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Publication Open Access Clinicopathologic and prognostic features in gallbladder malignancies: retrospective analysis of 5206 cases(Galenos Yayınevi, 2019) Ferhatoglu, Murat Ferhat; Kıvılcım, Taner; Kartal, Abdulcabbar; Gürkan, Alp; N/A; Şenol, Kazım; Doctor; School of MedicineAim: Gallbladder cancer is the sixth most common cancer of the gastrointestinal system. Clinical presentation may not be distinguished from cholelithiasis or cholecystitis and most patients are diagnosed intraoperatively or in the postoperative histologic examination. In this study, we aimed to investigate the association of incidentally detected gallbladder cancer with gallbladder premalignant lesions, age, gender, ultrasonography features and gallbladder stones. Methods: demographic and clinical characteristics and pathology results of 5206 patients who underwent cholecystectomy between January 2012 and December 2015 were evaluated retrospectively. Results: three thousand eight hundred and eighty four (74.6%) patients were female. Pathologic reports showed pre-malignant and malignant lesions in 102 (1.95%) cases. Metaplasia was significantly more common in females, while no significant difference was found in development of dysplasia and cancer between genders. Gallbladder stone was found to be a risk factor for the development of metaplasia. Gallbladder wall thickening and advanced age are the most important risk factors for gallbladder cancer. Conclusion: female gender and gallstone are important risk factors for the development of metaplasia. Advanced age, gallstone and gallbladder wall thickening on ultrasonography are the most important factors in the development cancer. Cholecystectomy should be kept in mind as the most effective method to prevent cancer development in elderly patients with gallbladder stones. / Amaç: safra kesesi kanseri, gastrointestinal sistemin en yaygın altıncı kanseridir. Klinik prezentasyon safra kesesi taşı veya kolesistitden ayırt edilemez ve çoğu hasta intraoperatif veya postoperatif histolojik incelemede tanı alır. Bu çalışmada, insidental olarak tespit edilmiş safra kesesi kanserli olguların safra kesesi pre-malign lezyonları, yaş, cinsiyet, ultrasonografi özellikleri ve safra kesesi taşı ile ilişkisi araştırılmıştır. Yöntemler: Ocak 2012-Aralık 2015 tarihleri arasında kolesistektomi uygulanan 5206 hastanın demografik ve klinik özellikleri, patoloji sonuçları retrospektif olarak değerlendirildi. Bulgular: hastaların 3884’ü (%74,6) kadındı. Patoloji raporlarında 102 (%1,95) olguda pre-malign ve malign lezyonlar olduğu tespit edildi. Metaplazi kadınlarda anlamlı olarak daha fazla iken, displazi ve kanser gelişimi arasında cinsiyete göre anlamlı bir fark bulunamadı. Safra kesesi taşı metaplazi gelişiminde bir risk faktörü olarak bulundu. Safra kesesi duvar kalınlaşmasının ve ileri yaşın safra kesesi kanseri gelişimi için en önemli risk faktörleri olduğu tespit edildi. Sonuç: metaplazi gelişiminde kadın cinsiyet ve taş varlığı önemli faktörlerdir. Ultrasonografide safra kesesi duvar kalınlaşması, ileri yaş, safra kesesinde taşı varlığı kanser gelişiminde en önemli faktörlerdir. Kolesistektomi, ileri yaşta safra kesesi taşı olan hastalarda kanser gelişimini önlemek için en etkili yöntem olarak akılda tutulmalıdır.Publication Open Access Molecular characterization of hepatitis B virus strains isolated from chronic hepatitis B patients in southeastern region of Turkey(Galenos Yayınevi, 2019) Aydın, Mehtap; Sayan, Murat; Akhan, Sıla; N/A; Tekin, Süda; Faculty Member; School of MedicineObjectives: the aim of the present study was to assess the molecular aspects of HBV strains isolated from chronic hepatitis B (CHB) patients, in the Southeastern region of Turkey. Materials and methods: the study involved a total of 110 patients, 57 of them were treatment naive. 