Researcher: Kulaç, İbrahim
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Kulaç, İbrahim
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Publication Metadata only Molecular pathology of prostate cancer(W B SAUNDERS CO-ELSEVIER INC, 2024) Roudier, Martine P.; Haffner, Michael C.; Kulaç, İbrahim; School of MedicineProstate cancer (PC) is the most common noncutaneous malignancy in men in the United States and makes up almost 20% of all newly diagnosed cancer cases. 1 The initial presentation and clinical course of PC can vary greatly between patients. The clinical spectrum ranges from indolent disease with an exceedingly low risk of progression to highly aggressive disease variants with early recurrence and high rates of cancer-related death. 234 Given this disease heterogeneity, understanding factors that predict the future clinical behavior of PC in an individual patient has been of the highest interest in the field. For decades, the assessment of histopathologic features such as Gleason grade and grade group tumor grade, tumor volume, and tumor stage have been the most pertinent prognostic parameters on which clinical decision-making is based. This factor strongly emphasizes the important relevance of the pathologist in the care of PC patients. Over the past years, molecular diagnostic applications have been penetrating more and more into the daily practice of genitourinary pathology. Many of these novel molecular tools have the potential to improve diagnostic accuracy and predictive values and ultimately lead to better clinical outcomes. In the multidisciplinary care for patients with PC, pathologists will play an essential role in bridging molecular studies and clinical decision-making. In this review, we aim to provide a concise overview of relevant molecular alterations in PC and highlight opportunities for precision pathology in clinical practice, as well as delineate the challenges posed by the complex biology of PC.Publication Metadata only [68Ga]Ga-PSMA-11 and [18F]FDG uptake of venous tumor thrombus in inferior vena cava and left common iliac vein from prostate cancer on positron emission tomography(Springer Science and Business Media Deutschland GmbH, 2023) Kabaoglu, Z.U.; Seymen, Hülya; Esen, Barış; Kulaç, İbrahim; Aksoy, Murat; Demirkol, Mehmet Onur; Kordan, Yakup; School of MedicineN/APublication Metadata only The role of PSMA PET/CT in predicting downgrading in patients with Gleason score 4+4 prostate cancer in prostate biopsy(Springer, 2024) N/A; Aykanat, İbrahim Can; Kordan, Yakup; Seymen, Hülya; Köseoğlu, Ersin; Özkan, Arif; Esen, Barış; Tarım, Kayhan; Kulaç, İbrahim; Falay, Fikri Okan; Gürses, Bengi; Baydar, Dilek Ertoy; Canda, Abdullah Erdem; Balbay, Mevlana Derya; Demirkol, Mehmet Onur; Esen, Tarık; School of Medicine; Koç University HospitalBackground To investigate the predictable parameters associated with downgrading in patients with a Gleason score (GS) 8 (4+4) in prostate biopsy after radical prostatectomy. Methods We retrospectively analyzed 62 patients with a GS of 4+4 on prostate biopsy who underwent robotic radical prostatectomy between 2017 and 2022. Results 38 of 62 (61.2%) were downgraded. In multivariable logistic regression model, Ga-68 prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) SUV max was independent predictor of downgrading (OR 0.904; p = 0.011) and a Logistic Regression model was constructed using the following formula: Y = 1.465-0.95 (PSMA PET/CT SUV max). The model using this variable correctly predicted the downgrading in 72.6% of patients. The AUC for PSMA PET/CT SUV max was 0.709 the cut off being 8.8. A subgroup analysis was performed in 37 patients who had no other European Association of Urology (EAU) high risk features. 