistological analysis of the tissue of the kidney excised using nephrectomy. All the three patients had organ-limited disease at the time of the diagnosis and they did not require additional therapy after surgical treatment. During the follow-up after nephrectomy from 6 months to 7 years, local recurrence or metastasis of RCC were not diagnosed. CONCLUSION: Acquired cystic kidney disease represents a predisposing factor for the development of renal cell carcinoma in dialysis patients and requires regular ultrasound examinations of the abdomen aimed at early diagnosis of malignancies. Prognosis for patients with end-stage renal disease and RCC is mostly good because these tumors are usually of indolent course.

The clinical course of non-muscle invasive bladder cancer after transurethral resection of the tumor with or without subsequent intravesical application of bacillus Calmette-Guérin: The influence of patients gender and age.

UNLABELLED: BACGROUND/AIM: The therapy with intravesical instillation of bacillus Calmette-Guérin (BCG) after transurethral resection (TUR) of tumor is the gold standard of treatment of non-muscle invasive bladder cancer (NMIBC). The role and importance of BCG intravesical therapy in various shape of tumors, were confirmed by our previous investigation. The aim of this study was to examine whether incidence of recurrence and tumor regression differs depending on sex and age of patients. METHODS: This study included a total of 899 patients suffering from NIMBC, treated at our institution from January 1, 2007 to March 1, 2013. Two groups of patients were formed: patients underwent TUR + BCG therapy (the group I) and the group II with patients in whom TUR was performed as only therapy. These two groups of patients were divided into subgroups of respondents male and female, age 60 years or younger and older than 60 years. Statistical analysis was performed using χ2 test and the Kolmogorov-Smirnov test. RESULTS: This research suggests that if the frequency of recurrence is seen as the only parameter, considering all the subjects, the lowest recurrence rate was determined in the male subjects, aged 60 years and younger who had received BCG after TUR. A high statistical significance was found in the incidence of recurrence in patients younger than 60 years, depending on the response to the therapy, while in those older than 60 years, the difference was at the level of statistical significance. This can be attributed to a certain degree of infravesical obstruction in older men. CONCLUSIONS: Sex and age of patients may have a significant influence on the course and outcome of NMIBC. The disease has the most malignant and most aggressive behavior when present in males older than 60 years.

Difference in recurrence frequencies of non-muscle-invasive-bladder tumors depending on optimal usage of intravesical immunotherapy of bacillus Calmette-Guérin.

BACKGROUND/AIM: The therapy with intravesical instillation of bacillus Calmette-Guérin (BCG) after transurethral resection (ITJR) of the tumor is the gold standard of treatment of non-muscle invasive bladder cancer (NMIBC). The aim of this study was to compare the frequencies of reccurence between a group of patients submitted to TUR + BCG therapy (group I) and a group of patients submitted only to TUR (group II). METHODS: The patients with NMIBC, a total of 899, treated in our Institution from January 1, 2007 to March, 2013, were included in this study and divided into two groups: group I and group II. These two groups were divided into three subgroups: solitary first diagnosed tumor ≤ 3 cm (SFDGT), solitary first diagnosed tumor > 3 cm and multiple first diagnosed tumors (MFDGT), and recedive tumors (RCT). Statistical analysis was performed by using χ2-test and Kolmogorov-Smirnov test. RESULTS: In the group I a total of 133 cases had reccurence contrary to 75 in the group II, making a statistically highly significant difference. Analysis of recurrences through the subgroups revealed: in the group I SFDGT recurrence occured in 27 of the cases vs 9 cases in the group II; in the group I MFDGT recurrence occured in 49 of the cases vs 31 in the group II (p < 0.001), and finally, in the group I RCT recurrence occured in 57 cases vs 35 cases in the group II (p < 0.001). CONCLUSION: The obtained results indicate no difference in the frequency of reccurence between the group I and group II regarding SFDGT, but a very high significant difference regarding those with MFDGT and RCT. These results should be taken into consideration in everyday clinical practise.

Radical cystectomy in eldery.

