Search

This study aimed to reveal the possible protective effect of dapagliflozin (DAPA) against acute kidney damage due to cyclosporine A (CsA). Thirty-two mice with an eight-week-old Balb\c albino strain were divided into four groups: control group, CsA group, DAPA group, and CsA + DAPA group. On day 9 of treatment, the animals were decapitated, and bilateral nephrectomy was performed. Oxidative stress and apoptosis were evaluated with caspase-3 activity, total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde (MDA), myeloperoxidase (MPO), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the right kidney resection material. The left kidney resection material was evaluated histopathologically. CsA increased caspase-3 activity, Bax, TOS, MDA, TAS, and MPO levels, and the administration of DAPA with CsA significantly reduced this increase in levels (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, and p < 0.001, respectively). CsA decreased Bcl-2 levels, and administration of CsA + DAPA significantly increased Bcl-2 levels compared with only CsA administration (p < 0.001). Additionally, administration of DAPA significantly reduced the histopathological findings (parenchymal inflammation, hyaline cast formation, vacuolization, and lysis of renal tubular cells) caused by CsA. DAPA reduces oxidative stress, apoptosis, and histopathological damage caused by CsA in renal tissue.

Although the prognostic significance of grade in endometrial cancer is well known, grade 2 cases have not been evaluated separately in most of the previous studies. In this study, we aim to investigate whether the oncologic outcomes of grade 2 endometrioid endometrial carcinomas trend towards grade 1 or 3 tumors. Patients' records and pathological reports were reviewed retrospectively and eligible patients with endometrioid endometrial carcinoma were determined and distributed into 3 groups according to their 1988 International Federation of Gynecology and Obstetrics (FIGO) grade. Groups' characteristics and oncologic outcomes were compared. Differences between grades were tested with z-test and adjusted by Bonferroni method. Kaplan-Meier method was performed for the survival analysis. In total, 776 patients of endometrioid endometrial carcinoma were included in this study. Mean follow-up time was 52 ± 14 months. Patients' mean age was 56.3 ± 10.8 years. Even though grade 2 endometrioid endometrial carcinomas were different from both grade 1 and 3 in terms of the pathological features, survival analyses demonstrated that their oncologic outcomes trended towards grade 1. The grade was determined as an independent prognostic factor for overall survival (OS). The interobserver reproducibility will be improved among pathologists by combining FIGO grade 1 and 2 endometrioid endometrial carcinomas, while prognosis prediction is not likely to be affected.

We herein describe two rare cases of unilateral hypoglossal nerve paralysis due to unusual causes. Two of the cases presented with progressive dysphagia and speech impairment. All laboratory investigation were unremarkable except radiologic finding related with the lesion which is pressed on the nerve. Diagnoses of the lesions were established with biopsy at the first patient and digital subtraction angiography (DSA).

Neuroendocrine carcinomas (NECs) of the urinary bladder are rare and aggressive, without an effective treatment approach. Immune checkpoint inhibitor agents targeting the interaction of programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) have been approved for urothelial carcinoma, but their use for small-cell carcinoma (SmCC) of the urinary bladder is unclear. Thus, we analyzed PD-1 and PD-L1 expression in NECs, particularly in SmCC of the urinary bladder. We used PD-1 antibody and two different biomarkers for PD-L1 antibodies, Ventana SP263 (Ventana Medical Systems, Inc.) and AM26531AF-N (Acris Antibodies GmbH). Among the 12 SmCC cases, 16.7% stained positive on immune cells for PD-1 and 33.0% for PD-L1. PD-L1 positivity on tumor cells was 25.0% of SmCC cases. The overall survival was shorter in PD-L1-positive patients compared with PD-L1-negative patients (15.4 months vs. 27.6 months). Large cell carcinoma (n = 1) was strongly and diffusely stained with PD-L1, and this case had the longest survival (68 months) in the group. Immune checkpoint inhibitors may be an alternative treatment option in SmCC of the urinary bladder. Furthermore, the absence of PD-L1 may be a good prognostic parameter.

Objective Lung cancer displays heterogeneity both in the tumor itself and in its metastatic regions. One interesting behavior of the tumor is known as Skip N2 metastasis, which N2 lymph nodes contain tumor cells while N1 are clean. In this study, mRNA levels of epithelial mesenchymal transition (EMT) related genes in skip N2 and normal N2 involvements of non-small cell lung cancer tissues were investigated to evaluate the possible molecular background that may contribute to the pathogenesis of Skip N2 metastasis. Materials and methods Eighty-three surgically resected and paraffin embedded lymph node samples of lung cancer patients were analyzed in this study, which 40 of them were Skip N2. N2 tissues were sampled from 50% tumor containing areas and total RNA was extracted. mRNA levels for 18S, E-cadherin, Vimentin, ZEB1 and SLUG were analyzed via qPCR and E-cadherin and vimentin protein levels via immunohistochemistry (IHC). Bioinformatic analysis were adopted using online datasets to evaluate significantly co-expressed genes with SLUG in lung cancer tissue samples. Results Skip-N2 patients who had adenocarcinoma subtype had better survival rates. Comparative analysis of PCR results indicated that Skip N2 tumor tissues had increased E-Cadherin/Vimentin ratio and ZEB1 mRNA expression, and significantly decreased levels of SLUG. E-cadherin IHC staining were higher in Skip N2 and Vimentin were in Non-Skip N2. TP63 had a strong correlation with SLUG expression in the bioinformatics analyses. Conclusion The results indicate that, at molecular level, Skip N2 pathogenesis has different molecular background and regulation of SLUG expression may orchestrate the process., Highlights Skip N2 metastasis is related with better on-year survival rates in Lung AdenocarcinomaEMT regulator gene SLUG expression is suppressed in Skip N2 compared to Non-Skip N2 metastasis.Tumor metastatic site exhibit less Vimentin staining at Skip N2 lymph nodeBioinformatic analyzes show that one of the genes with the highest expression correlation with SLUG was TP63, suggesting that they may be acting together in this process.

INTRODUCTION AND OBJECTIVE:To reveal the possible protective effect of dapagliflozin (DAPA) against acute kidney damage due to Cyclosporine A (CsA).METHODS:Thirty-two mice with an 8-week old Balb\c...

