Publications by authors named "Yasemin Ozluk"

73 Publications

Evaluation of Human Papillomavirus Genotype Distribution in Cervical Samples.

J Cytol 2021 Jan-Mar;38(1):44-49. Epub 2021 Feb 16.

Istanbul University, Istanbul Faculty of Medicine, Department of Medical Microbiology, Division of Virology and Fundamental Immunology, Istanbul, Turkey.

Background: The most common sexually transmitted infection in the world is human papillomavirus (HPV). HPV types 16 and 18 are responsible for 60-80% of cervical cancers and precancerous cervical lesions worldwide.

Aim: In this study, it was aimed to evaluate the correlation of HPV genotype distribution with cervical cytology results in cervical smear samples and to contribute to HPV epidemiology.

Materials And Methods: This study included 72 female patients. For detection of the HPV genotypes, a multiplex real-time polymerase chain reaction (PCR) method that could detect more than 25 different HPV types was used. The cervical cytology and histopathology results of the patients were also evaluated simultaneously.

Results: The frequency of high-risk HPV was 35% (25/72). The most common types were HPV51 (10%), HPV16 (8%), and HPV66 (8%), respectively. The most common type HPV51 and multiple HPV types were seen in 21-34 age groups. HPV DNA was detected in 21 of 43 samples that had cervical smear diagnosis grouping. Twelve samples (26%) had normal cytology. Low grade squamous intraepithelial lesions were the most common cytological diagnosis in HPV DNA positive samples. The most common HPV types in the patients diagnosed low grade squamous intraepithelial lesions and high grade squamous intraepithelial lesions were HPV16 and HPV52.

Conclusions: In this study, the frequency of high-risk HPV genotypes was 35% as similar to reports of the other studies conducted in our country. The most common types were HPV51, HPV16, and HPV66, respectively. The follow-up of patients with HPV51 infection in our area could help to improve the natural course of the disease and effective prevention programs.
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http://dx.doi.org/10.4103/JOC.JOC_19_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078615PMC
February 2021

LIMS1 Risk Genotype and T-Cell Mediated Rejection in Kidney Transplant Recipients.

Nephrol Dial Transplant 2021 Apr 28. Epub 2021 Apr 28.

Division of Nephrology, Saint Louis University, Saint Louis, MO, USA.

Background: This study aims to examine the association of LIM Zinc Finger Domain Containing 1 (LIMS1) genotype with allograft rejection in an independent kidney transplant cohort.

Methods: We genotyped 841 kidney transplant recipients for LIMS1 rs893403 variant by Sanger sequencing followed by PCR confirmation of the deletion. Recipients who were homozygous for LIMS1 rs893403 genotype GG were compared to AA/AG genotypes. The primary outcome was T-cell mediated (TCMR) or antibody mediated rejection (ABMR) and secondary outcome was allograft loss.

Results: After a median follow-up of 11.4 years, the rate of TCMR was higher in recipients with the GG (n = 200) compared to AA/AG (n = 641) genotypes [25 (12.5%) vs 35 (5.5%); p = 0.001] while ABMR did not differ by genotype [18 (9.0%) vs 62 (9.7%)]. Recipients with GG genotype had 2.4-times higher risk of TCMR than those who did not have this genotype (adjusted hazard ratio (aHR), 1.442.434.12, p = 0.001). A total of 189 (22.5%) recipients lost their allografts during follow up. Kaplan-Meier estimates of 5-year (94.3% vs. 94.4%, p = 0.99) and 10-year graft survival rates (86.9% vs. 83.4%, p = 0.31) did not differ significantly in those with GG compared to AA/AG groups.

Conclusions: Our study demonstrates that recipient LIMS1 risk genotype is associated with increased risk of TCMR after kidney transplantation, confirming the role of LIMS1 locus in allograft rejection. These findings may have clinical implications for the prediction and clinical management of kidney transplant rejection by pretransplant genetic testing of recipients and donors for LIMS1 risk genotype.
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http://dx.doi.org/10.1093/ndt/gfab168DOI Listing
April 2021

Significance of caveolin-1 immunohistochemical staining differences in biopsy samples from kidney recipients with BK virus viremia.

Transpl Infect Dis 2021 Mar 22:e13605. Epub 2021 Mar 22.

Department of Medical Biology, Istanbul School of Medicine, Istanbul University, Istanbul, Turkey.

BK virus infections which usually remains asymptomatic in healthy adults may have different clinical manifestations in immunocompromised patient population. BK virus reactivation can cause BK virus nephropathy in 8% of kidney transplant patients and graft loss may be seen if not treated. Clathrin or Caveolar system is known to be required for the transport of many viruses from Polyomaviruses family including BK viruses. In this study, kidney transplant patients with BK virus viremia were divided into two groups according to the BK virus nephropathy found in kidney biopsy (Group I: Viremia+, Nephropathy+ / Group II: Viremia+, Nephropathy-). Kidney biopsies were examined with immunohistochemical staining to determine the distribution and density of the Caveolin-1 and Clathrin molecules. Immunohistochemical staining of the 31 pathologic specimens with anti-caveolin-1 immunoglobulin revealed statistically significant difference between group-I and group-II. The number of the specimens stained with anti-caveolin-1 was less in group I. On the other hand, we did not find any difference between the groups regarding the anti-clathrin immunochemical analysis. According to these findings, caveolin-1 expression differences in kidney transplant patients may be important in disease progression.
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http://dx.doi.org/10.1111/tid.13605DOI Listing
March 2021

Nephrotic range proteinuria in an adolescent with a diagnosis of Wilson's disease: Answers.

