Tıp Fakültesi / Faculty of Medicine
Permanent URI for this collectionhttps://hdl.handle.net/11727/1403
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Item Reclassification of Clinical Exome Data Leads To Significant Clinical Assessment Changes in Almost Half of the Patients(2023) Bayraktar, Umut Arda; Sahin, Feride Iffet; Polat, Mert; Terzi, Yunus KastmPurpose: With the global accumulation of genetic/clinical data, we are understanding the clinical significance of the reclassification of pathogenicity for gene variants. We hypothesized that this evolution in classification(s) may cause clinically-relevant discrepancies in the genetic risk assessment of subjects. In this study, we sought to reclassify the clinical exome sequence (CES) data of our patients to assess whether these changes would have clinical significance.Materials and Methods: The study included CES data of 23 cases diagnosed with cancer or familial cancer predisposition. The variants were first classified in 2020 and then reclassified a year after based on the ACMG database. Chart reviews were performed to record clinical history and interventions.Results: In the first classification of CES data, a total of 80 variants were identified as being not benign (26 likely pathogenic/pathogenic and 54 variants of undetermined significance (VUS)). The clinical significance of fifteen variants (19%) changed after reclassification in 10 patients (43%). The only upgraded variant was the c.9097 dup in exon 23 of BRCA2 gene (likely pathogenic to pathogenic). Fourteen variants were downgraded at reanalysis in 9 patients: from pathogenic to likely pathogenic (2 variants), pathogenic to VUS (2), likely pathogenic to VUS (4), and VUS to benign (6).Conclusion: Considering that the clinical significance of CES data changed due to reclassification in almost half of the studied patients, we believe genetic variant-related data should be assessed at regular intervals, regardless of follow-up status in the clinic.Item Locoregional Therapy and Recurrence of Hepatocellular Carcinoma After Liver Transplant(2014) Kirnap, Mahir; Boyvat, Fatih; Akdur, Aydincan; Karakayali, Feza; Arslan, Gulnaz; Moray, Gokhan; Haberal, Mehmet; https://orcid.org/0000-0002-8726-3369; https://orcid.org/0000-0002-1874-947X; https://orcid.org/0000-0003-2498-7287; https://orcid.org/0000-0002-3462-7632; 24635819; AAH-9198-2019; F-4230-2011; AAA-3068-2021; AAB-3888-2021; AAE-1041-2021; AAJ-8097-2021Objectives: Locoregional therapy may decrease the tumor stage and enable liver transplant in patients who have hepatocellular cancer. The purpose of the present study was to assess the relation between locoregional therapy and recurrence of hepatocellular carcinoma after transplant. Materials and Methods: In 50 patients who had liver transplant for treatment of end-stage liver disease from hepatocellular carcinoma and cirrhosis, outcomes were evaluated for associations with locoregional therapy before transplant and Milan criteria. Results: Most patients had locoregional therapy before transplant (31 patients [62%]: transarterial catheter radiofrequency ablation alone, 16 patients; chemoembolization alone, 10 patients; both transarterial catheter radiofrequency ablation and chemoembolization, 5 patients). Follow-up at median 90 months after transplant showed that 9 patients (18%) had recurrence at median 45 months (range, 120 +/- 12 mo) (recurrence: locoregional therapy, 5 of 31 patients [16%]; no locoregional therapy, 4 of 19 patients [21%]; not significant). Locoregional therapy was associated with a significantly lower frequency of recurrence in patients who were outside the Milan criteria. Conclusions: In patients who have liver transplant for treatment of hepatocellular carcinoma, preoperative locoregional therapy may decrease recurrence in patients who are outside the Milan criteria.Item Burkitt Lymphoma After Transplant: An Aggressive Lymphoproliferative Disease(2014) Ozkan, Eylem Akar; Ozdemir, B. Handan; Akdur, Aydincan; Deniz, E. Ebru; Haberal, Mehmet; https://orcid.org/0000-0002-7528-3557; https://orcid.org/0000-0002-8726-3369; 24635811; X-8540-2019; AAA-3068-2021Posttransplant lymphoproliferative disorder (Burkitt lymphoma) may occur after liver transplant. A 3.5-year-old boy who was 17 months after liver transplant developed multiple millimeter-sized nodular lesions in the liver. Before transplant, the patient tested seronegative for Epstein-Barr virus; within 1 month after transplant, he tested seropositive for Epstein-Barr virus (1000 copies). Biopsy of the liver nodules showed posttransplant lymphoproliferative disorder (Burkitt lymphoma). Tacrolimus was stopped, sirolimus was started, and the patient was treated with chemotherapy (etoposide, doxorubicin, cyclophosphamide, corticosteroids and intrathecal methotrexate). Remission was achieved, and follow-up at 76 months after