Person: YILMAZLAR, AHMET TUNCAY
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YILMAZLAR
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AHMET TUNCAY
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Publication DPYD c.1905+1G>A promotes fluoropyrimidine-induced anemia, a prognostic factor in disease-free survival, in colorectal cancer(Mary Ann Liebert, Inc, 2021-04-01) Deligönül, Adem; Aksoy, Seçil; Tezcan, Gülçin; Tunca, Berrin; Kanat, Özkan; Çubukcu, Erdem; Yılmazlar, Tuncay; Öztürk, Ersin; Egeli, Ünal; Çeçener, Gülşah; Alemdar, Adem; Evrensel, Türkkan; DELİGÖNÜL, ADEM; AKSOY, SEÇİL; TEZCAN, GÜLÇİN; TUNCA, BERRİN; Kanat, Özka; ÇUBUKÇU, ERDEM; YILMAZLAR, AHMET TUNCAY; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; ALEMDAR, ADEM; EVRENSEL, TÜRKKAN; Sağlık Bilimleri Enstitüsü; Tıbbi Onkoloji Ana Bilim Dalı; 0000-0002-6400-4911; 0000-0002-5956-8755; 0000-0002-1619-6680; 0000-0001-8593-5101; 0000-0001-7904-883X; 0000-0002-3820-424X; HIZ-7332-2022; AAH-1420-2021; AAH-3843-2020; ESM-4544-2022; JDG-0330-2023; ABI-6078-2020; CYM-0930-2022; ETP-1691-2022; CKK-3621-2022; AAP-9988-2020; EXZ-0745-2022Background and Aim: In 10-30% of colorectal cancer (CRC) patients, toxic reactions occur after fluoropyrimidine-based chemotherapy. A dihydropyridine dehydrogenase (DPYD) gene variant, c.1905 + 1G>A, leads to intolerance to fluoropyrimidines. Due to the low frequency of this variant in many populations, the prevalence of fluoropyrimidine-induced hematologic side effects in CRC patients with the c.1905 + 1G>A variant is unclear. In this study, we investigated the prevalence of the DPYD c.1905 + 1 variants in a Turkish CRC cohort and the potential effects of these variants on fluoropyrimidine-induced hematologic side effects.Materials and Methods: The DPYD c.1905 + 1 variant was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis and confirmed by Sanger sequencing in peripheral blood samples of 100 CRC patients who received fluoropyrimidine-based chemotherapy and 60 healthy volunteers. The association of c.1905 + 1 variants with susceptibility to hematologic side effects was evaluated.Results: The DPYD c.1905 + 1G>A variant was more common in the CRC group than in the healthy control group (p = 0.001). The presence of the c.1905 + 1G>A variant was associated with thrombocytopenia (p = 0.039) and anemia (p = 0.035). CRC patients with fluoropyrimidine-induced anemia had shorter disease-free survival than CRC patients without fluoropyrimidine-induced anemia (p = 0.0009).Conclusions: Before administering fluoropyrimidine-based chemotherapy, genetic screening for the DPYD c.1905 + 1G>A variant should be performed with the aim of preventing anemia and anemia-induced complications in CRC patients.Publication Fall of another myth for colon cancer: Duration of symptoms does not differ between right- or left-sided colon cancers(Aves, 2019-08-01) Öztürk, Ersin; Kuzu, Mehmet Ayhan; Öztuna, Derya; Işık, Özgen; Canda, Aras Emre; Balık, Emre; Erkasap, Serdar; Yoldaş, Tayfun; Akyol, Cihangir; Demirbaş, Sezai; Özoğul, Bünyamin; Topcu, Ömer; Gedik, Ercan; Baca, Bilgi; Ergüner, İlknur; Aşoğlu, Oktar; Erkek, Bülent; Yılmazlar, Tuncay; Reis, Erhan; Gençosmanoğlu, Rasim; Aslar, Ahmet Kessaf; Konan, Ali; Öztürk, Ersin; IŞIK, ÖZGEN; YILMAZLAR, AHMET TUNCAY; Tıp Fakültesi; Genel Cerrahi Ana Bilim Dalı; 0000-0002-9541-5035; 0000-0001-8593-5101; 0000-0003-1924-0795; JGW-0566-2023; AAW-9602-2020; CKK-3621-2022Background/Aims: Patients with colorectal cancer continue to present with relatively advanced tumors that are associated with poor oncological outcomes. The aim of the present study was to assess