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Background The aim of this study was to evaluate the role of histopathological and biochemical parameters in the prediction of the presence and number of PSMA positive lesions consistent with the metastatic spread of prostate cancer on Ga-68-PSMA PET images. Methods Biochemical, histopathological and imaging data of 302 prostate cancer patients who underwent Ga-68-PSMA-11 PET/CT or PET/MR imaging for primary staging were retrospectively analyzed. Patients were divided into two groups as "PET positive" and "PET negative" according to the presence of pathologic extraprostatic PSMA involvement. "PET positive" patients were additionally divided into two groups: oligometastatic (1-3 metastatic lesion) and multimetastatic (>3 metastatic lesions). Results The mean age of patients was 66.8 +/- 7.6 years. Imaging modality was PET/MR in 223 (73.8%) and PET/CT in 79 (26.2%) of patients. Total PSA, PSA density (PSAD), ALP, and tumor ratio in biopsy specimens were found to be significantly higher in "PET positive" group compared to "PET negative" group and in multimetastatic group compared to oligometastatic group. PET positivity was observed in 3.8% of the low-intermediate risk groups (ISUP 1-3 and total PSA 20 ng/ml or PSAD >= 0.15 ng/ml/cc) with a relative risk of 12 (p < .001). The prediction models to predict the PET positivity and the presence of distant metastasis had AUCs of 0.901 and 0.925, respectively; with ALP, total PSA, and tumor ratio in needle biopsy specimen as significant independent predictors (p < .05). Conclusions In this study, Ga-68-PSMA-11 PET positivity was significantly higher in the high-risk patient group than in the low-intermediate risk groups. The prediction models used for predicting the PET positivity and the presence of distant metastasis on PET imaging were successful with high discriminatory powers. In addition to total PSA and ISUP GG, ALP and tumor ratio in biopsy specimens can be used to identify high-risk patients.

Gliomas are the most common primary tumors of CNS. Despite advance in elucidation of molecular pathogenesis, gliomas still remains incurable. In the study, it was aimed to investigate possible connection between ACE, AGTR1 polymorphism with glioma pathogenesis and also relationship between some angiogenic markers and gliomagenesis. 96 patients and 104 controls were included. ACE I/D, AGTR1 -168A/G, AGTR1 -535C/T, AGTR1 -825T/A, VEGF +936C/T and VEGF -2578C/A polymorphisms were investigated by PCR-RFLP. Allele/genotype frequencies between patients and controls were determined. Relative gene expressions of ACE, AGTR1 and VEGF were detected by Real Time-PCR while, ACE, VEGF, ET-1, eNOS and NO levels were measured in both serum and tissue by ELISA. In AGTR1 -168A/G polymorphism, the risk of glioma in AA genotype decreased, while increased by 2.27 times in G allele. Allele frequency and genotype distributions of other polymorphisms were found similar between two groups. Serum ACE, VEGF, eNOS, NO and tissue ACE, ET-1, eNOS, NO were also different between patients and controls. ACE, AGTR1 and VEGF expressions of patients were found significantly higher than controls. This results provide the first evidence linking polymorphism in AGTR1 -168A/G with glioma risk in Turkish population.

Neutrophil-to-lymphocyte ratio and platelet (thrombocyte)-to-lymphocyte ratio have become accepted markers of inflammation in recent years and are used to assess disease activity in some diseases. In this study, we investigated the relationship between these values and acute rejection attacks, as well as their role in determining chronic allograft nephropathy, in follow-up of pediatric kidney transplant recipients.Our study included 58 kidney transplant recipients (age 5-18 years) with at least 5-year follow-up at our center. Patients with history of secondary transplant, concomitant malignancy, and shorter follow-up were excluded. Medical history and laboratory parameters pretransplant and at 1, 3, and 6 months and 1, 2, 3, 4, and 5 years posttransplant, as well as kidney biopsy reports, were reviewed.Both neutrophil-to-lymphocyte (P = .003) and thrombocyte-to-lymphocyte (P = .002) ratios were significantly higher during acute rejection attacks. Although both values were higher in patients with chronic allograft nephropathy at 5 years posttransplant, differences were not statistically significant (P = .69 and P = .55). When patients with and without chronic allograft nephropathy within 5 years were compared, those who developed chronic allograft nephropathy had significantly higher neutrophil- tolymphocyte and thrombocyte-to-lymphocyte ratios at all periods in the first 2 and 4 years posttransplant, respectively. Among patients who had acute rejection attacks, those who subsequently developed chronic allograft nephropathy had higher neutrophil-tolymphocyte ratio in the first 3 years posttransplant, with higher thrombocyte-to-lymphocyte ratio at all posttransplant periods.This is the first study on neutrophil- tolymphocyte and thrombocyte-to-lymphocyte ratios in pediatric kidney transplant recipients. Our results indicated that both values can be useful and easily accessible markers in acute rejection diagnosis and determining chronic allograft nephropathy development risk, which are 2 major causes of kidney graft loss posttransplant. Pediatric studies with larger populations are needed to support our findings.

Introduction: In this study, we aimed to investigate the correlation between Cajal cell density and preoperative and postoperative radiological and scintigraphic parameters in ureteropelvic junction obstruction (UPJO). Methods: The study group consisted of 41 renal units (38 consecutive patients; 13 female and 25 male) surgically treated for UPJO. UPJ specimens from patients were immuno-stained with CD117 (c-kit) antibody for interstitial Cajal cells (ICCs). The relation between Cajal cell density and preoperative and postoperative radiological and scintigraphic parameters was evaluated. Results: The mean age of the patients was 8.52 ± 8.86 (0–35) years. The density of Cajal cells was defined in 2 groups for convenient analysis as 0–5 cells (low) in 19 (46.3%) patients and >5 cells (moderate-high) in 22 (53.6%). There was significant difference between the preoperative and postoperative anteroposterior diameters of the related kidneys in both Cajal groups (p = 0.001-low, p = 0.000-moderate-high) independent of Cajal cell density. Regression in hydronephrosis postoperatively was determined in both Cajal groups (77.8%-low, 64.7%-moderate-high); however, there was no difference between them (p = 0.39). Preoperative T1/2 was significantly longer in the low Cajal group (p = 0.02). Postoperative T1/2 decreased in both low (p = 0.000) and moderate-high (p = 0.001) Cajal groups, but no difference was found between them (p = 0.24). There was significant improvement in the kidney differential function after surgery in the low Cajal density group (p = 0.015) while there was no correlation between the scintigraphic success or improvement and Cajal cell density (p = 0.51). Discussion/Conclusion: ICC deficiency/density could not be shown as a predictive factor for the determination of success rate of pyeloplasty. Despite the lack of any evidence for the degree of deficiency as an indicator for the severity of obstruction and prediction of surgical success, further studies are needed for confirmation.