Pediatr Nephrol 2021 Jul 2;36(7):2103-2106. Epub 2021 Feb 2.

Istanbul Faculty of Medicine, Department of Pathology, Istanbul University, Istanbul, Turkey.

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http://dx.doi.org/10.1007/s00467-021-04961-9DOI Listing
July 2021

Nephrotic range proteinuria in an adolescent with a diagnosis of Wilson's disease: Questions.

Pediatr Nephrol 2021 Jul 2;36(7):2101-2102. Epub 2021 Feb 2.

Istanbul Faculty of Medicine, Department of Pathology, Istanbul University, Istanbul, Turkey.

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http://dx.doi.org/10.1007/s00467-021-04947-7DOI Listing
July 2021

Strong mesangial IgA staining-does it always refer to IgA nephropathy in a patient with proteinuria and hematuria? Answers.

Pediatr Nephrol 2021 Jul 18;36(7):2043-2045. Epub 2021 Jan 18.

Department of Pediatric Nephrology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey.

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http://dx.doi.org/10.1007/s00467-020-04899-4DOI Listing
July 2021

Strong mesangial IgA staining-does it always refer to IgA nephropathy in a patient with proteinuria and hematuria? Questions.

Pediatr Nephrol 2021 Jul 18;36(7):2039-2041. Epub 2021 Jan 18.

Department of Pediatric Nephrology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, 34098, Istanbul, Turkey.

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http://dx.doi.org/10.1007/s00467-020-04886-9DOI Listing
July 2021

Clinical significance of glomerular C3 deposition in primary membranous nephropathy.

J Nephrol 2021 Apr 2;34(2):581-587. Epub 2021 Jan 2.

Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Background: We aimed to investigate the effects of glomerular C3 deposition on clinical, histopathological features, and outcomes of patients with primary membranous nephropathy (MN).

Methods: A total of 261 patients with biopsy-proven primary MN, who were on follow up for at least 6 months, were included in the study. The patients were grouped according to their C3 immunostaining in kidney biopsy samples at the time of diagnosis: Low intensity [LI; (C3 1 +)] and high intensity [HI; (C3 2 + or C3 3 +)]. The primary outcome was the development of kidney failure. Complete (CR) or partial remission (PR) was defined as secondary outcome.

Results: Sixteen patients reached the primary outcome after a median follow-up of 33.8 months. Patients in the high intensity group (119 cases) had lower eGFR and higher proteinuria at admission and last follow-up compared to patients in the low intensity group (142 cases). Also, more patients in the high intensity group reached the primary outcome compared to patients in the low intensity group: twelve patients (10.1%) in the high intensity group and four patients (2.8%) in the low intensity group reached the primary outcome (p = 0.015). Kaplan-Meier analysis demonstrated that patients in the high intensity group had a higher risk for kidney failure (p = 0.02). In multivariate logistic regression analysis, high intensity C3 deposition and initial estimated glomerular filtration rate (eGFR) indepenently predicted primary outcome.

Conclusion: Extensive glomerular C3 deposition is a predictor of kidney failure in patients with MN.
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http://dx.doi.org/10.1007/s40620-020-00915-wDOI Listing
April 2021

An adolescent girl with obstructive uropathy requiring nephro-ureterectomy was subsequently diagnosed with renal tuberculosis: case report.

Paediatr Int Child Health 2020 Sep 29:1-4. Epub 2020 Sep 29.

Department of Pediatrics, Division of Pediatric Infectious Disease, Faculty of Medicine, Istanbul University, Istanbul, Turkey.

A 15-year-old girl was followed up for 2 years in a district hospital for management of vesicoureteral reflux and, subsequently, hydronephrosis of both kidneys and required bilateral ureteroneocystostomy. Despite surgery, there was continuous progression of the left hydronephrosis. Referral to a tertiary hospital because of continued sterile pyuria prompted investigation for tuberculosis (TB): she was diagnosed with bilateral pulmonary TB and urine culture confirmed . Despite tuberculous chemotherapy and dexamethasone, she required a left nephrectomy. Histology demonstrated necrotising granulomatous pyelonephritis. She remains well with normal function of the right kidney. Despite the rarity, chronic urinary tract disorders should always prompt investigation for tuberculosis.
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http://dx.doi.org/10.1080/20469047.2020.1822633DOI Listing
September 2020

Prognostic factors in patients undergoing pulmonary resection for sarcomatoid carcinomas of the lung.

Balkan Med J 2021 03;38(2):104-110

Department of Cardiovascular and Thoracic Surgery, West Virginia University Heart and Vascular Institute, Morgantown, USA.

Background: Pulmonary sarcomatoid carcinomas are very rare lung neoplasms, and no consensus exists regarding their optimal treatment. The prognosis of sarcomatoid carcinomas has been reported to be unfavorable compared with non-small-cell lung cancers; however, prognostic factors in patients undergoing surgery for sarcomatoid carcinomas remain unclear.

Aims: To analyze clinicopathologic prognostic factors and survival outcomes in patients who underwent surgery for pulmonary sarcomatoid carcinoma.

Study Design: Retrospective cross-sectional study.

Methods: We designed a retrospective cross-sectional study in patients who underwent surgery for pulmonary sarcomatoid carcinomas and statistically analyzed the prognostic factors regarding clinicopathologic features with respect to survival outcomes.