the association between localization, symptom duration, and tumor stage.Materials and Methods: A prospective, multicenter cohort study was conducted on patients newly diagnosed with a histologically proven colorectal adenocarcinoma. Standardized questionnaire-interviews were performed. Data were collected on principal presenting symptoms, duration of symptoms (time to first presentation to a doctor and time to diagnosis) and treatment, diagnostic procedures, tumor site, and stage of the tumor (tumor, node, and metastasis (TNM)).Results: A total of 1795 patients with colorectal cancer were interviewed (mean age: 60.76 +/- 13.50 years, male patients: 1057, patients aged >50 years: 1444, colon/rectal cancer: 899/850, right side/left side: 383/1250, stage 0-1-2/stage 3-4: 746/923). No statistically significant correlations were found between duration of symptoms and either tumor site or stage. Principal presenting symptoms were significantly associated with left colon cancer. Patients who had "anemia," "change in bowel habits," "anal pruritus or discharge," " weight loss," and "tumor in right colon" had a significantly longer symptom time.Conclusion: Symptom duration is not associated with localization, nor is the tumor stage. Diagnosis of colorectal cancer at an earlier stage may be best achieved by screening of the population.Publication Heat shock proteins(Türk Cerrahi Derneği, 2009-10-01) Özürk, Ersin; Kahveci, Nevzat; Özlük, Kasım; Yılmazlar, Tuncay; Özürk, Ersin; KAHVECİ, NEVZAT; Özlük, Kasım; YILMAZLAR, AHMET TUNCAY; Tıp Fakültesi; Genel Cerrahi Ana Bilim Dalı; 0000-0003-0841-8201; FRI-7780-2022; JJX-0104-2023; AAG-7070-2021; CKK-3621-2022Heat shock proteins (HSP) are a group of proteins that have a molecular weight less than 100 kDa and whose production is induced by heat (42-46 degrees C) shock. Infection, inflammation, some toxins such as ethanol, arsenic, trace metals and ultraviolet light, hunger, hypoxia, lack of nitrogen (in plants) and dehydration are the factors that could induce HSP production. HSPs are classified into four main groups according to their molecular weights; HSP 90 family, HSP 70 family, HSP 60 family and the small HSP family. They have functions mainly in cytoprotection, neurodegenerative pathologies, signal transduction pathways and cancer immunology.Publication Risk factors affecting oncological outcomes of surgical resections for middle and lower rectal cancer(Turkish Surgical Assoc, 2023-09-01) Tırnova, İsmail; Işık, Özgen; Yılmazlar, Ahmet Tuncay; Tırnova, İsmail; IŞIK, ÖZGEN; YILMAZLAR, AHMET TUNCAY; Tıp Fakültesi; Genel Cerrahi Ana Bilim Dalı; Kolorektal Cerrahi Bilim Dalı; 0000-0003-4488-1607; 0000-0002-9541-5035; AAW-9602-2020; ISB-9235-2023; T-7494-2017; JOH-0415-2023Objective: In our study, it was aimed to evaluate the factors affecting oncological outcomes in resections for rectal cancer.Material and Methods: Between January 2010 and December 2014, patients with rectal tumors were analyzed retrospectively. Demographic and pathological data and oncological outcomes were analyzed as disease-free survival, overall survival, and local recurrence.Results: A total of 158 patients' data were obtained. Median age was 60 (22-83). Fifty-three patients were older than 65 years of age (138). Ninety-five (60%) patients were males, and 63 (40%) were females. Eighty patients (50.4%) had middle rectal, and 78 (49.6) patients had lower rectal cancer. There was no effect of tumor localization on oncological outcomes. Univariate analyses revealed the effects of age (p= 0.003), operation type (p< 0.001), nodal status (p< 0.001), malignant lymph node ratio (p< 