PubMedID: 31076855 Purpose: The aim of this study was to evaluate prognostic importance of programmed death-1 (PD-1) and/ or programmed death-ligand 1 (PD-L1) expressions in type 2 endometrial cancer. Study design Formalin-fixed, paraffin-embedded tissue samples from 53 cases with type 2 endometrial cancer were analyzed. One-third of our cases had serous adenocarcinoma (32%), 11 had clear cell (21%) and 25 had mixed-type adenocarcinoma (47%). PD-1 and PD-L1 expressions in tumor tissue and microenvironment were detected by immunohistochemistry. Clinical and pathological characteristics including age, stage, initial symptom, surgical procedure, myometrial invasion, lymphovascular space invasion (LVSI), lymph node invasion, adjuvant therapy, and survival were reviewed. The Kaplan–Meier and Cox proportional hazards models were used to evaluate the prognostic factors. Results: PD-1 expression in tumor tissue and microenvironment was detected in 22 (42%) and 28 (53%) cases, respectively. PD-L1 expression was detected in tumor and microenvironment in 8 (15%) and in 15 cases (28%), respectively. Expression of PD-1 and PD-L1 expressions in tumor area was associated with shorter survival (p = 0.006 and 0.001, respectively) but PD-1 and PD-L1 expressions in microenvironment were not found to be related with survival. PD-1 (p = 0.006) and PD-L1 expressions (p = 0.001) in addition to LVSI (p = 0.005), myometrial invasion (p = 0.015), lymph node involvement (p = 0.019), and suboptimal cytoreduction (p = 0.042), were found to be associated with poor prognostic indicators. PD-1 and PD-L1 expressions in tumor and lymph node involvement were determined as independent prognostic factors. Conclusion: PD-1 and PD-L1 expressions in type 2 endometrial cancers were found to be poor prognostic indicators. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Çukurova Üniversitesi British Association for Psychopharmacology: TSA-2015–4843 Çukurova Üniversitesi Formalin-fixed, paraffin-embedded tissue samples from 53 cases with type 2 endometrial cancer who were operated and followed in our university clinic between January 1996 and December 2015 were analyzed. The patients who were operated in our clinic during this period but could not reach the paraffin blocks or were not followed up were not included in the study. Their pathologic diagnoses were established based on hysterectomy material evaluated by expert gynecological pathologists (E.K.B., D.G.) and the evaluation of the PD-1, PD-L1 staining was performed by one pathologist (E.K.B). This study was approved by Çukurova University, Faculty of Medicine, local ethical committee (2015.037.IRB.044) and was supported by the coordination unit of Scientific Research Projects (BAP–TSA-2015–4843) of Çukurova University. Funding This study was supported by the coordination unit of Scientific Research Projects (BAP-TSA-2015–4843) of Çukurova University.

Objectives: Grade 3 endometrioid adenocarcinomas (G3 EAC), type two endometrial carcinomas (Type 2 EC), and also uterine carcinosarcomas (UCS) are considered as high-grade endometrial adenocarcinomas. The aim of this study was to compare the clinicopathologic features and survival of patients with UCS, G3 EAC, Type2 EC. Material and methods: We included two hundred and thirty-five patients in this study. Patients were divided into three groups according to the type of tumor as uterine G3 EAC (group 1, n = 62), Type 2 EC (serous, clear and mixed types; group 2, n = 93), and UCS (group 3, n = 80). We compared the groups according to age, initial symptom, surgical approach, stage, myometrial invasion (MI), lymph node invasion (LNI), lymphovascular space invasion (LVSI), adjuvant therapy, and survival. When comparing the survival outcomes the Kaplan-Meier analysis was performed. Results: The groups were similar according to age, menopausal status, nulliparity, initial symptoms, stage, LVSI, and LNI. Positive cytology was determined significantly more in group 3. There was a significant difference between the groups in terms of myometrial invasion degree. Optimal cytoreduction was similar among the groups. The primary adjuvant treatment was chemotherapy for UCS and Type2 EAC whereas radiotherapy was the main adjuvant treatment for G3 EAC. There were no significant differences among the groups according to overall survival (OS) (p = 0.290). Conclusions: Although the survival difference among the groups can not be revealed, these patients have different clinical and pathological features and they should be considered as different groups.

PubMedID: 31739121 Objective: The aim of this study was to evaluate the clinical and prognostic importance of programmed death-1 (PD-1) and/ or programmed death-ligand 1 (PD-L1) in uterine carcinosarcoma (UCS). Study Design: Formalin-fixed, paraffin-embedded tissue samples from 59 cases with UCS were analyzed. PD-1 and PD-L1 expressions in tumor tissue and microenvironment were detected by immunohistochemistry. Clinical and pathological characteristics including age, stage, initial symptom, surgical approach, myometrial invasion, lymphovascular space invasion (LVSI), lymph node invasion, adjuvant therapy, and survival were evaluated. The Kaplan-Meier and Cox proportional hazards models were used to compare the outcomes and prognostic factors. Results: PD-1 expression in tumor tissue and microenvironment was detected in 15 (25 %) and 18 (30 %) cases, respectively. PD-L1 expression in tumor tissue and microenvironment was detected in 15 (25 %) and 12 cases (20 %), respectively. PD-L1 expression in tumor was associated with longer survival and median survival was 38 and 15 months in cases with and without PD-L1 expressions, respectively (p = 0.019). Lymphovascular space invasion (LVSI) (p = 0.014), myometrial invasion (p = 0.008) and PD-L1 expression were found to be prognostic for UCS's. PD-L1 expression was found to be an independent good prognostic factor with Cox regression analysis (OR 3.9; 95 % CI: 1.4–11.0) for overall survival. Conclusion: PD-1 and/or PD-L1 expression are important due to their expressions in one fourth of the cases with UCS and PD-1/PD-L1 blockade may be a new avenue in UCS. © 2019 British Association for Psychopharmacology: TSA-2015-4843 This study was supported by the coordination unit of Scientific Research Projects ( BAP- TSA-2015-4843 ) of Çukurova University.

