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The new second-generation tyrosine kinase inhibitors (TKIs) have superior survival outcome and worse toxicity profile when compared with first-generation TKIs according to the results of clinical trials. However, there are limited studies that investigate the efficacy and safety of the new generation TKIs in real-world patients. Thus, we aimed to compare the efficacy and safety of the afatinib, an irreversible inhibitor of ErbB family receptor, and first-generation TKIs in real-world patients. We included advanced nonsmall cell lung cancer (NSCLC) patients who had EGFR exon 19del mutation and treated with afatinib or first-generation TKIs as upfront treatment between 2016 and 2020. All patient's information was collected retrospectively. The study cohort was divided as afatinib arm and erlotinib/gefitinib arm. A total of 283 patients at the 24 oncology centers were included. The 89 and 193 of whom were treated with afatinib and erlotinib/gefitinib, respectively. After 12.9 months (mo) of follow-up, the median PFS was statistically longer in the afatinib arm than erlotinib/gefitinib arm (19.3 mo vs. 11.9 mo, p: 0.046) and the survival advantage was more profound in younger patients (

A 69-year-old man with prostate cancer presented to the hospital with 2 weeks' history of fever, abdominal distension, and fatigue. Laboratory findings showed signs of acute liver failure, and marked elevation of lactate dehydrogenase and tumor marker levels. Abdominal CT showed hepatomegaly with multiple hypodense lesions in both lobes, suggesting metastases. FDG PET/CT scan shows hypermetabolism unusually in the liver with significantly suppressed heart and brain activity, reminiscent of an FDG hepatic superscan. The hypermetabolic lesions confirmed with Tru-Cut needle biopsy of the liver as metastasis of prostate cancer.

Aim: Data about the relationship between oxidative stress and cancer pathogenesis has been increased in recent years. Thiol and disulphide play an important role in cell signal mechanisms, antioxidant protection, and detoxification. In this study, we aimed to evaluate the role of Thiol-Disulphide homeostasis (TDH) in colorectal cancer (CRC) by using a new method. Material and Method: The patients (pts) who diagnosed with CRC and healthy control subjects were included to study. Serum samples for the thiol-disulphide test were obtained at the time of diagnosis. TDH tests were measured by the automated spectrophotometric method by describing Erel and Neselioğlu. Thiol-disulphide homeostasis was also evaluated according to tumor stage and localization. Results: Eighty-eight pts with CRC and 110 control were enrolled. Native thiol (NT), disulphide and total thiol (TT) levels were significantly lower in patients compared with the control arm (Median NT: 402–424, p = 0.003; median Disulphide 18.7–21, p = 0.011; median TT: 437–467, p = 0.001). Thiol/disulphide balance was also maintained (p = 0.149). TT and NT levels were not differed according to tumor localization whereas disulphide level was significantly higher in left-sided tumors than right-sided (19.9–13.07 respectively, p = 0.007). In addition, disulphide/NT ratio was also significantly higher in left-sided than right-sided (0.1–0.12 respectively, p = 0.015). Thus, the balance of dynamic TDH is disrupted in favor of disulphide between left-sided and right-sided tumor. There was also no significant difference between thiol-disulphide levels and tumor stage whereas thiol level tends to lower in stage 4 disease (p = 0.7). Conclusion: This is the first trial that evaluates the relationship with dynamic TDH and CRC according to tumor stage and localization. Thiol and disulphide may play an important role in the pathogenesis of CRC. Keywords: Colorectal cancer, Disulphide, Oxidative stress, Thiols

We present demographic, clinical, laboratory characteristics, and outcomes of the patients with solid malignancies and Novel Coronavirus Disease (COVID-19) collected from the National COVID-19 Registry of Turkey. A total of 1523 patients with a current or past diagnosis of solid tumors and diagnosed with COVID-19 (confirmed with PCR) between 11 March and 20 May, 2020, were included. The primary outcome was 30-day mortality. Median age was 61 (range:18-94), and 752 (49%) were male. The most common types of cancers were breast (19.8%), prostate (10.9%), and colorectal cancer (10.8%). 65% of the patients had at least one comorbidity. At least one Covid-19 directed therapy was given in 73% of the patients.. Hospitalization rate of the patients was 56.6% and intensive care unit admission rate was 11.4%. 77 (5.1%) patients died within 30 days of diagnosis. The first multivariate model which included only the demographic and clinical characteristics showed older age, male gender, and presence of diabetes and receipt of cytotoxic therapy to be associated with increased 30-day mortality, while breast and prostate cancer diagnoses were associated with lower 30-day mortality. In the second set, we further included laboratory parameters. The presence of leukocytosis (OR 6.7, 95 % CI 3.3-13.7, p

Purpose Anaplastic lymphoma kinase (ALK) gene rearrangement exists in approximately 3-7% of non-small cell lung cancer (NSCLC) and more than 15% split or isolated red signals among 50 tumor nuclei scored in the FISH analysis defines as ALK-positive. The previous studies showed that the high EGFR mutational load related to better outcomes in EGFR mutant NSCLC. Therefore, we aimed to investigate the effect of the ALK break-apart ratio on treatment outcome in metastatic ALK-positive NSCLC. Methods The patients (pts) who ALK-positive and treated with crizotinib were retrospectively enrolled. The 30%, 40%, 50%, 60%, and 70% break-apart ratios were determined as a threshold value, and each of these was evaluated separately. Based on the results of these analyses, we detected the optimal threshold value and also performed further investigations. Results A total of 70 patients were enrolled in the study. The most significant decrease in the risk of the progression or death was detected at the 50% threshold value and it was accepted as the optimal threshold. The median PFS was 17.9 vs. 7.06 months (mo) in the pts with high ALK rearrangement than low (HR: 0.43, 95% CI 0.24-0.76, p 0.004). The median OS was also significant longer in high ALK rearrange group (44.6 mo vs. 16.8 mo; HR: 0.37, 95% Cl 0.1883-0.7315; p 0.004). The intracranial progression during crizotinib treatment was significantly frequent in the pts with high ALK rearrangement (62.5-32.5%, P 0.039) Discussion In this study, we found that the high break-apart ratio can predict the extent of benefit from targeted therapy in ALK-positive NSCLC patients. Based on the results of this study, the percentage of the ALK rearrangement can be used to predict treatment outcome and to choose the optimal targeted agent in the treatment of metastatic ALK-positive NSCLC.