0.001), stage of the disease (p< 0.001), distal resection margin (p= 0.047), perineural invasion (p< 0.001), lymphatic invasion (p< 0.001), venous-vascular invasion (p= 0.025), local recurrence (p< 0.001) and distant metastasis (p< 0.001) on overall survival rates. Univariate analyses revealed the effects of nodal status (p= 0.007), malignant lymph node ratio (p= 0.005), stage of the disease (p= 0.008), perineural invasion (p= 0.004) and venous-vascular invasion (p< 0.001) on disease-free survival rates. Univariate analyses revealed the effects of anastomotic leak (p= 0.015) and venous-vascular invasion (p= 0.001) on local recurrence rates.Conclusion: Older age, advanced nodal status, and distant metastasis were detected as independent risk factors for overall survival. Perineural and venous-vascular invasion were detected as independent risk factors for disease-free survival. Lastly, anastomotic leak and venous-vascular invasion were detected as independent risk factors for local recurrence.Publication Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (eagle): Pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries(Oxford Univ Press, 2023-11-29) Koklucan, A.; İnce, Gülberat; Kural, Said; Sen, M.; IŞIK, ÖZGEN; AKESEN, SELCAN; YILMAZLAR, AHMET TUNCAY; Tıp Fakültesi; 0000-0002-9541-5035; JZU-5283-2024; ISL-1970-2023; DQT-0384-2022; AAW-9602-2020; DAV-0921-2022; ELR-9087-2022; CKK-3621-2022Background: Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks.Methods: The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned.Results: A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31).Conclusion: Completion of globally available digital training by engaged teams can alter anastomotic leak rates.Publication Colorectal cancer surgery in octogenarians(Turkish Surgical Assoc, 2018-01-26) Gülcü, Barış; Yılmazlar, Tuncay; Işık, Özgen; Öztürk, Ersin; Gulcu, Baris; YILMAZLAR, AHMET TUNCAY; IŞIK, ÖZGEN; Öztürk, Ersin; Tıp Fakültesi; Genel Cerrahi Ana Bilim Dalı; 0000-0002-9541-5035; 0000-0002-9754-8755; 0000-0003-1924-0795; 0000-0001-8593-5101; AAW-9602-2020; T-7494-2017; JII-0241-2023; CKK-3621-2022; JGW-0566-2023Objective: The incidence of colorectal cancer becomes higher among octogenarians as the life expectancy increases. Whether advanced age is a risk factor for colorectal surgery is a matter of debate. In the present study, the clinical results of octogenarians who underwent colorectal cancer surgery are discussed to find an answer to this question.Material and Methods: Data of 63 octogenarians who were operated in a tertiary colorectal surgery department between January 1, 2010 and December 31, 2013 were reviewed retrospectively. Demographic data and preoperative, peroperative, and postoperative parameters were evaluated.Results: Overall, 57.2% of the patients were men, The median age was 81 (80-89) years, Cancer was located at the right colon in 17.5%, left colon in 50.2%, and rectum in 31.7%, Eleven patients underwent emergency surgery (17.5%). The most common surgical procedure was low anterior resection m elective (22.2%) and Hartmann's procedure in the emergency setting (9.5%). Stoma creation was more frequent among patients undergoing emergency procedures (42% vs, 6.8%; p=0.0018), Histopathological diagnosis was adenocarcmoma in 90.5% of the patients, and 34.9% of the patients had stage IIIB disease. Surgical morbidity was significantly higher among patients who underwent rectal resection (66% vs, 10.2%; p=0.0124). Medical morbidity was observed in 10 (15.9%) patients, Preoperative blood transfusion was a risk factor for morbidity (83.4% vs, 29.2%; p=0.0170). Length of total hospital stay was 14 (3-39) days, Surgical (p=0.0004) and medical (p=0.0282) morbidity prolonged the length of total hospital stay. The overall mortality rate was 1.6%.Conclusion: Colorectal surgery may be safely performed in octogenarians with acceptable morbidity and mortality in specialized centers.Publication Can heat shock protein 32 be used for the early diagnosis of acute mesenteric ischemia?