Introduction/Background The risk of endometrial cancer is known to be increased with the increasing body mass index (BMI). Patients with BMI more than 40 kg/m2 are identified as morbid obese according to the World Health Organization. Morbidly obese patients are an enormous problem regarding all of their health procedures including examination, evaluation with imaging methods, surgery, increased per-operative and postoperative morbidity and complications. The laparoscopic approach had been validated for the endometrial cancer surgery in many studies. The present study aimed to investigate the adequacy and oncological safety of laparoscopy compared to laparotomy in the surgery of the morbid obese women with endometrial cancer. Methodology Archival records and pathological reports of the endometrial cancer cases who were operated and followed up in Cukurova University Gynecologic Oncology Center between January 2008 and December 2018 were retrospectively reviewed. Patients with BMI ≥40 were divided into laparoscopy and laparotomy groups. Groups were compared concerning cases9 clinic, surgical and pathological features. In addition, survival analysis of the groups were performed using Kaplan-Meier and compared with the Log-rank method. Results A total of 146 morbidly obese endometrial cancer cases with sufficient data were determined during the study period. Laparoscopic surgery was performed in 65 (44.5%) and laparotomy in 81 (55.5%) of them. Mean age was 58 years for both groups. Mean BMI of the laparoscopy and laparotomy groups was 46.1 kg/m2 and 44.3 kg/m2, respectively. No difference between groups according to the main clinical, surgical and pathological characteristics. Five-year overall survival rates were 86.6% and 83.9% in the laparoscopy and laparotomy groups (p=0.571), respectively. No difference between groups concerning to the disease free survival was noted (p=0.184). Conclusion Laparoscopic surgery do not harm the long-term oncologic outcomes of the morbidly obese endometrial cancer patients, while its short-term advantages in this special population are undeniable. Disclosure Nothing to disclose.

Introduction/Background The prognostic significance of grade in the endometrial cancer is well known. However, grade 2 cases were not evaluated separately in most of the previous studies. In this study, we aimed to investigate whether the oncologic outcomes of grade 2 endometrioid endometrial carcinomas is trending to grade 1 or 3 tumors. Methodology Patients records and pathological reports were reviewed retrospectively and 776 patients of endometrioid endometrial carcinoma were distributed into 3 groups according to their 1988 FIGO grade. Groups9 characteristics and oncologic outcomes were compared. Difference between grades was tested with z-test and adjusted by Bonferroni method. Kaplan-Meier method were performed for the survival analysis. Results Mean follow-up time was 52 months. Patients9 mean age was 56.29±10.8 years. Five years OS, DFS rates were 95.1%, 83.3% and 91.6%, 79.1% for grade 1 and 2, respectively. These rates were not statistically different (OS: p=0.075, DFS: P=0.939). The statistically difference between grade groups in terms of OS and DFS was mainly noticed between grade 1 and 3 (OS: 75.6%, DFS: 60.3%) Even though, grade 2 endometrioid endometrial carcinomas were different from both grade 1 and 3 in terms of the pathological features, survival analyses demonstrated that their oncologic outcomes were trended to grade 1. Grade was determined as an independent prognostic factor for OS. Conclusion The interobserver reproducibility will be improved among pathologists by combining FIGO grade 1 and 2 endometrioid endometrial carcinomas, while prognosis prediction would not likely to be affected. Disclosure Nothing to disclose.

Introduction/Background Uterine carcinosarcoma (UCS), grade 3 endometrioid adenocarcinomas (G3 EAC) and type two adenocarcinomas (Type2 EAC) are considered as high-grade endometrial adonocarcinomas. The aim of this study was to compare the clinicopathologic features and survival of patients with UCS, G3 EAC, Type 2 EAC. Methodology A total of 235 patients were included in this study. Of them, 62 cases had uterine HGEAC (group 1), 93 cases had Type2 EAC (group 2), and 80 had UCS (group 3). The groups were compared in terms of clinical and pathological characteristics including age, initial symptom, surgical approach, stage, myometrial invasion (MI), lymphovascular space invasion (LVSI), lymph node invasion, adjuvant therapy, and survival. The Kaplan-Meier analysis was used to compare the survival outcomes. Results There were no statistically significant differences among the groups with regard to age, nulliparity, menopausal status, and the main initial symptom. Omentectomy was performed significantly more in group 2, but the rate of optimal cytoreduction was similar among the groups. All groups were similar in terms of stage, depth of myometrial invasion, LVSI and lymph node metastasis. Chemotherapy was the main adjuvant therapy for UCS and Type2 EAC while radiotherapy was the main adjuvant therapy for G3 EAC. There were no differences among the groups in terms of disease-free survival (DFS) (p=0.941) and overall survival (OS) (p=0.504). Conclusion Although the survival difference among the groups can not be revealed, these patients have different clinical and pathological features and they should be considered as different groups. Disclosure Nothing to disclose.

PubMedID: 29969202 Background. Recent reports have indicated an improved prognosis in sepsis with beta blocker agents; however, the underlying action mechanism is still under debate. Objectives. The aim of this study was to investigate the potential effect of propranolol on endothelial dysfunction in septic rats. Material and methods. The cecal ligation and puncture model (CLP) was used to generate sepsis. Adult male Wistar-Albino rats were divided into 4 groups: group 1 was a sham group, group 2 received sterile saline, group 3 received 10 mg/kg of propranolol 3 days before the intervention, and group 4 received 10 mg/kg of propranolol 30 min after CLP. Six rats from each group were sacrificed 24 h postoperatively. The remaining rats were followed for survival. We have also evaluated the effects on systemic inflammation, coagulation and the lung tissue with immunohistochemical and electron microscopic evaluation. Results. Serum tumor necrosis factor alpha (TNF-?) and plasminogen activator inhibitor-1 (PAI-1) levels, as well as tissue TNF-? scores were elevated in septic rats. Electron microscopic examination of the lung tissue showed endothelial dysfunction in the sepsis group. Pretreatment significantly improved survival. Moreover, pre-treatment altered serum vascular endothelial growth factor receptor-1 (VEGFR-1) levels and post-treatment reduced serum PAI-1 and VEGFR-1 levels. In both the pre- and post-treatment groups, electron microscopic examination revealed improvement of the destroyed lung endothelium and showed only mild alterations in the cytoplasmic organelles, especially in the mitochondria of the endothelial cells. Conclusions. These results suggest that the improved outcome with beta blockers in sepsis may be due to the ameliorated endothelial dysfunction. Further studies focusing on the potential effect of beta blockers on the endothelium may lead to a better understanding of sepsis. © 2019 by Wroclaw Medical University.