Background: Renal cell carcinoma (RCC) is the most common type of renal malignancy with 87% frequency. As a global health problem, kidney cancer is responsible for 2.2% of new cancer cases. One of the highly effective mechanisms that renal cancer cells avoid in the immune system is PD-1 and PD-L1 interaction.Scope: Literature search is made from PubMed, Medline, and ASCO and ESMO Annual Meeting abstracts using the following search keywords: "nivolumab," "pembrolizumab," "atezolizumab," "avelumab," "durvalumab," and "renal cell cancer." The last search was on November 1, 2019.Findings: The combination of nivolumab and ipilimumab have better survival results than sunitinib for intermediate and poor risk patients but not for favorable risk groups. In 2019, two combination regimens with pembrolizumab plus axitinib and avelumab plus axitinib demonstrated efficacy over sunitinib for every risk group. The overall survival data of these trials are still immature.Conclusions: Advanced RCC has high morbidity and mortality with an increasing prevalence. Following tyrosine kinase inhibitors, checkpoint inhibitors have a great influence on treatment of advanced RCC, especially the combination of these two strategies. In 2019 these combined strategies demonstrated 5% complete remission with up to 60% objective response rate. While not immediately, but perhaps in the near future, advanced RCC will become a manageable chronic disease, even if a cure is not possible.

Background: Gastric cancer is one the most diagnosed cancer and the third leading cause of death from cancer worldwide. As an indicator of antioxidant capacity thiol/disulfide homeostasis regulates detoxification, cell signal mechanisms, apoptosis, transcription and antioxidant defense mechanisms. Disregulation of thiol/disulfide homeostasis identified in other cancer types by recent data. In this study, we aimed to evaluate the thiol/disulfide homeostasis in advanced gastric cancer patients. Methods: The patients who diagnosed with gastric cancer and healthy control subjects were included to study. Serum samples for the thiol-disulphide test were obtained at the time of diagnosis. Thiol-disulphide homeostasis tests were measured by the automated spectrophotometric method. Thiol-disulphide homeostasis was also measured according to clinical and laboratory features. Results: Thirty newly diagnosed advanced gastric adenocarcinoma patients and 28 healthy controls were enrolled in the study. The native thiol (NT) and total thiol (TT) levels of patients' group were significantly lower compared with controls (p = 0.001 and p

The human epidermal growth factor receptor 2 (Her2/neu) signal pathway plays a significant role in the occurance of various solid tumor types. The rate of Her2/neu in colorectal carcinoma (CRC) is not clearly elucidated. In this study, we discuss the association between Her2/neu overexpression and clinicopathological parameters in CRC. Her2/neu immunohistochemical (IHC) staining was performed on whole sections of formalin fixed paraffin embedded tumor tissues of 100 CRC resections. Cases with score 3+ and score 2+ expressions were further evaluated by silver in-situ hybridization (ISH) for the existence of Her2/neu gene amplification. Her2/neu membranous overexpression was observed in 12 of the 100 cases (6 cases with a score 3+ and 6 cases with a score 2+) and 6 of these were heterogenous. There were 10 cases with Her2/neu amplification (6/6 score 3+, 4/6 score 2+). Strong cytoplasmic staining was observed in 5 cases. Membranous scores were either 3+ or 2+ in 3 of these 5 cases. Moreover, there was Her2/neu amplification in 2 of these 3 cases. Her2/neu amplification status and overexpression was not related to clinicopathological parameters and overall survival. More clear results can be obtained from studies with Her2/neu IHC and ISH test on whole sections.

VEGF, HER2 and EGFR targeted agents are currently used in gastric, esophageal and colorectal cancers. However, treatment outcomes are still poor in most gastrointestinal (GI) cancers. Immune checkpoints are one of the most promising immunotherapy approaches. In this review article, we aim to discuss the efficacy and safety of anti-PD-1/PD-L1 therapies in GI cancers, including gastric, esophageal and colorectal cancer in published or reported recent studies.A literature search was made from PubMed and ASCO Annual Meeting abstracts by using the following search keywords: "nivolumab", "pembrolizumab", "avelumab", "GI cancers" "anti-PD1 therapy" and "anti-PD-L1 therapy". The last search was on 2 November 2016. The most important limitation of our review is that most of the data on anti-PD-1/PD-L1 therapies in GI cancers relies on phase 1 and 2 trials.Currently, there are two anti-PD-1 (nivolumab and pembrolizumab) and one anti-PDL1 (atezolizumab) agents approved by FDA. After the treatment efficacy of immune checkpoint blockade was shown in melanoma, renal cell cancer and non-squamous lung cancer, trials which evaluate immune checkpoint blockade in GI cancers are ongoing. Early results of trials have been promising and encouraging for patients with advanced stage gastroesophageal cancer. According to early results of published trials, response to anti-PD1/PD-L1 agents appears to be associated with tumor PD-L1 levels. According to two recently published phase 2 trials, the clinical benefits of immune checkpoint blockade with both nivolumab and pembrolizumab were limited in patients with microsatellite instability (MSI) positive advanced colorectal cancer. However, several phase 2/3 trials are still ongoing.Both pembrolizumab and nivolumab show promising efficacy with acceptable safety data in published trials in GI cancers, especially in refractory MSI positive metastatic colorectal cancer.

Chemoradiotherapy (CRT) and chemotherapy in the perioperative or postoperative settings are the different neoadjuvant/adjuvant treatment approaches for resectable gastric cancer. After the results of the ARTIST trial, CRT lost its importance on a large scale in the adjuvant setting. Also, according to the results of the CRITICS trial, CRT does not seem beneficial in the perioperative treatment setting. The beneficial effect of neoadjuvant/adjuvant radiotherapy as a therapeutic option became more questionable as the evidence grows, but still needs further studies to identify its effects on a subgroup of patients who have R1 orD2 dissection and/or lymph node involvement.

