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Item A Retrospective Multicenter Evaluation of Cutaneous Melanomas in Turkey(ASIAN PACIFIC ORGANIZATION CANCER PREVENTION, 2014-01-01) Gamsizkan, Mehmet; Yilmaz, Ismail; Buyukbabani, Nesimi; Demirkesen, Cuyan; Demiriz, Murat; Cetin, Emel Dikicioglu; Ince, Umit; Akalin, Taner; Demirkan, Nese Calli; Lebe, Banu; Erdem, Ozlem; Gokoz, Ozay; Sakiz, Damlanur; Demireli, Peyker Temiz; Astarci, Hesna Muzeyyen; Adim, Saduman Balaban; Zemheri, Itir Ebru; Acikalin, Arbil; Yaman, Banu; Aydin, Ovgu; Bassorgun, Cumhur IbrahimBackground: We defined melanoma distribution in a large series of Turkish patients and evaluated the prognostic parameters of melanomas. Materials and Methods: A total of 1574 patients' data was retrospectively collected at 18 centers in Turkey. Demographic characteristics were questioned and noted. Prognostic parametres were evaluated based on sentinel lymph node involvement. Results: Mean age was 56.7 (4-99) years. While 844 (53.6\%) cases were male, 730 (46.4\%) cases were female. One thousand four hundred forty-seven (92\%) cases were invasive melanoma and 127 (8\%) cases were in-situ melanoma. The most common histopathological form was the superficial spreading melanoma (SSM) which was found in 549 patients (37.9\%). It was followed by nodular melanoma in 379 (26.2\%), acral lentiginous melanoma (ALM) in 191 (13.2\%) and lentigo maligna melanoma in 132 (9.1\%), respectively. On univariate analysis, lymphovascular invasion (p<0.001), tumor thickness (p<0.001), histopathological subtype (p<0.001), Clark level (p=0.001), ulceration (p<0.001), >= 6/mm(2) mitosis (p=0.005), satellite formation (p=0.001) and gender (p=0.03) were found to be associated with sentinel lymph node positivity. Regression was associated with sentinel lymph node negativity (p=0.017). According to multivariate analysis, lymphovascular invasion and tumor thickness were significant independent predictive factors of SLN positivity. Patient age, tumor localization, precursor lesions, lymphocytic infiltration and neurotropism were not related with sentinel lymph node involvement. Conclusions: In this retrospective analysis, it was found that the prevalence of SSM is at a lower rate while the prevalence of ALM is at a higher rate when compared to western countries. According to Breslow indexItem Vacuum-assisted stereotactic breast biopsy in the diagnosis and management of suspicious microcalcifications(TURKISH SOC RADIOLOGY, 2016-01-01) Esen, Gul; Tutar, Burcin; Uras, Cihan; Calay, Zerrin; Ince, Umit; Tutar, OnurPURPOSE We aimed to present our biopsy method and retrospectively evaluate the results, upgrade rate, and follow-up findings of stereotactic vacuum-assisted breast biopsy (VABB) procedures performed in our clinic. METHODS Two hundred thirty-four patients with mammographically detected nonpalpable breast lesions underwent VABB using a 9 gauge biopsy probe and prone biopsy table. A total of 195 patients (median age 53 years, range 32-80 years) with 198 microcalcification-only lesions with a follow- up of at least one year were included in the study. The location of the lesion relative to the needle was determined from the postfire images, and unlike the conventional technique, tissue retrieval was predominantly performed from that location, followed by a complete 360 degrees rotation, if needed. RESULTS The median core number was 8.5. Biopsy results revealed 135 benign, 24 atypical, and 39 malignant lesions. The total upgrade rate at surgery was 7.7\% (6.1\% for ductal carcinomas in situ and 10.5\% for atypical lesions). Patients with benign lesions were followed up for a median period of 27.5 months, with no interval change. At the follow-up, scar formation was seen in 23 patients (17\%)Item Endogenous c-Jun N-terminal kinase (JNK) activity marks the boundary between normal and malignant granulosa cells(NATURE PUBLISHING GROUP, 2018-01-01) Bildik, Gamze; Akin, Nazli; Senbabaoglu, Filiz; Esmalian, Yashar; Sahin, Gizem Nur; Urman, Defne; Karahuseyinoglu, Sercin; Ince, Umit; Palaoglu, Erhan; Taskiran, Cagatay; Arvas, Macit; Guzel, Yilmaz; Yakin, Kayhan; Oktem, OzgurGranulosa cell tumor of the ovary (GCT) is a very rare tumor, accounting for only 2\% of all ovarian tumors. It originates from sex cords in the ovary and can be divided into adult (95\%) and juvenile (5\%) types based on histologic findings. To date, no clear etiologic process has been identified other than a missense point mutation in the FOXL2 gene. Our previous works showed that c-Jun N-terminal kinase (JNK) pathway plays critical role in cell cycle progression and mitosis of normal and immortalized granulosa cells and follicle growth in rodent ovaries. These findings led us to investigate the role of JNK pathway