Results: We had a total of 44 patients with sarcomatoid carcinoma who had pulmonary resection. Sex distribution was 34 (77%) males and 10 (22.7%) females, which was determined by declaration. The mean age of patients was 57.3 ± 16 years with a median of 60 years. The 5-year progression-free survival and overall survival rates were 59% and 58%, respectively. The 5-year survival rates were significantly different for tumors > 5 cm (P = 0.044), tumorstatus (T) (P=0.016), lymph node status (N) (P=0.005), and pathologic tumor-node-metastasis (TNM) stage (P = 0.0001 ). However, histologic subtype (P = 0.628) and adjuvant treatment (P = 0.804) did not have any significant effect on survival. Similarly, the significant prognostic factors in univariate analysis were tumor size (P = 0.085), T status (P = 0.005), N status (P = 0.028), and pathologic TNM stage (P = 0.0001). Multivariate analysis showed only T status (P = 0.058), N status (P = 0.018), and pathologic TNM stage (P = 0.019) as independent prognostic factors, with statistical power of 87%, 43.1% and 21.2%.

Conclusion: Surgery appears to be an optimal treatment with favorable outcomes for patients with pulmonary sarcomatoid carcinoma. Patients with small tumors at earlier stages are very likely to benefit from surgery, regardless of histologic subtype.
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http://dx.doi.org/10.4274/balkanmedj.galenos.2020.2020.7.45DOI Listing
March 2021

Multiple combinations of melanocytic and vascular endothelial markers enhance the detection rate of lymphovascular invasion in cutaneous melanoma.

J Cutan Pathol 2021 Apr 15;48(4):472-478. Epub 2020 Nov 15.

Istanbul Faculty of Medicine, Department of Pathology, Istanbul University, Istanbul, Turkey.

Background: Lymphovascular invasion (LVI) is believed to be the mechanism by which melanoma cells can disseminate to regional lymph nodes and distant sites and may be predictive of adverse outcome. Lymphovascular invasion often difficult to detect on hematoxylin-eosin (HE) stained sections, are readily identified with dual immunohistochemistry (IHC) for melanocytic and vascular markers.

Methods: A total of 100 primary cutaneous malignant melanoma cases that had a Breslow thickness of 1-4 mm and lacked LVI by conventional HE assessment were included. We compared the LVI detection rates of double staining for CD31/S100 and CD34/S100, and D2-40/S100, and examined the association of LVI with clinical outcomes.

Results: The dual immunohistochemical positivity for CD31/S100, CD34/S100, and D2-40/S100 were 40(40%), 17(17%) and 35(35%), respectively. On multivariate analysis, LVI was an independent predictor of SLN status. Multivariate analysis revealed that LVI and male gender were independent risk factors for overall survival.

Conclusions: The recognition of LVI is improved by dual IHC and predicts SLN metastasis. The detection of LVI using dual IHC, especially by a combination of CD31/S100 and D2-40/S100 is a useful step that inclusion should be recommended in basic evaluation parameters for cutaneous melanoma.
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http://dx.doi.org/10.1111/cup.13874DOI Listing
April 2021

Amyloid A Amyloidosis After Renal Transplantation: An Important Cause of Mortality.

Transplantation 2020 08;104(8):1703-1711

Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Background: There are limited data on the outcome of transplant recipients with familial Mediterranean fever (FMF)-associated AA amyloidosis. The aim of the present study is to evaluate demographic, clinical, laboratory, and prognostic characteristics and outcome measures of these patients.

Methods: Eighty-one renal transplant recipients with FMF-associated AA amyloidosis (group 1) and propensity score-matched transplant recipients (group 2, n = 81) with nonamyloidosis etiologies were evaluated in this retrospective, multicenter study. Recurrence of AA amyloidosis was diagnosed in 21 patients (group 1a), and their features were compared with 21 propensity score-matched recipients with FMF amyloidosis with no laboratory signs of recurrence (group 1b).

Results: The risk of overall allograft loss was higher in group 1 compared with group 2 (25 [30.9%] versus 12 [14.8%]; P = 0.015 [hazard ratio, 2.083; 95% confidence interval, 1.126-3.856]). Patients in group 1 were characterized by an increased risk of mortality compared with group 2 (11 [13.6%] versus 0%; P = 0.001 [hazard ratio, 1.136; 95% confidence interval, 1.058-1.207]). Kaplan-Meier analysis revealed that 5- and 10-year patient survival rates in group 1 (92.5% and 70.4%) were significantly lower than in group 2 (100% and 100%; P = 0.026 and P = 0.023, respectively). Although not reaching significance, overall, 5- and 10-year graft survival rates (57.1%, 94.7%, and 53.8%, respectively) in group 1a were worse than in group 1b (76.2%, 95%, and 77.8%, respectively; P = 0.19, P = 0.95, and P = 0.27, respectively).

Conclusions: AA amyloidosis is associated with higher risk of mortality after kidney transplantation. Inflammatory indicators should be monitored closely, and persistent high levels of acute-phase reactants should raise concerns about amyloid recurrence in allograft.
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http://dx.doi.org/10.1097/TP.0000000000003043DOI Listing
August 2020

The clinical predictive factors and postoperative histopathological parameters associated with upgrading after radical prostatectomy: A contemporary analysis with grade groups.

Prostate 2020 02 3;80(2):225-234. Epub 2019 Dec 3.

Department of Urology, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey.

Background And Aim: Upgrading after radical prostatectomy (RP) is an ongoing problem since first description of Gleason score. In this retrospective study, our aim is to investigate upgrading after RP in grade groups (GG) and clinical predictive, and postoperative histopathological factors associated with GG upgrading (GGU).