Objective: In this report, we determined the efficacy and the toxicity of low dose weekly gemcitabine with radiotherapy, in medically unfit or refused surgery muscle-invasive bladder cancer (BC) patients. Materials and Methods: From 2008 to 2012, 15 patients were included into the retrospective analysis. Weekly gemcitabine was administered at a rate of 50 mg/m 2 with a median dose of 63 Gy radiotherapy. Results: The median age was 69 (range, 55-86). Median follow-up was 15 months (range, 5-53 months). A complete response was achieved in 12 patients (80%). Median progression free survival and overall survival were 15 months (range, 7-23 months) and 18 months (range not calculated), respectively. Local recurrence was found in 3 patients (20%) and distant recurrence was found in 5 patients (33.3%) for the entire group. While salvage surgery was performed on 1 patient, salvage chemotherapy was delivered for 4 patients. Treatment was well tolerated, there was no treatment interruption or instances of toxic death. A serious toxicity (grade 3) cystitis was seen in only 1 patient. Conclusions: Multimodality treatment of muscle invasive BC proved a feasible and effective treatment option. Gemcitabine based chemoradiation is an active treatment option with a low toxicity profile for patients with muscle invasive BC, who are not suitable medically or refused to surgery.

Resistance to endocrine treatment generally occurs over time, especially in the metastatic stage. In this paper, we aimed to review the mechanisms of cyclin-dependent kinase (CDK) 4/6 inhibition and clinical usage of new agents in the light of recent literature updates.A literature search was carried out using PubMed, Medline and ASCO and ESMO annual-meeting abstracts by using the following search keywords; "palbociclib", "abemaciclib", "ribociclib", "cyclin-dependent kinase inhibitors" and "CDK 4/6" in metastatic breast cancer (MBC). The last search was on 10 June 2017.CDKs and cyclins are two molecules that have a key role in cell cycle progression. Today, there are three highly selective CDK4/6 inhibitors in clinical development - palbociclib, ribociclib and abemaciclib. Palbociclib and ribociclib were recently approved by the US FDA in combination with letrozole for the treatment of MBC in a first-line setting, as well as palbociclib in combination with fulvestrant for hormone-receptor (HR)-positive MBC that had progressed while on previous endocrine therapy according to the PALOMA-1, MONALEESA-2 and PALOMA-3 trials, respectively. In the recently published randomized phase III MONARCH 2 trial, abemaciclib plus letrozole had longer progression-free survival and higher objective response rates with less serious adverse events in advanced HR-positive breast cancer previously treated with hormonal treatment.CDK4/6 inhibition is a new and promising target for patients with hormone-receptor-positive MBC. Both palbociclib and ribociclib showed significant additive benefit for patients receiving first-line treatment for HR-positive, epidermal growth factor receptor-2-negative advanced breast cancer. Palbociclib and abemaciclib also had significant activity in combination with fulvestrant for patients with MBC that progressed on previous endocrine therapy.

The aim is to evaluate the association between the Charlson Comorbidity Index (CCI), polypharmacy, inappropriate medication use and cognitive impairment in long-term care facility patients. A cross-sectional study including 105 long-term care facility residents was performed. The Charlson Comorbidity Index (CCI) was used. Inappropriate drug use (IDU) was defined according to the STOPP (Screening Tool of Older People’s Prescriptions) criteria. Univariate analysis to identify variables associated with patient outcome related with cognitive impairment was investigated with χ2, Pearson correlation, Fisher exact, and Mann–Whitney U test where appropriate. For the multivariate analysis, the possible factors identified with univariate analysis were further entered into logistic regression analysis. A significant difference was found between gender, CCI and cognitive impairment (p = 0.038, p = 0.01). While every one point increment in the CCI increases the risk of cognitive impairment 3.1 fold (95% CI = 1.8–5.4, p < 0.001), hypertension increases the risk 12 fold (95% CI = 2.5–67.8, p = 0.002). While the correlation between Mini-Mental Status Examination (MMSE) score and polypharmacy is significant (p = 0.015), the correlation between MMSE and IDU was insignificant (p = 0.739). The association of urogenital system drugs and dementia was significant (p = 0.044). Comorbidities, especially hypertension and old age, are risk factors for cognitive impairment. Polypharmacy correlates with MMSE and is considered a risk factor for cognitive impairment. Inappropriate medication use is high among long-term care facility residents. More studies on large cohorts are needed regarding optimal drug prescription and detection of specific drugs that may have an impact on cognitive performance.

10.2217/FON.15.6 © 2015 Future Medicine Ltd Antihormonal treatment with aromatase inhibitors or tamoxifen are the corner stone treatment options in the adjuvant treatment of hormone receptor-positive breast cancer. In last decade, resulted randomized trials showed that aromatase inhibitors provide more benefit than tamoxifen in hormone receptor-positive postmenopausal breast cancer [1]. Due to the significant diseasefree survival (DFS) and lower recurrences benefit with both upfront aromatase inhibitors for 5 years or sequential therapy with tamoxifen for 2–3 years followed by aromatase inhibitors in early breast cancer, aromatase inhibitors have been accepted as first line endocrine treatment in hormone receptor-positive postmenopausal breast cancer [2]. Obesity and overweight patients have independent risk factor for the development of breast cancer and the outcome of breast cancer was significantly poor in obese patients compared with nonobese patients especially in postmenopausal women [3,4]. Overweight or obese postmenopausal women exhibit a threefold increased risk for developing breast cancer compared with normal weight postmenopausal women [5,6]. Weight gain after diagnosis of breast cancer is also associated with decreased survival and less favorable clinical characteristics such as greater tumor burden, higher grade and poorer prognosis [4,7]. Obesity has been accepted the source of abnormal expression of aromatase enzyme in the breast that leads to increase local estrogen production and predisposition to developing breast cancer and the risk of recurrence has been increased significantly compared with nonobese patients especially in postmenopausal breast cancer patients [8]. In contrast to postmenopausal patients, an increased BMI is associated with a lower risk of breast cancer in premenopausal women and in the pooled analysis of seven prospective cohort studies that comprise 337,819 women and 4385 invasive breast cancer patients showed that BMI ≥31 kg/m were 46% less likely to develop breast cancer than those with a BMI