WOS: 000493372200002 PubMed ID: 31709947 Introduction: Mesothelioma is an aggressive tumour that originates in serous surfaces. The primary end point of this study was to invastigate the relationship of progression free survival (PFS) and overall survival (OS) with the c-Met, EGFR, PTEN, PDGFR-alpha, PI3K/AKT and mTOR expression levels in the tumour tissue of pleural and peritoneal mesothelioma cases. Materials and Methods: The study included 53 patients diagnosed with mesothelioma between 2005 and 2016. The cases were separated into 2 groups as pleural and peritoneal. The effects on OS and PFS were examined of the c-Met, EGFR, PTEN, PDGFR-alpha, PI3K/AKT and mTOR expression levels and also clinicopathological parameters and the treatments given. In the statistical analysis of the data obtained, IBM SPSS vn 20.0 software was used. Results: Of the 53 patients included in the study, 39 (73.6%) were diagnosed with pleural mesothelioma and 14 (26.4%) with peritoneal mesothelioma. According to the c-Met and mTOR expression, OS and PFS of the peritoneal cases with high expression (2+, 3+) was seen to be significantly better than that of the peritoneal cases with low expression (0, 1+) (p < 0.05). According to the PDGFR expression, OS and PFS of the pleural cases with low expression (0, 1+) was seen to be significantly better than that of the pleural cases with high expression (2+, 3+) (p < 0.05). Conclusion: The examination of c-MET, PDGFR-alpha and m-TOR expression in the in the tumor tissue of mesothelioma cases may be important in determining prognosis.

WOS: 000469053500001 PurposeThe aim of this study was to compare the clinical characteristics and outcomes of the cases with uterine high-grade endometrioid adenocarcinoma (HGEAC) and uterine carcinosarcoma (UCS).MethodsA total of 141 patients were included in this study. Of them, 61 cases had uterine HGEAC (group 1) and 80 had UCS (group 2). Both groups were compared in terms of clinical and pathological characteristics including age, stage, initial symptom, surgical approach, myometrial invasion, lymphovascular space invasion (LVSI), lymph node invasion, adjuvant therapy, and survival. The Kaplan-Meier and Cox proportional hazards models were used to compare the outcomes and prognostic factors.ResultsThere were no statistically significant differences between the groups with regard to age, nulliparity, menopausal status, and the main initial symptom. Both groups were similar in terms of stage, depth of myometrial invasion, and lymph node metastasis. Lymphadenectomy was performed in 74% and 91% of the cases in group 1 and group 2, respectively (p

Amaç: Prostat karsinomu (PK) önemli oranda ölümcül ve morbiditesi olan, sık görülen kanser türlerinden biridir. PK'nin etiyolojisi net değildir. Enflamatuvar yolaktaki sitokin ve mediatörler; kronik enflamasyon ve kanser arasındaki ilişkide, çeşitli basamaklarda rol oynamaktadır. Bu çalışmanın amacı, PK'li hastalarda siklooksijenaz-2 (COX), apopitozis ve anjiyogenezis arasında ilişki olup olmadığını belirlemektir.Gereç ve Yöntem: 2005-2010 yılları arasında, patolojik evresi pT2 olup radikal prostetektomi uygulanan 49 olgu, Çukurova Üniversitesi Tıp Fakültesi Patoloji arşivinden retrospektif olarak seçilmiştir. Histolojik slaytlar tanısal açıdan tekrar gözden geçirilmiş ve Gleason skorlama sistemine göre derecelendirilmiştir. Olgulara immünohistokimyasal olarak COX-2, vasküler endotelyal büyüme faktörü (VEBF), monoklonal antikor (M30), bcl-2 uygulanarak değerlendirilmiştir. Bulgular: Hastaların ortalama yaşı 63,8 idi. Yirmi bir hasta Gleason skor =7 olarak derecelendirildi. COX-2 ekspresyonu %81,6 hastada tespit edildi. COX-2 ekspresyonu bcl-2 ekspresyonu ile korele olarak bulunurken, VEBF ile COX-2 arasında korelasyon saptanmadı. Gleason skor ile M30 arasında negatif korelasyon saptandı. Ortalama yaşam ve COX-2 arasında negatif korelasyon saptandı. COX-2 ekspresyonu arttıkça sağkalım süresinin anlamlı olarak azaldığı saptandı.Sonuç: Çalışmamız PK karsinogenezisinde COX-2'nin anjiyogenezisi arttırmaktan çok apopitozisi inhibe ederek etki ettiğini düşündürmektedir. Bu sonuçların, tedavi stratejilerine yeni bakış açıları sunabileceği gibi, hastaların klinik takiplerinin sonuçlarını öngörmede faydalı olabileceğini düşünmekteyiz. Objective: Prostate carcinoma (PC) is one of the most commonly diagnosed cancer types with significant rates of mortality and morbidity. The etiology of PC is not clear. Cytokine and mediators at the inflammatory pathway plays role at the various steps of the relation between chronic inflammation and cancer. The objective of this study is to determine if there is relationship between cyclooxygenase-2 (COX) apoptosis and angiogenesis in patients with PC.Materials and Methods: Sample of 49 cases who were at pathologic stage pT2 and underwent radical prostatectomy, were selected retrospectively between 2005-2010, from the archives of Pathology Department of Çukurova University Faculty of Medicine. Histologic slides of each case were reviewed for the diagnostic reassessment and graded by the Gleason scoring system. COX-2, vascular endothelial growth factor (VEGF), monoclonal antibody (M30) and bcl-2 were immunohistochemically applied to the cases and they were evaluated.Results: The mean age of the patients were 63.8. Twenty-one cases had their Gleason score =7. COX-2 expression was detected in 81.6% of cases. While COX-2 expression was significantly correlated with bcl-2 expression, there was no correlation between VEGF and COX-2 expression. Gleason score was negatively correlated with M30. It was detected that as COX-2 expression increased mean survival time significantly decreased.Conclusion: This study makes us think that in the PC carcinogenesis COX2 inhibits apoptosis rather than promoting angiogenesis. These results may offer new insights for the treatment strategies, also they may be useful for the prediction of clinical outcomes.

