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Publication Metadata only Adrenocortical cancer in the real world: a comprehensive analysis of clinical features and management from the Turkish Oncology Group (TOG)(Elsevier Inc., 2024) Yasar,H.; Aktas,B.Y.; Ucar,G.; Goksu,S.S.; Bilgetekin,I.; Cakar,B.; Sakin,A.; Ates,O.; Basoglu,T.; Arslan,C.; Demiray,A.G.; Paydas,S.; Cicin,I.; Sendur,M.A.N.; Karadurmus,N.; Kosku,H.; Uner,A.; Utkan,G.; Kefeli,U.; Tanriverdi,O.; Cinkir,H.; Gumusay,O.; Turhal,N.S.; Menekse,S.; Kut,E.; Beypinar,I.; Sakalar,T.; Demir,H.; Yekeduz,E.; Kilickap,S.; Erman,M.; Urun,Y.; Yumuk, Perran Fulden; School of MedicineIntroduction: Adrenocortical carcinoma (ACC) is a rare yet highly malignant tumor associated with significant morbidity and mortality. This study aims to delineate the clinical features, survival patterns, and treatment modalities of ACC, providing insights into the disease's prognosis. Materials and Methods: A retrospective analysis of 157 ACC patients was performed to assess treatment methodologies, demographic patterns, pathological and clinical attributes, and laboratory results. The data were extracted from the hospital's database. Survival analyses were conducted using the Kaplan–Meier method, with univariate and multivariate analyses being performed through the log-rank test and Cox regression analyses. Results: The median age was 45, and 89.4% had symptoms at the time of diagnosis. The median tumor size was 12 cm. A total of 117 (79.6%) patients underwent surgery. A positive surgical border was detected in 26 (24.1%) patients. Adjuvant therapy was administered to 44.4% of patients. The median overall survival for the entire cohort was 44.3 months. Median OS was found to be 87.3 months (95% confidence interval [CI] 74.4-100.2) in stage 2, 25.8 (95% CI 6.5-45.1) months in stage 3, and 13.3 (95% CI 7.0-19.6) months in stage 4 disease. Cox regression analysis identified age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as significant factors associated with survival in patients with nonmetastatic disease. In metastatic disease, only patients who underwent surgery exhibited significantly improved overall survival in univariate analyses. Conclusion: ACC is an uncommon tumor with a generally poor prognosis. Understanding the defining prognostic factors in both localized and metastatic diseases is vital. This study underscores age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as key prognostic determinants for localized disease, offering critical insights into the complexities of ACC management and potential avenues for targeted therapeutic interventions.Publication Metadata only A potential approach toward the management of sepsis: the extracorporeal cytokine hemadsorption therapy(Wiley, 2023) Yıldız, Abdullah Burak; Çöpür, Sidar; Tanrıöver, Cem; Yavuz, Furkan; Vehbi, Sezan; Hasbal, Nuri Barış; Kanbay, Mehmet; School of MedicineInfectious diseases are among the most common cause of morbidity and mortality among hospitalized patients while systemic inflammatory response syndrome is primarily attributed to the imbalance between pro-inflammatory and anti-inflammatory cytokines. Despite the improvements in the antibiotherapy alternatives and diagnostic modalities, the morbidity and mortality rates of sepsis and septic shock are relatively high among patients admitted to the intensive care units. Extracorporeal cytokine hemadsorption therapies are therapeutic approaches for such patient group with promising early results that especially have grown during Covid-19 pandemic. In this narrative review, our aim is to evaluate the current pre-clinical and clinical knowledge regarding the use of cytokine filtration systems among patients with septic shock.Publication Metadata only An update review on hemodynamic instability in renal replacement therapy patients(Springer Science and Business Media B.V., 2023) Covic, A.; Burlacu, A.; Covic, A; Yıldız, Abdullah Burak; Vehbi, Sezan; School of MedicineBackground: Hemodynamic instability in patients undergoing kidney replacement therapy (KRT) is one of the most common and essential factors influencing mortality, morbidity, and the quality of life in this patient population. Method: Decreased cardiac preload, reduced systemic vascular resistance, redistribution