Amaç: Çalışmanın amacı, böbrek hücreli karsinomlu (BHK) hastaların demografik özellikleri ve tedavi sonuçlarını değerlendirmektir.Materyal-Metot: 2005- 2014 yılları arasında Ankara Atatürk Eğitim ve Araştırma Hastanesi’nde BHK tanısı ile takip edilen 100 hastaya ait veriler geriye dönük olarak incelendi. Sağkalım analizi için Kaplan–Meier yöntemi kullanıldı.Bulgular: Hastaların ortanca yaşı 62 (25.0 -89.0) olup, %40’ı 65 yaş üstündeydi. Erkek / kadın hasta oranı 2.1 olarak saptandı. Hastaların %64’üne radikal nefrektomi, %7’sine parsiyel nefrektomi uygulanmıştı. Histopatolojik olarak berrak hücreli tip %84 oranındaydı. Çoğunluğunu evre IV hastalar oluşturmaktaydı (%55.0) ve en sık metastaz bölgesi akciğerdi (%34). Hastaların 62’si metastaz sonrası ilk basamakta interferon (IFN) tedavisi, IFN sonrası tirozin kinaz inhibitörünü (TKI) ise 49 hasta almıştı. Tüm hastaların ortanca takip süresi 24 ay ve ortanca genel sağkalım (GS) 36 ay idi. Sunitinib kullanan hastalarda ise ortanca GS 30.0 ay ve ortanca progresyonsuz sağkalım (PS) 15 ay bulundu. Sunitinib tedavisi sırasında hastaların %53.8’inda doz azaltımı yapıldı ve %36.6’sında tedaviye ara verildi. Grade 3-4 toksisiteler içinde en sık halsizlik (%34.9) ve anemi (%27.9) saptandı. Sunitinib kullanan hastalarda Memorial Sloan Kettering Cancer Center (MSKCC) kriterlerine göre iyi, orta, kötü riskli hastalarda ortanca PS’ler ise sırasıyla 45, 15 ve 6 ay idi (p=0.05). Çok değişkenli analizde yaşın 65’in üstünde olması (p=0.04), gradın 3-4 olması (p=0.05) ve MSKCC kriterlerine (sunitinib için) göre kötü riskli olmanın (p=0.04) GS’ı kısalttığı saptandı. Sonuç: Çalışmamızda hastalarımızın çoğu erkek, 65 yaşından genç ve tanıda ileri evredeydi. Kliniğimizde takip ettiğimiz BHK’li nefrektomi geçiren hastalarda ve metastatik aşamada bir TKI olan sunitinib kullanan hastalarda sağkalım sürelerinde belirgin iyileşme olduğu gözlendi., Objectives: The aim of the study was to evaluate demographic characteristics and treatment outcomes of patients with renal cell cancer. Materials and Methods: Data of 100 patients diagnosed with RCC at Atatürk Research and Education Hospital between the years 2005-2014 are analyzed retrospectively. Kaplan-Meier test were performed for survival analysis. Results: Median age of patients was 62 (25-89) and 40% of the population was over 65 years old. Sex ration (male/female) was 2/1. Radical nephrectomy was perfomed 64 % of patients also partial nephrectomy rate was 7%. Histopathologically, clear cell varient’s rate was 84 %. Most of the patients were stage 4 (55%) and the most common metastatic site was lung (34%). After the development of metastases, first line interferone (IFN) treatment was administered to 62 of patients and 49 of these took tirosine kinase inhibitor after IFN treatment. For all patients, median follow-up time was 24 months and median overall survival (OS) was 36 months. We determined that OS was 30 months and progression free survival (PFS) was 15 months among patients had recieved sunitinib. During sunitinib treatment, dose reduction was performed in 53.8% of the patients and treatment was interrupted in 36.6% of the patients. Fatigue (34.9%) and anemia (27.9%) were the most common grade 3-4 toxicities. In patients who used sunitinib, median PFS in the good, intermediate and poor risk patients according to Memorial Sloan Kettering Cancer Center (MSKCC) criteria respectively were 45, 15 and 6 months (p=0.05). In multivariate analysis, we found that age over 65 years (p=0.04), grade 3-4 tumors (p=0.05) and the poor risk according to MSKCC criteria (p=0,04) are associated with decreased overall survival.Conclusion: The majority of our patients were male, younger than 65 years and had advanced disease at diagnosis. The significantly improvement in survival has been observed between the nephrectomized and metastatic RCC patients who used sunitinib at our clinic.

Though not very common, solid tumor involvement of the bone marrow (BM) may have serious consequences. Recent studies have shown that mean platelet volume (MPV) is a good indicator for BM disease in the differential diagnosis of thrombocytopenia. We investigated the significance of MPV in the diagnosis of BM metastasis in patients with solid tumors. Patients with histologically-verified solid tumors for whom BM biopsy specimens were available (n = 121) and healthy controls (n = 62) were included in this retrospective study. A total of 183 individuals were analyzed. Of the patients, 61 had a diagnosis of BM metastasis (Group A), 60 did not have BM metastasis (Group B). Group B and C (healthy controls) constituted the control group without BM metastasis (n = 122). The mean MPV was 7.0 +/- 0.8 fl in patients with BM metastasis and 8.4 fl in the control group (P < 0.001). A cut-off point of

OBJECTIVES: To compare endothelial function of people with Alzheimer's disease (AD) with that of people without. DESIGN: Case-control study. SETTING: Geriatric medicine outpatient clinic of a university hospital. PARTICIPANTS: Twenty-five patients with AD who were free of vascular risk factors and 24 healthy elderly controls were enrolled. Exclusion criteria were diabetes mellitus, hypertension, dyslipidemia, evident stroke, smoking, documented coronary artery disease, history of myocardial infarction, heart failure, acute or chronic infection, malignancy, peripheral artery disease, renal disease, rheumatologic diseases, alcohol abuse, and certain drugs that may affect endothelial function. Both groups underwent comprehensive geriatric assessment and neuropsychiatric assessment. MEASUREMENTS: Endothelial function was evaluated according to flow-mediated dilation (FMD) from the brachial artery. RESULTS: Mean age ± standard deviation was 78 ± 5.9 in the group with AD (11 female and 14 male) and 72.1 ± 5.8 in the control group (9 female and 11 male). Multiple linear regression analysis revealed that FMD was significantly lower in patients with AD (median 3.45, range 0–7) than controls (median 8.41, range 1–14) (P < .001), independent of age. It was also found that FMD values were inversely correlated with the stage of the disease as determined according to the Clinical Dementia Rating scale (r=−0.603, P < .001). CONCLUSION: Endothelial function is impaired in patients with AD. Endothelial function was worse in patients with severe AD. These findings provide evidence that vascular factors have a role in the pathogenesis of AD.

