Caries Experience in Primary and Permanent Dentition in Children Up to 15 Years of Age from Bosnia and Herzegovina-A Retrospective Study.

The purpose of the study was to analyze caries experience in primary and permanent dentition in children up to 15 years of age located in Banja Luka, Bosnia and Herzegovina. METHODS: The research was conducted as a retrospective cross-sectional study. Analyzes and comparisons of caries indices were performed using groups formed according to their gender (male-M and female-F) and age, i.e., the first group-children in early childhood, ≤5 years; the second group, middle childhood 6-8 years; the third group, preadolescents 9-11 years old; fourth group, adolescents 12-15 years old. RESULTS: Overall prevalence of caries in primary dentition was 89.1%, while in permanent dentition, it was 60.7%. The overall mean decayed, missing, and filled teeth- dmft in male participants was 5.4, while in female participants, it was 5.1. By contrast, a higher overall mean DMFT was established in the female participants (2.7 vs. 3.0). CONCLUSIONS: We can see a high prevalence in all of the examined groups. In primary dentition, males examined during the course of the study had a higher overall mean dmft and the mean number of untreated decayed primary teeth, whereas females up to age 15 examined during the course of the study had more DMF teeth.

Reliability of CKD-EPI predictive equation in estimating chronic kidney disease prevalence in the Croatian endemic nephropathy area.

INTRODUCTION: Chronic kidney disease (CKD) is a significant public health problem and it is not possible to precisely predict its progression to terminal renal failure. According to current guidelines, CKD stages are classified based on the estimated glomerular filtration rate (eGFR) and albuminuria. Aims of this study were to determine the reliability of predictive equation in estimation of CKD prevalence in Croatian areas with endemic nephropathy (EN), compare the results with non-endemic areas, and to determine if the prevalence of CKD stages 3-5 was increased in subjects with EN. MATERIALS AND METHODS: A total of 1573 inhabitants of the Croatian Posavina rural area from 6 endemic and 3 non-endemic villages were enrolled. Participants were classified according to the modified criteria of the World Health Organization for EN. Estimated GFR was calculated using Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). RESULTS: The results showed a very high CKD prevalence in the Croatian rural area (19%). CKD prevalence was significantly higher in EN then in non EN villages with the lowest eGFR value in diseased subgroup. CONCLUSIONS: eGFR correlated significantly with the diagnosis of EN. Kidney function assessment using CKD-EPI predictive equation proved to be a good marker in differentiating the study subgroups, remained as one of the diagnostic criteria for EN.

Low-Coverage Exome Sequencing Screen in Formalin-Fixed Paraffin-Embedded Tumors Reveals Evidence of Exposure to Carcinogenic Aristolochic Acid.

BACKGROUND: Dietary exposure to cytotoxic and carcinogenic aristolochic acid (AA) causes severe nephropathy typically associated with urologic cancers. Monitoring of AA exposure uses biomarkers such as aristolactam-DNA adducts, detected by mass spectrometry in the kidney cortex, or the somatic A>T transversion pattern characteristic of exposure to AA, as revealed by previous DNA-sequencing studies using fresh-frozen tumors. METHODS: Here, we report a low-coverage whole-exome sequencing method (LC-WES) optimized for multisample detection of the AA mutational signature, and demonstrate its utility in 17 formalin-fixed paraffin-embedded urothelial tumors obtained from 15 patients with endemic nephropathy, an environmental form of AA nephropathy. RESULTS: LC-WES identified the AA signature, alongside signatures of age and APOBEC enzyme activity, in 15 samples sequenced at the average per-base coverage of approximately 10×. Analysis at 3 to 9× coverage revealed the signature in 91% of the positive samples. The exome-wide distribution of the predominant A>T transversions exhibited a stochastic pattern, whereas 83 cancer driver genes were enriched for recurrent nonsynonymous A>T mutations. In two patients, pairs of tumors from different parts of the urinary tract, including the bladder, harbored overlapping mutation patterns, suggesting tumor dissemination via cell seeding. CONCLUSIONS: LC-WES analysis of archived tumor tissues is a reliable method applicable to investigations of both the exposure to AA and its biologic effects in human carcinomas. IMPACT: By detecting cancers associated with AA exposure in high-risk populations, LC-WES can support future molecular epidemiology studies and provide evidence-base for relevant preventive measures.

Chronic dietary exposure to aristolochic acid and kidney function in native farmers from a Croatian endemic area and Bosnian immigrants.