of fluids, fluid overload, inflammatory factors, and changes in plasma osmolality have all been implicated in the pathophysiology of hemodynamic instability associated with KRT. Result: A cascade of these detrimental mechanisms may ultimately cause intra-dialytic hypotension, reduced tissue perfusion, and impaired kidney rehabilitation. Multiple parameters, including dialysate composition, temperature, posture during dialysis sessions, physical activity, fluid administrations, dialysis timing, and specific pharmacologic agents, have been studied as possible management modalities. Nevertheless, a clear consensus is not reached. Conclusion: This review includes a thorough investigation of the literature on hemodynamic instability in KRT patients, providing insight on interventions that may potentially minimize factors leading to hemodynamic instability.Publication Metadata only Propensity score-matched analysis of long-term outcomes for living kidney donation in alternative complement pathway diseases: a pilot study(Springer Science and Business Media Deutschland GmbH, 2023) Caliskan,Y.; Safak,S.; Oto,O.A.; Velioglu,A.; Mirioglu,S.; Dirim,A.B.; Yildiz,A.; Guller,N.; Yazici,H.; Ersoy,A.; Turkmen,A.; Lentine,K.L.; Yelken, Berna; Koç University HospitalBackground: Atypical hemolytic syndrome (aHUS) and C3 glomerulopathy (C3G) are complement-mediated rare diseases with excessive activation of the alternative pathway. Data to guide the evaluation of living-donor candidates for aHUS and C3G are very limited. The outcomes of living donors to recipients with aHUS and C3G (Complement disease-living donor group) were compared with a control group to improve our understanding of the clinical course and outcomes of living donation in this context. Methods: Complement disease-living donor group [n = 28; aHUS(53.6%), C3G(46.4%)] and propensity score-matched control-living donor group (n = 28) were retrospectively identified from 4 centers (2003–2021) and followed for major cardiac events (MACE), de novo hypertension, thrombotic microangiopathy (TMA), cancer, death, estimated glomerular filtration rate (eGFR) and proteinuria after donation. Results: None of the donors for recipients with complement-related kidney diseases experienced MACE or TMA whereas two donors in the control group developed MACE (7.1%) after 8 (IQR, 2.6–12.8) years (p = 0.15). New-onset hypertension was similar between complement disease and control donor groups (21.4% vs 25%, respectively, p = 0.75). There were no differences between study groups regarding last eGFR and proteinuria levels (p = 0.11 and p = 0.70, respectively). One related donor for a recipient with complement-related kidney disease developed gastric cancer and another related donor developed a brain tumor and died in the 4th year after donation (2, 7.1% vs none, p = 0.15). No recipient had donor-specific human leukocyte antigen antibodies at the time of transplantation. Median follow-up period of transplant recipients was 5 years (IQR, 3–7). Eleven (39.3%) recipients [aHUS (n = 3) and C3G (n = 8)] lost their allografts during the follow-up period. Causes of allograft loss were chronic antibody-mediated rejection in 6 recipients and recurrence of C3G in 5. Last serum creatinine and last eGFR of the remaining patients on follow up were 1.03 ± 038 mg/dL and 73.2 ± 19.9 m/min/1.73 m2 for aHUS patients and 1.30 ± 0.23 mg/dL and 56.4 ± 5.5 m/min/1.73 m2 for C3G patients. Conclusion: The present study highlights the importance and complexity of living related-donor kidney transplant for patients with complement-related kidney disorders and motivates the need for further research to determine the optimal risk-assessment for living donor candidates to recipients with aHUS and C3G.Publication Metadata only Impact of persistent PSA after salvage radical prostatectomy: a multicenter study(Springernature, 2023) Preisser, Felix; Incesu, Reha-Baris; Rajwa, Pawel; Chlosta, Marcin; Nohe, Florian; Ahmed, Mohamed; Abreu, Andre Luis; Cacciamani, Giovanni; Ribeiro, Luis; Kretschmer, Alexander; Westhofen, Thilo; Smith, Joseph A.; Steuber, Thomas; Calleris, Giorgio; Raskin, Yannic; Gontero, Paolo; Joniau, Steven; Sanchez-Salas, Rafael; Shariat, Shahrokh F.; Gill, Inderbir; Karnes, R. Jeffrey; Cathcart, Paul; Van Der