transplant showed no recurrence of the posttransplant lymphoproliferative disorder. In conclusion, posttransplant lymphoproliferative disorder (Burkitt lymphoma) may occur after liver transplant, and monitoring Epstein-Barr virus level may helpful after transplant because of the association between Epstein-Barr virus and Burkitt lymphoma.Item The Perspective of Non-oncologist Physicians on Patients with Metastatic Cancer and Palliative Care (ALONE Study): A Study of the Palliative Care Working Committee of the Turkish Oncology Group (TOG)(2015) Tanriverdi, Ozgur; Yavuzsen, Tugba; Akman, Tulay; Senler, Filiz Cay; Taskoylu, Burcu Yapar; Turhal, Serdar; Komurcu, Seref; Cehreli, Ruksan; Yaren, Arzu; Ozyilkan, Ozgur; 0000-0001-8825-4918; 0000-0001-9375-8133; 0000-0002-7714-5385; 0000-0002-0598-7284; 25631655; AAD-2817-2021; Q-1628-2019; F-1577-2019; M-2172-2015; AAB-7092-2022; AAI-1824-2019The aim of our study was to determine the perspective of non-oncologist physicians regarding their attitudes and beliefs associated with palliative care for patients with metastatic cancer. The study was planned as a cross-sectional survey, and non-oncologist physicians were reached via e-mail and social networking sites. The first part of the questionnaire involved demographic properties, the second part inquired as to the perspectives of participants regarding metastatic disease, and the third part was used to determine beliefs and attitudes about palliative care. All of the questions were five-point Likert-type questions. A total of 1734 physicians completed the questionnaire. The majority of participants were general surgeons or internal medicine specialists (21 and 18 %, respectively), were male (61 %), were younger than 50 years of age (54 %), worked in the town center (67 %), had more than 11 years of professional experience (57 %), and worked in a hospital without an active oncology service (86 %). A total of 71 % of participants identified all patients with metastatic cancer as being terminal stage, 62 % were unaware of palliative care techniques, 64 % did not know about common supportive care options, 59 % were against hospice, and 63 % had no opinion on resuscitation. We determined that non-oncologist physicians believed that all patients with metastatic cancer are at the terminal stage and that palliative/supportive care is the oncologist's task. These data suggest that non-oncologist physicians would benefit from additional graduate and postgraduate courses on these topics.Item Oncofertility for Gynecologic and Non-Gynecologic Cancers: Fertility Sparing in Young Women of Reproductive Age(2014) Dursun, Polat; Dogan, N. Utku; Ayhan, Ali; 25090914; AAJ-5802-2021About ten percent of all female cancer survivors is younger than 40 years of age. For these young women the primary goal is to ensure the highest possibility of cure and to maintain the reproductive functions as well. Oncofertility is a new concept including both oncology and reproductive medicine. By this recently defined concept young women will have maximal chance to make an optimal decision without any significant impact and delay in oncologic outcome. Oncofertility concept could be applied for genital cancer as well as non-genital cancer of reproductive age. Currently sperm and embryo banking are the standard methods used for young patients with cancer whose future fertility is under risk. In contrary oocyte banking, ovarian tissue cryopreservation are all controversial procedures and still accepted as experimental by many authors although American Society of Reproductive Medicine (ASRM) consideres oocyte cryopreservation "no longer experimental". For genital cancers procedures for oncofertility depends on the type of the cancer and the treatment of choice. In this review the current data and concepts regarding oncofertility concept including the gynecologic oncologic perspective is reviewed. (C) 2014 Elsevier Ireland Ltd. All rights reserved.Item The effect of a mobile application on treatment adherence and symptom management in patients using oral anticancer agents: A randomized controlled trial(2021) Karaaslan Eser, Akile; Ayaz Alkaya, Sultan; 0000-0002-2405-0040; 33991868Purpose: The use of mobile health technologies in the management of oral anticancer agents (OAA) can be beneficial in terms of treatment adherence and symptom management. This study was conducted to investigate the effect of a mobile application developed for patients using OAA on treatment adherence and symptom management. Method: The study was conducted using a randomized controlled trial design, and it was carried out on 77 patients. Data were collected from the Oral Chemotherapy Adherence Scale (OCAS), and the Memorial Symptom Assessment Scale (MSAS). Data were collected at the beginning of the research, and face-to-face interviews were conducted after one, three, and six months. Patients