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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/3

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    Predicting graft survival in paediatric kidney transplant recipients using machine learning
    (Springer , 2024) Aksoy, Gulsah Kaya; Akcay, Huseyin Gokhan; Adar, Mehtap; Koyun, Mustafa; Comak, Elif; Akman, Sema; Department of Industrial Engineering; Department of Industrial Engineering; College of Engineering
    Background Identification of factors that affect graft survival in kidney transplantation can increase graft survival and reduce mortality. Artificial intelligence modelling enables impartial evaluation of clinician bias. This study aimed to examine factors that affect the survival of grafts in paediatric kidney transplantation through the use of machine learning. Methods A retrospective review was conducted on records of paediatric patients who underwent kidney transplantation between 1994 and 2021 and had post-transplant follow-up > 12 months. The nearest neighbour method was used to impute missing fields from a total of 48 variables in the dataset. Models including Naive Bayes, logistic regression, support vector machine (SVM), multi-layer perceptron, and XGBoost were trained to predict graft survival. The study used 80% of the patients for training and the remaining 20% for testing. Modelling success was evaluated based on accuracy and F1 score metrics. Results The study analysed 465 kidney transplant recipients. Of these, 56.7% were male. The mean age at transplantation was 12.08 +/- 5.01 years. Of the kidney transplants, 73.1% (n = 339) were from living donors, 34.5% (n = 160) were pre-emptive transplants, and 2.2% (n = 10) were second-time transplants. The machine learning model identified several features associated with graft survival, including antibody-mediated rejection (+ 0.7), acute cellular rejection (+ 0.66), eGFR at 3 years (+ 0.43), eGFR at 5 years (+ 0.34), pre-transplant peritoneal dialysis (+ 0.2), and cadaveric donor (+ 0.2). The successes of the logistic regression and SVM models were similar. The F1 score was 91.9%, and accuracy was 96.5%. Conclusion Machine learning can be used to identify factors that affect graft survival in kidney transplant recipients. By expanding similar studies, risk maps can be created prior to transplantation.
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    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 Hospital
    Background 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.
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    Survival benefit of nephroureterectomy in systemic therapy exposed metastatic upper tract urinary urothelial carcinoma patients
    (Springer, 2024) Morra, Simone; Incesu, Reha-Baris; Scheipner, Lukas; Baudo, Andrea; Jannello, Letizia Maria Ippolita; Siech, Carolin; de Angelis, Mario; Tian, Zhe; Creta, Massimiliano; Califano, Gianluigi; Colla Ruvolo, Claudia; Saad, Fred; Shariat, Shahrokh F.; Chun, Felix K. H.; de Cobelli, Ottavio; Musi, Gennaro; Briganti, Alberto; Ahyai, Sascha; Carmignani, Luca; Longo, Nicola; Karakiewicz, Pierre I.; N/A; Tilki, Derya; School of Medicine
    Background It is unknown whether the stage of the primary may influence the survival (OS) of metastatic upper tract urothelial carcinoma (mUTUC) patients treated with nephroureterectomy (NU) and systemic therapy (ST). We tested this hypothesis within a large-scale North American cohort. Methods Within Surveillance Epidemiology and End Results database 2000-2020, all mUTUC patients treated with ST+NU or with ST alone were identified. Kaplan-Maier plots depicted OS. Multivariable Cox regression (MCR) models tested for differences between ST+NU and ST alone predicting overall mortality (OM). All analyses were performed in localized (T1-T2) and then repeated in locally advanced (T3-T4) patients. Results Of all 728 mUTUC patients, 187 (26%) harbored T1-T2 vs 541 (74%) harbored T3-T4. In T1-T2 patients, the median OS was 20 months in ST+NU vs 10 months in ST alone. Moreover, in MCR analyses that also relied on 3 months' landmark analyses, the combination of ST+NU independently predicted lower OM (HR 0.37, p < 0.001). Conversely, in T3-T4 patients, the median OS was 12 in ST+NU vs 10 months in ST alone. Moreover, in MCR analyses that also relied on 3 months' landmark analyses, the combination of ST+NU was not independently associated with lower OM (HR 0.85, p = 0.1). Conclusions In mUTUC patients, treated with ST, NU drastically improved survival in T1-T2 patients, even after strict methodological adjustments (multivariable and landmark analyses). However, this survival benefit did not apply to patients with locally more advanced disease (T3-T4).
