N. Zengin

Comparison of the long term cardiac effects associated with 9 and 52 weeks of trastuzumab in HER2-positive early breast cancer

Abstract Purpose: Trastuzumab induced cardiotoxicity (TIC) was defined as the most serious side effect. Long term cardiac effects of trastuzumab are still not known, thus we aimed to compare the long term cardiac effects of adjuvant trastuzumab therapies of HER2-positive breast cancer according to the treatment duration. Methods: Patients who completed adjuvant trastuzumab treatment at least 6 months before for the adjuvant setting in HER2-positive breast cancer were included in the study. A total of 164 patients were included in this study: 108 and 56 patients were treated with 9 weeks and 52 weeks of trastuzumab, respectively. The main limitation of our study is that due to the cross-sectional evaluation of cardiac biomarkers we cannot predict the status of baseline cardiac biomarkers of this population. Results: The median follow-up of the study was 32 (10–95) months. The accompanying chronic diseases were similar in both groups. Baseline left ventricular ejection fraction (LVEF) was 65.5 ± 3.4% vs 67.1 ± 4.5% in the 9 weeks and 52 weeks trastuzumab treatment groups, respectively (p = 0.13). Symptomatic heart failure was not observed during trastuzumab treatment in either group. Trastuzumab induced cardiotoxicity (TIC) was observed in 2 (1.9%) and 17 (30.3%) patients in the 9 and 52 weeks trastuzumab treatment groups, respectively (p < 0.001). After a median 24 months of follow-up from the last dose of trastuzumab, mean LVEF values were similar between the two treatment arms (p = 0.29). In the subgroup analyses, mean LVEF values were significantly lower in patients who developed TIC compared to those who did not develop TIC (61.9 ± 3.6% vs 64.4 ± 2.6%, p = 0.04). Average mean LVEF loss from baseline was significantly higher in patients who developed TIC compared to those who did not develop TIC (10.0 ± 6.0% vs 1.5 ± 6.2%, p < 0.001). Cardiac biomarkers were similar in both treatment groups. In the subgroup analyses serum High-sensitivity C-reactive protein (hs-CRP) and prohormone brain natriuretic peptide (pro-BNP) levels were significantly higher in patients who developed TIC compared to those who did not develop TIC. Conclusions: TIC was observed to be significantly higher in the 52 weeks trastuzumab group. At the end of 32 months of follow-up mean LVEF values and cardiac biomarkers were similar between the two treatment groups. In the subgroup analyses, significant LVEF loss and higher cardiac biomarkers which show cardiac damage in patients who developed TIC can be permanent in some of the patients and long term cardiac damage may be underestimated.

Is There an Association between Blood Group and Survival in Pancreatic Cancer

BACKGROUND An association between the ABO groups and pancreatic cancer has been shown previously, group A being significantly commoner in affected patients. We conducted the present study to investigate the prognostic effect of ABO blood group on overall survival of pancreas cancer patients. METHODS Patients who were diagnosed between 2005 and 2010 with pancreas cancer at Ankara Numune Education and Research Hospital were analyzed retrospectively. Patient demographics and ABO blood groups were obtained from medical charts. RESULTS Fifty pancreas cancer patients with known ABO blood group were included, 26 (52%) group A, 12 patients (24%) group 0, 9 (18%) group B, and 3 (6%) group AB. Blood group A pancreas cancer patient median age was 61.5 (39-80) years, with the median age of the other blood groups (B, AB,O) being 55.5 (32-74) years (p=0.14). 18% of patients with blood group A and11%of the other blood group patients had metastasis (p=0.17) at the time of diagnosis. The median overall survival of blood group A pancreas patients was significantly lower than the other blood group patients, 7.6 (95%CI: 5.0-10.2) months versus 29.0 (95%CI: 0.0-68.8) months (p=0.05). CONCLUSIONS Acccording to previously published cohort studies a relation may exist between ABO blood groups and cancer of pancreas. In this study we observed that pancreas cancer patients with blood group A have significantly worse overall survival than other blood groups.