Patients And Methods: A total of 753 patients undergoing RP between January 2006 and June 2019 at our institution were investigated. Overall cohort were divided into two groups according to GGU status after RP as nonupgrading and upgrading. Retrospectively documented preoperative clinical and postoperative histopathological parameters were compared between two groups. Furthermore, we investigated a subgroup of institutional cohort (n = 398) whose prostate biopsy (Pbx) and RP were performed in our institution and we also divided this cohort into two groups according to GGU status. χ and Mann-Whitney U tests were used for comparative analyses. The independent preoperative predictive and postoperative histopathological factors associated with GGU were investigated using multivariate logistic regression analysis.

Results: The total GGU was 55.8% in overall cohort and 45.2% in institutional cohort. The GGU was found as the most common in bioptic GG1 group in both overall (64.0%), and institutional (54.5%) cohorts. In multivariate analyses, the noninstitutional Pbx (odds ratio [OR] = 2.56; 95% confidence interval [CI]: 1.86-3.51; P < .001), tumor positive core numbers in Pbx (OR = 1.11; 95%CI: 1.04-1.19; P = .003), increased prostate specific antigen (PSA) density (OR = 3.59; 95%CI: 1.03-12.52, P = .045) and age (OR = 1.03; 95%CI: 1.00-1.05, P = .046) were independent clinical predictors of GGU in overall cohort whereas only increased PSA density (OR = 5.94; 95%CI: 1.28-27.50; P = .023) was independent predictor in institutional cohort. Among postoperative histopathological factors, perineural invasion (OR = 1.57; 95%CI: 1.70-3.87; P < .001 and OR = 2.53; 95%CI: 1.46-4.40; P = .001, respectively), increased maximum tumor diameter (OR = 1.46; 95%CI: 1.23-1.73; P < .001 and OR = 1.33; 95%CI: 1.07-1.66; P = .010, respectively), and high-grade prostatic intraepithelial neoplasia (HGPIN) existence at tumor surrounding tissue (OR = 1.96; 95%CI: 1.32-2.90; P = .001 and OR = 1.87; 95%CI: 1.10-3.21; P = .022, respectively) were independently associated with GGU after RP, in both of overall and institutional cohorts.

Conclusions: Noninstitutional prostate biopsy, increased PSA density, higher tumor positive cores in Pbx and older age are the clinical predictors of upgrading after RP in contemporary GG. Perineural invasion, increased maximum tumor diameter, and HGPIN existence at tumor surrounding tissue are postoperative histopathological factors associated with GGU.
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http://dx.doi.org/10.1002/pros.23936DOI Listing
February 2020

Co-Deposition of IgM and C3 May Indicate Unfavorable Renal Outcomes in Adult Patients with Primary Focal Segmental Glomerulosclerosis.

Kidney Blood Press Res 2019 22;44(5):961-972. Epub 2019 Aug 22.

Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Background/aims: We aimed to investigate the effects of glomerular IgM and C3 deposition on outcomes of adult patients with primary focal segmental glomerulosclerosis (FSGS).

Methods: In this retrospective analysis, 86 consecutive adult patients with biopsy-proven primary FSGS were stratified into 3 groups according to their histopathological features: IgM- C3-, IgM+ C3-, and IgM+ C3+. Primary outcome was defined as at least a 50% reduction in baseline estimated glomerular filtration rate (eGFR) or development of kidney failure, while complete or partial remission rates were secondary outcomes.

Results: Glomerular IgM deposits were found in 44 (51.1%) patients, 22 (25.5%) of which presented with accompanying C3 deposition. Patients in IgM+ C3+ group had higher level of proteinuria (5.6 g/24 h [3.77-8.5], p = 0.073), higher percentage of segmental glomerulosclerosis (20% [12.3-27.2], p = 0.001), and lower levels of eGFR (69 ± 37.2 mL/min/1.73 m2, p = 0.029) and serum albumin (2.71 ± 0.85 g/dL, p = 0.045) at the time of diagnosis. Despite 86.3% of patients in IgM+ C3+ group (19/22) received immunosuppressive treatment, the primary outcome was more common in patients in the IgM+ C3+ group compared with patients in IgM+ C3- and IgM- C3- groups (11 [50%] vs. 2 [9%] and 11 [26.1%] respectively [p = 0.010]). Complete or partial remission rates were lower in patients in the IgM+ C3+ group (5/22, 22.7%), as well (p = 0.043). Multivariate Cox regression analysis revealed that IgM and C3 co-deposition was an independent risk factor associated with primary outcome (hazard ratio 3.355, 95% CI 1.349-8.344, p = 0.009).

Conclusions: Glomerular IgM and C3 co-deposition is a predictor of unfavorable renal outcomes in adult patients with primary FSGS.
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http://dx.doi.org/10.1159/000501827DOI Listing
March 2020

Infectious Complications of Induction Therapies in Kidney Transplantation.

Ann Transplant 2019 Jul 12;24:412-417. Epub 2019 Jul 12.

Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Istanbul University, Istanbul, Turkey.