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    Uncovering the penile clock: expression of molecular clock proteins in human penile cavernous tissue
    (Korean Soc Sexual Medicine and Andrology, 2024) Alkan, Ilter; Bozkurt, Muammer; Canat, Halil Lutfi; N/A; Durkut, Begüm; Uçak, Melike; Özenci, Çiler Çelik; Koç University Research Center for Translational Medicine (KUTTAM); Graduate School of Health Sciences; School of Medicine
    Purpose: To evaluate the expression of core molecular clock genes/proteins in penile cavernous tissue from healthy male subjects and to determine whether their expression has circadian variation. Materials and Methods: Corpus cavernosum biopsy samples were obtained from 10 healthy males with penile deviation or fracture who underwent surgical intervention during the day and night. The daytime group (n=5) underwent corpus cavernosum tissue sampling during zeitgeber time (ZT) 8-12, while the nighttime group (n=5) underwent sampling during ZT 20-24. The expression and localization of BMAL1, CLOCK, PER1, PER2, PER3, CRY1, and CRY2 proteins were analyzed using immunohistochemistry and quantified using H-score analysis. RT-qPCR analysis was performed to assess the expression of core molecular clock genes in the corpus cavernosum tissue of 5 additional daytime patients. Results: The expression of core molecular clock proteins was detected in vascular endothelial cells (VECs) and smooth muscle cells (SMCs) in corpus cavernosum during daytime and nighttime. BMAL1 exhibited the most significant nuclear expression during daytime in both cell types, whereas its expression decreased significantly at night. In VECs, a significant decrease in the nuclear expression of CRY1 was observed at night. In SMCs, a significant decrease in the cytoplasmic expression of PER3 was observed at night. The expression patterns of the core molecular clock genes were ascertained through a RT-qPCR analysis. Conclusions: Our research provides compelling evidence that core molecular clock genes are distinctly expressed in penile tissue in humans. Furthermore, we observed the expression of molecular clock proteins within the VECs and SMCs of the corpus cavernosum, with BMAL1 being the most prominently expressed. The discovery of core molecular clock genes in penile tissue, as well as proteins within the SMCs and VECs of the corpus cavernosum, introduces the potential significance of the molecular clock mechanism in the physiology of penile erection.
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    Entrapped surgical needle in the valveless AirSeal trocar: a case report and literature review
    (Elsevier Science Inc., 2024) N/A; Aykanat, İbrahim Can; Balbay, Mevlana Derya; School of Medicine; Koç University Hospital
    Background: Valveless trocars like AirSeal system are maintain a stable pneumoperitoneum and reduce instrument friction. Case presentation: A 65-year-old man's robotic radical cystectomy was complicated by a missing needle while using AirSeal system. The needle was detected via backward inspection using the endo camera inserted through the trocar, tip at its most distal end let the visualization of the needle within the air channels and confirmed with a trocar X-ray. Conclusion: Our findings suggest that retrograde inspection and targeted radiography of the trocar, prior to patient imaging, can be helpful in locating the lost needle and prevent prolongation of surgeries.
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    The role of neoadjuvant chemotherapy for patients with variant histology muscle invasive bladder cancer undergoing robotic cystectomy: data from the International Robotic Cystectomy Consortium
    (Elsevier Inc., 2024) Cooke, Ian; Abou Heidar, Nassib; Mahmood, Abdul Wasay; Ahmad, Ali; Jing, Zhe; Stöckle, Michael; Wagner, Andrew A; Roupret, Morgan; Kim, Eric; Vasdev, Nikhil; Rha, Koon Ho; Aboumohamed, Ahmed; Dasgupta, Prokar; Maatman, Thomas J.; Richstone, Lee; Wiklund, Peter; Gaboardi, Franco; Li, Qiang; Hussein, Ahmed A.; Guru, Khurshid; N/A; Balbay, Mevlana Derya; School of Medicine
    Objective: To assess the role of neoadjuvant chemotherapy (NAC) before robot-assisted radical cystectomy (RARC) for patients with variant histology (VH) muscle-invasive bladder cancer (MIBC). Methods: Retrospective review of 988 patients who underwent RARC (2004–2023) for MIBC. Primary outcomes included the utilization of NAC among this cohort of patients, frequency of downstaging, and discordance between preoperative and final pathology in terms of the presence of VH. Secondary outcomes included disease-specific (DSS), recurrence-free (RFS), and overall survival (OS). Results: A total of 349 (35%) had VH on transurethral resection or at RARC. The 4 most common VH subgroups were squamous (n = 94), adenocarcinoma (n = 64), micropapillary (n = 34), and sarcomatoid (n = 21). There was no difference in OS (log-rank: P = 0.43 for adenocarcinoma, P = 0.12 for micropapillary, P = 0.55 for sarcomatoid, P = 0.29 for squamous), RFS (log-rank: P = 0.25 for adenocarcinoma, P = 0.35 for micropapillary, P = 0.83 for sarcomatoid, P = 0.79 for squamous), or DSS (log-rank P = 0.91 for adenocarcinoma, P = 0.15 for micropapillary, 0.28 for sarcomatoid, P = 0.92 for squamous) among any of the VH based on receipt of NAC. Patients with squamous histology who received NAC were more likely to be downstaged on final pathology compared to those who did not (P < 0.01). Conclusion: Our data showed no significant difference in OS, RFS, or DSS for patients with VH MIBC cancer who received NAC before RARC. Patients with the squamous variant who received NAC had more pathologic downstaging compared to those who did not. The role of NAC among patients with VH is yet to be defined. Results were limited by small number in each individual group and lack of exact proportion of VH. © 2024
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    Multicentric evaluation of high and low power lasers on RIRS success using propensity score analysis
    (Springer, 2024) Erol, Eren; Ecer, Gokhan; Gokce, Mehmet Ilker; Balasar, Mehmet; Babayigit, Muammer; Aksoy, Elif Ipek; Sarica, Kemal; Ahmed, Kamran; Guven, Selcuk; N/A; Kiremit, Murat Can; Sarıkaya, Ahmet Furkan; Karaarslan, Umut Can; School of Medicine
    In this study, we aimed to evaluate the effect of HPL on different parameters by different centers and urologists. While doing this, we evaluated different parameters by comparing HPL(High Power laser) and LPL(Low-power laser). This is an observational, retrospective, comparative, multicentric study of prospectively organised database. A total of 217 patients who underwent RIRS for kidney stones smaller than 2 cm in three different centers were included in the study. The patients were divided into two groups; LPL used (Group1, n:121 patients) and HPL used (Group2, n:96). Propensity score matching was done in the data analysis part. After matching, a total of 192 patients, 96 patients in both groups, were evaluated. There was no difference between the groups regarding age, gender, stone side, and stone location. The stone-free rate on the first day was 80.3% in Group 1, it was 78.1% in Group 2 (p = 0.9). In the third month, it was 90.7% in Group 1 and 87.5% in Group 2 (p:0.7).Hospitalization duration was significantly higher in Group 1. (2.35 +/- 2.27 days vs. 1.42 +/- 1.10 days; p < 0.001).The operation duration was 88.70 +/- 29.72 min in Group1 and 66.17 +/- 41.02 min in Group2 (p < 0.001). The fluoroscopy time (FT) was 90.73 +/- 4.79 s in Group 1 and 50.78 +/- 5.64 s in Group 2 (p < 0.001). Complications according to Clavien Classification, were similar between the groups(p > 0.05). According to our study similar SFR and complication rates were found with HPL and LPL. In addition, patients who used HPL had lower operation time, hospital stay, and fluoroscopy time than the LPL group. Although high-power lasers are expensive in terms of cost, they affect many parameters and strengthen the hand of urologists thanks to the wide energy and frequency range they offer.
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    The effect of endoscopic renal and ureteral stone surgeries on renal blood flow in children: a prospective trial
    (Springer, 2024) Topbas, Fevzi Batuhan; Sekerci, Cagri Akin; Soydemir, Efe; Yapici, Ozge; Akbas, Serkan; Yucel, Selcuk; Tanidir, Yiloren; N/A; Tarcan, Tufan; School of Medicine
    Aim: To assess the impact of endoscopic stone surgeries on renal perfusion and blood flow in children. Materials and methods: Children who underwent percutaneous nephrolithotomy (PCNL), retrograde intrarenal surgery (RIRS), ureterorenoscopy (URS), endoscopic combined intrarenal surgery (ECIRS) were included to the study. Renal Doppler ultrasonography (RDUS) was performed one day before the operation, and on the postoperative 1st day and 1st month. Peak systolic velocity (PSV) and end-diastolic velocity (EDV) were measured, and resistive index (RI) was calculated with the (PSV-EDV)/PSV formula. RDUS parameters were compared before and after surgery and between ipsilateral and contralateral kidneys. Results: A total of 45 children with a median age was 8 (2-17) years were included (15 (33.3%) girls, 30 (66.7%) boys). PCNL was performed in 13 children (28.9%), RIRS 11 (24.4%), URS 12 (26.7%), and ECIRS 9 (20%). There was no significant difference in renal and segmental PSV, EDV and RI values of operated kidney in the preoperative, postoperative periods. There was no significant difference between RDUS parameters of the ipsilateral and contralateral kidneys in preoperative or postoperative periods. PSV and EDV values were significantly higher in the 1st postoperative month in the group without preoperative DJ stent than in the group with DJ stent (p = 0,031, p = 0,041, respectively). However, RI values were similar. The mean RI were below the threshold value of 0.7 in each period. Conclusion: RDUS parameters didn't show a significant difference in children. Endoscopic surgeries can be safely performed in pediatric stone disease.