BACKGROUND/AIM: Radical cystectomy is the method of choice for the treatment of muscle invasive bladder cancer. This major surgery is associated with many complications, especially in older patients. The aim of this study was to analyze preoperative comorbidity, and intraoperative and postoperative complicatons in patients older than 75 years. METHODS: This clinical, retrospective study included 46 patients over 75 years, who underwent radical cystectomy. Indications for surgery, and complications during and after the surgery were followed up. RESULTS: Preoperatively, anemia caused by hematuria was registered in 76% of the patients. In 52% of the patients urine derivation was performed by ileal conduit, in 35% by ureterocutaneostomy and in 13% orthotopic ileal neobladder was created. The average duration of surgery was 190 (120-300) min. A total of 76% of the patients were treated by blood supstitution intraoperatively, average 630 (310-1230) mL. Concerning pathological stage of transitional cell carcinoma of urinary bladder, 26% of the patients had T2, 4% T3a, 52% T3b, and 14% T4a stage. In one case, planocellular carcinoma was diagnosed by patohistological examination, and in 2 cases prostate carcinoma was incidentally found. The average duration of hospitalization was 16 (8-35) days. CONCLUSION: The main reason for cystectomy in patients over 70-and 80 years was gross hematuria caused by bladder cancer, with consecutive anemia which could not be solved using endoscopic treat- ment or blood supstitution. As expected, a prolonged stay in hospital after cystectomy, and a higher rate of complications were recorded in this population.

Association between genetic variant in hsa-miR-146a gene and prostate cancer progression: evidence from Serbian population.

PURPOSE: Two previous studies of association between rs2910164 in miR-146a gene and prostate cancer (PCa) risk have provided opposing results. Furthermore, no evidence of association of this SNP with standard prognostic parameters of PCa progression was obtained in mentioned studies. The main aim of this study was to evaluate the possible association between PCa onset and progression to a more aggressive form, since it has not been assessed in a population of European descent. METHODS: In this study, 286 samples of peripheral blood were obtained from patients with PCa, while the control group comprised 199 volunteers derived from general population who gave samples of buccal swabs. For individuals diagnosed with PCa clinicopathological characteristics including serum prostate-specific antigen level at diagnosis, Gleason score (GS), and clinical stage were determined. Genotyping of rs2910164 was performed using Taqman(®) SNP Genotyping Assay. Analysis of SNP association was done using PLINK and SNPStats software. RESULTS: rs2910164 showed no association with PCa risk. Nevertheless, heterozygous genotype was found to be associated with higher GS, as well as with the presence of distant metastases. rs2910164 was also shown to be associated with cancer aggressiveness (p = 0.0067; ORGC = 2.22, 95 %CI 1.24-3.97; ORCC = 0.47, 95 %CI 0.13-1.68). CONCLUSIONS: Our results show no evidence of association between rs2910164 and PCa risk in Serbian population. Conversely, this variant was found to be associated with PCa aggressiveness.

Assessment of association between common variants at 17q12 and prostate cancer risk-evidence from Serbian population and meta--analysis.

This study aimed to evaluate possible association between genotypes and alleles of two 17q12 polymorphisms (rs3760511 and rs7501939) and prostate cancer (PCa) risk and progression. Two hundred seventy-one patients with PCa, 261 patients with benign prostatic hyperplasia (BPH), and 171 controls were included in the study. Single nucleotide polymorphisms (SNPs) were genotyped by using PCR followed by restriction fragment length (PCR-RFLP) analysis. We conducted meta-analysis of published studies regarding association of these SNPs with PCa risk. Evidence of positive association between the AC genotype of the SNP rs3760511 and BPH risk for the best-fitting overdominant model of association (BPH vs. controls comparison, p = 0.026; odds ratio [OR] = 1.58; 95% confidence interval [95%CI] 1.05-2.36) were obtained. The association between T allele of rs7501939 and PCa risk was determined in PCa versus controls comparison (p = 0.0032; OR = 0.66, 95%CI 0.50-0.87) with the best-fitting model of inheritance being log-additive. This variant was also found to be associated with the risk of BPH (p = 0.0023; OR = 0.65, 95%CI 0.49-0.86). We found no association between parameters of PCa progression and the analyzed SNPs. Meta-analysis showed strong association between these variants and PCa risk. Our study shows association between SNPs at locus 17q12 and the risk of prostatic diseases in Serbian population. At the same time, results of meta-analysis suggest the association of these SNPs with PCa risk.

Endothelial nitric oxide synthase gene polymorphisms and prostate cancer risk in Serbian population.