Recently, a human/mouse chimeric monoclonal antibody, rituximab, has been successfully used to treat cases of B-cell non-Hodgkin's lymphoma and some autoimmune diseases. However, several viral infections related to rituximab have been reported in the literature, but were not well characterized. To further investigate this topic, relevant English language studies were identified through Medline. There were 64 previously reported cases of serious viral infection after rituximab treatment. The median age of the cases was 61 years (range: 21 - 79). The median time period from the start of rituximab treatment to viral infection diagnosis was 5.0 months (range: 1 - 20). The most frequently experienced viral infections were hepatitis B virus (HBV) (39.1%, n = 25), cytomegalovirus infection (CMV) (23.4%, n = 15), varicella-zoster virus (VZV) (9.4%, n = 6), and others (28.1%, n = 18). Of the patients with HBV infections, 13 (52.0%) died due to hepatic failure. Among the 39 cases that had viral infections other than HBV, 13 died due to these specific infections. In this study, about 50% of the rituximab-related HBV infections resulted in death, whereas this was the case in only 33% of the cases with other infections. Close monitoring for viral infection, particularly HBV and CMV, in patients treated with rituximab should be recommended.

Background: Medication errors in oncology may cause severe clinical problems due to low therapeutic indices and high toxicity of chemotherapeutic agents. We aimed to investigate unintentional medication errors and underlying factors during chemotherapy preparation and administration based on a systematic survey conducted to reflect oncology nurses experience. Materials and Methods: This study was conducted in 18 adult chemotherapy units with volunteer participation of 206 nurses. A survey developed by primary investigators and medication errors (MAEs) defined preventable errors during prescription of medication, ordering, preparation or administration. The survey consisted of 4 parts: demographic features of nurses; workload of chemotherapy units; errors and their estimated monthly number during chemotherapy preparation and administration; and evaluation of the possible factors responsible from ME. The survey was conducted by face to face interview and data analyses were performed with descriptive statistics. Chi-square or Fisher exact tests were used for a comparative analysis of categorical data. Results: Some 83.4% of the 210 nurses reported one or more than one error during chemotherapy preparation and administration. Prescribing or ordering wrong doses by physicians (65.7%) and noncompliance with administration sequences during chemotherapy administration (50.5%) were the most common errors. The most common estimated average monthly error was not following the administration sequence of the chemotherapeutic agents (4.1 times/month, range 1-20). The most important underlying reasons for medication errors were heavy workload (49.7%) and insufficient number of staff (36.5%). Conclusions: Our findings suggest that the probability of medication error is very high during chemotherapy preparation and administration, the most common involving prescribing and ordering errors. Further studies must address the strategies to minimize medication error in chemotherapy receiving patients, determine sufficient protective measures and establishing multistep control mechanisms.

The phenomenon of falls is not well studied in developing world. However, being aware of possible correlates for falls specific to different populations and trying to eliminate these factors is very important to prevent falls. This study investigated occurrence and correlates of falls among elderly in a developing country, Turkey. A total of 2322 patients aged 65 years and over presented to outpatient clinics of a reference hospital were included in this cross-sectional study. All patients had a complete comprehensive geriatric assessment and questioned for fall history. Correlates for falls were analyzed by using logistic regression. The mean age of participants was 71.8 years; 63.5% were female and 28.5% were found to have fallen within one year. Female sex, visual problems, auditory problems, use of mobility aids, mobility problems and depression were the only independent correlates for falls. Although the cross-sectional design of this study may not prove the causal role of the risk indicators, the size of the study group as well as the large number of possible correlates examined enriches the study. The results from this cross-sectional study form a basis for further prospective study on falls in the Turkish elderly population.

Objective: To report a case of severe rhabdomyolysis that developed after administration of atorvastatin to a patient receiving regular colchicine treatment. Case Summary: A 45-year-old man with nephrotic syndrome and amyloidosis presented with dyspnea, altered mentation, and severe fatigue. He had been taking colchicine 1.5 mg/day for amyloidosis for 3 years without adverse effects. Atorvastatin 10 mg/day was prescribed for hypercholesterolemia one month prior to admission. After 2 weeks of atorvastatin treatment, he began to experience myalgia and reduced muscle strength. The creatinine and creatine kinase concentrations on admission were 8.1 mg/dL and 9035 U/L, respectively. The patient was diagnosed with rhabdomyolysis with the findings of myoglobinuric, oliguric acute renal failure, and more than 50–fold elevated creatine kinase concentration. His muscle strength improved after withdrawal of atorvastatin and colchicine. However, he died because of nosocomial pneumonia that developed during his hospital stay. The Naranjo probability scale indicated that atorvastatin and colchicine were probable causes of rhabdomyolysis. Discussion: Atorvastatin and colchicine have well-known myotoxic adverse effects. Despite atorvastatin's proven safety, its use with certain drugs, such as colchicine, makes it a potential myotoxic drug. This might be because concomitant administration of P-glycoprotein substrates, such as statins, and colchicine, which is a P-glycoprotein inhibitor, modifies pharmacokinetics by increasing bioavailability and organ uptake of the substrates, leading to more adverse reactions and toxicities. Conclusions: We recommend checking the creatine kinase level one week after prescribing 2 or more potentially myotoxic drugs concomitantly, after dose increase of a myotoxic drug, or after prescribing a new drug to a patient already using other myotoxic agents.