BACKGROUND AND OBJECTIVES: Improvements in agricultural practices in Croatia have reduced exposure to consumption of aristolochic acid-contaminated flour and development of endemic (Balkan) nephropathy. Therefore, it was hypothesized that Bosnian immigrants who settled in an endemic area in Croatia 15-30 years ago would be at lower risk of developing endemic nephropathy because of reduced exposure to aristolochic acid. To test this hypothesis, past and present exposure to aristolochic acid, proximal tubule damage as a hallmark of endemic nephropathy, and prevalence of CKD in Bosnian immigrants were analyzed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this cross-sectional observational study from 2005 to 2010, 2161 farmers were divided into groups: indigenous inhabitants from endemic nephropathy and nonendemic nephropathy villages and Bosnian immigrants; α-1 microglobulin-to-creatinine ratio >31.5 mg/g and eGFR<60 ml/min per 1.73 m(2) were considered to be abnormal. RESULTS: CKD and proximal tubule damage prevalence was significantly lower in Bosnian immigrants than inhabitants of endemic nephropathy villages (6.9% versus 16.6%; P<0.001; 1.3% versus 7.3%; P=0.003, respectively); 20 years ago, Bosnian immigrants observed fewer Aristolochia clematitis in cultivated fields (41.9% versus 67.8%) and fewer seeds among wheat seeds (6.1% versus 35.6%) and ate more purchased than homemade bread compared with Croatian farmers from endemic nephropathy villages (38.5% versus 14.8%, P<0.001). Both Croatian farmers and Bosnian immigrants observe significantly fewer Aristolochia plants growing in their fields compared with 15-30 years ago. Prior aristolochic acid exposure was associated with proximal tubule damage (odds ratio, 1.64; 95% confidence interval, 1.04 to 2.58; P=0.02), whereas present exposure was not (odds ratio, 1.31; 95% confidence interval, 0.75 to 2.30; P=0.33). Furthermore, immigrant status was an independent negative predictor of proximal tubule damage (odds ratio, 0.40; 95% confidence interval, 0.19 to 0.86; P=0.02). CONCLUSIONS: Bosnian immigrants and autochthonous Croats residing in endemic areas are exposed significantly less to ingestion of aristolochic acid than in the past. The prevalence of endemic nephropathy and its associated urothelial cancers is predicted to decrease over time.

Value of cytology in small cell lung carcinoma diagnostic--single-center study.

Small cell carcinoma of the lung (SCLC) together with the large cell neuroendocrine carcinoma (LCNEC), typical carcinoid (TC), and atypical carcinoid (AC) make a group of morphologically identifiable neuroendocrine tumors. The differential diagnosis of SCLC includes, first of all, other neuroendocrine tumors, and primary or metastatic non-small cell carcinomas. Although the criteria for the morphologic separation from other tumors of the lung are defined, in everyday practice it can be a problem, both in cytology and with histological samples. Accurate and early differentiation of the SCLC is important because it exhibits aggressive behavior, rapid growth, early spread to distant sites, but also exquisite sensitivity to chemotherapy and radiation. The study included 127 patients who underwent bronchoscopic examination or percutaneous transthoracic fine-needle aspiration (PTTFNA) during the period from early 2003 to 2007 in University Hospital Center Osijek whose cytological diagnosis was SCLC. The value of cytological diagnosis was determined by comparing it with histological findings obtained from a biopsy sample during bronchoscopy or on a resection specimen in 50 patients. In the remaining 77 patients, histological verification of cytological diagnosis was not made and the patients were treated based on cytological diagnosis of small cell carcinoma. In 76% of cases (38/50) cytological diagnosis of small cell lung carcinoma was also confirmed histologically. In 8% of cases (4/50) adenocarcinoma was histologically confirmed, in 10% (5/50) of the cases the squamous carcinoma was confirmed, and there was one case of urothelial carcinoma, one case of sarcoma and one undifferentiated carcinoma. Cytological diagnosis of SCLC was made in all cases in a brush smear while the catheter aspirate was positive in only 32 cases (25.8%). Median survival in the group of patients with histologically confirmed small cell cancer was 238 days, for women 250 days, and for men 237 days. Cumulative survival was 63.2% for 6 months, 26.3% for 12 months, 13.2% for 18 months and 7.9% for two years. In conclusion, cytology is a reliable and relatively non-invasive method for patients. Our results confirm that there is a good correlation between cytology and histology diagnoses, especially when it comes to malignant lesions. In determining the type of tumor cytology must be supported with additional methods, especially in cases when it is not possible to take samples for histological verification.

Evaluation of diagnostic criteria for endemic nephropathy.

Diagnosis of endemic nephropathy (EN) is based on the combination of several clinical and laboratory criteria. Despite extensive research no specific diagnostic biomarker for EN has yet been identified. The aim of the study was to evaluate the diagnostic significance of the variables previously proposed as diagnostic criteria, but also new ones. After an extended questionnaire, the clinical and laboratory examination population in EN villages was classified according to the modified WHO criteria. The urinary active form of TGF-ß was measured with a bioassay using a cell line which expresses luciferase activity. In the study we used ROC analysis to examine the predictive value of the tested variables. In the study there was no difference in haemoglobin level between the study subgroups. Leucine aminopeptidase (LAP) in urine and active urinary TGF-ß levels were increased in the EN diseased group when compared to other subgroups, but they did not fulfil the statistical criteria needed for differentiating a diseased form from other study subgroups. Both kidney length and parenchima thickness, alfa1-microglobulinuria, and kidney function assessed by MDRD formula were the variables that differentiated the study subgroups well. Based on our results the cut-off value of alfa1-microglobulin for screening should be 23.5 mg/g creatinine instead of 15 mg/g creatinine in the present criteria, and for making a diagnosis of EN 31,5 mg/g creatinine. Persons with a positive family history for EN had a 5.8 times greater risk of developing EN when compared to a negative one. Taken together, the above-mentioned variables should be implemented in new uniform diagnostic criteria for EN.