BACKGROUND Cytomegalovirus (CMV) and BK virus (BKV) are post-transplant opportunistic viral infections that affect patient and graft survival. This study was designed to evaluate the risk of BKV nephropathy and CMV disease in kidney transplant recipients who received induction therapy with ATG or basiliximab. MATERIAL AND METHODS We retrospectively analyzed information on 257 adult patients who underwent kidney transplantation between January 2007 and 2017. Patients were categorized into 3 groups according to the induction therapies. The primary endpoint was the onset of CMV disease or biopsy-confirmed BKV nephropathy. The secondary endpoints were biopsy-proven rejection episodes, graft loss, loss to follow-up, and death. RESULTS We followed 257 patients for a median of 55.5 months. The incidence of CMV disease was significantly higher in the only ATG group compared to the group without induction treatment (p<0.001). There was no significant difference in the incidence of BKV nephropathy among groups (p>0.05). The dosage of ATG (OR, 10.685; 95% CI, 1.343 5 to 85.009; P=0.025) was independent risk factor for death. CONCLUSIONS This study demonstrated that a higher dosage of ATG in high-risk patients is associated with an increased risk of CMV disease and patient death, also, reducing the dosage may be a rational strategy for increasing graft and patient's survival.
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http://dx.doi.org/10.12659/AOT.915885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6652377PMC
July 2019

The pathological upgrading after radical prostatectomy in low-risk prostate cancer patients who are eligible for active surveillance: How safe is it to depend on bioptic pathology?

Prostate 2019 09 3;79(13):1523-1529. Epub 2019 Jul 3.

Department of Urology, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey.

Background: Active surveillance (AS) is one of the treatment alternatives in low-risk prostate cancer (PCa). The pathological upgrading after radical prostatectomy (RP) were investigated in patients who were eligible for AS in the present study.

Methods: Between August 2006 and July 2017, 627 patients underwent RP in our institution. One hundred and thirty-six patients who were eligible for AS at the time of RP were included in this study. The previously defined AS criteria Gleason 3 + 3=6 adenocarcinoma at maximum two biopsy cores, prostate-specific antigen (PSA) < 10 ng/mL and clinical T stage ≤ 2a were used in the study. The demographics, clinical, and histopathological outcomes were retrospectively compared between two groups, which were divided in accordance with the upgrading status at final pathology as Group 1 (n = 67, upgrading) and Group 2 (n = 69, nonupgrading).

Results: Gleason upgrading (GU) was found in 67 (49.3%) patients, and 17 patients (12.5%) were upstaged to pT3a. The upgrading to Gleason 3 + 4 was reported in 38.7% of patients, however, 7.4%, and 3.7% of the patients were upgraded to Gleason 4 + 3, and Gleason 4 + 4, respectively. The 10.3% of the patients had extraprostatic involvement, and the rate (19.4% vs 1.4%, P = .002) was significantly higher in Group 1. PSA density (P = .001), tumor size (P < .001), tumor percentage (P < .001), apical involvement (P = .013), and perineural invasion (P < .001) in RP specimen were higher in Group 1. Multivariate analysis showed that perineural invasion (OR = 4.26; 95%CI: 1.76-10.33; P = .001) and pathologic T stage (OR = 5.45; 95%CI: 1.08-27.4; P = .04) were independently associated with GU.

Conclusions: Since 12.5% of the patients upstaged to pT3a disease, and there is a possible risk of Gleason 4 pattern, upgrading of the tumor should carefully be kept in mind before offering AS to low-risk patients with PCa.
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http://dx.doi.org/10.1002/pros.23873DOI Listing
September 2019

A rare cause of proteinuria after kidney transplantation: Answers.

Pediatr Nephrol 2019 11 30;34(11):2333-2335. Epub 2019 Apr 30.

Cerrahpaşa Faculty of Medicine, Department of Pediatric Nephrology, Istanbul University-Cerrahpaşa, Istanbul, Turkey.

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http://dx.doi.org/10.1007/s00467-019-04263-1DOI Listing
November 2019

A rare cause of proteinuria after kidney transplantation: Questions.

Pediatr Nephrol 2019 11 30;34(11):2331-2332. Epub 2019 Apr 30.

Cerrahpaşa Faculty of Medicine, Department of Pediatric Nephrology, Istanbul University-Cerrahpaşa, Istanbul, Turkey.

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http://dx.doi.org/10.1007/s00467-019-04262-2DOI Listing
November 2019

Reproducibility of the Oxford classification of immunoglobulin A nephropathy, impact of biopsy scoring on treatment allocation and clinical relevance of disagreements: evidence from the VALidation of IGA study cohort.

Nephrol Dial Transplant 2019 10;34(10):1681-1690

Medical University of Warsaw, Warsaw, Poland.

Background: The VALidation of IGA (VALIGA) study investigated the utility of the Oxford Classification of immunoglobulin A nephropathy (IgAN) in 1147 patients from 13 European countries. Methods. Biopsies were scored by local pathologists followed by central review in Oxford. We had two distinct objectives: to assess how closely pathology findings were associated with the decision to give corticosteroid/immunosuppressive (CS/IS) treatments, and to determine the impact of differences in MEST-C scoring between central and local pathologists on the clinical value of the Oxford Classification. We tested for each lesion the associations between the type of agreement (local and central pathologists scoring absent, local present and central absent, local absent and central present, both scoring present) with the initial clinical assessment, as well as long-term outcomes in those patients who did not receive CS/IS.