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    Prognostic significance of lymph node count in surgically treated patients with T2-4 stage nonmetastatic adrenocortical carcinoma
    (Elsevier Inc., 2024) Assad, Anis; Barletta, Francesco; Incesu, Reha-Baris; Scheipner, Lukas; Morra, Simone; Baudo, Andrea; Garcia, Cristina Cano; Tian, Zhe; Ahyai, Sascha; Longo, Nicola; Chun, Felix K.H.; Shariat, Shahrokh F.; Briganti, Alberto; Saad, Fred; Karakiewicz, Pierre I.; N/A; Tilki, Derya; School of Medicine
    Purpose: The role of lymphadenectomy and the optimal lymph node count (LNC) cut-off in nonmetastatic adrenocortical carcinoma (nmACC) are unclear. Methods: Within the Surveillance, Epidemiology, and End Results (SEER) database, surgically treated nmACC patients with T2-4 stages were identified between 2004 and 2020. We tested for cancer-specific mortality (CSM) differences according to pathological N-stage (pN0 vs. pN1) and two previously recommended LNC cut-offs (≥4 vs. ≥5) were tested in pN0 and subsequently in pN1 subgroups in Kaplan-Meier plots and multivariable Cox regression models. Results: Of 710 surgically treated nmACC patients, 185 (26%) underwent lymphadenectomy and were assessable for further analyses based on available LNC data. Of 185 assessable patients, 152 (82%) were pN0 and 33 (18%) were pN1. In Kaplan-Meier analyses, CSM-free survival was 74 vs. 14 months (Δ 60 months, P ≤ 0.001) in pN0 vs. pN1 patients, respectively. In multivariable analyses, pN1 was an independent predictor of higher CSM (HR:3.13, P < 0.001). In sensitivity analyses addressing pN0, LNC cut-off of ≥4 was associated with lower CSM (multivariable hazard ratio [HR]: 0.52; P = 0.002). In sensitivity analyses addressing pN0, no difference was recorded when a LNC cut-off of ≥5 was used (HR:0.60, P = 0.09). In pN1 patients, neither of the cut-offs (≥4 and ≥5) resulted in a statistically significant stratification of CSM rate, and neither reached independent predictor status (all P > 0.05). Conclusions: Lymphadenectomy provides a prognostic benefit in nmACC patients and identifies pN1 patients with dismal prognosis. Conversely, in pN0 patients, a LNC cut-off ≥4 identifies those with particularly favorable prognosis. © 2024 Elsevier Inc.
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    Impact of PSA nadir, PSA response and time to PSA nadir on overall survival in real-world setting of metastatic hormone-sensitive prostate cancer patients
    (Wiley, 2024) Wenzel, Mike; Hoeh, Benedikt; Hurst, Fabienne; Koll, Florestan; Cano Garcia, Cristina; Humke, Clara; Steuber, Thomas; Traumann, Miriam; Banek, Severine; Chun, Felix K. H.; Mandel, Philipp; Tilki, Derya; School of Medicine; Koç University Hospital
    Background: To evaluate the impact of prostate-specific antigen (PSA) nadir, PSA response and time to PSA nadir (TTN) in metastatic hormone-sensitive prostate cancer (mHSPC) patients on overall survival (OS) in the era of combination therapies. Methods: Different PSA nadir cut-offs (including ultra-low PSA) were tested for OS analyses. Additionally, PSA response >= 99% was evaluated, as well as TTN categorized as <3 versus 3-6 versus 6-12 versus >12 months. Multivariable Cox regression models predicted the value of PSA nadir cut-offs, PSA response and TTN on OS. Sensitivity analyses were performed in de novo and high volume mHSPC patients. Results: Of 238 eligible patients, PSA cut-offs of <0.2 versus 0.2-4.0 versus >4.0 ng/mL differed significantly regarding median OS (96 vs. 56 vs. 44 months, p < 0.01), as well as in subgroup analyses of de novo mHSPC patients and multivariable Cox regression models. A more stringent PSA cut-off of <0.02 versus 0.02-0.2 versus >0.2 ng/mL also yielded significant median OS differences (not reached vs. 96 vs. 50 months, p < 0.01), even after additional multivariable adjustment. A PSA response >= 99% was also significantly associated with better OS than counterparty with <99% response, even after multivariable adjustment (both p < 0.02). When TTN groups were compared, patients with longer TTN harbored more extended OS than those with short TTN (<3 vs. 3-6 vs. 6-12 vs. >12 months: 34 vs. 50 vs. 67 vs. 96 months, p < 0.01). Virtually similar results were observed in sensitivity analyses for high volume mHSPC patients. Conclusions: In times of combination therapies for mHSPC, a PSA nadir of respectively, <0.2 and <0.02 ng/mL are associated with best OS rates. Moreover, a relative PSA response >= 99% and a longer TTN are clinical important proxies for favorable OS estimates.