Hypertrophic osteoarthropathy (HOA) is a condition characterized by arthralgia/arthritis, clubbing, and periosteal reaction. Primary form of HOA is observed at early ages of life and is hereditary in nature. Secondary HOA is more frequently seen in clinical setting and occurs as a result of various disorders including inflammatory and malignant diseases. Regression in HOA may be seen after the treatment of underlying condition. In this report, we presented a case of HOA coexisted with myelofibrosis and reviewed the current literature.

Hypertrophic osteoarthropathy (HOA) is a condition characterized by arthralgia/arthritis, clubbing, and periosteal reaction. Primary form of HOA is observed at early ages of life and is hereditary in nature. Secondary HOA is more frequently seen in clinical setting and occurs as a result of various disorders including inflammatory and malignant diseases. Regression in HOA may be seen after the treatment of underlying condition. In this report, we presented a case of HOA coexisted with myelofibrosis and reviewed the current literature. © 2014 Elsevier Editora Ltda. All rights reserved. Coexistencia de osteoartropatia hipertrofica e mielofibrose

Primary melanoma of the urinary tract is a very rare and aggressive cancer. It accounts for less than 1% of all the melanoma cases, making it difficult to histopathologically diagnose and manage. We present a retrospective case series of eight primary urinary tract melanoma with clinical, pathological, and molecular findings to add more insight to this challenging disease. These cases were evaluated for histopathological, immunohistochemical, and molecular features of melanoma that were most commonly found in the urethra, followed by those in the bladder and ureter. Identification of nested growth patterns and in situ melanocytic components at cell edges are helpful in the histopathological diagnosis of amelanotic or hypomelanotic tumors. Our results indicate that urinary tract melanoma has several molecular traits, such as gene expression patterns. Genetic mutations may be related to metastasis, as well as provide targets for the management programs.

Background: Thyroid cancer is the most common endocrine cancer, with an increasing incidence around the world in the last three decades. The increased risk of secondary cancer is associated with a genetic predisposition or radioactive iodine used in the treatment. Case Report: A 65-year old male patient was operated on for thyroid papillary cancer. He received radioactive iodine on two occasions postoperatively. After six years, he presented with malaise and fatigue with leukocytosis and eosinophlilia. The physical examination revealed inguinal lymphadenopathies and splenomegaly, after examining the bone marrow and lymph node biopsies, he was diagnosed with eosinophilic myeloproliferative neoplasia and T-cell lymphoblastic leukaemia/lymphoma. Conclusion: Leukaemia and other haematological malignencies may develop after radioactive iodine treatment. Patients with radioactive iodine ablation history should be monitored for a long time. Background: Thyroid cancer is the most common endocrine cancer, with an increasing incidence around the world in the last three decades. The increased risk of secondary cancer is associated with a genetic predisposition or radioactive iodine used in the treatment. Case Report: A 65-year old male patient was operated on for thyroid papillary cancer. He received radioactive iodine on two occasions postoperatively. After six years, he presented with malaise and fatigue with leukocytosis and eosinophlilia. The physical examination revealed inguinal lymphadenopathies and splenomegaly, after examining the bone marrow and lymph node biopsies, he was diagnosed with eosinophilic myeloproliferative neoplasia and T-cell lymphoblastic leukaemia/lymphoma. Conclusion: Leukaemia and other haematological malignencies may develop after radioactive iodine treatment. Patients with radioactive iodine ablation history should be monitored for a long time.

Purpose: The aim of this study was toexplore the histopathologic subtypes of pediatric lymphomas and their relation with Ebstein-Barr virus infection in our region. Materials and Methods: In this retrospective study, 87 children including 36 cases with Hodgkin lymphoma and 51 cases with non-Hodgkin lymphoma were included in the study. The pathologic slides were used to investigate immunohistochemical staining with ebstein-barr virüs latent membrane protein-1 and in-situ hybridization. Results: The most common histopathological subtype in hodgkin lymphoma cases was mixed cellular classical hodgkin lymphoma (55.6%). The most common histopathological subtype in Non-Hodgkin lymphoma cases was Burkitt lymphoma (51.0%). Ebstein-Barr virüs latent membrane protein-1 was positive in 29 Hodgkin lymphoma. All non-Hodgkin lymphoma cases were stained negative with ımmunohistochemical. The positive staining rate of Hodgkin lymphoma cases with in-situ hybridization was 83.3% and this rate was 27.5% in non-Hodgkin lymphoma cases. The differences between groups for both staining methods were significant. Conclusion: The results of this study show that the distribution of histopatholojik subtypes of pediatric lymphomas similar to in developing countries. And we have observed that in-situ hybridization is more specific than immunohistochemistry because Ebstein-Barr virus positivity is more detected in in-situ hybridization. Amaç: Bu çalışmanın amacı bölgemizdeki pediatrik lenfomaların histopatolojik alt tiplerinin oranını ve bunların Ebstein-Barr virüs enfeksiyonu ile olan ilişkisini incelemektir. Gereç ve Yöntem: Hodgkin lenfoma tanısı alan 36 olgu ve non-hodgkin lenfoma tanısı alan 51 olgu retrospektif arşiv taraması yapılarak çalışmaya dahil edildi. Olgulara immünohistokimyasal olarak Ebstein-Barr virüs latent membran proteini-1 ve in-situ hibridizasyon uygulandı. Bulgular: Hodgkin lenfoma olgularında; en sık rastlanan histopatolojik alt tipler sırası ile mikst sellüler klasik hodgkin lenfoma (%55,6) idi. Non-Hodgkin lenfoma olgularında en sık rastlanan histopatolojik alt tip Burkitt lenfoma (%51) idi. Ebstein-Barr virüs latent membran proteini-1 ile 29 hodgkin lenfoma olgusunda pozitif iken non-hodgkin lenfoma olgularında immünohistokimya ile pozitif boyanma saptanmadı. Hodgkin lenfoma olgularında in situ hibridizasyon ile boyanma oranı % 83.,3 iken non-Hodgkin lenfoma olgularında bu oran % 27.5 idi.. Her iki boyama yöntemi için gruplar arasındaki fark istatistiksel olarak anlamlıydı. Sonuç: Bu çalışmada, olgularımızın histopatolojik dağılımlarının gelişmekte olan ülkelerdeki pediatrik lenfoma olguları ile benzer olduğunu göstermektedir. Aynı zamanda in situ hibridizasyon’da Ebstein-Barr virüs pozitifliği daha fazla olması nedeniyle in situ hibridizasyonun ebstein barr virüs tespitinde immünohistokimyadan daha spesifik olduğunu düşünmekteyiz.