53 were undergoing nucleos(t)ide analogue (NUC) therapy, whom were diagnosed with CHB between July 2010 and April 2011 in the Southeastern region of Turkey. We analysed the HBV pol gene by amplification and direct sequencing with using polymerase chain reaction. Results: the phylogenetic and genotype analysis showed that all (100%) of the patients were infected with HBV genotype D. The prevalence of antiviral drug-associated potential vaccine-escape mutant was 10.5% among treatment naive and 15% NUC therapy group. S gene mutation among treatment naive group and NUC therapy group were 19% and 26.4%. Conclusion: determination of genotypes/subgenotypes of HBV may provide robust epidemiological data related to their circulation as well as their transmissibility. However, the findings of HBV pol gene mutations may be helpful in the management of rescue strategies in NUCs resistant patients in Southeastern region of Turkey. / Amaç: Türkiye’deki hepatit B enfeksiyonunun prevalansı Güneydoğu Bölgesi’nde diğer bölgelere göre daha yüksektir. Hepatit B genomundaki mutasyonlar kronik hepatit B hastalarının tanı ve tedavisinde güçlüklere sebep olmaktadır. Bu çalışmanın amacı, yüksek endemisiteye neden olan sebeplerinin ve belirli bir suşun bölgede yaygın olup olmadığının değerlendirilmesidir. Gereç ve yöntemler: Haziran 2010 ve Nisan 2011 tarihleri arasında Türkiye’nin Güneydoğu Bölgesi’nde kronik hepatit B tanısı alan toplam 110 hasta çalışmaya katıldı. Hastaların 57’si tedavi deneyimsiz iken 53’ü nükleosid analog (NUC) tedavisi almaktaydı. HBV pol geni amplifikasyon ve direct sekanslama polimeraz zincir reaksiyonu ile analiz edildi. Bulgular: HBV virusunun filogenetik ve genotip analizi sonucunda hastaların hepsinin (%100) HBV genotip D ile enfekte olduğu görüldü. Antiviral ilaç ilişkili potansiyel aşı kaçak mutantlarının prevalansının tedavi deneyimsiz grupta %10,5 NUC tedavisi alan grupta %15 olduğu bulundu. S gen mutasyonu tedavi deneyimsiz grupta ve NUC tedavisi alan grupta sırasıyla %19 ve %26,4 olarak saptandı. Sonuç: HBV’nin genotip/subgenotip tayini, virusun yaygınlığı ve bulaşıcılığı hakkında güçlü epidemiyolojik veriler sağlayabilir. Bununla birlikte HBV pol gen mutasyonları ile ilgili bu bulgular, Türkiye’nin Güneydoğu bölgesindeki NUC dirençli hepatit B hastalarında tedavi stratejilerinin yönetiminde yararlı olabilir.Publication Open Access Intravenous iron and maintenance hemodialysis(Massachusetts Medical Society (MMS), 2019) Afşar, Barış; Afşar, Rengin Elsürer; N/A; Kanbay, Mehmet; Faculty Member; School of Medicine; 110580Publication Open Access Comparison of clinical outcomes of single-incision versus conventional multiport laparoscopic distal pancreatectomy: a single institution experience(Kare Yayıncılık, 2019) Aksakal, Nihat; Azamat, İbrahim Fethi; Doğan, Selim; Mercan, Selçuk; Barbaros, Umut; N/A; Ağcaoğlu, Orhan; Faculty Member; School of Medicine; 175476Objectives: single-incision laparoscopic procedures have been gaining popularity in recent years due to their minimal incisional morbidity and improved cosmetic outcomes. Herein, we will compare the feasibility and outcomes of single-incision and conventional multiport laparoscopic distal pancreatectomy. Methods: this study involves consecutive patients who underwent either single-incision or conventional multiport laparoscopic distal pancreatectomy from March 2007 to February 2014. The patients were divided into two groups, based on the surgical approach: single-incision laparoscopic surgery (Group 1) and conventional multiport laparoscopic surgery (Group 2). The parameters evaluated included estimated blood loss, operative time, postoperative pain, duration of hospital stay, complications, conversion, and final pathology. Results: there were a