Background Hypospadias is a common congenital anomaly which is determined as an abnormal urethral opening on the ventral face of penis. The purpose of this rat model study was to research the effect of topically applied Aloe vera after a tubularized incised plate urethroplasty (TIPU). Methods The TIPU model was applied to male Wistar albino rats. A total of 30 rats were randomly grouped into 3 groups of 10. Group I was assigned as the control group, treated with 0.9% saline only twice a day for 15 days. Group II received topical Aloe vera gel once a day and Group III received Aloe vera gel twice a day. Spongiofibrosis was graded as 0: none, 1+:≤10% tissues involved, 2+:10%-49% tissues involved, 3+: ≥ 50% tissues involved. Results A higher degree of fibrosis and inflammation was determined in the Group I subjects than in Groups II and III. Fibrosis of grade 3+ was observed in 33% of the control group and not in any of the two Aloe groups (p = 0.043). Inflammation of grade 3+ was seen in 66.7% of the control group, in 10% of Group II, and in 33% of Group III (p = 0.02). Conclusions The topical application of Aloe vera to a surgically created tubularized incised plate urethroplasty model decreased inflammation and fibrosis that may affect the success rates of this operation.

OBJECTIVE To evaluate the diagnostic accuracy of the 68 gallium (68 Ga) prostate-specific membrane antigen (PSMA) positron emission tomography/magnetic resonance imaging (PET/MRI) and multiparametric MRI (mpMRI) by region-based comparison of index tumour localisations using histopathological tumour maps of patients who underwent radical prostatectomy because of clinically significant prostate cancer. PATIENTS AND METHODS The study included 64 patients who underwent radical prostatectomy after primary staging with mpMRI and 68 Ga-PSMA PET/MRI. Diagnostic analysis was performed by dividing the prostate into four anatomic regions as left/right anterior and left/right posterior. The extension of the lesions in mpMRI and the pathological uptake in 68 Ga-PSMA PET/MRI were matched separately for each region with the extension of the index tumour into each region. RESULTS The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and the accuracy of mpMRI and 68 Ga-PSMA PET/MRI are shown as 55.7%, 91.8%, 80.6%, 77.2%, 78.1%, and 60.8%, 94.3%, 86.8% 79.8%, 83.5%, respectively. 68 Ga-PSMA PET/MRI has higher sensitivity and specificity compared with mpMRI. However, no statistically significant difference was found (P = .464). Combined imaging had significantly higher diagnostic accuracy compared with mpMRI and 68 Ga-PSMA PET/MRI (change in AUC: 0.084 and 0.046, P

Introduction. More than 50% of glomerular crescent formation is required for a diagnosis of crescentic glomerulonephritis in a kidney biopsy. Although treatment protocols have been established for diffuse crescentic glomerulonephritis, there is no standard treatment for patients with fewer crescents in renal biopsies. In this study the importance of crescent percentage and clinical features on renal survival independent of underlying disease was investigated. Methods. This retrospective observational study was conducted between 2013 and 2017. Forty-nine patients with crescent formation in their kidney biopsies were evaluated. We compared clinicopathological features and renal survival. We evaluated the factors affecting the course of end stage renal disease (ESRD). Results. A total of 49 patients (57% male and median age 49 years) were enrolled in this study. 39% of patients developed ESRD at follow-up. Logistic regression analysis showed that the requirement for renal replacement treatment on admission (p < 0.001), serum creatinine level above 2.7 mg/dL (p < 0.001), the presence of more than 50% glomerulosclerosis (p = 0.04) and more than 34% crescent formation (p = 0.002) were significantly associated with ESRD. Kaplan-Meier survival analysis revealed that patients with less than 34% crescent in kidney biopsy and a serum creatinine level less than 2.7 mg/dL had increased kidney survival (log-rank test p: 0.01 and p: 0.002). Conclusion. Patients with crescent formation in kidney biopsy more than 34% should be evaluated for more aggressive treatment modalities regardless of the underlying disease, especially if the serum creatinine level is above 2.7 mg/dL.

Adipose tissue is the primary source of many pro-inflammatory cytokines in obesity. Macrophage numbers and pro-inflammatory gene expression are positively associated with adipocyte size. Free fatty acid and tumor necrosis factor-α involve in a vicious cycle between adipocytes and macrophages aggravating inflammatory changes. Thereby, M1 macrophages form a characteristic ‘crown-like structure (CLS)’ around necrotic adipocytes in obese adipose tissue. In obese women, CLSs of breast adipose tissue are responsible for both increase in local aromatase activity and aggressive behavior of breast cancer cells. Interlinked molecular mechanisms between adipocyte–macrophage–breast cancer cells in obesity involve seven consecutive processes: Excessive release of adipocyte- and macrophage-derived inflammatory cytokines, TSC1–TSC2 complex–mTOR crosstalk, insulin resistance, endoplasmic reticulum (ER) stress and excessive oxidative stress generation, uncoupled respiration and hypoxia, SIRT1 controversy, the increased levels of aromatase activity and estrogen production. Considering elevated risks of estrogen receptor (E2R)-positive postmenopausal breast cancer growth in obesity, adipocyte–macrophage crosstalk is important in the aforementioned issues. Increased mTORC1 signaling in obesity ensures the strong activation of oncogenic signaling in E2Rα-positive breast cancer cells. Since insulin and insulin-like growth factors have been identified as tumor promoters, hyperinsulinemia is an independent risk factor for poor prognosis in breast cancer despite peripheral insulin resistance. The unpredictable effects of adipocyte-derived leptin–estrogen–macrophage axis, and sirtuin 1 (SIRT1)–adipose-resident macrophage axis in obese postmenopausal patients with breast cancer are unresolved mechanistic gaps in the molecular links between the tumor growth and adipocytokines.

Objective Sunitinib is a novel oral multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activities. This study evaluates ezrin expression in sunitinib-treated metastatic clear cell renal cell carcinoma (ccRCC) patients and elucidates its role as a possible marker for survival. Materials and methods The expression of ezrin was measured by immunohistochemistry in 80 patients with ccRCC treated by first-line sunitinib between January 2007 and June 2012. Kaplan-Meier curves and log-rank tests were used for analysis of progression-free survival and overall survival (OS), and a multivariate Cox proportional hazard model was employed to identify factors with an independent effect on the survival. Results In multivariate analysis, liver metastasis (P = 0.018; hazard ratio [HR]: 3.707 (1.257-10.931) and overexpression of ezrin (P = 0.006; HR: 2.993 (1.373-6.523 95% confidence interval) were remained significant factors influencing OS. Overexpression of ezrin in the patients who had progressed in the first 3 months was higher than in the patients who had progressed after 3 months (P = 0.003). The median OS was longer in patients with low levels of ezrin expression (27 months) compared to patients overexpressing ezrin (12 months) (P = 0.001). Conclusion This is the first study in the literature showing that ezrin status is related with prognosis in patients with metastatic ccRCC.