Erdogan, Kivilcim Eren/0000-0002-4951-8703; kilic bagir, Emine/0000-0002-1447-1060; Celik, Betul/0000-0001-9731-9939; Tatli Dogan, Hayriye/0000-0003-4318-2775; Cakir, Asli/0000-0003-0128-6947 WOS: 000414649400006 PubMed: 28272675 Objective: There is no other screening program close to the success rate of PAP test. Cervical cytology constitutes a large workload so that quality control in cervical cytology is important for the quality assurance of pathology laboratories. Material and Method: In this study, we collected the cervical cytology results from all over Turkey and discussed the parameters influencing the quality of the PAP test. The study was conducted with Turkish gynaecopathology working group and 38 centers (totally 45 hospitals) agreed to contribute from 24 different cities. The study was designed to cover the cervical cytology results during 2013. The results were evaluated from the data based on an online questionnaire. Results: The total number of Epithelial Cell Abnormality was 18,020 and the global Epithelial Cell Abnormality rate was 5.08% in the total 354,725 smears and ranging between 0.3% to 16.64% among centers. The Atypical squamous cells/Squamous intraepithelial lesion ratios changed within the range of 0.21-13.94 with an average of 2.61. When the centers were asked whether they performed quality assurance studies, only 14 out of 28 centers, which shared the information, had such a control study and some quality parameters were better in these centers. Conclusion: There is an increase in the global Epithelial Cell Abnormality rate and there are great differences among centers. Quality control studies including the Atypical squamous cells/Squamous intraepithelial lesion ratio are important. Corrective and preventive action according to quality control parameters is a must. A cervical cytology subspecialist in every center can be utopic but a dedicated pathologist in the center is certainly needed.

Kulchitsky hücrelerinden kaynaklanan primitif nöroektodermal tümörler (PNET), kadın genital sisteminde oldukça nadir görülen tümörlerdir. PNET'in ayırıcı tanısı immünohistokimyasal ve genetik özelliklerine göre yapılabilir. Genital sistemdeki PNET'ler klinik ve moleküler açıdan farklılıklar gösteren oldukça agresif tümörlerdir ve standart bir tedavi yaklaşımları yoktur. Farklı belirti ve klinik bulgular ile seyreden uterus kaynaklı 2 PNET olgusunu sunmayı amaçladık Primitive neuroectodermal tumor (PNET) arise from Kulchitsky cells and are rarely seen in the female genital tract. Differential diagnosis of PNET can be made based on immunohistochemical profiles and genetic analyses. Genital tract pNETs are very aggressive pathologies with different clinical and molecular manifestations and there are no standard guidelines for treatment. We aimed to present two cases of uterine PNETs with different symptomatology and clinical findings

Amaç: Bu çalışmada, kliniğimizde son 5 yılda opere edilen bordeline overtümörlü vakaların değerlendirilmesi amaçlanmıştır.Gereç veYöntem: Çukurova Üniversitesi Tıp FakültesiJinekolojik Onkoloji biriminde son 5 yıl içerisinde opere edilen borderlineover tümörlü olguların, patoloji raporları ve birimin bilgisayar kayıtları ilearşiv dosyaları retrospektif bir şekilde tarandı. Toplam 41 vaka tespit edilipçalışmaya dahil edildi. Olguların demografik karakteristikleri, preoperatifmuayene bulguları, operasyon ve patoloji özellikleri değerlendirildi.Bulgular: Hastaların ortalama yaşı 41 idi ve %85’i premenopozal dönemde idi.Preoperatif dönemde bakılan ultrasonda, tümörün ortalama çapı 10 cm olarakölçüldü. Operasyon öncesi ortalama ca125 değeri 120 olarak tespit edildi. Totalhisterektomi + bilateral salpingooferektomi 12 hastaya uygulanırken, geri kalan29 hastaya unilateral salpingooferektomi uygulandı. Lenfadenektomi, hastaların%41.5’inde gerçekleştirildi. En sık seröz histopatolojik tip (%70.7) izlendi.Hastaların çoğunda (%90.2) tümör, evre I’de idi. Hiç bir olguda nüks tespitedilmedi.Sonuç: Borderline over tümörleri, iyi prognoza sahipolduğundan, fertilite arzusu olan hastalarda, unilateral salpingoferektomigüvenle önerilebilecek bir tedavi şeklidir., Purpose: The aim of this study was to evaluate the borderline ovarian tumor cases who were operated in our clinic. Material and Methods: The last 5 years’ pathology reports, computer records and archival files of the Çukurova University Medical Faculty Gynecologic Oncology Unit were retrospectively reviewed for the borderline ovarian tumor patients. A total of 41 cases were detected and included in the study. Patients’ demographic characteristics, preoperative assessments, operation and pathological features were evaluated.Results: Patients’ mean age was 41 and 85% of them were premenopausal. Average of the tumor diameter was found to be 10cm in the preoperative ultrasound examination. Mean of the preoperative ca125 value was 120. While total hysterectomy + bilateral salpingo-oophorectomy was applied to 12 cases, unilateral salpingo-oophorectomy was performed in the remaining 29 patients. Lymphadenectomy was carried out in 41.5% of the patients. Serous borderline was the most common histology (70.7%). Majority of the cases was with stage I disease (90.2%). No recurrences were determined among the study population.Conclusion: Borderline ovarian tumors have a favorable prognosis and therefore, unilateral salpingo-oophorectomy can be suggested to be a safely treatment approach for patients who desire to protect their fertility.

e12584Background: Immune checkpoint ligand PD-L1 and transmembrane oncogenic protein MUC-1 are upragulated in TNBC and contribute aggressive behavior of this disease. It has been shown that pharmac...