total of 20 patients, 10 in each study group. Baseline characteristics were similar, and there was no mortality in either of the groups. The low-flow pancreatic fistula was the most commonly seen morbidity, but it was ceased spontaneously in each group by a ratio of 30%. The operative time was significantly shorter in Group 2, with a mean of 116 minutes versus a mean of 180 minutes for Group 1 (p<0.001). One of the procedures in Group 2 was converted to open surgery due to peroperative bleeding. The median follow-up periods of the patients were 22 months and 56 months. The spleen was preserved in only 1 patient from Group 1, whereas in Group 2, the spleen preservation was achieved in 5 patients.Publication Open Access Radiyal ışın defektlerinin klinik sınıflandırması ve etyopatogenezinin araştırılması(İstanbul Üniversitesi Yayınevi, 2018) Avcı, Şahin; Toksoy, Güven; Bağırova, Gülendam; Altunoğlu, Umut; Karaman, Birsen; Başaran, Seher; Uyguner, Z. Oya; N/A; Kayserili, Hülya; PhD Student; School of Medicine; 7945Objective: radial ray defects (RRDs) are the most common congenital abnormality of the upper extremities, with a prevalence of 1:30,000. 70% of RRDs are syndromic or accompanied by additional malformations, whereas 30% are in isolated form. Definitive diagnosis is critical for follow-up and provides an opportunity for prenatal diagnosis. The aim of this study was to provide a guide for the differential diagnosis of patients with RRD via contributing to their molecular diagnosis by constructing a next-generation sequencing (NGS) gene-panel test. Materials and methods: 48 probands from 37 families, referred for genetic consultation due to RRD, between the years of 2004-2014, were evaluated by cytogenetic and molecular tools following clinical examinations. 31 probands, with normal karyotype, were screened for 43 RRD associated genes of 14 syndromes by using in-house-designed targeted NGS gene-panel. Results: chromosomal abnormalities [a trisomy 18 and a familial reciprocal translocation t(2;12)(q31;q24.3)] in two families and mutations in related genes (SF3B4, SALL4, TBX5, FANCA) in four families were known before the initiation of this study. In remaining 31 probands, five families identified to have six different mutations in four different genes (FANCA, NIPBL, ESCO2, BRIP1). Conclusion: chromosomal abnormalities in two of the 37 families (5.4%) and gene mutations in nine of the 37 families (24.3%) were identified. Our study demonstrated that an in-house-designed targeted NGS containing 43 genes made considerable contribution to the diagnosis of RRD. Moreover, chromosomal abnormalities must always be considered in the differential diagnosis and excluded before gene-panel screening. / Amaç: radiyal ışın defektleri (RID) 1/30.000 prevalansı ile üst ekstremitenin en sık gözlenen konjenital anomalisidir. Olguların yaklaşık %30’unda RID izole olarak, %70’inde ek anomaliler veya sendromlar ile birlikte gözlenir. Bu nedenle, olgularda tanının kesinleşmesi, izlemi, ailelere özgün genetik danışma verilmesi ve sonraki gebeliklerinde prenatal tanı seçeneğinin sunulabilmesi için önemlidir. Bu çalışma ile RID olgularının ayırıcı tanısında yol gösterici olması, moleküler tanıya katkı sağlaması amacıyla yeni nesil dizileme (YND) gen-paneli oluşturuldu ve panelin moleküler tanıdaki etkinliği araştırıldı. Gereç ve yöntem: bu çalışmada, 2004-2014 yılları arasında kliniğimizde RID bulgusu ile değerlendirilen 37 aileden 48 etkilenmiş olgunun klinik, moleküler ve sitogenetik bulguları değerlendirildi. Karyotipi normal saptanan ve moleküler tanısı olmayan 31 ailenin indeks olgusunda 14 farklı fenotip ile ilişkili 43 gen, RID için tasarladığımız hedefe yönelik YND paneli ile dizilendi. Bulgular: sitogenetik analiz ile bir olguda trizomi 18 ve diğer bir olguda ise ailevi