Objective To evaluate the diagnostic accuracy of the 68Gallium (68Ga) - prostate specific membrane antigen (PSMA) positron emission tomography/magnetic resonance imaging (PET/MRI) and multiparametric MRI (mpMRI) by region-based comparison of index tumour localisations using histopathological tumour maps of patients who underwent radical prostatectomy due to clinically significant prostate cancer. Patients and Methods The study included 64 patients who underwent radical prostatectomy after primary staging with mpMRI and 68Ga-PSMA PET/MRI. Diagnostic analysis was performed by dividing the prostate into four anatomic regions as left/right anterior and left/right posterior. The extension of the lesions in mpMRI and the pathological uptake in 68Ga-PSMA PET/MRI were matched separately for each region with the extension of the index tumour into each region. Results The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and the accuracy of mpMRI and 68Ga-PSMA PET/MRI are shown as 55.7%, 91.8%, 80.6%, 77.2%, 78.1% and 60.8%, 94.3%, 86.8% 79.8%, 83.5%, respectively. 68Ga-PSMA PET/MRI has higher sensitivity and specificity compared with mpMRI. However, no statistically significant difference was found (p = 0.464). Combined imaging had significantly higher diagnostic accuracy compared with mpMRI and 68Ga-PSMA PET/MRI (change in AUC: 0.084 and 0.046, p < 0.001 and p = 0.028, respectively), while no statistically significant difference was found between mpMRI and 68Ga-PSMA PET/MRI (change in AUC: 0.038, p = 0.246). Conclusion 68Ga-PSMA PET/MRI had higher clinical diagnostic accuracy in prostate cancer compared with mpMRI. Diagnostic accuracy was significantly increased in the combined use of both imaging modalities.

To evaluate the diagnostic accuracy of theThe study included 64 patients who underwent radical prostatectomy after primary staging with mpMRI andThe sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and the accuracy of mpMRI and

The aim of this study was to define the clinicopathologic features of phospholipase A2 receptor (PLA2R) and/or thrombospondin type-1 domain-containing 7A (THSD7A) associated membranous nephropathy(MN) focusing on their impact to disease relapse and response to treatment. A total of 201 patients were enrolled for baseline clinical and histopathological features and 102 patients with a clinical follow-up for more than 1 year were evaluated for outcomes. Immunohistochemical staining was performed with PLA2R and THSD7A antibodies on kidney biopsies and glomerular staining was evaluated. PLA2R expression was observed in 75% of the patients’ biopsies; however, THSD7A expression was present only in 7 patients’ biopsies (3.5%). No significant difference was found between histopathological and clinical features of PLA2R positive and negative patients, collectively. Glomerular PLA2R expression was significantly associated with complete and complete/partial remission with first-line treatment; however, overall complete, and complete/partial remission rates did not differ from PLA2R negative patients (p = 0.2 and p = 0.8). Male gender, the presence of IgG4 staining and a necessity of immunosuppressive treatment were significantly associated with glomerular PLA2R expression. One patient, who developed end-stage renal disease, had glomerular expression for both PLA2R and THSD7A. Three patients with THSD7A-positive MN achieved complete remission. The probability of achieving complete remission is high in patients with PLA2R-positive MN for whom the relapse rate was also higher. The overall renal outcome did not differ from PLA2R negative cases. Low incidence of THSD7A-positive MN reduces the possibility of future randomized controlled trials.

Objective: To compare the ameliorating effects of carvedilol and nebivolol on kidney Ischemia/Reperfusion Injury (IRI).

© 2022Purpose: To evaluate the European Society of Urogenital Radiology (ESUR) score, the Likert scale, tumor contact length (TCL) > 1 cm, and EPE (extraprostatic extension) grade in predicting EPE at multiparametric magnetic resonance imaging (mp-MRI). Methods: Seventy-nine patients who underwent 3-T MRI and were histopathologically confirmed by microblocks were enrolled in this retrospective study. The index lesions were interpreted by two experienced radiologists. Apparent diffusion coefficient (ADC) values were also noted. Weighted κ statistics were used to compare interreader agreement. Univariate logistic regression analysis was performed to define independent predictors of EPE status. Multivariable logistic regression and receiver operating characteristic (ROC) analysis were performed to compare the MRI-based methods and clinical variables (ISUP grade, prostate volume and PSA density) + MRI-based methods for pathologic EPE prediction by using the area under the curve (AUC) value. Results: The mean age was 64.5 years ± 6.2. 33/79 (41.8%) patients had pathologic EPE. As ESUR score showed weak interreader agreement (κ = 0.537), Likert scale, TCL, and EPE grade showed moderate agreement (κ = 0.608, κ = 0.747, κ = 0.647 respectively). Univariate ROC analysis result showed that all MRI-based score systems, mean ADC value, the ISUP grade, prostate volume, PSA density were the best variables in predicting EPE. ROC analysis results of four MRI-based methods showed good diagnostic performance. At multivariate analysis, all clinical models showed excellent diagnostic performance. Conclusion: All four MRI-based methods had good diagnostic performance. Furthermore, consisting of both qualitative and quantitative parameters and being less reader experience dependent, EPE grade was a promising method in predicting EPE. All clinical models showed excellent diagnostic performance.

Introduction. IgA nephropathy (IgAN) is a heterogeneous disease with highly variable clinical and histopathological features. We investigated the effects of Oxford classification and clinical features on renal survival in patients with IgAN. Methods. This retrospective observational study conducted from 2013 to 2017. Ninety-seven patients who were followed up more than six months were examined. Results. A total of 97 patients (68% male and median age 40 years) were enrolled in this study. 13% of patients developed end stage renal disease (ESRD) within the median of 37 months of follow-up. Need for renal replacement therapy at the time of diagnosis, serum creatinine level of higher than 1.97 mg/dl, serum albumin level less than 3.5 gr/dl, 24-hour urine protein level of higher than > 3.5 g/day, the percentage of glomerulosclerosis higher than 53%, T2 score and total MEST-C score higher than two were found to be significant predictors of development of ESRD. None of the clinical or histopathological features were found to be significant predictor of steroid treatment sensitivity except T1-2 scores. Conclusion. We think that IgA nephropathy is a heterogeneous disease that requires clinical and histopathological features to be evaluated together, but not individually, to determine renal survival. What is new. Iga nephropathy is a heterogeneous disease and modern pathologic classification systems is not enough to predict to prognosis. Histopathological features to be evaluated with clinical features, but not individually, to determine renal survival. Also glucocorticoid treatment response seems to be independent from clinical and histopathological features except T1-2 score.