e13536 Background: We aimed to assessed thePD-L1, PD-1 expression, TILs and IDH-1 mutation associations and their prognostic importance in GBM. Methods: Newly diagnosed and all were operated GBM patients who folllowed between February 2006 to February 2017 were included retrospectively in the study. We assessed the PD-L1, PD-1 expression, CD4(+) ve CD8(+)TILs, IDH-1 mutation in initial tumor specimens. Immunohistochemistry was performed using Ventana® antibody (clon-SP263, ROCHE) for PD-L1 and PD-1, real time PCR used for IDH-1 mutation analysis. Intensity was graded as low, moderate, dense for PD-1, CD4, CD8 TILs. PD-L1 evaluated in percents. The cutoff value assumed as ≥5% for PD-L1 positivity. We used Kaplan Meier, Cox regression tests and SPSS 23. Results: Fourty eight patients included in the study. The mean age was 54± 14,4 and 34 (70%) patients were male. Thirty (70 %) patients were received chemoradiotherapy with temozolamide and 20 (41%) of them also received chemotherapy.We identified two different staining pattern of PD-L1 expression as diffuse fibrillary [13(27%)] and membranous staining [14(29%)]. IDH-1 mutation was found in 30 (62%) patients. We found that TILs were more intensely located in the perivascular area than intratumoral area and in that TILs, PD-1 intensity were dense. We also found a correlation between the percentages of PD-L1 positivity and the density of TILs in the intratumoral and perivascular areas (p < 0,002, r = 0,46). The intensity of both TILs in perivascular areas were significantly lower in PD-L1 (-) tumors than in PD-L1 (+) tumors (p < 0,001). We didn’t find any association between IDH-1 and PD-L1 or TILs. According to survival and multivariate analysis; age, sex, PD-L1 positivity and IDH-1 mutation status did not appear to have a significant effect on survival. (log rank 0,08; 0,30; 0,89; 0,14 respectively) The presence of dense intratumoral CD8(+) and PD-1 (+)TILs were found as positive; advanced age and membranous PD-L1 staining was found as negative independent prognostic factors. Conclusions: Different staining pattern of PD-L1 in tumor tissue and PD-1 positivity in TILs may be a prognostic importance in GBM

Thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy that is characterized by microvascular thrombosis, thrombocytopenia, hemolysis and end organ damage. An extensive variety of drugs, including certain chemotherapeutic agents, have been associated with TTP. However, paclitaxel, cisplatin and ifosfamide regimen (TIP)-induced TTP has not previously been described. The present study reports the case of a 43-year-old patient with a refractory testicular germ cell tumor who developed acute TTP during TIP chemotherapy. Following the third cycle of TIP chemotherapy, the patient developed fever, anemia, thrombocytopenia and confusion. A diagnosis of TTP was established. Plasmapheresis was initiated as daily treatment in the first week, then continued every other day for 4 weeks. TIP chemotherapy was discontinued. The patient's clinical and neurological symptoms improved markedly after a week. Renal function and hemolysis improved, and the patient was discharged in a stable condition. The patient did not develop any complications and has been in remission for 5 months. The Naranjo adverse drug reaction probability scale indicated a likely association between TTP and the TIP chemotherapy regimen in this patient. This case is also investigated with regard to the associated literature to increase the awareness of TTP following chemotherapy.

Background: Upper tract transitional cell carcinomas (UTCC) are relatively uncommon but prognosis is generally worse than TCC of bladder. Methods: Between March 2004 and June 2012, patients with initial nonmetastatic UTCC were assessed in the Medical Oncology and Urology Departments of Ataturk Training and Research Hospital. Results: A total of 11 patients with initially non-metastatic UTCC were detected in the 8 year period, all males. Median age of was 62 (range, 38-74). Six lesions were located in the renal pelvis and 5 in the ureter. Nephroureterectomy was performed in 9 patients, and distal ureterectomy and cuff excision of the bladder in the remaining 2. The majority (n= 9) had high grade tumors. Median primary tumor diameter was 3.5 cm (range, 0.7-10). Five patients (45.5%) were stage I, 2 (18.2%) were stage II, and 4 (36.4%) were stage III. While adjuvant chemotherapy was not applied for stage I and II disease (n= 7), 4 to 6 courses were applied for 3 of the stage III patients. Also one stage III case received adjuvant radiotherapy. Up to 100 months follow-up, median overall survival was 13 months (range, 5-100 months). While stage I and II patients are following-up without muscle-invasive progression, 2 of stage III patients demonstrated progression. Conclusion: We need more collaborative studies to determine management of especially pT3-pT4 patients with UTCC.

Background: We assessed the efficacy and toxicity of ifosfamide and doxorubicin combination chemotherapy (CT) regimen retrospectively in Turkish patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) previously treated with platinum-based chemotherapy. Methods: A total of thirty patients who had received cisplatin based chemotherapy/chemoradiotherapy as a primary treatment received ifosfamide 2500 mg/m(2) days 1-3, mesna 2500 mg/m(2) days 1-3, doxorubicin 60 mg/m(2) day 1 (IMA), repeated every 21 days. Eligible patients had ECOG PS< 2, measurable recurrent or metastatic disease, with adequate renal, hepatic and hematologic functions. Results: Median age was 47 (min-max; 17-60). Twenty six (86.7 %) were male. Median cycles of chemotherapy for each patient were 2 (range: 1-6). Twenty patients were evaluable for toxicity and response. No patient achieved complete response, with nine partial responses for a response rate of 30.0% in evaluable patients. Stable disease, and disease progression were observed in five (16.7%) and six (20.0%) patients, respectively. Clinical benefit was 46.7%. Median time to progression was 4.0 months. Six patients had neutropenic fever after IMA regimen and there were one treatment-related death due to tumor lysis syndrome in first cycle of the CT. No cardiotoxicity was observed after CT and treatments were generally well tolerated. Conclusion: Ifosfomide and doxorubicin combination is an effective regimen for patients with recurrent and metastatic NPC. For NPC patients demonstrating failure of cisplatin based regimens, this CT combination may be considered as salvage therapy.