Case report: cavernous sinus metastasis of the parotid carcinoma: a very unusual case

Cavernous sinus is an uncommon site of metastasis for the head and neck tumors, and especially for the tumors of parotid gland. The case reported here is the second reported case of parotid carcinoma metastatic to the cavernous sinus, proven by histopathology. Also it is the first reported parotid gland acinic cell carcinoma metastasis to the cavernous sinus.

Impact of Laboratory Test Use Strategies in a Turkish Hospital

Objectives Eliminating unnecessary laboratory tests is a good way to reduce costs while maintain patient safety. The aim of this study was to define and process strategies to rationalize laboratory use in Ankara Numune Training and Research Hospital (ANH) and calculate potential savings in costs. Methods A collaborative plan was defined by hospital managers; joint meetings with ANHTA and laboratory professors were set; the joint committee invited relevant staff for input, and a laboratory efficiency committee was created. Literature was reviewed systematically to identify strategies used to improve laboratory efficiency. Strategies that would be applicable in local settings were identified for implementation, processed, and the impact on clinical use and costs assessed for 12 months. Results Laboratory use in ANH differed enormously among clinics. Major use was identified in internal medicine. The mean number of tests per patient was 15.8. Unnecessary testing for chloride, folic acid, free prostate specific antigen, hepatitis and HIV testing were observed. Test panel use was pinpointed as the main cause of overuse of the laboratory and the Hospital Information System test ordering page was reorganized. A significant decrease (between 12.6–85.0%) was observed for the tests that were taken to an alternative page on the computer screen. The one year study saving was equivalent to 371,183 US dollars. Conclusion Hospital-based committees including laboratory professionals and clinicians can define hospital based problems and led to a standardized approach to test use that can help clinicians reduce laboratory costs through appropriate use of laboratory tests.

Hospital-Based HTA in Turkey

The Turkish health system is financed through a mixed system with features of both the Bismarck and Beveridge models.

Efficacy of Dose Dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel versus Conventional Dose Doxorubicin, Cyclophosphamide Followed by Paclitaxel or Docetaxel in Patients with Node-Positive Breast Cancer

BACKGROUND Adding taxanes to adjuvant antracycline and cyclophosphamide (AC) in combination may provide significant improvement in node-positive and high risk node-negative breast cancer (BC) patients. However, the optimal dose and the role of dose-dense (DD) chemotherapy have yet to be determined. The aim of this study was to compare the efficacy of a DD paclitaxel (P)-AC combination with conventional weekly P-AC or docetaxel D-AC combinations in patients with node-positive breast cancer. MATERIALS AND METHODS Newly diagnosed 280 node-positive BC patients diagnosed from 1998 to 2013 in three clinics were retrospectively analyzed. Demographic and medical data were collected from the medical charts. Patients were categorized to 3 groups according to treatment arms: arm A, ddAC-P; arm B, weekly P and AC combination; and arm C; T and AC combination. Adjuvant trastuzumab was added for HER2-positive patients. Kaplan-Meier survival analysis was carried out for disease free survival (DFS) and overall survival (OS). The log-rank test was used to examine the statistical significance of the differences observed between the groups. Two-sided P values <0.05 were considered statistically significant. RESULTS Of the total of 280 patients, 101 were in arm A, 114 in arm B and 65 in arm C.The median ages were 49, 50 and 46, respectively (p=0.11). Median follow-up was 39 (3-193) months. Stage, lymphovascular and perineural invasion, receptor patern, and menopausal status were similar in the 3 treatment arms, but HER2 positivity was significantly lower in arm A, compared to arms B and C (25.7%, 53.1%, 41.5% in arms A, B and C, respectively; p<0.001). Also grade 3 tumors were significantly less frequent in treatment arm A compared to arm B and C (27.3%, 56.8% and 49.2% , respectively, p=0.01). Afterunivariate and multivariate analysis were performed, 3-year DFS rates were 89%, 81%, and 75%, respectively (p=0.12) and three year OS rates were 96.6%, 89%, and 75% (p=0.62). CONCLUSIONS In this study, no significant difference was found between adjuvant dose dense and conventional taxane treatment regimens.