PubMedID: 26305144 Objective: Necrotizing enterocolitis has been investigated and debated extensively in recent years; however, there is still no effective treatment. The aim of this study was thus to examine the effects of ß-estradiol on intestinal injury in rats. Methods: Twenty-four newborn female rat pups were divided into three groups. In group 1 (sham), hypoxia-re-oxygenation was not performed. In group 2 (saline), the rats were injected with saline after hypoxia-re-oxygenation, and the process was repeated for 5 d. In group 3 (ß-estradiol treatment), the rats were subjected to hypoxia-re-oxygenation and then given ß-estradiol intraperitoneally once a day for 5 d. After these procedures, the terminal ileum was removed for analysis. Results: Statistically significant differences in histological grades were found between groups 1 and 2 (p = 0.000), groups 1 and 3 (p = 0.028), and groups 2 and 3 (p = 0.021). There were also differences in TNF-? and IL-6 levels between groups 2 and 3 (p = 0.000 and p = 0.038, respectively) and between groups 1 and 2 (p = 0.000 and p = 0.000); there was no difference between groups 1 and 3 (p = 0.574 and p = 0.195, respectively). Electron microscopy examination revealed a decrease in lipid droplets at the apical cytoplasm of the columnar cells in group 2; in group 3, the absorption of the lipids as lipid droplets was similar to that of group 1. Conclusion: In this study, ß-estradiol was found to decrease the intensity of intestinal injury significantly by inhibiting TNF-? and IL-6. © 2015 Taylor & Francis.

Objectives: Although Hodgkin's lymphoma (HL) is one of the most curable cancers in adult patients, new targets have to be defined in cases resistant to traditional chemotherapy. The preferentially expressed antigen of melanoma (PRAME) is a cancer testis antigen and its expression is very scarce or absent in normal tissues. For this reason PRAME is a promising candidate for tumor immunotherapy. The aim of this study is to understand the correlation of PRAME expression with prognostic factors in HL, to determine the utility of PRAME as a targeted molecule for immunotherapy and to compare real-time polymerase chain reaction (real-time PCR) and immunohistochemistry (IHC) for the detection of PRAME. Methods: In 82 patients, PRAME was studied using real-time PCR and IHC. Data analyses were performed using statistical methods such as t test, Mann-Whitney U test, χ2 test, Kaplan-Meier method, log-rank test and Cox regression analysis. Results: PRAME was detected in 15 (18.3%) patients using IHC and in 8 (9.8%) patients using real-time PCR. A correlation was found between PRAME positivity and higher International Prognostic Score (p = 0.039). PRAME positivity detected using real-time PCR was found to be correlated with shorter disease-free survival (DFS) and overall survival (OS, p = 0.0005). Discussion: The demonstration of PRAME especially in histiocytes and Reed-Sternberg cells may provide guidance for immunotherapy. Although PRAME positivity increases the risk for death (3.56), independent risk factors that affected DFS and OS occurred in advanced age and high-risk groups. Conclusion: Although real-time PCR is sensitive in the detection of PRAME, IHC can be another useful method. Despite the need for studies conducted on larger patient samples, PRAME expression is considered as a poor prognostic parameter in HL.

PubMedID: 26004934 Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are new targets in cancer immunotherapy. PD-1 protein is an immune checkpoint expressed in many tumors. Epstein–Barr virus (EBV) is present in malignant Hodgkin/Reed–Sternberg (HRS) cells in approximately 40–50 % of Hodgkin lymphoma (HL). The aim of this study is to evaluate the clinical and prognostic importance of PD-1 and/or PD-L1 in HL and also to determine the association between EBV-encoded RNA (EBER) and PD-1/PD-L1. Formalin-fixed, paraffin-embedded tissue samples from 87 cases with HL were analyzed in this study. Immunohistochemical staining was performed to detect the PD-1 and PD-L1 expressions. Chromogenic in situ hybridization for EBER was performed using fluorescein-labeled oligonucleotide probes. PD-1 and PD-L1 expressions were found in 20 % of the cases. The EBER positivity was found in 40 cases (45 %). It has been found that co-expression of PD-1 and PD-L1 was associated with shorter survival although PD-1 or PD-L1 expressions were not found to be related with survival. Overall survival (OS) and disease-free survival (DFS) in cases without PD-1 and PD-L1 expressions were 135 and 107 months, respectively. OS and DFS in cases with co-expression for PD-1 and PD-L1 were 24 and 20 months, respectively, and these differences were found to be statistically significant for both OS and DFS (p = 0.002 and p = 0.003, respectively). Cox regression analysis showed that co-expression of PD-1 and PD-L1 was found to be an independent risk factor for prognosis (OR 6.9, 95 % CI 1.9–24.3). Targeting PD-1 and/or PD-L1 is meaningful due to the 20 % expression of each in HL, and we did not find an important association between PD-1 and PD-L1 and EBER expression in HL. Very poor outcome in cases with co-expression of PD-1/PD-L1 suggests new avenues to detect the new prognostic markers and also therapeutic approaches in HL. © 2015, Springer-Verlag Berlin Heidelberg.

PubMedID: 29798961 BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia among adults in Western populations. CLL has a wide range of clinical presentations and varied outcomes. For CLL, cytogenetic assessment is essential for estimating prognoses and determining the treatment of choice. The fluorescence in situ hybridization (FISH) technique is widely used for genetic assessment due to its high sensitivity. AIM: This study aimed to evaluate the frequencies of deletions of 13q14.3, 17p13.1, 11q22.3, and 13q34 and of trisomy 12 and to observe their effects on survival in 226 Turkish CLL patients using FISH analysis. RESULT AND CONCLUSION: The frequencies of abnormalities were 65.4% for del 13q14.3, 39.8% for del 17p13.1, 19% for del 11q22.3 (del ATM), and 15.9% for trisomy 12. No patients had a 13q34.3 aberration. Our results are partially consistent with literature findings. However, certain conflicts with prior results were observed, particularly with respect to the high prevalence of 17p13.1 deletions and the enhanced survival of patients with such deletions. These inconsistencies may represent population-based differences in the genetic epidemiology of CLL. © 2018 Indian Journal of Cancer | Pulished by Wolters Kluwer-Medknow.