Ogut, Betul/0000-0002-1385-7324; Pasaoglu, Ozge Tugce/0000-0002-5221-9034; sutcuoglu, osman/0000-0003-3835-2741; DERICI, ULVER/0000-0002-9741-6779 WOS: 000520339700001 PubMed: 32174194 Silymarin (Silybum marianum) has some protective effects against drug toxicity (cisplatin, acetaminophen, adriamycin, gentamicin etc.). Colistin is a strong antimicrobial, which is frequently used in the treatment of resistant gram-negative bacterial infections in recent years although it has nephrotoxic potential. This study was aimed to determine the role of silymarin against colistin-induced acute nephrotoxicity (CIN). Rats were randomly divided into four groups. The control group was treated with tap water whereas groups 2 and 3 received silymarin (orally, 100 mg/kg/day) and colistin (intraperitoneally, 750.000 IU/kg/day) for seven days, respectively. Group 4 received both 750,000 IU/kg/day colistin and 100 mg/kg/day silymarin for seven days. After euthanasia, histopathological and biochemical examinations were completed for the kidney tissue specimens and blood samples. All parameters of the control and silymarin groups were similar. Severe weight loss was seen in the groups receiving colistin (groups 3 and 4). Silymarin significantly increased glutathione peroxidase and superoxide dismutase levels when administered with colistin in group 4 only. Acute tubular injury, tubular necrosis, meduller congestion, interstitial inflammation and apoptotic indices of colistin group were significantly higher than the control group. The administration of colistin with silymarin (group 4) was able to make some improvements in tubular necrosis and significant increase in antioxidant capacity. Silymarin increased antioxidant enzyme activity only when used in combination with colistin. The effects of silymarin may become more pronounced when used at higher doses or with a longer duration of treatment and may prevent nephrotoxicity. Turkish Society of Hypertension and Kidney Diseases This study was supported by Turkish Society of Hypertension and Kidney Diseases.

The identification of prognostic factors in patients with glioblastoma multiforme (GBM) represents an area of increasing interest. Carbonic anhydrase IX (CA-IX), a hypoxia marker, correlates with tumor progression in a variety of human cancers. However, the role of CA-IX in GBM remains largely unknown. In the present study, we evaluated the prognostic role of CA-IX in GBM patients. In total, 66 consecutive patients with GBM who received concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide were retrospectively reviewed, and all patients received temozolomide chemotherapy for at least 3 months. Kaplan-Meier curves and log-rank tests were used for analysis of progression-free survival (PFS) and overall survival (OS), and a multivariate Cox proportional hazard model was employed to identify factors with an independent effect on survival. The median OS was longer in patients with low levels of CA-IX expression (18 months) compared to patients overexpressing CA-IX (9 months) (P = 0.004). There was not a statistically significant difference in median PFS (3.5 vs. 8 months, P = 0.054) between patients with high or low levels of CA-IX expression. In multivariate analysis, the variables that were identified as significant prognostic factors for OS were preoperative Karnofsky performance scale score (KPS) (hazard ratio (HR), 3.703; P = 0.001), CA-IX overexpression (HR, 1.967; P = 0.019), and incomplete adjuvant temozolomide treatment (HR, 2.241; P = 0.003) and gross-total resection (HR, 1.956; P = 0.034). Our findings indicated that CA-IX may be a potential prognostic biomarker in the treatment of GBM.

Objective: Biochemical recurrence (BCR) does not occur in all patients with surgical margin (SM) positivity after radical prostatectomy (RP). The aim of our study is to evaluate the effect of additional features such as length, extent and Gleason grade on BCR in the positive SM determined in patients undergoing RP in our clinic. Materials and Methods: Clinicopathologic data and SM characteristics of 56 patients with pathologic stages of pT2-3aN0M0 and surgical border positivity were recorded from patients admitted to our RP database with retropublic RP between August 2001 and January 2015 and their relationship with BCR was evaluated statistically. Results: The median follow-up time of the patients was 39.4 (13-208) months. BCR was detected in 17 (30.3%) of the patients. Prostate specific antigen levels, tumor volumes and tumor percentages were found significantly higher in the patients with BCR (p0.05). According to the Kaplan-Meier survival analysis, the relationship between SMGG and the time of BCR was statistically significant (p=0.04). In SMGG 5 patients, the duration of BCR development was found significantly shorter. According to multivariable Cox regression analysis none of the factors were found to be effective on BCR (p>0.05). Conclusion: SM positivity is one of the important factors for BCR. However, patients with positive SMs are quite heterogeneous and it is obvious that not all patients should be treated in the same way. It is wise to assess adjunctive SM features such as SM, length, Gleason score and grade, and decide according to the patients’ risk groups to decide on adjuvant treatment.

Ewing's family of tumors is aggressive tumors and frequently arises from bone and soft tissue. They might also arise from nonosseous structures such as gastrointestinal tract, adrenal glands, or kidney. Primary renal Ewing's sarcoma (ES)/primitive neuroectodermal tumor is an extremely rare entity which has aggressive clinical course. These high-grade malignant tumors predominantly affect adolescents and young adults. Patients mostly present with nonspecific symptoms such as pain, hematuria, mass, and sensitivity. It is confused with renal cell cancer in imaging techniques. The definitive diagnosis is based on the histopathological examination. Surgical or radiotherapy treatment is used for local control and multiagent chemotherapy used for systemic treatment. Despite all treatment options, prognosis is poor. We aimed to describe the diagnosis and follow-up and treatment of renal ES case that was considered as renal cell carcinoma in imaging but diagnosed as ES via histopathology.

Background/aim: C3 glomerulopathy (C3GP) defines a rare group of glomerulonephritis (GN), which could lead to end stage renal disease (ESRD). Histopathologic features of the disease have yet to be defined and the prognostic factors and optimal treatment are not fully known. The purpose of this study was to determine the demographic, histological change, treatment modalities and outcomes among patients with C3GP. Material and method: This retrospective observational study was conducted in the Department of Nephrology, Gazi University, Ankara, from 2013 to 2017. All patients with kidney biopsies fulfilling the criteria for C3GP were included in the study. Results: Twenty-four patients with C3GP (50% male and of middle age - 43 years old) were enrolled in this study. 21% (5/24) patients developed ESRD. Renal biopsy findings such as crescent formation, glomerulo-sclerosis and tubular atrophy were similar in patients with ESRD, when compared to patients who did not develop ESRD. The treatment modalities of the patients were examined in two groups as MMF based and non-MMF based. The difference in the preservation of eGFR did not reach statistical significance between these two groups. The success rate of complete remission was similar between both groups. Serum creatinine levels >2.3 mg/dl at admission and need for renal replacement treatment (RRT) were associated with decreased renal survival. Conclusion: MMF based or non-MMF based treatments have similar efficacy in C3GP. Serum creatinine level higher than 2.3 mg/dl at the time of diagnosis and need for RRT during admission are a strong predictor of ESRD with high sensitivity and specificity.