(Türk Cerrahi Derneği, 2016-03-01) Berhuni, Sait; Öztürk, Ersin; Oral, Arzu Yılmaztepe; Sarkut, Pınar; Kahveci, Nevzat; Yılmazlar, Tuncay; Özlük, Kasım; Yerci, Ömer; Berhuni, Sait; Öztürk, Ersin; YILMAZTEPE ORAL, ARZU; Sarkut, Pınar; KAHVECİ, NEVZAT; YILMAZLAR, AHMET TUNCAY; Özlük, Kasım; YERCİ, ÖMER; Tıp Fakültesi; Genel Cerrahi Ana Bilim Dalı; 0000-0002-8962-9758; 0000-0003-0841-8201; AAG-7070-2021; A-5841-2017; CEH-4566-2022; JGW-0566-2023; HKB-5363-2023; CKK-3621-2022; JJX-0104-2023; EIS-5114-2022Objective: Acute mesenteric ischemia is a challenging and fatal disease. The aim of this study was to detect the heat shock protein 32 (HSP32) response in intestinal tissue and systemic blood to intestinal ischemia and ischemia/reperfusion to define a tool for the early diagnosis of acute mesenteric ischemia.Material and Methods: Thirty female Wistar albino rats were equally divided into 3 groups. Group 1 rats underwent simple laparotomy and closure (control). In Group 2 rats, 1-hour intestinal ischemia followed by 5-hour reperfusion was performed, and Group 3 rats were subjected to 6-hour intestinal ischemia. The experiment was repeated with a 24-hour waiting period. At the end of the waiting period, blood was withdrawn from the tail veins of the rats and the rats were sacrificed via cardiac puncture. Re-laparotomy was subsequently performed and intestinal tissue and luminal samples were obtained for biochemical and pathological investigations. The HSP32 levels of intestinal tissues, luminal contents and blood levels were compared among the groups.Results: At the end of the 24-hour waiting period, the median tissue HSP32 levels were 0.43 (0-6.6) ng/mL for Group 1, 9.51 (2.5-49.9) ng/mL for Group 2 and 43.13 (6.3-121.3) ng/mL for Group 3 (p= 0.001). The median blood HSP32 levels were 0.11 (0.1-1.4) ng/mL for Group 1, 0.42 (0.1-0.7) ng/mL for Group 2, and 0.25 (0.1-1.2) ng/mL for Group 3 (p= 0.047). The HSP levels in the luminal contents were undetectable.Conclusion: Both ischemia and ischemia/reperfusion significantly raised intestinal tissue HSP32 levels in comparison with the control group. However, this change was not reflected in the circulating blood or luminal contents.Publication Is stoma care effective in terms of morbidity in complicated ileostomies?(Dove Medical Press Ltd, 2015-01-01) DÜNDAR, HALİT ZİYA; Sarkut, Pınar; Dündar, Halit Ziya; Tirnova, İsmail; Öztürk, Ersin; Yılmazlar, Tuncay; YILMAZLAR, AHMET TUNCAY; Tıp Fakültesi; Genel Cerrahi Ana Bilim Dalı; 0000-0003-4488-1607; 0000-0001-8593-5101; ISB-9235-2023Background: Performing transient or permanent ileostomy is one of the common procedures involved in colorectal surgery. Complication rates up to 40% have been reported in ileostomies. In this report, the effect of specific stoma care unit on ileostomy and its complications were investigated.Methods: A total of 141 patients, who were operated and underwent ileostomy, due to different causes, at Department of General Surgery, Uludag University, Bursa, Turkey, between 2003 and 2006, were examined, retrospectively. Patient records were examined in terms of age, sex, surgery indications, urgent/elective state, benign/malign origin, ileostomy type, complications and stoma care, and