t(2;12)(q31;q24.3) translokasyonu saptandı. Dört ailede ilişkili genlerdeki (SF3B4, SALL4, TBX5, FANCA) mutasyonlar çalışma öncesinde moleküler analizlerle belirlenmişti. Tanısı olmayan 31 indeks olgunun 5’inde (%16), 4 farklı gende (FANCA, NIPBL, ESCO2, BRIP1) 6 farklı mutasyon saptandı. Sonuç: RID nedeniyle değerlendirilen 37 ailenin 2’sinde (%5.4) kromozom anomalisi ve 9’unda (%24.3) 7 farklı gende 9 farklı mutasyon saptandı. Bulgularımız, RID olgularında özgün tasarlanan yeni nesil dizileme panelimizin moleküler tanıya önemli oranda katkı sağladığını; RID’ın etyopatogenezinde kromozom anomalilerinin de yer aldığını, ayırıcı tanıda yer alması ve RID-panel çalışmasından önce kromozom anomalilerinin dışlanması gerektiğini gösterdi.Publication Open Access Application of MLPA (multiplex ligation-dependent probe amplification) in fetuses with an abnormal sonogram and normal karyotype(İstanbul Üniversitesi Yayınevi, 2019) Toksoy, Güven; Karaman, Birsen; Uyguner, Zehra Oya; Yılmaz, Kader; Has, Recep; Miny, Peter; Başaran, Seher; N/A; Kayserili, Hülya; Doctor; School of Medicine; 7945Objective/material and method: cryptic chromosomal imbalances contribute significantly to the etiology of multiple congenital anomalies with or without mental retardation (MCA/MR). Current approaches in prenatal diagnosis include targeted high resolution analyses by MLPA and some microarray platforms or a genomewide screening at maximal resolution using oligonucleotide or SNP arrays. The major disadvantages of the latter approach are cost and the inadvertent detection of copy number variation of unknown clinical significance. In this prospective work, fetal DNA samples from 66 fetuses who had pathological antenatal ultrasonography findings with normal karyotype and Multiprobe T-FISH results were tested using commercially available targeted MLPA probe-sets to compare the efficacy and the impact of MLPA testing at prenatal setting. Results: three submicroscopic deletions (3.66; 4.5%) were detected in the cohort. Two of them were de novo deletions, 18ptel and 7q11.23. The third finding was a 75 kb duplication at 18q, which was maternally inherited and probably a benign copy number variation unrelated to the pathological ultarsonography findings. Conclusion: the observed detection rate by MLPA testing can be considered within the expected range. Furthermore, benign copy number variation was identified with the targeted diagnostic approach as an unexpected finding. This study shows that MLPA is a practical and cost-effective technique to investigate submicroscobic chromosomal aberrations in fetuses.Publication Open Access Hammering nail to the head for suicide; a case report and literature review(Galenos Yayınevi, 2019) Öğrenci, Ahmet; Koban, Orkun; Yılmaz, Mesut; Dalbayrak, Sedat; N/A; Yaman, Onur; Doctor; School of MedicineSuicide is the process that an individual ends his/her own life, and usually methods providing a quick death are chosen. The most common methods are jumping from heights and firearm shots. However, in some suicide attempts, some unusual methods are used. These can be seen in patients with psychiatric disorders such as severe depression and schizophrenia. The idea of suicide by hammering nail into the head is uncommon because it is a method that cannot lead to a quick death and cause suffering. Beside these, it does not lead to death with a single action. We present a case of a young male patient who attempted suicide with hammering nail into the head and review the literature on this subject. / İntihar insanın kendi hayatına son vermesi işlemidir ve genellikle ölümü aniden getirecek yöntemler seçilmektedir. Bunlardan en sık olanları yüksekten atlama, ateşli silah kullanımıdır. Ancak bazı intihar şekilleri de hiç tahmin edilemeyecek yöntemlerle olabilir. Ağır depresyon, şizofreni