WOS: 000382974300005 PubMed ID: 27284123 Objectives. The aims of this study are to evaluate expressions of Ki67, RacGAP1 (MgcRacGAP) and topoisomerase 2 alpha (TOP2a), the markers related with cell proliferation that have been proposed to affect the prognosis in the literature and correlate the results with clinicopathological parameters of breast cancer patients. Methods. Ki67, RacGAP1, and TOP2a antibodies were applied immunohistochemically to the tissue micrarray blocks of 457 female breast cancer patients. The results were correlated with clinical, prognostic, histopathological features, and other immunohistochemical findings (estrogen receptor [ER], progesterone receptor [PR], HER2, cytokeratin [CK]5/6, CK14, epidermal growth factor receptor [EGFR] and vimentin), statistically. Results. Ki67 expression demonstrated direct correlation with TOP2a expression, mitotic count, tumor grade, geographic necrosis, basal-like phenotype. RacGAP1 expression was directly correlated with TOP2a expression, nipple invasion, and number of metastatic lymph nodes, and it was inversely correlated with PR expression. TOP2a expression was directly correlated with vimentin and Ki67 expressions, mitotic count, tumor grade, and geographic necrosis, and nipple invasion, and negatively correlated with ER and PR expressions. Higher TOP2a and Ki67 expressions were correlated with shorter overall survival. Higher TOP2a expression and RacGAP1 positivity were directly correlated with shorter disease-free survival. Conclusion. This study showed that the overexpressions of Ki67, RacGAP1, and TOP2a affect the prognosis adversely, thus to develop target therapies against RacGAP1 and TOP2a as well as using Ki67 as a part of routine pathology practice might be beneficial in breast cancer therapy and prediction of prognosis. Bozok University Scientific Research Projects Unit [2014TF/A92] The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported financially by Bozok University Scientific Research Projects Unit (Project No. 2014TF/A92).

OBJECTIVE: Focal segmental glomerulosclerosis and minimal change disease are primary renal diseases representing with proteinuria. Following the identification of the role of podocyte-related molecules in the glomerular filtration barrier and the detection of the pivotal role of nephrin in the development of congenital nephrotic syndrome, the assessment and expression profiles of these proteins in acquired nephrotic syndrome have also come into question.

Background This study aims to investigate whether preconditioning with alpha-lipoic acid has any protective effect in neuronal damage in an experimental spinal cord ischemia-reperfusion injury model. Methods Eighteen adult male New Zealand rabbits (2.4-3.5 kg) were equally divided into sham, control and treatment groups. The abdominal aorta was occluded for 30 min proximally 1 cm below the renal artery and distally 1 cm above the bifurcation using aneurysm clips in control and treatment groups. Treatment group received intraperitoneal 100 mg/kg lipoic acid 20 min before aortic cross-clamping. The animals were sacrificed 48 hours after the operation and spinal cord segments between L2 and L5 were removed for biochemical and histopathological analysis. Levels of glutathione, malondialdehyde, total nitrate/nitrite, advanced oxidation protein products, catalase, superoxide dismutase, and glutathione peroxidase were examined in spinal cord. Results Preconditioning with alpha-lipoic acid demonstrated significantly favorable effects in all measured parameters of oxidative stress. Histopathological evaluation of the tissues also demonstrated significantly decreased neuronal degeneration, axonal damage, and microglial and astrocytic infiltration in the treatment group compared to the control group. Conclusion The results of this study indicate that alpha-lipoic acid administration before aortic cross-clamping has significant neuroprotective effect on spinal cord injury in rabbits.

WOS: 000439282500010 PubMed ID: 30004053 Background: Mucins may show aberrant expression, localization, and/or glycosylation in multiple malignancies. However, information regarding expression of these mucins is mostly unknown in urothelial tumors. Aim: This study was conducted for examining the expressions of membrane associated and secreted mucin (MUC1) and a secreted gel-forming mucin (MUC2) in urothelial tumors of the urinary bladder. Subjects and Methods: Archival transurethral resection materials of 97 urothelial carcinoma cases were reexamined light microscopically and graded according to the 2004 WHO Classification. Pathological stage was given as pTa, pT1, and pT2. Demonstrative sections were recut for immunohistochemistry for MUC1 and MUC2. The results were statistically analyzed, and P < 0.05 was considered statistically significant. Results: The positivity for MUC1 and MUC2 was 89.7% and 44.3%, respectively. Independent from pathological stage of the tumor, MUC1 expression showed statistically significant correlation with tumor grade (P < 0.05). We did not find any correlation between pathological stage and MUC1 and MUC2 expression (P > 0.05). MUC1 staining pattern in papillary urothelial neoplasm of low malignant potential cases was more commonly apical and superficial (luminal cell layer only). Intermediate cells +/- basal cells or isolated cells or islands of tumor cells with cytoplasmic and/or circumferential membrane positivity for MUC1 and MUC2 were more commonly observed in both low- and high-grade carcinomas. The difference between groups in terms of MUC1 and MUC2 staining was statistically significant (P < 0.05). Conclusions: The staining patterns of both mucins are different between urothelial papillary tumors and may be used to make a differentiation, especially for low-grade papillary urothelial lesions. This difference may also be important in the carcinomatous transformation of urothelial neoplastic and preneoplastic lesions.

Renal biopsy is an important diagnostic procedure in pediatric nephrology. This study retrospectively investigates the indications, results and complications in a single tertiary children’s hospital in Turkey. We evaluated the native and transplant kidney biopsies in Gazi University Pediatric Nephrology Department between 2001 and 2015. A total of 196 biopsies (144 natives and 52 transplants) were included into the study. The mean age of the patients was respectively 10.8 ± 3.5, 13.9 ± 1.5 years. The main indication for a biopsy was non-nephrotic proteinuria with or without hematuria (n= 35), followed by steroid-resistance nephrotic syndrome (SRNS) (n = 34) and Henoch-Schönlein purpura (HSP)–related proteinuria (n = 20) for native kidneys. We found that focal segmental glomerulosclerosis (FSGS) (11.7%) was the most common histopathologic diagnosis for native kidneys, but acute cellular rejection (7.6%) was the most common histopathologic diagnosis for transplant kidneys. The complication rate in our study was founded 6.6% totally. Different complication rates were found in other studies; however, we think that this difference comes from the inspecting methodology of the complications. Hence, we wanted to share our own experience in the context of other studies in the literature.

Purpose: To determine whether prophylaxis with etanercept, an anti-inflammatory drug, would decrease the severity of lung injury in a neonatal rat model of bronchopulmonary dysplasia (BPD); Materials and Methods: Rat pups were divided into three groups: pups exposed to room air (group 1; n = 10), to hyperoxia + placebo (group 2; n = 9), and to hyperoxia + etanercept (group 3; n = 8). Lung morphology was assessed by alveolar surface area percentage, which is a measure of alveolar size. The severities of lung inflammation and antioxidant capacity were assessed by quantifying tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), malondialdehyde (MDA), and superoxide dismutase (SOD) from lung homogenate; Results: The percentage of alveolar surface areas were significantly higher in group 3 compared to group 2 (p = .004) and similar in both group 1 and group 3 (p = .21). The mean level of lung MDA was significantly higher in group 2 compared to group 1 and group 3 (p < .05 for both). Lung homogenate SOD activities in group 3 was significantly higher than group 2 (p < .001). Furthermore, group 3 pups had lower levels of TNF-alpha and TGF-beta in lung homogenate than that in group 2 (p < .05 for both) but similar in both group 1 and group 3; Conclusion: Etanercept has favorable effects on alveolarization as well as inflammation and oxidative stress markers in a neonatal rat model of BPD.