education. chi(2) test was used to compare the categorical data.Results: Among the patients, 95 (67%) were male and 46 (33%) were female. The mean age was 47 years (17-67). Some of the subjects (49%) were operated urgently and some (51%) were under elective conditions. The ileostomy types used included the following: end ileostomy (43%), loop ileostomy (46%), and double-barrel ileostomy (11%). Permanent ileostomy was performed in 23 patients and transient ileostomy was performed in 118 patients. The patients were operated because of either benign (48%) or malign (52%) causes. Complications developed in 37 (26%) patients. The rate of development of complication was markedly higher in ileostomies performed under urgent conditions (61% vs 39%) (P<,0.001). The complications included mucocutaneous separation (12 patients), maceration in the peristomal skin (ten patients), retraction (five patients), necrosis (three patients), prolapsus (three patients), and other metabolic complications (four patients). The complications were treated with care (68%) and surgical revision (32%).Conclusion: The rate of ileostomy was found to be higher in the male patients compared to female patients. The risk of development of complications was found to be higher in ileostomies performed under urgent conditions. The most common complication observed was mucocutaneous separation. Ileostomy complications can be treated conservatively with professional care and education.Publication Early-stage colon cancer with high malat1 expression is associated with the 5-fluorouracil resistance and future metastasis(Springer, 2022-07-06) Öztürk, Ersin; Aksoy, Seçil Ak; Tunca, Berrin; TUNCA, BERRİN; Erçelik, Melis; Tezcan, Gulcin; TEZCAN, GÜLÇİN; Çeçener, Gülşah; ÇEÇENER, GÜLŞAH; UĞRAŞ, NESRİN; YILMAZLAR, AHMET TUNCAY; Yerci, Omer; YERCİ, ÖMER; Tıp Fakültesi; Tıbbi Biyoloji Ana Bilim Dalı; 0000-0002-1619-6680; 0000-0002-5956-8755; 0000-0001-8593-5101; 0000-0002-3820-424X; ADM-8457-2022; AAH-3843-2020Background This study aimed to investigate the role of long noncoding RNA (LncRNA) expression profiles to predict relapse and 5-FU response in patients with stage I/II colon cancer (CC). Methods and Results The expression level of 15 LncRNA was analyzed in stage I/II colon tumors of 126 CC patients. To confirm the findings in-vitro, 5FU-resistant HT29 cells were generated by subjecting HT-29 cells to the increasing concentrations of 5FU for 6 months. The 5FU resistance was observed in WST-1 and Annexin V analyses. The colony formation and wound healing assays were assessed to determine the metastatic properties of the cells. Expression levels of LncRNAs and mRNA of EMT-related genes were determined by RT-PCR. The role of LncRNA on metastasis and 5FU sensitivity were confirmed in pcDNA3.0-PTENP1 and si-MALAT1 expressed 5FU-resistant HT29 cell lineages. Results High MALAT1 (p = 0.0002) and low PTENP1 (p = 0.0044) expressions were significantly associated with 5-FU resistance and tumor relapse in stage I/II CC. The invasiveness and colony-forming characteristics of 5-FU-resistant cell lineages were higher as compared to the parent HT-29. Moreover, the expression of MALAT1 (p = 0.0009) was increased while the expression of PTENP1 (p = 0.0158) decreased in 5FU-resistant-HT-29 cells. Si-MALAT1 treatment increased cell sensitivity to 5FU, whereas it decreased invasive behaviors of 5 FU-resistant-HT-29 cells. Conclusion MALAT1 may be a biomarker in predicting recurrence in early-stage CC. Our findings suggest that a cell-based therapy to target MALAT1 could be established for these patients to prevent metastasis and 5-FU resistance.