in the granulosa cell tumor of the ovary. We used two different GCT cell lines (COV434 and KGN) and fresh GCT samples of adult and juvenile types obtained from the patients during surgery. We have discovered that endogenous kinase activity of JNK is markedly enhanced in the GCT samples and cell lines, whereas it was almost undetectable in mitotic non-malignant human granulosa cells. The inhibition of JNK pathway in GCT cell lines with two different pharmacologic inhibitors (SP600125 and AS601245) or siRNA resulted in a dose-dependent reduction in in vitro cell growth, increased apoptosis and diminished estradiol and AMH productions. JNK inhibition was also associated with a decrease in the number of cells positive for mitosis marker phospho-histone H3(Ser) 10 in the asynchronous cellsItem Association of B7-H4 gene polymorphisms in urothelial bladder cancer(TUBITAK SCIENTIFIC \& TECHNICAL RESEARCH COUNCIL TURKEY, 2017-01-01) Ozgoz, Asuman; Samli, Murat; Dincel, Deniz; Sahin, Ahmet; Ince, Umit; Saglican, Yesim; Balci, Faruk; Samli, HaleBackground/aim: We aimed to study polymorphisms of the B7-H4 gene in order to evaluate a possible association in urothelial carcinoma, as it is highly expressed in cancer tissues. Materials and methods: In this study B7-H4 gene rs10754339, rs10801935, and rs3738414 SNPs were studied by PCR-RFLP method in paraffin-embedded tumor specimens from 62 urothelial carcinoma patients and in a control group including 30 patients without bladder cancer. Results: We detected that the rs10754339 polymorphism was more frequent in the cancer patients when compared with the control group (P < 0.05). Only the rs3738414 polymorphism showed a statistically significant difference in frequency between pathologic diagnostic groups. Conclusion: The rs10754339 AA genotype distribution was found to have a higher frequency whereas the rs3738414 AG genotype distribution was lower in the bladder cancer group (P < 0.05). None of the genotype distributions showed a significant difference from the control group for the rs10801935 polymorphism. We conclude that B7-H4 has the potential to be a useful prognostic marker in urothelial carcinoma.Item MITNET: a novel dataset and a two-stage deep learning approach for mitosis recognition in whole slide images of breast cancer tissue(SPRINGER LONDON LTD, 2022-01-01) Cayir, Sercan; Solmaz, Gizem; Kusetogullari, Huseyin; Tokat, Fatma; Bozaba, Engin; Karakaya, Sencer; Iheme, Leonardo Obinna; Tekin, Eren; Yazici, Cisem; Ozsoy, Gulsah; Ayalti, Samet; Kayhan, Cavit Kerem; Ince, Umit; Uzel, Burak; Kilic, OnurMitosis assessment of breast cancer has a strong prognostic importance and is visually evaluated by pathologists. The inter, and intra-observer variability of this assessment is high. In this paper, a two-stage deep learning approach, named MITNET, has been applied to automatically detect nucleus and classify mitoses in whole slide images (WSI) of breast cancer. Moreover, this paper introduces two new datasets. The first dataset is used to detect the nucleus in the WSIs, which contains 139,124 annotated nuclei in 1749 patches extracted from 115 WSIs of breast cancer tissue, and the second dataset consists of 4908 mitotic cells and 4908 non-mitotic cells image samples extracted from 214 WSIs which is used for mitosis classification. The created datasets are used to train the MITNET network, which consists of two deep learning architectures, called MITNET-det and MITNET-rec, respectively, to isolate nuclei cells and identify the mitoses in WSIs. In MITNET-det architecture, to extract features from nucleus images and fuse them, CSPDarknet and Path Aggregation Network (PANet) are used, respectively, and then, a detection strategy using You Look Only Once (scaled-YOLOv4) is employed to detect nucleus at three different scales. In the classification part, the detected isolated nucleus images are passed through proposed MITNET-rec deep learning architecture, to identify the mitosis in the WSIs. Various deep learning classifiers and the proposed classifier are trained with a publicly available mitosis datasets (MIDOG and ATYPIA) and then, validated over our created dataset. The results verify that deep learning-based classifiers trained on MIDOG and ATYPIA have difficulties to recognize mitosis on our dataset which shows that the created mitosis dataset has unique features and characteristics. Besides this, the proposed classifier outperforms the state-of-the-art classifiers significantly and achieves a 68.7\% F1-score and 49.0\% F1-score on the MIDOG and the created mitosis datasets, respectively. Moreover, the experimental results reveal that the overall proposed MITNET framework detects the nucleus in WSIs with high detection rates and recognizes the mitotic cells in WSI