INTRODUCTION: Glomerulonephritis is still the primary cause among the diseases causing end stage renal disease. Helicobacter pylori (HP), also having a local proinflammatory effect on gastric mucosa, can trigger a local and systemic inflammatory response, and consequently have a role in the development of extragastrointestinal defects. MATERIAL AND METHODS: The study was composed of patients diagnosed with primary glomerulonephritis who had dyspeptic complaints throughout the diagnosis. Patients who received endoscopic biopsy upon the determination of pathologic findings in their upper gastrointestinal endoscopy were HP positive in their biopsy material. A triple eradication therapy was initiated for HP. RESULTS: The study included 14 female and 19 male patients, 33 in total, whose biopsy material was determined to be HP positive. Before the eradication for HP, we found serum albumin to be 34.0 (19.0-51.0) g/l, serum total protein 58.6 ±12.9 g/l, serum creatinine 0.9 (0.5-1.2) and proteinuria 3069 (652-12392) mg/day in 24-hour urine. After the eradication, however, serum albumin was found to be 40 (20-52) g/l, serum total protein 62.3 ±11.1 g/l, serum creatinine 1.02 (0.6-1.29) mg/dl and proteinuria was 2850 (172-15181) mg/day in 24-hour urine. A comparison of the results showed that a statistically significant difference is established between the serum albumin, total protein and creatinine values (p = 0.001, p = 0.001 and p = 0.021, respectively), but not between proteinuria values in 24-hour urine (p = 0.990). CONCLUSIONS: Patients with primary glomerulonephritis, HP eradication treatment has an effect on serum albumin levels.

Angiogenesis plays a major role not only in the growth of the primary tumor, but also in metastasis. Due to the angiogenesis in granulation tissue, the tumor cells easily migrate to and locate in this region, thereby accelerating the pathological angiogenesis process and proliferation via presence of the angiogenesis-stimulating factors in this site. In this case report, we present tumor homing to granulation tissue following tooth extraction in a 68-year-old male patient with metastatic lung adenocarcinoma. He applied to hospital due to delayed wound healing after tooth extraction for tooth decay approximately 5 months after the diagnosis. A superficially swollen mass of 6 × 6 cm was detected in the tooth extraction site. The histopathological examination suggested that it was a lung carcinoma metastasis. The presence of tooth extraction history together with the pulmonary adenocarcinoma metastasis in the extraction site was explained as “tumoral homing” to granulation tissue following tooth extraction. This patient is of significance since it is the first case in the literature with “tumor homing” observed in the granulation tissue following tooth extraction.

Renal microangiopathies and membranoproliferative GN (MPGN) can manifest similar clinical presentations and histology, suggesting the possibility of a common underlying mechanism in some cases. Here, we performed homozygosity mapping and whole exome sequencing in a Turkish consanguineous family and identified DGKE gene variants as the cause of a membranoproliferative-like glomerular microangiopathy. Furthermore, we identified two additional DGKE variants in a cohort of 142 unrelated patients diagnosed with membranoproliferative GN. This gene encodes the diacylglycerol kinase DGK epsilon, which is an intracellular lipid kinase that phosphorylates diacylglycerol to phosphatidic acid. Immunofluorescence confocal microscopy demonstrated that mouse and rat Dgk epsilon colocalizes with the podocyte marker WT1 but not with the endothelial marker CD31. Patch-clamp experiments in human embryonic kidney (HEK293) cells showed that DGK epsilon variants affect the intracellular concentration of diacylglycerol. Taken together, these results not only identify a genetic cause of a glomerular microangiopathy but also suggest that the phosphatidylinositol cycle, which requires DGKE, is critical to the normal function of podocytes. J Am Soc Nephrol 24: 377-384, 2013. doi: 10.1681/ASN.2012090903

Lung cancer is the most frequent cause of cancer-related death worldwide. Metastases of non-small cell lung carcinoma to the oral and maxillofacial region are rare. Thus, the diagnosis of a metastatic lesion in the oral cavity is challenging to the clinician and to the pathologist. This report presents a case of a 72-year-old man with metastatic lung adenocarcinoma located in the posterior mandibular region. Next-generation sequencing analysis showed no important mutations in the relevant genes except in the TP53 tumor suppressor gene. (C) 2016 American Association of Oral and Maxillofacial Surgeons

Renal biopsy is the gold standard method for determining the diagnosis, treatment, and prognosis in children with renal disease. This study aims to evaluate the histopathological features of pediatric renal biopsies obtained from the national nephrology registry in the last two decades. Data recorded in the Turkish Society of Nephrology Registry System (TSNRS) in 1991 as well as in between 2001 and 2010 were analyzed. A total of 3892 biopsies were recorded; with the least number in 1991 (total 103 biopsies from 17 centers) and the highest number in 2008 (total 654 biopsies from 23 centers). Glomerular diseases constituted the main group in the registry (62.64%), followed by systemic diseases (20.06%). Focal and segmental glomerulosclerosis (FSGS) and Henoch-Schonlein purpura (HSP) nephritis (IgA vasculitis) were the most common glomerular and systemic diseases, respectively. Overall prevalence of renal amyloidosis and membranous nephropathy (MN) was quite low (1.87% and 1.56%, respectively) in all periods. Compared to 1991, there was an increasing trend in the frequencies of certain disorders including hemolytic uremic syndrome (HUS), IgA nephropathy, and HSP nephritis; and there was a decrease in acute proliferative glomerulonephritis (GN) in 2008. As well as demonstrating the etiologies of renal diseases which can only be identified by renal biopsies, this study provides important information regarding the changing patterns of histopathological findings due to better management of pediatric renal diseases over the years in Turkey.

Summary Introduction Congenital ureteropelvic junction obstruction is one the most common causes of neonatal hydronephrosis. The etiology of the ureteropelvic junction (UPJ) obstruction has not been clearly established. The presence of a hypoplastic, adynamic ureteral segment is thought to be the major cause of an UPJ obstruction. Objective We evaluated the distribution of Cajal cells using immunohistologic methods coupled with light microscopy of the UPJ tissues in obstructed and normal UPJs. Study design The study group consisted of 19 patients who underwent pyeloplasty for UPJ obstruction. Twelve patients who had been operated on for oncological indications constituted the control group. The sections were stained immunohistochemically using CD117 (c-kit) antibody; the numbers of CD117 (+) interstitial cells of Cajal were counted in 10 consecutive high-power fields under the light microscope and the cell density was determined for each case. Results The mean age of the cases who underwent dismembered pyeloplasty and the control group were 116 ± 116 months (14 male, 5 female; 6–420 months) and 279 ± 312 months (9 male, 3 female; 24–948 months) (p = 0.1), respectively. The mean interstitial Cajal cell number in the UPJ obstruction and the control groups were 2.37 ± 2.19 and 24.5 ± 9.73, respectively (p Discussion We found that in cases of UPJ, obstruction the numbers of interstitial Cajal cells were decreased, being either absent or significantly reduced. Although data about the motility are currently not sufficient, the decrease in the number of Cajal cells in patients with UPJ highlights that they might be responsible for the initiation, coordination, and conduction of peristaltic activity along the pelvicalyceal system. Improvement and enhancement of contraction waves arising from the upper urinary system depend on interstitial cells of Cajal, which are the pacemaker cells in smooth muscles. We think that a decreased number of interstitial cells of Cajal have a close relationship with changing ureteral motility when we compare our UPJ obstruction cases with the limited data in the literature. Conclusion Further investigations on these cells will probably give detailed information about the neurophysiology of the urinary system and the diseases that cause congenital hydronephrosis. Download : Download high-res image (132KB) Download : Download full-size image Figure . CD117 (+) Cajal cells (arrows) in the material from patients who had ureteropelvic junction obstruction.