Poel, Henk; Marra, Giancarlo; Tilki, Derya; School of Medicine; Koç University HospitalBackground and Objective: Persistent prostatic specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP). However, the impact of persistent PSA on oncologic outcomes in patients undergoing salvage RP is unknown. To investigate the impact of persistent PSA after salvage RP on long-term oncologic outcomes. Material and Methods: Patients who underwent salvage RP for recurrent prostate cancer between 2000 and 2021 were identified from twelve high-volume centers. Only patients with available PSA after salvage RP were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of persistent PSA on biochemical recurrence (BCR), metastasis and any death after salvage RP. Persistent PSA was defined as a PSA-value >= 0.1 ng/ml, at first PSA-measurement after salvage RP. Results: Overall, 580 patients were identified. Of those, 42% (n = 242) harbored persistent PSA. Median follow-up after salvage RP was 38 months, median time to salvage RP was 64 months and median time to first PSA after salvage RP was 2.2 months. At 84 months after salvage RP, BCR-free, metastasis-free, and overall survival was 6.6 vs. 59%, 71 vs. 88% and 77 vs. 94% for patients with persistent vs. undetectable PSA after salvage RP (all p < 0.01). In multivariable Cox models persistent PSA was an independent predictor for BCR (HR: 5.47, p < 0.001) and death (HR: 3.07, p < 0.01). Conclusion: Persistent PSA is common after salvage RP and represents an independent predictor for worse oncologic outcomes. Patients undergoing salvage RP should be closely monitored after surgery to identify those with persistent PSA.Publication Metadata only Regional differences in clear cell metastatic renal cell carcinoma patients across the USA(Springer, 2023) Scheipner, Lukas; Tappero, Stefano; Piccinelli, Mattia Luca; Barletta, Francesco; Garcia, Cristina Cano; Incesu, Reha-Baris; Morra, Simone; Baudo, Andrea; Tian, Zhe; Saad, Fred; Shariat, Shahrokh F.; Terrone, Carlo; De Cobelli, Ottavio; Briganti, Alberto; Chun, Felix K. H.; Tilki, Derya; Longo, Nicola; Carmignani, Luca; Pichler, Martin; Hutterer, Georg; Ahyai, Sascha; Karakiewicz, Pierre I.; Tilki, Derya; School of Medicine; Koç University HospitalPurpose: To test for regional differences in clear cell metastatic renal cell carcinoma (ccmRCC) patients across the USA. Methods: The Surveillance, Epidemiology, and End Results (SEER) database (2000-2018) was used to tabulate patient (age at diagnosis, sex, race/ethnicity), tumor (N stage, sites of metastasis) and treatment characteristics (proportions of nephrectomy and systemic therapy), according to 12 SEER registries. Multinomial regression models, as well as multivariable Cox regression models, tested the overall mortality (OM) adjusting for those patient, tumor and treatment characteristics. Results: In 9882 ccmRCC patients, registry-specific patient counts ranged from 4025 (41%) to 189 (2%). Differences across registries existed for sex (24-36% female), race/ethnicity (1-75% non-Caucasian), N stage (N1 25-35%, NX 3-13%), proportions of nephrectomy (44-63%) and systemic therapy (41-56%). Significant inter-registry differences remained after adjustment for proportions of nephrectomy (46-63%) and systemic therapy (35-56%). Unadjusted 5-year OM ranged from 73 to 85%. In multivariable analyses, three registries exhibited significantly higher OM (SEER registry 5: hazard ratio (HR) 1.20, p = 0.0001; SEER registry 7:HR 1.15, p = 0.008M SEER registry 10: HR 1.15, p = 0.04), relative to the largest reference registry (n = 4025).Conclusion: Important regional differences including patient, tumor and treatment characteristics exist, when ccmRCC patients included in the SEER database are studied. Even after adjustment for these characteristics, important OM differences persisted, which may require more detailed analyses to further investigate these unexpected differences.Publication Metadata only Differences in overall survival of penile cancer patients versus population-based controls(Wiley, 2023) Scheipner, Lukas; Tappero, Stefano; Piccinelli, Mattia Luca; Barletta, Francesco; Garcia, Cristina Cano; Incesu, Reha-Baris; Morra, Simone; Tian, Zhe; Saad, Fred; Shariat, Shahrokh F.; Terrone, Carlo; De Cobelli, Ottavio; Briganti, Alberto; Chun, Felix