25 out of 37 (67.5%) were downgraded, and 21 of these 25 had organ confined disease. Low PSMA SUV max (<8.1) and percentage of GS 4+4 biopsy cores to cancer bearing cores (45.0%) were independently associated with downgrading to GS 7. Conclusion PSMA PET/CT can be used to predict downgrading in patients with GS 4+4 PCa. Patients with GS 4+4 disease, but no other EAU high risk features, low percentage of GS 4+4 biopsy cores to cancer bearing cores, and a low PSMA PET/CT SUV max are associated with a high likelihood of the cancer reclassification to intermediate risk group.Publication Metadata only Large language models as a rapid and objective tool for pathology report data extraction(Federation Turkish Pathology Soc., 2024) Department of Computer Engineering; Department of Computer Engineering; Bolat, Beyza; Eren, Özgür Can; Dur Karasayar, Ayşe Hümeyra; Meriçöz, Çisel Aydın; Demir, Çiğdem Gündüz; Kulaç, İbrahim; Koç Üniversitesi İş Bankası Enfeksiyon Hastalıkları Uygulama ve Araştırma Merkezi (EHAM) / Koç University İşbank Center for Infectious Diseases (KU-IS CID); Koç Üniversitesi İş Bankası Yapay Zeka Uygulama ve Araştırma Merkezi (KUIS AI)/ Koç University İş Bank Artificial Intelligence Center (KUIS AI); Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Health Sciences; College of EngineeringMedical institutions continuously create a substantial amount of data that is used for scientific research. One of the departments with a great amount of archived data is the pathology department. Pathology archives hold the potential to create a case series of valuable rare entities or large cohorts of common entities. The major problem in creation of these databases is data extraction which is still commonly done manually and is highly laborious and error prone. For these reasons, we offer using large language models to overcome these challenges. Ten pathology reports of selected resection specimens were retrieved from electronic archives of Ko & ccedil; University Hospital for the initial set. These reports were de-identified and uploaded to ChatGPT and Google Bard. Both algorithms were asked to turn the reports in a synoptic report format that is easy to export to a data editor such as Microsoft Excel or Google Sheets. Both programs created tables with Google Bard facilitating the creation of a spreadsheet from the data automatically. In conclusion, we propose the use of AI-assisted data extraction for academic research purposes, as it may enhance efficiency and precision compared to manual data entry.Publication Metadata only Natural history of histologically benign PIRADS 4-5 lesions in multiparametric MRI: real-life experience in an academic center(Wiley, 2024) Madendere, Serdar; Kılıç, Mert; Zoroğlu, Hatice; Coşkun, Bilgen; Vural, Metin; Sarıkaya, Ahmet Furkan; Veznikli, Mert; Armutlu, Ayşe; Kulaç, İbrahim; Gürses, Bengi; Kiremit, Murat Can; Baydar, Dilek Ertoy; Canda, Abdullah Erdem; Balbay, Mevlana Derya; Kordan, Yakup; Esen, Tarık; School of Medicine; Koç University HospitalIntroductionThe follow-up findings of patients who underwent prostate biopsy for prostate image reporting and data system (PIRADS) 4 or 5 multiparametric magnetic resonance imaging (mpMRI) findings and had benign histology were retrospectively reviewed. MethodsThere were 190 biopsy-naive patients. Patients with at least 12 months of follow-up between 2012 and 2023 were evaluated. All MRIs were interpreted by two very experienced uroradiologists. Of the patients, 125 had either cognitive or software fusion MR-targeted biopsies with 4 + 8/10 cores. The remaining 65 patients had in-bore biopsies with 4-5 cores. Prostate-specific antigen (PSA) levels below 4 ng/mL were defined as PSA regression following biopsy. PIRADS 1-3 lesions on new MRI images were classified as MRI regression. ResultsMedian patient age and PSA were 62 (39-82) years and six (0.4-33) ng/mL, respectively, at the initial work-up. During a median follow-up period of 44 