Evidence regarding the vascular basis of Alzheimer’s disease (AD) is growing. In vascular damage thrombomodulin tears of the cell wall and its level increases in the plasma. von Willebrand factor (vWF) is also thought to be a biomarker for vascular damage. The aim of this study was to examine the levels of vWF and thrombomodulin in AD as possible markers for vascular damage and to test their utility as an early biomarker in AD. Case-control study. Geriatric medicine outpatient clinic of a university hospital. Twenty Alzheimer’s disease patients free from vascular risk factors and 20 controls were enrolled in the study. Thrombomodulin and VWF levels of 20 AD patients and 20 controls were analyzed by commercial kits. Thrombomodulin levels were not different between Alzheimer’s disease and control groups [median (range) = 4.25 (2.27–37.00) ng/ml in Alzheimer’s disease and 3.55 (2.27–14.00) in control group, p=0.15]. Von Willebrand Factor antigen (%) levels were 188.5 (96–306) in Alzheimer’s disease, and 181 (112–284) in control group (p=0.74). Although vascular damage is thought to play role in the pathogenesis of AD, vWF and thrombomodulin failed to demonstrate the vascular damage in AD. Their utility to be used as early biomarkers of AD could not be shown.

We investigate retrospectively the demographic and clinico-pathological characteristics of patients with triple-negative breast cancer (TNBC) compared to those with non-TNBC. Patients with breast cancer diagnosed from 1981 to 2008 in our clinic were retrospectively analyzed. Patient demographics including survival data and tumor characteristics were obtained from charts. A total of 795 patients were assessed in the study, including 140 patients (17.6%) with TNBC and 655 patients (82.4%) with non-TNBC. Patients with non-TNBC were further classified into 3 groups according to hormone receptor (HR) and HER-2 status. Median age was 49 (range 38–60 years) and similar between patients with TNBC and non-TNBC. Patients with TNBC had an increased likelihood of a higher histological grade III compared with HR(+) HER-2(−) subgroup (P > 0.001) and lower stage compared with HR(+)/HER2(+) and HR(−)/HER2(+) subgroups (P < 0.001 and P = 0.002, respectively). In patients with TNBC, the disease-free survival (DFS) rate was 66% at 5 years. In subgroup analysis of non-TNBCs, 5-year-DFS rates of the patients in HR(+)/HER2(−), HR(+)/HER2(+) and HR(−)/HER2(+) subgroups were 59, 66, and 57%, respectively. There was no significant difference between the TNBC and non-TNBC subgroups (P = 0.238). In multivariate analysis, nodal involvement (RR = 2.8, 95% CI: 0.99–8.3, P = 0.052) and the presence of lymphovascular invasion (RR = 3.2, 95% CI: 1.1–9.2, P = 0.029) were significantly associated with increased recurrence risk in patients with TNBC. Although there are differences in patient and tumor features, patients with TNBC had similar clinical course with those with non-TNBC.

Treatment with a bisphosphonate was found to be associated with a significantly increased risk for atrial fibrillation (AF) in a few studies. A recent study showed that once-yearly infusions of intravenous zoledronic acid (ZA) significantly increased the risk of serious AF in postmenopausal women with osteoporosis. This study was conducted to determine the frequency of atrial fibrillation among cancer patients receiving the standard treatment of ZA.Patients with bone metastases who presented to our outpatient clinic for any reason (routine control, chemotherapy, or ZA administration) were included in the study. All patients had been receiving 4 mg ZA at 4-week intervals, with each dose administered over 15 min. A short survey was completed and standard 12-lead ECG recordings were obtained.One hundred and twenty-four cancer patients with documented bone metastases were evaluated. Mean age of the patients was 55 ± 13.0 years, 60% of the patients were female. Forty-one percent of the patients had breast cancer, 18% had non-small cell lung cancer, and the remainder had other solid tumors. Mean duration of ZA administration was 13.4 ± 15.0 months. Mean total cumulative dose was 54 ± 15.0 mg per patient. Sixty patients (48%) had previously been treated with anthracycline-containing regimens, and 37 (30%) had received chest radiotherapy that might affect the heart. Twenty-three percent of the patients had hypertension, 10% had diabetes mellitus, 3.7% had myocardial infarction history, 1.9% had congestive heart failure, and 1% had valvular disease; 10.5% were current smokers and 32% ex-smokers. On ECG evaluation, we observed normal sinus rhythm in 58%, sinus tachycardia in 15%, sinus bradicardia in 3.2%, and ventricular extrasystole in 5.7% of the patients. There was no AF in any of the cases.There was no increase in the risk of AF frequency in cancer patients who were treated with intravenous ZA, although most of the patients had additional risk factors including previous treatment with cardiotoxic agents or with chest radiotherapy. We believe that the risk of AF is negligible in this patient population and does not affect treatment decisions.

To the editor ABO blood group has been previously found to be associated with the risk of gastrointestinal malignancies including gastric cancer and pancreas cancer [1, 2]. However, there is no data about the association of breast cancer with ABO blood groups. Thus, we aimed to investigate the relationship between ABO blood group and breast cancer risk by comparing the blood groups of breast cancer patients with healthy female donors in a cross-sectional model. Patients with breast cancer (n = 565) who were admitted to our clinic between 2004 and 2009 were retrospectively evaluated. The control group comprised healthy female blood-bank donors (n = 1853). The frequency of distributions of ABO blood groups and Rh types was nearly identical among the patients and the controls (Table 1). When the clinical and pathological characteristics of the patients with different blood groups were compared, again no significant difference was observed considering age at the time of diagnosis, menopausal state, disease stage, hormone receptor and HER2 expression, tumor size, lymph node involvement, lymphovascular/perineural invasion and tumor grade. In conclusion, there seems to be no association between ABO blood type and the risk of breast cancer or any specific clinical or pathological feature of breast cancer in our patient population.