K. H.; Longo, Nicola; Seles, Maximilian; Ahyai, Sascha; Karakiewicz, Pierre I.; Tilki, Derya; School of Medicine; Koç University HospitalPurpose: To assess whether 5-year overall survival (OS) of squamous cell carcinoma of the penis (SCCP) patients differs from age-matched male population-based controls. Methods: We relied on the Surveillance Epidemiology and End Results database (2004-2018) to identify newly diagnosed (2004-2013) SCCP patients. For each case, we simulated an age-matched control (Monte Carlo simulation), relying on the Social Security Administration (SSA) Life Tables with 5 years of follow-up. We compared OS between SCCP patients and population-based controls in a stage-specific fashion. Smoothed cumulative incidence plots displayed cancer-specific mortality (CSM) versus other-cause mortality (OCM). Results: Of 2282 SCCP patients, the stage distribution was as follows: stage I 976 (43%) versus stage II 826 (36%) versus stage III 302 (13%) versus stage IV 178 (8%). At 5 years, OS of SCCP patients versus age-matched population-based controls was as follows: stage I 63% versus 80% (Delta = 17%), stage II 50% versus 80% (Delta = 30%), stage III 39% versus 84% (Delta = 45%), stage IV 26% versus 87% (Delta = 61%). At 5 years, CSM versus OCM in SCCP patients according to stage was as follows: stage I 12% versus 24%, stage II 22% versus 28%, stage III 47% versus 14%, and stage IV 60% versus 14%. Conclusion: SCCP patients exhibit worse OS across all stages. The difference in OS at 5 years between SCCP and age-matched male population-based controls ranged from 17% to 61%. At 5 years, CSM accounted for 12% to 60% of all deaths, across all stages.Publication Metadata only Collecting duct carcinoma: epidemiology, clinical characteristics and survival(Elsevier Science Inc, 2023) Panunzio, Andrea; Tappero, Stefano; Hohenhorst, Lukas; Garcia, Cristina Cano; Piccinelli, Mattia; Barletta, Francesco; Tian, Zhe; Tafuri, Alessandro; Briganti, Alberto; De Cobelli, Ottavio; Chun, Felix K. H.; Terrone, Carlo; Kapoor, Anil; Saad, Fred; Shariat, Shahrokh F.; Cerruto, Maria Angela; Antonelli, Alessandro; Karakiewicz, Pierre I.; Tilki, Derya; School of Medicine; Koç University HospitalIntroduction: Collecting duct carcinoma (CDC) is a rare renal malignancy. We relied on a large population-based cohort to address epidemiology, clinical characteristics, and treatment of CDC patients. We also tested survival in the overall cohort, as well as in stage-specific fashion. Materials and methods: Within Surveillance, Epidemiology, and End Results (2004- 2018) database, we identified 399 CDC patients. Based on Kaplan-Meier plots survival estimates, conditional survival rates were derived according to disease stage. Cox regression models tested for predictors of cancer specific mortality (CSM). Results: Overall, 273 (68.4%) patients were male, 236 (59.2%) had T3-4 stages, 148 (37.1%) had lymph node invasion, and 156 (39.1%) had distant metastases at initial diagnosis. Nephrectomy alone was commonest in stage I-II (n = 91/99, 92%) and III (n = 94/116, 81%). Combination of both nephrectomy and systemic therapy was commonest in stage IV (n = 62/172, 36%). In the overall cohort, median cancer specific survival was 18 months. Provided a disease-free interval of 24 months, five-year Kaplan-Meier estimated survival at diagnosis increased from 74.2 to 91.0% in stage I-II, from 31.1 to 65.3% in stage III, and from 6.3 to 34.1% in stage IV. In multivariable Cox regression models addressing CSM, systemic therapy (Hazard Ratio [HR]: 0.47, P = 0.020), nephrectomy (HR: 0.37, P < 0.001) and combination of both (HR: 0.28, P < 0.001) exhibited a strong protective effect. Conclusion: Despite its highly aggressive phenotype and dismal survival, CDC is sensitive to nephrectomy and/or systemic therapy. Moreover, even for advanced stage, a more favorable prognosis can be achieved in patients, who benefit of disease-free interval after diagnosis and initial treatment.Publication Metadata only Real-world evidence of outcomes of oligometastatic hormone-sensitive prostate cancer patients treated with metastasis-directed therapy(Wiley, 2023) Wenzel, Mike; Garcia, Cristina C. C.; Hoeh, Benedikt; Jorias, Charlotte; Humke, Clara; Koll, Florestan; Tselis, Nikolaos; Roedel, Claus; Graefen, Markus; Chun, Felix