PD-1 and PD-L1 expressions in primary refractory and relapse/refractory cases with Hodgkin Lymphoma (HL) Background and aim: Programmed death 1 (PD-1) pathway has emerged as a mechanism in immune tolerance in various malignant tumors including hemopoietic neoplasias. PD-1 and its ligands PD-L1 and PD-L2 expressions have been detected both on tumor cells and also in the tumor microenvironment/tumor infiltrating cells. Checkpoint inhibitors are the new class of immunotherapy agents and they are monoclonal antibodies targeting PD-1 or PD-L1 and show promising activity in malignant tumors. Generally, but not in all tumors, there is a relationship between response to therapy and PD-1 / PD-L1 expression. Here we wanted to detect the PD-1 and PD-L1 expression before and after treatment in primary refractory HL (PR HL) and relapsed/refractory cases with HL (R/R HL). Patients and methods: PD-1 and PD-L1 expressions were evaluated in seventeen cases with R/R HL. Female/male ratio was 9/8, age range was between 19 and 59. All cases had classical HL; 12 had nodular sclerosing subtype, 4 had mixed cellular type and subtype could not be determined in one case. Eight cases had PR HL and 9 cases had R/R HL. Immunohistochemistry assay was used to detect PD-1 pathway. More than 5% expression in microenvironment (ME) and/or Reed Sternberg (RS) cells was accepted as positive. Results: PR HL cases: PD-1 expression in ME was detected in 2 cases and 4 cases, and in RS cells in none and 2 cases, before and after chemotherapy, respectively. PD-L1 expression in ME was detected in none and 2 cases, and in RS cells in none of the cases, before and after chemotherapy. R/R HL cases: PD-1 expression in ME was detected in none and 2 cases, and PD-1 expression in RS cells in none and 2 cases, before and after chemotherapy, respectively. PD-L1 expression in ME was detected in 3 and 7 cases, and in RS cells in 2 and 5 cases before and after chemotherapy, respectively. When we evaluated all cases, we found that PD-1 expression was detected in ME in 4 cases at the beginning and in 8 cases after treatment. PD-1 expression in RS cells was not detected at the beginning while in 4 cases after treatment. PD-L1 expression at the beginning was detected in 3 cases in ME and in 9 cases after treatment. PD-L1 expression at the beginning in ME was detected in 3 cases and in 9 cases after treatment. PD-L1 expression at the beginning in RS cells was detected in 2 cases and after treatment in 5 cases. Table 1 shows the PD-1 and PD-L1 expressions in PR HL and R/R HL cases. Discussion: PD-1 and/or PD-L1 expressions after treatment are seen in the majority of cases with PR HL and R/R HL both in ME and in RS cells. It is very well known that standard treatment is not clear and there is no good choice in cases with PR HL. On the other hand salvage chemotherapy and high dose chemotherapy/stem cell transplantation is standard in R/R HL cases, but this approach is beneficial in only a limited number of these cases. Brentuximab vedotin is an important molecule in these cases as a bridge for transplantation. In a similar way successfull results have been reported with checkpoint inhibitors in cases with R/R HL. We showed that PD-1/PD-L1 expression is frequent in cases with PR and R/R HL. For this reason both PD-1 or PD-L1 blockade are important therapeutic oppurtunities in cases with PR and R/R HL cases and these agents must be considered in earlier treatment steps of these cases before other too toxic and ineffective chemotherapeutic drugs. Disclosures No relevant conflicts of interest to declare.

Background: Radiotherapy (RT) is used as an indispensable treatment approach for cancer therapy as an adjuvant or alone for definitive option. For early stage endometrial cancer, RT is applied after operation as an adjuvant. Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a type of lymphoma which is seen rarely and has excellent prognosis with accurate treatment. It is another indication for RT. Developments in the diagnosis and the treatment of PCALCL have improved the disease prognosis and outcomes. Case Presentation: We present a case of a 55-years-old patient who had endometrial cancer and PCALCL, whose 9 years follow-up period was excellent with no recurrences and no metastasis. The outcome was achieved with the combination of surgery and RT. Conclusion: The presented case is important for long follow-up duration with no metastasis and/or no recurrences with single RT usage in both primary cancers. Single RT applications may be considered as an initial treatment option for surgically excised PCALCL with excellent outcome.

Second malignancies develop with increased incidence in patients with herediter retinoblastoma. The most common second malignancies in retinoblastoma survivors are soft tissue sarcoma and osteosarcoma. Lymphoma developing as a second malignancy has rarely been reported. Here we report a case of lymphoma diagnosed in a 13 year-old-boy, 12 years after the diagnosis of unilateral retinoblastoma having heterozygous p.R552 (c.1654C> T) mutation, treated with enucleation and radiotherapy. The risk of second tumour is higher in the hereditary retinoblastoma, especially in cases undergoing external beam radiation therapy, İkincil malign hastalıklar herediter retinoblastomlu hastalarda artmış bir sıklıkta gelişebilmektedir. Retinoblastom yaşayanlarında en sık rastlanan malign hastalıklar yumuşak doku sarkomları ve osteosarkomdur. İkincil tümör olarak lenfoma gelişmesi ise nadiren bildirilmiştir. Bu yazıda ünilateral retinoblastom nedeniyle enükleayon ve radyoterapi ile tedavi edilen, 12 yıl sonra lenfoma tanısı alan ve heterozigot p.R552 (c.1654C> T) mutasyonu saptanan 13 yaşında bir hasta rapor edilmiştir. İkincil tümör gelişme riski özellikle radyoterapi verilmiş herediter retinoblastomlu hastalarda daha fazladır