with high F1-score which leads to the improvement of the accuracy of pathologists' decision.Item The effect of femoral nerve block on fracture healing via expressions of growth factors and beta-catenin(VIA MEDICA, 2016-01-01) Uslu, Serap; Irban, Arzu Gercek; Gereli, Arel; Aydinlar, Elif Ilgaz; Elpen, Pinar; Ince, UmitIntroduction. Many patients of all ages are admitted to hospital due to bone fractures. The etiology of fracture has a very wide spectrum, ranging from motor accidents to pathological conditions such as tumors, osteoporosis, and others. Bone fracture healing is a well-programmed and well-organized process, but is also long and intractable. The outcome of this process is therefore affected by many factors, such as the patient's age, ethnicity, nutritional status, and extent of the fracture. At present, regional analgesic techniques are frequently applied in order to avoid the complications of systemic opioid administration, central block applications. Femoral block is one of the regional analgesic techniques frequently applied by anesthesiologists when the lower extremities are involved. In this study, we evaluated the effect of femoral nerve block on the healing of an experimental non-stabilized femur fracture via expression of TGF-beta, VEGF, and beta-catenin and bone histomorphometry in rats. Material and methods. In the control group, only the femoral fracture was performed and the bone was not fixated, similarly as in other groups. In the One-Day Block group, a one-time femoral nerve block was applied after the femoral fracture. In the Three-Day Block group, a daily femoral nerve block was performed for three days after the femoral fracture. On Days 4, 7, and 13, femurs were excised. The bone sections were stained with hematoxylin-eosin to evaluate bone tissue and Safranin O to assess callus tissue, cartilaginous tissue, and new bone areas. TGF-beta, VEGF, and beta-catenin were assessed by immunohistochemistry. Results. Histomorphometric analysis revealed that femoral block application had a positive impact on bone healing. TGF-beta expression in the One-Day and Three-Day Block Groups was significantly higher than in the control group at all times, as was also the case with VEGF expression. On day 13, beta-catenin expression was significantly higher in the Three-Day Block group than the others. Conclusions. The results of the study suggests that the applications of a femoral nerve block for perioperative analgesia, for either one day or three days, resulted in better and more rapid bone healing.Item Does it take three to tango? An unsuspected multimorbidity of CD8(+) T cell lymphoproliferative disorder, malaria, and EBV infection(BMC, 2018-01-01) Ekemen, Suheyla; Uzay, Ant; Bassullu, Nuray; Dikicioglu-Cetin, Emel; Matsuda, Kyoko; Ince, Umit; Coban, CevayirBackground: Malaria is known to cause acute and deadly complications. However, malaria can cause unforeseen pathologies due to its chronicity. It increases the risk of endemic Burkitt Lymphoma development by inducing DNA damage in germinal centre (GC) B cells, and leading higher frequency of Epstein-Barr virus (EBV)-infected cells in GCs. EBV is well known for its tropism for B cells. However, less is known about EBV's interaction with T cells and its association with T cell lymphoma. Case presentation: A 43-year-old Sudanese male admitted to hospital in Istanbul, Turkey, a non-endemic country, with hyperpigmented painful skin rashes on his whole body. A complete blood count and a peripheral blood smear during admission revealed large granular lymphocytes (LGLs) with abnormally higher CD8 T cell numbers. Additional skin biopsy and pathology results were compatible with CD8(+) T cell lymphoproliferative disorder with skin involvement. Patient was treated and discharged. However, a pathologist noticed unusual structures in skin tissue samples. Careful evaluation of skin biopsy samples by polarized microscopy revealed birefringent crystalloid structures resembling malarial haemozoin mainly loaded in macrophages and giant histiocytes. After purification of DNA from the skin biopsy samples, nested PCR was performed for the detection of Plasmodium parasites and Plasmodium falciparum DNA was amplified. Because, the co-presence of EBV infection with malaria is a well-known aetiology of lymphoma, EBV-early RNA (EBER) transcripts were investigated in paraffin-embedded tissue samples and found to be positive in macrophage-like histiocytes. Conclusions: This is a unique case of malaria and EBV infection in a T-LGL lymphoma patient who presented in a non-endemic country. This case emphasizes the clinical importance of EBV monitoring in T-LGL patients with skin involvement. Notably, Plasmodium infection should be examined in patients from malaria endemic regions by pathological and molecular investigations.Item BRAF(V600E) Mutation: Has It a Role in Cervical Lymph Node Metastasis of Papillary Thyroid Cancer?