K. H.; Mandel, Philipp; Tilki, Derya; School of Medicine; Koç University HospitalObjective: To investigate characteristics and outcomes of oligometastatic hormone-sensitive prostate cancer (mHSPC) patients undergoing metastases-directed therapy (MDT) with external beam radiation therapy (EBRT). Materials and Methods: We relied on an institutional tertiary-care database to identify mHSPC patients who underwent EBRT as MDT between 12/2019 and 12/2022. Main outcomes consisted of progression to metastatic castration-resistant prostate cancer (mCRPC) and overall mortality (OM). Oligometastatic was defined as & LE;3 metastases and bone and/or lymph node deposits were treated with conventional doses up to 54 Gy or with hypofractionated stereotactic regimes of median 24 Gy (20-27 Gy). Results: Overall, 37 patients treated with EBRT as MDT were identified. The median follow-up was 13 months. Median age at MDT was 71 years and 84% exhibited ECOG performance status 0. The median baseline PSA at diagnosis was 10 ng/mL. Overall, primary local therapy consisted of radical prostatectomy (65%), followed by external beam radiation therapy to the prostate (11%), focal therapy (8%), and palliative transurethral resection of the prostate (5%). Overall, 32% exhibited de novo oligometastatic mHSPC. Bone metastases were present in 78% versus 19% lymph node metastases versus 3% both. The distribution of targeted oligo-metastases was 62% versus 38% for respectively one metastasis versus more than one metastasis. Androgen deprivation therapy (ADT) was combined with MDT in 84%. Moreover, 19% received combination therapy with apalutamide/enzalutamide and 12% with abiraterone or docetaxel. The median time to mCRPC was 50 months. In incidence analyses, 13% developed mCRPC after 24 months. OM after 24 months was 15% in mHSPC patients receiving MDT. Significant OM differences were observed after stratification into targeted metastatic burden (<0.05). No high-grade adverse events were recorded during MDT. Conclusion: Our real-world data suggest that MDT represents a safe treatment option for well-selected oligometastatic mHSPC patients.Publication Metadata only Characteristics of incidental prostate cancer in the United States(Springernature, 2023) Scheipner, Lukas; Incesu, Reha-Baris; Morra, Simone; Baudo, Andrea; Assad, Anis; Jannello, Letizia Maria Ippolita; Siech, Carolin; de Angelis, Mario; Barletta, Francesco; Tian, Zhe; Saad, Fred; Shariat, Shahrokh F.; Briganti, Alberto; Chun, Felix K. H.; Longo, Nicola; Carmignani, Luca; De Cobelli, Ottavio; Ahyai, Sascha; Karakiewicz, Pierre I.; Tilki, Derya; School of Medicine; Koç University HospitalBackground: Data regarding North-American incidental (cT1a/b) prostate cancer (PCa) patients is scarce. To address this, incidental PCa characteristics (age, PSA values at diagnosis, Gleason score [GS]), subsequent treatment and cancer-specific survival (CSS) rates were explored. Methods: Incidental PCa patients were identified within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015). Descriptive statistics, annual percentage changes (EAPC), Kaplan-Meier estimates, as well as Cox regression models were used. Bootstrapping technique was used to generate 95% confidence intervals for CSS at 6 years. Results: Of all 344,031 newly diagnosed non metastatic PCa patients, 5155 harbored incidental PCa. Annual rates of incidental PCa increased from 1.9% (2004) to 2.5 % (2015; p = 0.02). PSA values at diagnosis were 0-4 ng/ml in 48% vs. 4-10 ng/ml in 31% vs. > 10 ng/ml in 21%. Of all incidental PCa patients, 64% harbored GS 6 vs. 25% GS 7 vs. 11% GS >= 8. Of all incidental PCa patients, 47% were aged < 70, 35% were between 70 and 79 and 18% were >= 80 years. Subsequently, 71% underwent no local treatment (NLT) vs. 16% radical prostatectomy (RP) vs. 14% radiotherapy (RT). Proportions of patients with NLT increased from 65 to 81% (p = 0.0001) over the study period (2004-2015). CSS at six years ranged from 58% in GS >= 8 patients with NLT to 100% in patients who harbored GS 6 and underwent either RP or RT. Conclusion: Incidental PCa in the United States is rare. Most incidental PCa patients are diagnosed in men aged less than 80 years of age. The majority of incidental PCa patients undergo NLT and enjoy excellent CSS.