To the Editor, Cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) are often used in follow up care of breast cancer and provide important clues to the clinicians for disease progression in metastatic and recurrent breast cancer. However, use of CA 15-3 and CEA levels are not recommended for surveillance after primary therapy of breast cancer at ASCO guideline [1]. Triple-negative breast cancers (TNBC) are frequently defined as a single group identifiable using routine clinical tests. They are negative for estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2), the so-called ‘triple-negative’ breast cancers. We retrospectively analyzed serum CEA and CA 15-3 levels of 544 consecutive non-metastatic breast cancer patients presenting at Hacettepe University Institute of Oncology. The 15.1% of the patients were TNBC. There were no statistically significant differences in clinical characteristics of the disease between TNBC and non-TNBC patients. At the time of diagnosis TNBC group have lower serum CEA (2.5 ± 5.9 vs. 4.0 ± 16.4; P = 0.35) and CA 15-3 (23.7 ± 14.6 vs. 37.1 ± 117; P = 0.021) levels compared to non-triple negative (non-TN) group (3). This may be explained in part by undifferentiated characteristics of triple negative breast cancers. In conclusion, serum levels of CEA and CA 15-3 may be different in breast cancer subgroups. Our findings need to be confirmed in further studies.

Objectives The aim of this study was to investigate the link between the risk of developing coronary heart disease as determined by Framingham risk score (FRS) and the novel cardiac risk factors including serum levels of ferritin, C reactive protein (CRP), homocysteine, creatinine, and uric acid. Methods A total of 1698 patients aged 65 years or more were examined. Plasma concentrations of lipids, CRP, ferritin, homocysteine, uric acid, and creatinine were measured in all the patients. The FRS was calculated for each patient who were divided into three groups according to their FRSs: score 0–9, score 10–19, and score 20 or more group. Results Levels of creatinine, uric acid, CRP, triglyceride, high-density lipoprotein, folate, ferritin, and homocysteine were significantly different between the three groups. Homocysteine, ferritin, triglyceride, uric acid, and creatinine significantly increased the risk of passing from score 0–9 group to 10–19 group. Triglyceride and creatinine also increased the risk of passing from score 10–19 group to 20 or more group. Conclusion An increase in homocysteine, uric acid, ferritin, creatinine, and triglyceride levels is associated with an increase in FRS in elderly people. The current findings support the use of these novel risk factors for diagnosis of coronary heart disease in elderly patients.

To compare endothelial function of people with Alzheimer's disease (AD) with that of people without.Case-control study.Geriatric medicine outpatient clinic of a university hospital.Twenty-five patients with AD who were free of vascular risk factors and 24 healthy elderly controls were enrolled. Exclusion criteria were diabetes mellitus, hypertension, dyslipidemia, evident stroke, smoking, documented coronary artery disease, history of myocardial infarction, heart failure, acute or chronic infection, malignancy, peripheral artery disease, renal disease, rheumatologic diseases, alcohol abuse, and certain drugs that may affect endothelial function. Both groups underwent comprehensive geriatric assessment and neuropsychiatric assessment.Endothelial function was evaluated according to flow-mediated dilation (FMD) from the brachial artery.Mean age +/- standard deviation was 78 +/- 5.9 in the group with AD (11 female and 14 male) and 72.1 +/- 5.8 in the control group (9 female and 11 male). Multiple linear regression analysis revealed that FMD was significantly lower in patients with AD (median 3.45, range 0-7) than controls (median 8.41, range 1-14) (P.001), independent of age. It was also found that FMD values were inversely correlated with the stage of the disease as determined according to the Clinical Dementia Rating scale (r=-0.603, P.001).Endothelial function is impaired in patients with AD. Endothelial function was worse in patients with severe AD. These findings provide evidence that vascular factors have a role in the pathogenesis of AD.

Grade-III invasive ductal carcinomas of no special type (IDCs-NST) constitute a heterogeneous group of tumours with different clinical behaviour and response to chemotherapy. As many as 25% of all grade-III IDCs-NST are known to harbour a basal-like phenotype, as defined by gene expression profiling or immunohistochemistry for basal cytokeratins. Patients with basal-like breast carcinomas (BLBC) are reported to have a shorter disease-free and overall survival.A retrospective analysis of 49 patients with BLBC (as defined by basal cytokeratin expression) and 49 controls matched for age, nodal status and grade was carried out. Histological features, immunohistochemical findings for oestrogen receptor (ER), progesterone receptor (PgR) and HER2, and clinical outcome and survival after adjuvant chemotherapy were compared between the two groups.It was more likely for patients with BLBCs to be found negative for ER (p0.0001), PgR (p0.0001) and HER2 (p0.01) than controls. Patients with BLBCs were found to have a significantly higher recurrence rate (p0.05) and were associated with significantly shorter disease-free and overall survival (both p0.05). In the group of patients who received anthracycline-based adjuvant chemotherapy (BLBC group, n = 47; controls, n = 49), both disease-free and overall survival were found to be significantly shorter in the BLBC group (p0.05).BLBCs are a distinct clinical and pathological entity, characterised by high nuclear grade, lack of hormone receptors and HER2 expression and a more aggressive clinical course. Standard adjuvant chemotherapy seems to be less effective in these tumours and new therapeutic approaches are indicated.

EGb 761 is widely used in the management of mild cognitive impairment in the elderly population. Elucidation of the effects of EGb 761 on primary haemostasis via PFA-100 could represent an important step for better understanding of the haemostatic safety of EGb 761. The purpose of this prospective study is to assess the effects of Ginkgo biloba special extract, EGb 761, on PFA-100 in vitro bleeding time in elderly patients with mild cognitive impairment. A total of 40 elderly patients aged 65-79 years who were referred for geriatric assessment and who were diagnosed as having mild cognitive impairment were included. Patients were started on 80 mg EGb-761 three times daily. The complete set of PFA-100 in vitro bleeding time and coagulation parameters including prothrombin time, activated partial thromboplastin time and International Normalized Ratio were assessed before and on the seventh day of treatment with EGb 761. There was no statistically significant prolongation in PFA-100 in vitro bleeding time or coagulation parameters in patients receiving EGb 761 after 7 days. The data about the safety of EGb 761 from the point of primary haemostasis in our elderly patient population with mild cognitive impairment casts hope for the future management of this 'difficult-to-treat' population with the promising Ginkgo extracts.