(KARGER, 2016-01-01) Kurtulmus, Neslihan; Ertas, Burak; Saglican, Yesim; Kaya, Hakan; Ince, Umit; Duren, MeteBackground: The BRAF(V600E) mutation is common in papillary thyroid cancer (PTC). Lymph node metastasis (LNM) may be associated with poor prognosis. However, the LNM mechanism remains unclear. Objectives: Our aim was to evaluate the prevalence of the BRAF(V600E) mutation in primary tumors and accompanying LNM at the time of diagnosis. Methods: This retrospective study included 51 PTC patients (40 women, 11 menItem Expression of vascular endothelial growth factor in follicular cell-derived lesions of the thyroid: Is NIFTP benign or precancerous?(TURKISH SURGICAL ASSOC, 2022-01-01) Kurtulmus, Neslihan; Tokat, Fatma; Duren, Mete; Kaya, Hakan; Ertas, Burak; Ince, UmitObjective: Vascular endothelial growth factor (VEGF) is an angiogenic factor that plays an important role in physiological and pathological angiogenesis of the thyroid. The aim of the current study was to determine the expression characteristics of VEGF in follicular cell-derived lesions of the thyroid and to assess whether a new entity noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is precancerous. Material and Methods: Patients diagnosed with 33 follicular adenomas (FA), 41 invasive follicular variant papillary thyroid cancer (IN-FVPTC), and 40 NIFTP in surgical resection materials were evaluated retrospectively. Immunostaining was performed on 5-mu m paraffin tissue sections. The percentages of immunostaing for VEGF were evaluated on pathological materials. We used a percentage of labeled thyrocytes score (0, no labelingItem Autologous omentum transposition for regeneration of a renal injury model in rats(BMC, 2022-01-01) Bilgic, Tayfun; Ince, Umit; Narter, FehmiBackground After renal trauma, surgical treatment is vital, but sometimes there may be loss of function due to fibrosis. This study aimed to evaluate the effect of autologous omentum flaps on injured renal tissues in a rat model. Methods A total of 30 Wistar albino rats were included and randomly divided equally into a control group and four intervention groups. Iatrogenic renal injuries were repaired using a surgical technique (primary repair 1 group and primary repair 2 group) or transposition of the autologous omentum (omentum repair 1 group and omentum repair 2 group). Blood samples were taken preoperatively and on the 1st and 7th postoperative days in all groups and on the 18th postoperative day in the control and two intervention groups. All rats were sacrificed on the 7th or 18th day postoperatively, and their right kidneys were taken for histopathological evaluation. Results The mean urea level significantly decreased from day 1 to day 7 and from day 1 to day 18 in the omentum repair 2 group (P = 0.005 and P = 0.004, respectively). There were no other significant changes in urea or creatinine levels within the intervention groups (P > 0.05). There was no significant correlation between the urea and creatinine levels and the histological scores (P > 0.05). The primary repair 1 and 2 groups had significantly higher median granulation and inflammation scores in the kidney specimen than the control and omentum repair groups (P < 0.05). The omentum repair 2 group had significantly lower median granulation and inflammation scores in the surrounding tissues than the primary repair 2 group (P < 0.05). The completion score for the healing process in the kidney specimen was significantly higher in the omentum repair groups than in the primary repair groups (P < 0.05). The omentum repair 2 group had significantly lower median granulation and inflammation scores in the surrounding tissues than the primary repair 2 group (P < 0.05). Granulation degree in the kidney specimen was strongly and positively correlated with the inflammation degree (r = 0.824, P < 0.001) and foreign body reaction in the kidney specimen (r = 0.872, P < 0.001) and a strong and negative correlation with the healing process completion score in the kidney (r = - 0.627, P = 0.001). Inflammation degree in the kidney specimen was strongly and positively correlated with the foreign body reaction in the kidney specimen (r = 0.731, P = 0.001) and strongly and negatively correlated with the healing process completion score in the kidney specimen (r = - 0.608, P = 0.002). Conclusion Autologous omentum tissue for kidney injury repair attenuated inflammation and granulation. Additionally, the use of omental tissue to facilitate healing of kidney injury may theoretically lead to a more effective healing process and reduced fibrosis and tissue and function loss.