Results: All glomerular lesions (M, E, C and S) assessed by local pathologists were independently associated with the decision to administer CS/IS therapy, while the severity of tubulointerstitial lesions was not. Reproducibility between local and central pathologists was moderate for S (segmental sclerosis) and T (tubular atrophy/interstitial fibrosis), and poor for M (mesangial hypercellularity), E (endocapillary hypercellularity) and C (crescents). Local pathologists found statistically more of each lesion, except for the S lesion, which was more frequent with central review. Disagreements were more likely to occur when the proportion of glomeruli affected was low. The M lesion, assessed by central pathologists, correlated better with the severity of the disease at presentation and discriminated better with outcomes. In contrast, the E lesion, evaluated by local pathologists, correlated better with the clinical presentation and outcomes when compared with central review. Both C and S lesions, when discordant between local and central pathologists, had a clinical phenotype intermediate to double absent lesions (milder disease) and double present (more severe).

Conclusion: We conclude that differences in the scoring of MEST-C criteria between local pathologists and a central reviewer have a significant impact on the prognostic value of the Oxford Classification. Since the decision to offer immunosuppressive therapy in this cohort was intimately associated with the MEST-C score, this study indicates a need for a more detailed guidance for pathologists in the scoring of IgAN biopsies.
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http://dx.doi.org/10.1093/ndt/gfy337DOI Listing
October 2019

Giant Rhabdomyoma Requiring Emergency Resection Early After Birth.

Ann Thorac Surg 2019 01;107(1):e65

Department of Cardiovascular Surgery, Istanbul University Istanbul Medical Faculty, Istanbul, Turkey.

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http://dx.doi.org/10.1016/j.athoracsur.2018.05.093DOI Listing
January 2019

Giant Renal Hemangioma in an Adolescent Girl: A Very Rare Entity.

Urology 2018 Aug 17;118:198-201. Epub 2018 Apr 17.

Department of Urology, Division of Pediatric Urology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey.

Hemangiomas are benign vascular tumors of childhood and they usually tend to be located in the upper parts of the body (head and neck). However, renal hemangiomas are very rare and usually occur to be small (1-2 cm) in size. Here, we report an adolescent girl with a giant renal hemangioma of 15 cm diameter.
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http://dx.doi.org/10.1016/j.urology.2018.04.005DOI Listing
August 2018

The association between variant urothelial histologies, pathological stage and disease specific survival in patients with bladder cancer.

Turk J Urol 2018 Jan 19;44(1):24-30. Epub 2017 Dec 19.

Department of Urology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey.

Objective: We aimed to compare the oncological outcomes of patients with variant urothelial histologies (VH) with pure urothelial histology (PUH) in bladder cancer (BC) patients.

Material And Methods: This study includes 223 patients who underwent radical cystectomies (RCs) between September 2006 and July 2016 with complete follow-up data A retrospective screening was performed to identify the patients with PUH and VH. The primary outcomes of interest were pathological stage of disease at RC and disease-specific survival (DSS). For comparison of categorical variables, Fisher's exact test and Pearson chi- square and for continuous variables Wilcoxon rank-sum and Mann-Whitney U tests were used. Kaplan-Meier (KM) method was used for survival analysis and log-rank test was used for comparison of survival rates. Predictors of survival were detected with mulitivariable Cox-proportional hazards model including the variables such as gender, age, existence of VH, lymph node dissection (LND) type and pathological stage of the disease.

Results: A moderate-degree correlation was detected between VH and pathological stages of RC (r=0.45, p<0.001). In PUH group, 39 (25.8%) of 151 patients died after a median follow-up of 20 (0-107) months; whereas 37 (51.4%) of 72 patients with VH died after a median follow-up of 16.5 (0-104) months (p<0.001). In terms of pathological stage, the number of patients with PUH and VH were at stages pT0-2 (n=100; 66.2% vs. n=19; 26.4%), pT3-4 (n=35; 23.2% vs. 38; 52.8%, and in 16 (10.6%) and 15 (20.8%) patients with LN positivity, respectively (p<0.001). KM survival analysis revealed a significantly decreased DSS in patients with VH compared to PUH (p<0.001). Meanwhile, pathological disease stage and existence of VH were found to be associated with decreased DSS in the multivariate model.

Conclusion: The present study revealed that VH is associated with advanced pathological tumor stage at RC and decreased DSS compared to patients with PUH in patients with BC.
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http://dx.doi.org/10.5152/tud.2017.48107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821278PMC
January 2018

Mycophenolate Mofetil in Combination with Steroids for Treatment of C3 Glomerulopathy: A Case Series.

Clin J Am Soc Nephrol 2018 03 11;13(3):406-413. Epub 2018 Jan 11.

Division of Nephrology, Department of Medicine, Columbia University Medical Center, New York, New York; and.

Background And Objectives: C3 glomerulopathy is a form of complement-mediated GN. Immunosuppressive therapy may be beneficial in the treatment of C3 glomerulopathy. Mycophenolate mofetil is an attractive treatment option given its role in the treatment of other complement-mediated diseases and the results of the Spanish Group for the Study of Glomerular Diseases C3 Study. Here, we study the outcomes of patients with C3 glomerulopathy treated with steroids and mycophenolate mofetil.

Design, Setting, Participants, & Measurements: We conducted a retrospective chart review of patients in the C3 glomerulopathy registry at Columbia University and identified patients treated with mycophenolate mofetil for at least 3 months and follow-up for at least 1 year. We studied clinical, histologic, and genetic data for the whole group and compared data for those who achieved complete or partial remission (responders) with those who did not achieve remission (nonresponders). We compared remission with mycophenolate mofetil with remission with other immunosuppressive regimens.