in the intervention group were followed up for six months using the mobile application. Results: It was found that there was no difference between the intervention and control groups in the baseline OCAS mean scores (p > 0.05), and the mean score of the intervention group increased over the first, third- and sixth-month measurements (p < 0.05). It was found that there was no difference between the intervention and control groups in the MSAS mean scores (p > .05), and there was a decrease in the mean MSAS score of the intervention group between the third- and sixth-month follow-up (p < .05). Conclusion: The present study results showed that the mobile application is effective in managing symptoms and increasing treatment adherence. A well-designed mobile health application that increases treatment adherence, decreases symptom severity, and supports patients' self-management could be beneficial for patients using OAA. ClinicalTrials.gov Identifier: NCT04626830Item Predictors of parenting stress in parents of children with cancer(2021) Ay, Ayse; Başkent Üniversitesi; 34507150Purpose: In the present study, we investigated the parenting stress experienced by parents of children with cancer and the influencing factors. Method: This was a cross-sectional and descriptive correlational study that consisted of parents of 136 children in the age group of 0-18 years who were followed up for cancer in the outpatient clinics and services of a university hospital in Turkey. Parenting Stress Index, Burden Interview, Multidimensional Scale of Perceived Social Support, Marital Life Satisfaction Scale, and Ways of Coping Questionnaire were used to collect the data. Results: No statistically significant difference was found between the parenting stress mean scores and gender of the parents of children with cancer (t = -0.350; P = 0.727). The results of the present study showed that the economic status (t = -4.16; P = 0.000), parents' physical (t = 3.606; P = 0.000) and mental health status after the child is diagnosed (t = 5.647; P = 0.000), accompanying mental health problems of the child (t = 2.567; P = 0.011), and diagnosis of children at a young age (t = -2.776; P = 0.006) increased the parenting stress of the parents. Conclusions: Nursing interventions can reduce parental stress by providing sufficient care and support during the disease process.Item Perspective of Turkish Medicine Students on Cancer, Cancer Treatments, Palliative Care, and Oncologists (ARES Study): a Study of the Palliative Care Working Committee of the Turkish Oncology Group (TOG)(2020) Oktay, Esin; Levent, Mustafa; Gelincik, Hakan; Aktas, Gizem; Yumuk, Fulden; Koral, Lokman; Arpaci, Erkan; Keser, Murat; Akan, Ali; Kaci, Ebru; Karadurmus, Nuri; Degirmencioglu, Serkan; Turan, Merve; Uyeturk, Ummugul; Cabuk, Devrim; Avci, Nilufer; Toprak, Omer; Ergen, Arzu; Urvay, Semiha; Bayram, Evrim; Petekkaya, Emine; Nayir, Erdinc; Paydas, Semra; Yavuzsen, Tugba; Senler, Filiz Cay; Yaren, Arzu; Barutca, Sabri; Sahinler, Ismet; Ozyilkan, Ozgur; Tanrıverdi, Ozgur; 0000-0001-8825-4918; 30446981; AAD-2817-2021Cancer is one of the most common causes of death all over the World (Rahib et al. in Cancer Res 74(11):2913-2921, 2014; Silbermann et al. in Ann Oncol 23(Suppl 3):iii15-iii28, 2012). It is crucial to diagnose this disease early by effective screening methods and also it is very important to acknowledge the community on various aspects of this disease such as the treatment methods and palliative care. Not only the oncologists but every medical doctor should be educated well in dealing with cancer patients. Previous studies suggested various opinions on the level of oncology education in medical schools (Pavlidis et al. in Ann Oncol 16(5):840-841, 2005). In this study, the perspectives of medical students on cancer, its treatment, palliative care, and the oncologists were analyzed in relation to their educational status. A multicenter survey analysis was performed on a total of 4224 medical school students that accepted to enter this study in Turkey. After the questions about the demographical characteristics of the students, their perspectives on the definition, diagnosis, screening, and treatment methods of cancer and their way of understanding metastatic disease as well as palliative care were analyzed. The questionnaire includes questions with answers and a scoring system of Likert type 5 (absolutely disagree = 1, completely agree = 5). In the last part of the questionnaire, there were some words to detect what the words "cancer" and "oncologist" meant for the students. The participant students were analyzed in two study groups; "group 1" (n = 1.255) were phases I and II students that had never attended an oncology lesson, and "group 2" (n = 2.969) were phases III to VI students that had attended oncology lessons in the medical school. SPSS v17 was used for