Fine needle aspiration cytology of adrenocortical carcinoma--case report.

A 49-year-old woman presented for hirsutism, deep voice and hypertension. Ultrasonography (US) revealed a solitary tumor mass, eight cm in size, of the right adrenal gland. Laboratory tests showed it to be a hormonally active, androgen secreting tumor (elevated testosterone level), which was consistent with the clinical picture of the disease. After histopathological analysis tumor was signed out as adrenocortical carcinoma, a low risk carcinoma according to Weiss' classification. One year later on regular follow up, US revealed a suspicious growth measuring 65 x 43 mm in the projection of the lower pole of the right kidney. The finding was verified by computerized tomography and the patient was reoperated on. Exploration revealed secondary growth in the region of greater omentum, without infiltration of adjacent organs. Histopathologic analysis confirmed metastatic ACC. 8 months after the second operation and after 6 chemotherapy cycles according to EAP protocol, control CT showed enlarged para-aortic lymph nodes and a node along the upper pole of the right kidney. Cytologic puncture was performed. Cytologic opinion was recidive of primary malignant disease. ACC is a rare malignant epithelial tumor of adrenal cortical cells, with high malignant potential. Morphologically (histopathology and cytology), differential diagnosis includes adenoma on the one hand, and renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) on the other hand. A combined evaluation of clinical features, size or weight, microscopic appearance, immunohistochemical and molecular genetic data is necessary to ensure a correct diagnosis. The purpose of this case report is to present clinical and cytomorphologic features of our case of adrenocortical carcinoma which is very rare in cytology practice.

The value of urinary decoy cells finding in patients with kidney transplantation.

Childhood infection with polyomaviruses leads to a life-long latent infection of renal and urinary tract epithelia. Replication in the reno-urinary epithelium is associated with viral cytopathic changes such as nuclear inclusions and decoy cells. During the 2005-2009 period, cytological urine analysis was performed in 154 samples (94 male and 60 female) from patients with kidney transplantation (n = 19), simultaneous pancreas-kidney transplantation (SPKT) (n = 9) and simultaneous kidney and liver transplantation (n = 2). Urine samples were analyzed monthly following transplantation according to the protocol. The period from transplantation to the first occurrence of decoy cells in the urine and the period of decoy cell persistence in the urine were assessed. The presence of decoy cells (< 10 and > 10 decoy cells) and red blood cells (< 20 E, 20-100 E and > 100 E) per cytospin smear was semiquantitatively determined, along with analysis of inflammatory cells (neutrophilic granulocytes) and fungi. In patients with decoy cells detected, their sensitivity, specificity, and negative and positive predictive value for BK virus nephropathy were calculated. Correlation of the study parameters was estimated by use of Kruskal-Wallis test (Statistica 7.1, StatSoft Inc., Tulsa, USA). Decoy cells were found in 30 patients (20 male and 10 female), age median 40 (range 16-69) years, at a mean of day 115 (range day 5-747) post transplantation, whereas their presence was recorded for a mean of 141 (range 77-771) days. Immunohistochemical staining of kidney biopsy sample for polyomavirus (SV40 large T-antigen) yielded positive reaction in 2/30 (7%) patients. Erythrocyturia was present in 29/30 patients with decoy cells. The number of decoy cells per cytospin smear generally ranged less than 10 in 25/30 patients, whereas more than 10 decoy cells per cytospin smear were only recorded in 5/30 patients. Immunohistochemistry produced positive finding for BK virus in one patient with SPKT and simultaneous kidney and liver transplantation each, which was statistically significantly more common as compared with patients with kidney transplantation alone (p = 0.0244). Immunohistochemical positivity for BK virus was more significant in cases with more than 10 decoy cells detected in cytospin smear (p = 0.013). In BK nephropathy, the finding of urinary decoy cells showed a 100% sensitivity, 84% specificity, 100% negative predictive value and 6% positive predictive value. BK virus nephropathy remains a significant post transplantation complication.

Comparison of occurrence of upper urinary tract carcinomas in the region with endemic villages and non-endemic nephropathy region in Croatia.

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial renal disease of a still unknown etiology, associated with an increased frequency of urothelial carcinoma, particularly of the upper urinary tract (UUT). The aim of the study was to compare the occurrence of UUT carcinomas between Brodsko-Posavska Region (BPR) which is the region with endemic villages and the non-endemic region of Zagreb (ZG) in two six-year periods with a 20 year period separating the two, pointing out a possible difference in occurrence regarding war in Croatia (1991-1995). Comparing BPR and ZG regions we found a more then 5 times higher frequency of UUT carcinomas in BPR in the first period and more than 4.5 times higher frequency in the second period. Women in BPR were more frequently affected with UUT carcinomas.