Results: We identified 30 patients who met inclusion criteria. Median age was 25 years old (interquartile range, 18-36), median creatinine was 1.07 mg/dl (interquartile range, 0.79-1.69), and median proteinuria was 3200 mg/g creatinine (interquartile range, 1720-6759). The median follow-up time was 32 months (interquartile range, 21-68). Twenty (67%) patients were classified as responders. There were no significant differences in baseline characteristics between responders and nonresponders, although initial proteinuria was lower (median 2468 mg/g creatinine) in responders compared with nonresponders (median 5000 mg/g creatinine) and soluble membrane attack complex levels were higher in responders compared with nonresponders. For those tapered off mycophenolate mofetil, relapse rate was 50%. Genome-wide analysis on complement genes was done, and in 12 patients, we found 18 variants predicted to be damaging. None of these variants were previously reported to be pathogenic. Mycophenolate mofetil with steroids outperformed other immunosuppressive regimens.

Conclusions: Among patients who tolerated mycophenolate mofetil, combination therapy with steroids induced remission in 67% of this cohort. Heavier proteinuria at the start of therapy and lower soluble membrane attack complex levels were associated with treatment resistance.
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http://dx.doi.org/10.2215/CJN.09080817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5967675PMC
March 2018

Case report: C3 glomerulopathy advancing atypical hemolytic uremic syndrome.

Nefrologia (Engl Ed) 2018 Jul - Aug;38(4):450-452. Epub 2017 Nov 14.

Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

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http://dx.doi.org/10.1016/j.nefro.2017.09.010DOI Listing
April 2019

Recurrent and de novo glomerulonephritis following renal transplantation: higher rates of rejection and lower graft survival.

Int Urol Nephrol 2017 Dec 16;49(12):2265-2272. Epub 2017 Oct 16.

Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Capa, Fatih, 34093, Istanbul, Turkey.

Purpose: In this retrospective study with case-control design, we aimed to determine the clinical and pathological characteristics of post-transplant glomerulonephritis (GN), and their effects on transplant recipients.

Methods: One hundred and twenty renal transplant recipients with biopsy-proven recurrent or de novo primary GN were compared with two matched control groups including 120 transplant recipients with nonrecurrent primary GN (nonrecurrent GN group) and 120 transplant recipients with non-GN etiology (non-GN group). Primary outcome was allograft loss, and secondary outcomes were biopsy-confirmed cellular or antibody-mediated rejection.

Results: In recurrent/de novo GN, nonrecurrent GN and non-GN groups, 54.2% (n = 65), 16.7% (n = 20) and 8.3% (n = 10) of patients reached primary outcome after a median follow-up of 96 (IQR: 56-149) months, respectively. Allograft loss was significantly higher in recurrent/de novo GN group compared to nonrecurrent GN and non-GN groups (p < 0.001). At 10 years, allograft loss rates in recurrent/de novo GN group were 54.2% for focal segmental glomerulosclerosis, 53.2% for membranoproliferative glomerulonephritis, and 33.4% for IgA nephropathy cases. Biopsy-confirmed rejection rate was significantly higher in the recurrent/de novo GN group (n = 25, 20.8%) compared to non-GN (n = 8, 6.7%) group (p = 0.001).

Conclusions: Recurrent/de novo GN is associated with higher risk of rejection and worse allograft survival.
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http://dx.doi.org/10.1007/s11255-017-1719-3DOI Listing
December 2017

Relationships between serum PSA levels, Gleason scores and results of 68Ga-PSMAPET/CT in patients with recurrent prostate cancer.

Ann Nucl Med 2017 Nov 12;31(9):709-717. Epub 2017 Sep 12.

Department of Nuclear Medicine, Istanbul Faculty of Medicine, Istanbul University, Ic Hastalıkları Binasi, Nukleer Tip Anabilim Dali, Istanbul, Turkey.

Aim: To investigate the relationship between serum PSA level, Gleason score of PCa and the outcomes of Ga-PSMA PET/CT in patients with recurrent PCa.

Methods: A total of 109 consecutive patients (median age 71 years; range 48-89 years) who had PSA recurrence after RP and/or hormonotherapy and/or radiotherapy were included in this study. Local recurrences, lymph node metastasis (pelvic, abdominal and/or supradiaphragmatic), bone metastases (oligometastatic/multimetastatic) and other metastatic sites (lung, liver, brain, etc) were documented.

Results: In 91(83.4%) patients at least one lesion characteristic for PCa was detected byGa-PSMA PET/CT. The median serum total PSA (tPSA) was 6.5 (0.2-640) ng/ml.There was a significant difference between Ga-PSMA PET/CT positive and negative patients in terms of serum total PSA value. No statistical significance was found between positive and negative Ga-PSMA PET/CT findings in terms of Gleason score. Local recurrence was detected in 56 patients. whereas lymph node metastases were demonstrated in 46 patients. Pelvic nodal disease was the most frequent presentation followed by abdominal and supradiaphragmaticnodal involvement. Bone metastases [oligometastasis, (n = 20); multimetastasis, (n = 35)⦌ were also detected in 55 patients. In the ROC analysis for the study cohort, the optimal cut-off value of total serum PSA was determined as 0.67 ng/ml for distinguishing between positive and negative Ga-PSMA PET/CT images, with an area under curve of 0.952 (95% CI 0.911-0.993).

Conclusions: Ga-PSMA PET/CT was found to be an effective tool for the detection of recurrent PCa. Even though no relationship was detected between the GS and Ga-PSMA PET/CT findings, serum total PSA values may be used for estimating the likelihood of positive Ga-PSMA PET/CT results.
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http://dx.doi.org/10.1007/s12149-017-1207-yDOI Listing
November 2017

Immunosuppressive Treatment in C3 Glomerulopathy: Is it Really Effective?