the database and statistical analyses. A value of p < 0.05 was noted as statistically significant. Group 1 defined cancer as a contagious disease (p = 0.00025), they believed that early diagnosis was never possible (p = 0.042), all people with a diagnosis of cancer would certainly die (p = 0.044), and chemotherapy was not successful in a metastatic disease (p = 0.003) as compared to group 2. The rate of the students that believed gastric cancer screening was a part of the national screening policy was significantly more in group 1 than in group 2 (p = 0.00014). Group 2 had a higher anxiety level for themselves or their family members to become a cancer patient. Most of the students in both groups defined medical oncologists as warriors (57% in group 1 and 40% in group 2; p = 0.097), and cancer was reminding them of "death" (54% in group 1 and 48% in group 2; p = 0.102). This study suggested that oncology education was useful for the students' understanding of cancer and related issues; however, the level of oncology education should be improved in medical schools in Turkey. This would be helpful for medical doctors to cope with many aspects of cancer as a major health care problem in this country.Item Posttransplant Malignancies in Adult Renal and Hepatic Transplant Patients(2020) Rahatli, Samed; Altundag, Ozden; Soy, Ebru Ayvazoglu; Moray, Gokhan; Haberal, Mehmet; 0000-0003-2498-7287; 0000-0002-3462-7632; 0000-0002-0993-9917; 0000-0003-3163-7429; 30119617; AAE-1041-2021; AAJ-8097-2021; AAC-5566-2019; AAJ-3047-2021Objectives: The risk of some cancer types increases after organ transplant compared with that shown in the general population; this has been well documented in clinical studies. With patients having longer survival and with the higher number of transplant procedures, cancer is an increasing health concern at high-volume transplant centers. Malignancy has an important effect on short- and long-term graft and patient survival. In this study, we evaluated cancer frequency during transplant patient follow-up. Materials and Methods: This single-center retrospective study included patients who underwent solid-organ transplant at the Baskent University Medical Faculty Hospital from 1997 to 2017. Renal and hepatic transplant patients older than 16 years at the time of transplant and diagnosed with cancer after transplant were included the study. In total, 1176 of 2018 renal transplant recipients and 274 of 548 hepatic transplant recipients met the inclusion criteria. Results: We determined that 52 of 1176 renal transplant (4.5%) and 9 of 274 hepatic transplant patients (3.3%) developed posttransplant cancer during followup. Of 61 total patients with cancer posttransplant, 44 were males (72.1%) and 17 were females (27.9%), with median age at transplant of 39.2 years. Overall, the incidence of cancer in transplant recipients was 4.2%. The most frequent cancers were basal and squamous skin cancers, which were seen in 18 patients (29%), and Kaposi sarcoma, which was seen in 11 patients (18%). Of the 61 patients who developed cancer, 43 (70%) were still alive at the time of this study. Conclusions: Despite recent positive developments in the use of immunosuppressive drugs, posttransplant malignancy is still a health problem. Fortunately, most cancers in this patient group have good prognosis and can be cured by surgical resection. Transplant physicians should aim for early detection of these diseases.Item Novel pyrrolopyrimidine derivatives induce p53-independent apoptosis via the mitochondrial pathway in colon cancer cells(2020) Kilic-Kurt, Zuhal; Aka, Yeliz; Kutuk, Ozgur; 0000-0001-9854-7220; 32866467; AAH-1671-2019A series of novel pyrrolopyrimidine urea derivatives were synthesized and evaluated for their anticancer activity against colon cancer cell lines. Compounds showed the remarkable cytotoxic activity on HCT-116 wt cell line. The most potent compound 4c (IC50 = 0.14 mu M) induced apoptosis in HCT-116 wt and HCT-116 p53-/- cell lines. Otherwise, treatment of HCT-116 BAX-/-BAK-/- cells with compound 4c didn't lead to activation of apoptosis, suggesting that compound 4c induces apoptotic cell death by activating BAX/BAK-dependent pathway. Moreover, while the compound 4c increase the activation of caspase-3 and caspase-9 levels in HCT116 wt and HCT-116 p53-/- cells, caspase-3 or caspase-9 activation was not observed in HCT-116 BAX-/-BAK-/- cells. In addition, compound 4c induced mitochondrial apoptosis in cells grown as oncospheroids, which better mimic the in vivo milieu of tumors. 4c treatment also activated JNK along with inhibition of prosurvival kinases such as Akt and ERK 1/2 in HCT-116 wt and HCT-116 p53 -/- cells as well as in HCT-116 BAX-/-BAK-/- cells. Notably, our results indicated that compound 4c induced mitochondrial apoptosis through activation p53-independent apoptotic signaling pathways.