Small cell carcinoma (SmCC) is a rare and aggressive neuroendocrine carcinoma of the bladder. Neuroendocrine carcinomas expressing somatostatin receptors (SSTR) in other viscera such as lung, pancreas, and gastrointestinal system respond to therapy with somatostatin analogs. In the present study, expressions of SSTRs 1 to 5 including type 2A are investigated by immunohistochemistry (IHC) and their relationship with clinicopathologic factors was evaluated. Hundred primary bladder SmCC cases were collected from 12 centers in Turkey. Forty-three cases were pure SmCC. Other cases had mostly papillary urothelial carcinoma as a second component. The percentage of the SmCC component ranged from 5% to 100%. SSTR-2A expression was membranous, whereas the other receptors showed cytoplasmic staining. The percentages of positive cases for SSTR-1, SSTR-2A, SSTR-3, SSTR-4, and SSTR-5 were 4% (3/75), 61.4% (54/88), 2.4% (2/84), 24.4% (20/82), and 6.25% (5/80), respectively. The percentage of SmCC component was positively correlated with the percentage of SSTR-2A expression (P=0.003) while negatively correlated with patient age (P=0.032). SSTR-2A expression was correlated with survival as a bad prognostic factor (P=0.018). SSTR-1, SSTR-3, SSTR-4, and SSTR-5 expressions did not show any statistical significance with any parameter. In conclusion, although the limited number of cases with adequate term follow-up, SSTR-2A expression could be a prognostic factor and somatostatin analogs therapeutic candidate for SmCCs of the bladder as these tumors show high percentage of SSTR-2A expression. © 2016 Wolters Kluwer Health, Inc. All rights reserved.

In this report, we describe a case of fibrillary glomerulonephritis associated with thyroid papillary microcarcinoma arising in a 54-year-old female patient suffering from Hashimoto's thyroiditis. The patient presented with mild edema and a palpable mass on right thyroid lobe. Examinations revealed 1053 mg daily protein excretion and an approximately 1 cm highly vascularized thyroid nodule. She underwent total thyroidectomy and histopathological examination provided evidence of the encapsulated follicular variant of multifocal thyroid papillary microcarcinoma. Thereafter, percutaneous kidney biopsy identified the fibrillary glomerulonephritis for which renin angiotensin system blockage was targeted and, in time, daily protein excretion decreased. The favorable clinical outcome after treatment of carcinoma suggests that there might be a pathophysiological link between autoimmune/malignant pathology and fibrillary glomerulonephritis development.

WOS: 000382210800001, PubMed: 27601882, Objectives: To evaluate the effects of alprostadil (prostaglandin [PGE1] analog) and iloprost (prostacyclin [PGI2] analog) on renal, lung, and skeletal muscle tissues after ischemia reperfusion (I/R) injury in an experimental rat model. Materials and methods: Wistar albino rats underwent 2 hours of ischemia via infrarenal aorta clamping with subsequent 2 hours of reperfusion. Alprostadil and iloprost were given starting simultaneously with the reperfusion period. Effects of agents on renal, lung, and skeletal muscle (gastrocnemius) tissue specimens were examined. Results: Renal medullary congestion, cytoplasmic swelling, and mean tubular dilatation scores were significantly lower in the alprostadil-treated group than those found in the I/R-only group (P

Background/aims: The risk of gastric cancer is increased in patients with intestinal metaplasia. Cyclooxygenase-2 activity is crucial for gastric cancer cell survival and proliferation. We aimed to assess cyclooxygenase-2 expression in patients with intestinal metaplasia or chronic active gastritis and in patients with or without a family history of gastric cancer, i.e. a first-degree relative with gastric cancer. Materials and Methods: One hundred and six patients with histologically proven intestinal metaplasia, chronic active gastritis or normal gastric mucosa were included. Immunohistochemical staining was performed using the immunoperoxidase method. Results: Cyclooxygenase-2 expression was detected in 23.1% of normal gastric mucosa, 70.6% of chronic active gastritis, and 90.5% of intestinal metaplasia. patients. Cyclooxygenase-2 expression was significantly higher in intestinal metaplasia than in chronic active gastritis (p=0.018). Cyclooxygenase-2 expression was significantly more severe in the intestinal metaplasia group when compared to the chronic active gastritis group (p=0.017). Severe cyclooxygenase-2 expression (>60% of cells) was more frequent in the intestinal metaplasia group. Cyclooxygenase-2 expression was higher in the Helicobacter pylori-positive group when compared to the Helicobacter pylori-negative group (80.3% vs 57.1%, respectively; p=0.012). Cyclooxygenase-2 expression did not significantly differ according to presence of a first-degree relative with gastric cancer. Conclusions: Patients with intestinal metaplasia demonstrated increased presence and severity of cyclooxygenase-2 expression. Our findings suggest that cyclooxygenase-2 plays an important role in the stepwise process that eventually leads to gastric cancer. There was no statistically significant difference between the patients with and without a first-degree relative with a history of gastric cancer in terms of cyclooxygenase-2 expression.

The current study is the first to evaluate the protective effect of everolimus on biochemical and histopathological features with an experimental hepatic ischemia reperfusion (I/R) injury model. Twenty-four Wistar Albino rats were randomized into four groups: Group 1 (sham group) was subjected to laparotomy. Group 2 (I/R group) was subjected to ischemia for 1 hour and reperfusion for 24 hours without treatment. Group 3 was treated with 1.5 mg/kg/day everolimus perorally for 7 days without performing I/R. Group 4 was treated with 1.5 mg/kg/day everolimus perorally for 7 days followed with performing I/R. Blood samples and liver tissues were obtained to assess serum aspartate aminotransferase (AST), alanin aminotransferase (ALT), albumin, tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6) and tissue malonyl dialdehyde (MDA), and superoxide dismutase (SOD) levels and histopathologic examination. Serum AST and ALT levels of I/R group were significantly higher than sham group. Serum transaminase levels were significantly decreased after treatment with everolimus (group 4) when compared with I/R group (group 2). TNFα and MDA levels were decreased; however, SOD levels were increased in group 4. The sham group and group 3 showed normal histological findings. Morphologic analysis showed reduced degrees of injury in group 4 than group 2 with regards to cholestasis, sinusoidal dilatation, congestion, hydropic degeneration, and subcapsular necrosis. This is the first report as regards everolimus attenuates biochemical and histopathological alterations of hepatic I/R injury. Everolimus can be a choice for preventing I/R injury during liver transplantation surgery in the future besides its well-known immunosuppressive property.