Am J Nephrol 2017 13;46(2):96-107. Epub 2017 Jul 13.

Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Background: C3 glomerulopathy (C3GP) is a recently identified and described disease that has a high risk of progressing into end-stage renal disease. We aimed to evaluate the effects of various immunosuppressive regimens on C3GP progression because there are conflicting data on the treatment modalities.

Methods: In this retrospective study of 66 patients with C3GP, 27 patients received mycophenolate mofetil (MMF)-based treatment, 23 received non-MMF-based treatment (prednisolone or cyclophosphamide), and 16 received conservative care. The study groups were compared with each other with specific focus on primary outcomes defined as (1) kidney failure and (2) estimated glomerular filtration rate (eGFR) decline ≥50% from the baseline value.

Results: Overall, 17 (25.8%) patients reached the primary outcome after a median period of 28 months. The number of patients who reached the primary outcome were similar among the study groups (MMF-based: 8/27 [29.6%], non-MMF-based: 4/23 [17.4%], and conservative care: 5/16 [31.3%], p = 0.520). In the Cox regression analysis, age (HR 0.912, p = 0.006), eGFR (HR 0.945, p = 0.001), and proteinuria levels (HR 1.418, p = 0.015) at the time of biopsy, percentage of crescentic (HR 1.035, p = 0.001) and sclerotic glomeruli (HR 1.041, p = 0.006), severity of interstitial fibrosis (HR 1.981, p = 0.048), as well as no remission of proteinuria (HR 2.418, p = 0.002) predicted the primary outcome.

Conclusion: Although patients receiving immunosuppressive treatments had higher proteinuria and lower serum albumin at baseline, there were no differences between these patients and those receiving conservative care alone in proteinuria remission or in the decline of renal function. Younger age, higher proteinuria, lower eGFR, and the presence of crescentic and sclerotic glomeruli, severity of interstitial fibrosis, and no remission of proteinuria predicted the progression of kidney disease.
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http://dx.doi.org/10.1159/000479012DOI Listing
May 2018

Vascular function and arginine and dimethylarginines in gentamicin-induced renal failure: a possible effect of heme oxygenase 1 inducer hemin.

Can J Physiol Pharmacol 2017 Dec 10;95(12):1406-1413. Epub 2017 May 10.

a Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Capa 34093, Istanbul, Turkey.

Increased oxidative stress and disturbance in nitric oxide bioavailability lead to endothelial dysfunction and cardiovascular complication in renal disease. Gentamicin (GM), a commonly used antibiotic, exhibits a toxic effect on renal proximal tubules. Prevention of its nephrotoxicity is important. Therefore, we investigated whether heme oxygenase 1 HO-1) induction influenced kidney and vascular function in GM-administered rats. GM (100 mg·kg·day; i.p.) was given to rats alone or together with hemin (20 mg·kg on alternate days; i.p.) for 14 days. Plasma and kidney l-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) as well as kidney 4-hydroxynonenal (HNE) levels and myeloperoxidase (MPO) activity were measured. Histopathological examinations of kidney and relaxation and contraction responses of aorta were also examined. GM increased serum SDMA, urea nitrogen (BUN), and creatinine levels and caused histopathological alterations in the kidney. GM elevated HO-1 protein and mRNA expressions, 4-HNE level, and MPO activity and decreased antioxidant enzyme activities and l-arginine levels in the kidney. Decreased relaxation and contraction were detected in the aorta. Hemin restored renal oxidative stress and inflammatory changes together with vascular dysfunction, but did not affect SDMA, BUN, or creatinine levels. We conclude that HO-1 induction may be effective in improving renal oxidative stress, inflammation, and vascular dysfunction mediated by GM.
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http://dx.doi.org/10.1139/cjpp-2016-0578DOI Listing
December 2017

Comparison of Renal Anastomosing Hemangiomas in End-Stage and Non-End-Stage Kidneys: A Meta-Analysis With a Report of 2 Cases.

Int J Surg Pathol 2017 Sep 24;25(6):488-496. Epub 2017 Apr 24.

1 Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Background: Renal anastomosing hemangioma (RAH) is a very rare distinct entity composed of anastomosing sinusoidal (spleen-like) capillary-sized vessels lined by flat or hobnail endothelial cells. Most of the published cases of RAH occurred in the setting of end-stage renal disease (ESRD).

Methods: We present 2 cases of RAH in ESRD along with a literature review. We compared clinicopathologic features of RAHs in end-stage and non-end-stage kidneys. A meta-analysis was conducted with PubMed and a manual search through references of relevant publications. Individual patient data gathered from the literature were used in the analysis.

Results: Our systematic review revealed 49 RAHs, including our 2 cases. Thirty-two (65.3%) cases were in ESRD, only 17 (34.7%) were in patients with non-ESRD. RAHs in ESRD were in younger patients, smaller in size, multifocal, and seen more with renal epithelial neoplasms when compared with RAHs in non-ESRD ( P < .05). Extramedullary hematopoiesis was seen mostly in RAHs in ESRD kidneys (85% vs 41.7%) ( P = .018). Follow-up data were available for 25 cases with a mean follow-up of 24.58 ± 38.54 months. Recurrence, metastasis, or death have never been described related to RAH in any patients.

Conclusions: In conclusion, RAHs are rare and mostly arise in kidneys with end-stage damage. RAHs in ESRD and non-ESRD differ in terms of clinicopathologic features.
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http://dx.doi.org/10.1177/1066896917706025DOI Listing
September 2017