months, 37 (19.4%) patients were lost to follow-up. Of the remaining 153 patients, 82 (53.6%) had persistently high PSA. Among them, 72 (87.8%) had repeat mpMRI within 6-24 months which showed regressive findings (PIRADS 1-3) in 53 patients (73.6%) and PIRADS 4-5 index lesion persistence in 19 cases (26.4%). The latter group was recommended to have rebiopsy. Of these 19 patients, 16 underwent MRI-targeted rebiopsy. Prostate cancer was diagnosed in six (37.5%) patients and of these four (25%) were clinically significant (>Grade Group 1). Totally, clinically significant prostate cancer was detected in 4/153 (2.6%) patients followed up. ConclusionPatients should be warned against the relative relaxing effect of a negative biopsy after identification of PIRADS 4-5 index lesion. While PSA decrease was observed in many patients during follow-up, persistent MRI findings were present in nearly a quarter of patients with persistently high PSA. A rebiopsy is warranted in these patients, with significant prostate cancer diagnosed in a quarter of patients with rebiopsy.Publication Metadata only Assessing risk of prostate cancer metastasis by deep learning in surgically-treated patients(Elsevier Science Inc, 2023) Oliveira, Lia DePaula; Erak, Eric; Mendes, Adrianna A.; Gomes-Alexandre, Carolina; Salles, Daniela; Ertunc, Onur; Baena-Del Valle, Javier; Jones, Tracy; Hicks, Jessica; Glavaris, Stephanie; Guner, Gunes; Vidal, Igor Damasceno; Han, Misop; Trock, Bruce; Joshi, Uttara; Kondragunta, Chaith; Chattopadhyay, Nilanjan; Bonthu, Saikiran; Singhal, Nitin; De Marzo, Angelo; Lotan, Tamara; Kulaç, İbrahim; School of MedicineN/APublication Metadata only Predicting prostate cancer molecular subtype with artificial intelligence(Elsevier Science Inc, 2023) Erak, Eric; Oliveira, Lia DePaula; Mendes, Adrianna A.; Ertunc, Onur; Valle, Javier Baena-Del; Jones, Tracy; Hicks, Jessica; Glavaris, Stephanie; Guner, Gunes; Vidal, Igor Damasceno; Han, Misop; Markowski, Mark; Trock, Bruce; Joshi, Uttara; Kondragunta, Chaith; Chattopadhyay, Nilanjan; Bonthu, Saikiran; Singhal, Nitin; De Marzo, Angelo; Lotan, Tamara; Kulaç, İbrahim; School of MedicineN/APublication Metadata only A simplified grid method of camera-captured images may be a practical alternative if validated ai-assisted counting is inaccessible(Elsevier Science Inc, 2023) Adsay, David; Eren, Ozgur; Basturk, Olca; Department of Computer Engineering; Department of Computer Engineering; Esmer, Rohat; Armutlu, Ayşe; Taşkın, Orhun Çığ; Koç, Soner; Tezcan, Nuray; Aktaş, Berk Kaan; Kulaç, İbrahim; Kapran, Yersu; Demir, Çiğdem Gündüz; Saka, Burcu; School of Medicine; Graduate School of Sciences and Engineering; College of EngineeringN/APublication Metadata only Can the Briganti 2019 nomogram be modified to predict lymph node metastasis risk in patients with prostate cancer detected with in-bore biopsy?(Wiley, 2024) Madendere, Serdar; Kılıç, Mert; Vural, Metin; Gürses, Bengi; Armutlu, Ayşe; Kulaç, İbrahim; Tarım, Kayhan; Esen, Barış; Aykanat, İbrahim Can; Veznikli, Mert; Canda, Abdullah Erdem; Balbay, Mevlana Derya; Baydar, Dilek Ertoy; Kordan, Yakup; Esen, Tarık; Koç University RMK Academy of Interventional Medicine, Education, and Simulation (RMK AIMES) / Koç Universitesi RMK İleri Düzey Girişimsel Tıp, Eğitim ve Simülasyon Merkezi (RMK AIMES); School of Medicine; Koç University HospitalObjectives: We aimed to modify the Briganti 2019 nomogram and to test whether it is valid for patients who were diagnosed with prostate cancer through in-bore prostate biopsies. Methods: Data for 204 patients with positive multiparametric prostate MRI and prostate cancer identified either by mpMRI-cognitive/software fusion or in-bore biopsy and who underwent robot-assisted radical prostatectomy and extended pelvic lymph node dissection between 2012 and 2023 were retrospectively analyzed. The