gibi psikiyatrik hastalıkları olan hastalarda bunlar görülebilmektedir. Başına çivi çakarak intihar etme düşüncesi de sık görülen bir durum değildir. Çünkü ani ölüm getirmeyecek ve acı çekerek ölüme sebep olabilecek bir yöntemdir ve tek bir hamlede bitirelecek bir intihar girişimi değildir. Başına çekiçle çivi çakma usulü ile intihar eden genç erkek hasta olgusunu sunup literatürü gözden geçireceğiz.Publication Open Access Deep learning assisted automated assessment of thalassaemia from haemoglobin electrophoresis images(Multidisciplinary Digital Publishing Institute (MDPI), 2022) Salman, Khan M.; Khan, K.N.; Riaz, H.; Yousafzai, Y.M.; Rahman, T.; Chowdhury, M.E.H.; Abul Kashem, S.B.; N/A; Ullah, Azmat; Graduate School of Sciences and EngineeringHaemoglobin (Hb) electrophoresis is a method of blood testing used to detect thalassaemia. However, the interpretation of the result of the electrophoresis test itself is a complex task. Expert haematologists, specifically in developing countries, are relatively few in number and are usually overburdened. To assist them with their workload, in this paper we present a novel method for the automated assessment of thalassaemia using Hb electrophoresis images. Moreover, in this study we compile a large Hb electrophoresis image dataset, consisting of 103 strips containing 524 electrophoresis images with a clear consensus on the quality of electrophoresis obtained from 824 subjects. The proposed methodology is split into two parts: (1) single-patient electrophoresis image segmentation by means of the lane extraction technique, and (2) binary classification (normal or abnormal) of the electrophoresis images using state-of-the-art deep convolutional neural networks (CNNs) and using the concept of transfer learning. Image processing techniques including filtering and morphological operations are applied for object detection and lane extraction to automatically separate the lanes and classify them using CNN models. Seven different CNN models (ResNet18, ResNet50, ResNet101, InceptionV3, DenseNet201, SqueezeNet and MobileNetV2) were investigated in this study. InceptionV3 outperformed the other CNNs in detecting thalassaemia using Hb electrophoresis images. The accuracy, precision, recall, f1-score, and specificity in the detection of thalassaemia obtained with the InceptionV3 model were 95.8%, 95.84%, 95.8%, 95.8% and 95.8%, respectively. MobileNetV2 demonstrated an accuracy, precision, recall, f1-score, and specificity of 95.72%, 95.73%, 95.72%, 95.7% and 95.72% respectively. Its performance was comparable with the best performing model, InceptionV3. Since it is a very shallow network, MobileNetV2 also provides the least latency in processing a single-patient image and it can be suitably used for mobile applications. The proposed approach, which has shown very high classification accuracy, will assist in the rapid and robust detection of thalassaemia using Hb electrophoresis images.Publication Open Access Effects of different percentages of body weight-supported treadmill training in Parkinson’s disease: a double-blind randomized controlled trial(TÜBİTAK, 2019) Atan, Tuğba; Tokçaer, Ayşe Bora; Karataş, Gülçin Kaymak; Çalışkan, Aslı Karakuş; Karaoğlan, Belgin; N/A; Taşkıran, Özden Özyemişçi; Faculty Member; School of Medicine; 133091Background/aim: body weight-supported treadmill training (BWSTT) might have greater effects than conventional treadmill training (TT) in neurological diseases such as Parkinson’s disease (PD). The aim of this study was to evaluate the effects of different percentages of BWSTT on gait, balance, quality of life, and fatigue in PD. Materials and methods: thirty-five patients with moderate to advanced PD were randomized into three BWSTT groups according to the supported percentage of body weight: 