Genome-wide association studies (GWAS) have identified over 46 SNPs associated with human prostate cancer (PCa). Some studies have shown correlation of the nitric oxide synthase (NOS) NOS3 gene polymorphisms with the risk and/or progression of PCa. This study aimed to evaluate the association of NOS3 gene polymorphisms (-786T>C, -764A>G, -714G>T, -690C>T, -649G>A and 894G>T) with PCa risk and progression. 150 patients with PCa, 150 patients with BPH and 100 age-matched healthy controls were recruited in this study. Genotyping of promoter polymorphisms was performed by bi-directional DNA sequencing, and for 894G>T by RFLP analysis. There was no significant association between the alleles and genotypes of these genetic variants and PCa risk. For -786T>C polymorphism, we found that C allele is associated with absence of metastases, assuming dominant genetic model (P = 0.049; OR, 0.50; 95% CI, 0.25-1.00). It was found that, compared with NOS3 -690C>T variant CC genotype, CT and TT genotypes confer decreased risk of developing metastases (dominant model, P = 0.015, OR, 0.24; 95% CI, 0.07-0.88) and show association with low clinical tumour stage, compared with stages T3 and T4 (dominant model, P = 0.046, OR, 0.20; 95% CI, 0.04-1.02). Genetic variants -764A>G, -714G>T, -649G>A were not detected in our study group. There is evidence of an inverse correlation of the NOS3 894G>T minor allele with high serum PSA (>20 ng/ml) (dominant model, P = 0.013, OR, 0.37; 95% CI, 0.17-0.82). Our results suggest that NOS3 gene polymorphisms are genetic susceptibility factors for the progression of PCa and patient outcome.

Early reconstruction of bone defect created after initial surgery of a large keratocystic odontogenic tumor: a case report.

INTRODUCTION: Keratocystic odontogenic tumor (KCOT) is defined as a benign cystic neoplasm of the jaws of odontogenic origin with a high rate of recurrence. The most lesions occur in the posterior part of the mandible. Treatment of KCOT remains controversial, but the goals of treatment should involve eliminating the potential for recurrence while minimizing surgical morbidity. However, another significant therapeutic problem related to the management of KCOT is an adequate and early reconstruction of the existing jaw defect, as well as appropriate aesthetic and functional rehabilitation of a patient, especially in cases of a very large destruction of the jaws bone. CASE REPORT: We presented a 65-year-old female patient with very large KCOT of the mandible. Orthopantomographic radiography showed a very large elliptical multilocular radiolucency, located on the right side of the mandible body and the ascending ramus of the mandible, with radiographic evidence of cortical perforation at the anterior border of the mandibular ramus and the superior border of the alveolar part of the mandible. The surgical treatment included two phases. In the first phase, the tumor was removed by enucleation and additional use of Carnoy solution, performing peripheral ostectomy and excision of the affected overlying mucosa, while in the second phase, restorative surgery of the existing mandibular defect was performed 6 months later. Postoperatively, we did not register any of postoperative complications, nor recurrence within 2 years of the follow-up. CONCLUSION: Adequate and early reconstruction of the existing jaw defect and appropriate aesthetic and functional rehabilitation of the patient should be the primary goal in the treatment of KCOT, having in mind the need for a long-term post-surgical follow-up.

Disseminated typical bronchial carcinoid tumor.

INTRODUCTION: Bronchial carcinoids belong to a rare type of lung tumors. If they do not expose outstanding neuroendocrine activity, they develop without clearly visible symptoms. They are often detected during a routine examination. According to their clinical pathological features, they are divided into typical and atypical tumors. Typical bronchial carcinoids metastasize to distant organs very rarely. Localized forms are effectively treated by surgery. The methods of conservative treatment should be applied in other cases. CASE REPORT: We presented a 65-year-old patient with carcinoid lung tumor detected by a routine examination. Additional analysis (chest X-ray, computed tomography of the chest, ultrasound of the abdomen, skeletal scintigraphy, bronhoscopy, histopathological analysis of the bioptate of bronchial tumor, as well as bronchial brushing cytology and immunohistochemical staining performed with markers specific for neuroendocrine tumor) proved a morphologically typical lung carcinoid with dissemination to the liver and skeletal system, which is very rarely found in typical carcinoids. CONCLUSION: The presented case with carcinoid used to be showed morphological and pathohistological characteristics of typical bronchial carcinoid. With its metastasis to the liver and skeletal system it demonstrated unusual clinical course that used to be considered as rare phenomenon. Due to its frequent asymptomatic course and varied manifestation, bronchial carcinoid could be considered as a diagnostic challenge requiring a multidisciplinary approach.