Briganti 2019 nomogram was applied to the mpMRI-cognitive/software fusion biopsy group (142 patients) in the original form, and then, two modifications were tested for the targeted component. Original and modified scores were compared. These modifications were adapted for the in-bore biopsy group (62 patients). The final histopathologic stage was regarded as the gold standard. Results: Nodal metastases were identified in 18/142 (12.6%) of mpMRI-cognitive/software fusion biopsy patients and 8/62 (12.9%) of the in-bore biopsy patients. In the mpMRI-cognitive/software fusion biopsy group, tumor size/core size (%) of targeted biopsy cores and positive core percentage on systematic biopsy were significant parameters for lymph node metastasis based on univariate logistic regression analyses (p < 0.05). With the modifications of these parameters for the in-bore biopsy group, V1 modification of the Briganti 2019 nomogram provided 100% sensitivity and 31.5% specificity (AUC:0.627), while V2 modification provided 75% sensitivity and 46.3% specificity (AUC:0.645). Conclusions: Briganti 2019 nomogram may be modified by utilizing tumor size/core size (%) for targeted biopsy cores instead of positive core percentage on systematic biopsy or by not taking both parameters into consideration to detect node metastasis risk of patients diagnosed with in-bore biopsies.Publication Metadata only Targeting the mutant SOD1G93A protein-induced oxidative stress in the central nervous system and peripheral tissues can be a promising therapeutic approach in als disease(Elsevier Science Inc, 2023) Aydemir, Duygu; Kulaç, İbrahim; Sürücü, Hüseyin Selçuk; Başak, Ayşe Nazlı; Ulusu, Nuriye Nuray; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of MedicineBackground: ALS is the most common motor neuron disease, and the incidence of the disease is increasing worldwide. Since there is no effective treatment for ALS, urgent therapeutic approaches are required to cure the disease. 1–3 . Aim: We investigated oxidative stress metabolism and antioxidant capacity of the central nervous system and peripheral tissues at the pre-symptomatic and Abstracts Free Radical Biology and Medicine 201 (2023) 1–64 57 symptomatic stages of ALS. Method: SOD1G93A mutated albino male rats were used for the experiments. Histopathological, molecular, and biochemical examinations of the brain, spinal cord, testis, spleen, liver, kidney, and heart tissues were performed. H&E, OLIG2, and myelin staining were performed to evaluate histopathological changes. Mitochondrial and cytosolic fractions of the tissues were prepared and used for the biochemical and molecular evaluation. Glucose-6 phosphate dehydrogenase (G6PD), 6-phosphoglucanate dehydrogenase (6-PGD), glutathione reductase (GR), glutathione-s transferase (GST), catalase (CAT), superoxide dismutase 1 (SOD1), isocitrate dehydrogenase 1,2,3 (IDH1,2,3) were evaluated in all tissues. Human mutant SOD1G93A protein accumulation in the tissues was assessed via western blot. Results: Cytosolic and mitochondrial G6PD, 6-PGD, GR, GST, CAT, SOD1, IDH1, IDH2, and IDH3 enzyme activities were impaired in the SOD1G93A mutated rats compared to the wild-type rats of each group in all tissues. OLIG2 expression increased in the central nervous system of the ALS rats, where histopathological alterations were observed in all SOD1G93A rats. Additionally, SOD1G93A protein aggregation was observed in the cytosol and mitochondria of all tissues at the pre-symptomatic and symptomatic stages. Conclusion: Oxidative stress metabolism and pentose phosphate pathway (PPP) have been impaired because of human mutant SOD1G93A protein accumulation in ALS rats that result in histopathological changes in all tissues. Therefore, targeting oxidative stress metabolism and PPP can be promising therapeutic targets to cure people with ALS in the future.