Background and Aims Fibrinogen gene mutations can rarely result in hepatic fibrinogen storage disease (HFSD). Herein, we report on the first Turkish family carrying the mutation p.Arg375Trp (fibrinogen Aguadilla) in the γ-chain of the fibrinogen (FGG) gene. Methods Clinical, laboratory and histopathological findings of the patient were documented. Molecular study of fibrinogen gene was performed in the patient and her family members. Results The proband was 5 years old girl presenting with advanced liver fibrosis of unknown origin. The child had very low plasma levels of fibrinogen and hypobetalipoproteinemia. Immunomorphologic and electron microscopic studies showed selective and exclusive accumulation of fibrinogen within the endoplasmic reticulum in liver biopsy of the patient. Patient, mother, two sisters and one brother carried p.Arg375Trp mutation (fibrinogen Aguadilla) in FGG gene. The patient was treated with ursodeoxycholic acid and carbamazepine. After 3 months, carbamazepine was suspended upon family decision and unresponsiveness of carbamazepine. Conclusions HFSD is characterized by hypofibrinogenemia and accumulation of abnormal fibrinogen within hepatocytes. In addition, hypofibrinogenemia is associated with hypobetalipoproteinemia in Aguadilla mutation.

Amac: Bu calismada mesane urotelyal kanserlerinin, bi­linen cevresel faktorler esliginde epidemiyolojik analizinin yapilmasi amaclanmistir. Gerec ve yontem: Retrospektif olan bu calismaya 350\'si erkek (%83.4), 70\'i kadin (%16,6) hasta olmak uzere toplam 420 hastaya ait mesane transuretral rezeksiyon, sistektomi ve sistoprostatektomi patoloji arsiv materyal­lerinde; histopatolojik olarak urotelyal karsinom ve dusuk malign potansiyelli papiller urotelyal neoplazi tanisi almis vakalar dahil edildi. Tumor tipi, yas-cinsiyet, invaziv-no­ninvaziv gibi parametrelere ait veriler degerlendirilerek istatistiksel analizleri yapildi. Bulgular: Bu calismada dusuk malign potansiyele sahip papiller urotelyal neoplazi %24.7, dusuk dereceli urotelyal karsinom %46.1 ve yuksek dereceli urotelyal karsinom %29.0 oranlarinda bulundu. Mesane urotelyal karsinom­larinin erkeklerde kadinlara gore 5 kat daha fazla gorul­dugu saptandi. Ayrica, yuksek dereceli papiller urotelyal karsinomun kadinlara kiyasla daha cok erkeklerde (sira­siyla %23,1 ve %31,2), dusuk dereceli papiller urotelyal karsinomun ise erkeklere kiyasla daha cok kadinlarda (sirasiyla %18,5 ve %32,9) goruldugu saptandi. Sonuc: Calisma sonucunda, mesane urotelyal karsinom­larinin erkeklerde kadinlara gore daha fazla goruldugu ve ayrica lamina propria ve muskularis propria invazyonu gosteren yuksek dereceli urotelyal karsinomlarin da yine erkek cinsiyette daha yuksek oranda bulundugu tesbit edildi. Bu tumorlerin, ozellikle de yuksek dereceli olan tip­lerinin neden erkek cinsiyette daha sik goruldugune iliskin kapsamli klinik ve deneysel calismalara ihtiyac vardir.

Background. Infiltration of inflammatory cells into the renal allograft interstitium is the biologic hallmark of alloimmune responses that leads to tubulointerstitial injury and subsequent interstitial fibrosis and chronic allograft failure. The proliferation, stimulation, and infiltration of these inflammatory cells are governed by various proinflammatory and regulatory cytokines. We assessed whether the differences in the genes encoding cytokines (producing low, moderate, or high expression profiles) may affect the infiltration of inflammatory cells into the renal allograft and the histologic changes characteristics of chronic allograft failure. Methods. A total of 218 kidney transplant recipients were genotyped for 15 single-nucleotide polymorphisms located in the gene promoter or exonic regions of 10 different cytokines or their receptors. Six- to 12-month posttransplant surveillance biopsies were scored using 11 individual histologic parameters and the combined grade of interstitial fibrosis and tubular atrophy (IF/TA). B-cell, T-cell, and macrophage infiltrates were quantified by immunostaining. Results.Thelow-expressinginterleukin(IL)-10genepromotergenotypeswerefoundsignificantlyassociatedwithhigh IF/TA grade (IL-10 819 TT; P0.035; odds ratio3.27; 95% confidence interval 1.1–9.8). At individual histologic indices, recipients carrying low-expressing IL-10genotypes showed 2.5-fold higher scores for interstitial fibrosis, inflammation,andtubularatrophy.HighinfiltrationofTcellsand macrophagesbutnotBcellsintotherenalallograftinterstitium was found strongly associated with the carriage of low-expressing IL-10 genotypes. Conclusions. The results suggest that renal transplant recipients genetically predisposed to low expression of the regulatory cytokine IL-10 are more susceptible to high grades of IF/TA scores, graft inflammation, and high influx of inflammatory cells into the graft interstitium.

To evaluate the effects of topical cyclosporine A (CsA) 0.05% (Restasis) on the signs and symptoms of dry eye, on apoptosis, and on MMP-9 expression in conjunctiva epithelial cells in thyroid orbitopathy (TO)-related dry eye patients.Prospective, clinical study. Twenty-four eyes of 12 consecutive TO patients with dry eye findings instilled CsA twice daily for 2 months. Ocular surface disease index, Schirmer tear test, tear breakup time (TBUT), conjunctival apoptosis index, and conjunctival MMP-9 expression were evaluated before and after 2 months treatment. Conjunctival biopsies were harvested from all eyes at baseline and after 2 months treatment. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) assay. MMP-9 expression was determined by immunohistochemistry.After 2 months of topical CsA treatment, the mean OSDI score was significantly decreased from 58.08 +/- 6.28 to 36.41 +/- 11.75 (P = 0.001). At baseline, the mean Schirmer tear test score was 8.92 +/- 5.52 mm. It was increased to 11.25 +/- 4.71 mm after treatment (P0.05). The mean TBUT increased significantly from 3.92 +/- 2.18 sec to 9.16 +/- 3.34 sec (P = 0.001). The mean percentage of apoptosis index at baseline was 72.10 +/- 35.82%. This was significantly decreased to 53.29 +/- 34.46% after treatment (P = 0.008). The mean percentage of MMP-9 expression of the conjunctival epithelial cells was significantly decreased from 48.12 +/- 28.58% to 26.66 +/- 25.13% following treatment (P = 0.005).Topical CsA treatment appears to improve the signs and symptoms of dry eye and inhibits apoptosis and MMP-9 expression in conjunctival epithelial cells in TO-related dry eye patients after 2 months of treatment.