0% BWSTT (control group; unsupported TT), 10% BWSTT, or 20% BWSTT. Five patients were excluded due to early discharge and 30 patients completed BWSTT sessions lasting 30 min, 5 days a week, for 6 weeks during their inpatient rehabilitation stay. The primary outcome was 6-min walk distance (6MWD). Secondary outcomes were Unified Parkinson’s Disease Rating Scale (UPDRS), Berg Balance Scale (BBS), Nottingham Health Profile (NHP), Fatigue Impact Scale, and Fatigue Severity Scale scores. Measurements were performed before and after the training. Results: the unsupported TT group demonstrated no significant improvement in the outcome measures after a 6-week training except for BBS and NHP emotional subscores. Moreover, the NHP pain subscore increased in the unsupported TT group after training. The 10% and 20% supported BWSTT groups demonstrated significant improvements in 6MWD (P = 0.004 and P < 0.001, respectively), UPDRS - motor score (P = 0.012 and P = 0.005, respectively), NHP pain subscore (P = 0.003 and P = 0.002, respectively), and fatigue (P = 0.005 for both) after training. The 20% BWSTT provided the highest improvement in balance among the three groups (P < 0.001) and greater relief of fatigue than 10% BWSTT (P = 0.002). Conclusion: six weeks of BWSTT improved walking distance and balance ability, relieved fatigue, and additionally reduced pain in patients with moderate to advanced PD.Publication Open Access Targeting nNOS ameliorates the severe neuropathic pain due to chronic pancreatitis(Elsevier, 2019) Demir, İhsan Ekin; Heinrich, Tobias; Carty, Dominique G.; Sarıcaoğlu, Ömer Cemil; Klauss, Sarah; Teller, Steffen; Kehl, Timo; Reyes, Carmen Mota; Tieftrunk, Elke; Lazarou, Maria; Maak, Matthias; Diakopoulos, Kalliope N.; Lesina, Marina; Schemann, Michael; Krueger, Achim; Algül, Hana; Friess, Helmut; Ceyhan, Güralp O.; N/A; Uçurum, Bahar Ezgi; Erkan, Murat Mert; Faculty Member; School of Medicine; N/A; N/A; N/A; 214689Background: pain due to pancreatic cancer/PCa or chronic pancreatitis/CP, is notoriously resistant to the strongest pain medications. Here, we aimed at deciphering the specific molecular mediators of pain at surgical-stage pancreatic disease and to discover novel translational targets. Methods: we performed a systematic, quantitative analysis of the neurotransmitter/neuroenzmye profile within intrapancreatic nerves of CP and PCa patients. Ex vivo neuronal cultures treated with human pancreatic extracts, conditional genetically engineered knockout mouse models of PCa and CP, and the cerulein-induced CP model were employed to explore the therapeutic potential of the identified targets. Findings: we identified a unique enrichment of neuronal nitric-oxide-synthase (nNOS) in the pancreatic nerves of CP patients with increasing pain severity. Employment of ex vivo neuronal cultures treated with pancreatic tissue extracts of CP patients, and brain-derived-neurotrophic-factor-deficient (BDNF+/−) mice revealed neuronal enrichment of nNOS to be a consequence of BDNF loss in the progressively destroyed pancreatic tissue. Mechanistically, nNOS upregulation in sensory neurons was induced by tryptase secreted from perineural mast cells. In a head-to-head comparison of several genetically induced, painless mouse models of PCa (KPC, KC mice) or CP (Ptf1a-Cre;Atg5fl/fl) against the hypersecretion/cerulein-induced, painful CP mouse model, we show that a similar nNOS enrichment is present in the painful cerulein-CP model, but absent in painless genetic models. Consequently, mice afflicted with painful cerulein-induced CP could be significantly relieved upon treatment with the specific nNOS inhibitor NPLA. Interpretation: we propose nNOS inhibition as a novel strategy to treat the unbearable pain in CP. Fund: Deutsche Forschungsgemeinschaft/DFG (DE2428/3-1 and 3-2).