Metastatic parenchymal renal squamous cell carcinoma with hypercalcemia

Renal tumors originated from renal parenchyme or renal pelvis with different histological subtypes. The most common observed malign renal tumors are clear cell renal cell carcinoma (CCRCC), multilocular cystic renal cell carcinoma (MCRCC), papillary renal cell carcinoma (PRCC), chromophobe RCC and carcinoma of the collecting ducts of Bellini, respectively [1]. Primary squamous cell carcinoma (SCC) of the renal parenchyme or renal pelvis is very unusual and rare entity which accounts less than 1 % of renal malign tumors [2]. To our knowledge, there are only two renal parenchymal SCC cases reported until today [3]. This letter presents a case of metastatic renal parenchymal squamous cell carcinoma associated with hypercalcemia, which is not reported until now. A 53-year-old male patient was admitted to our clinic with severe left-sided flank pain and intermittent hematuria. The patient was non-smoker and had a history of intermittent flank pain due to nephrolithiasis. Laboratory evaluation revealed mild anemia and hypercalcemia with microscopic hematuria. Serum calcium level was 13.2 mg/ dl (normal range 8.6–10.2 mg/dl) and serum albumin was 2.9 g/dl (normal range 3.5–4.5 mg/dl) with suppressed parathyroid hormone levels and normal renal functions. Corrected calcium level was calculated as 14.1 mg/dl. By intense hydration and zoledronic acid treatment, serum calcium level was corrected to normal levels. Thoracic and abdominal computed tomography (CT) was performed, and multiple metastatic nodular lesions in both lung and multilocular metastatic hypodense masses with the largest 61 9 55 mm in the right posterior lobe of liver were revealed. Additionally, prominent parenchymal mass in the right kidney and perirenal multiple lymphadenopathies with the biggest size of 18 9 33 mm were found. The patient underwent cytoreductive nephrectomy and right hemicolectomy due to direct tumoral invasion. On the gross examination, the tumor measuring 6.2 9 4.2 9 3.1 cm diameter with multiple calculus was seemed as ulcerative and necrotic confined to the upper pole of right kidney. No tumoral invasion to the renal pelvis was found. Pathological examination of the surgical material revealed moderately differentiated SCC in the renal parenchyma directly invasive to the serosal surface of the right colon without mucosal involvement. Then, due to the extensive disease, patient was treated with six cycles of gemcitabine and carboplatin regimen every 3 weeks plus zoledronic acid. After six cycles of chemotherapy, the patient was progressively deteriorated and died. Squamous cell carcinomas are associated with chronic inflammatory conditions such as renal calculi, recurrent urinary tract infections and schistosomiasis. So, a patient with SCC should be evaluated for such predisposing risk factors that associated with squamous metaplasia and subsequently SCC [4]. In our case, renal calculi were established in both radiologic studies and gross examination of the surgical material. Due to the renal pelvis SCCs tend to be invasive and sessile, the diagnosis of the renal parenchymal SCC should be confirmed with the evaluation Y. Acikgoz Department of Internal Medicine, Ankara Numune Education and Research Hospital, Ankara, Turkey

Serum 25-hydroxy vitamin D status is not related to osteopenia/osteoporosis risk in colorectal cancer survivors.

BACKGROUND The incidence of colorectal cancer increases with vitamin D deficiency as shown in recently published studies. In addition, prospective investigations have indicated that low vitamin D levels may be associated with increased mortality of colorectal cancer, especially in stage III and IV cases. However, the exact incidence of vitamin D deficiency and the relation between vitamin D deficiency and osteopenia/osteporosis is still not known. The aim of this study is to identify severity of vitamin D deficiency and absolute risk factors of osteopenia/osteoporosis in colorectal cancer survivors. MATERIALS AND METHODS A total of 113 colorectal cancer survivors treated with surgery and/or chemotherapy ± radiotherapy were recruited from medical oncology outpatient clinics during routine follow-up visits in 2012-2013. Bone mineral densitometry (BMD) was performed, and serum 25-OH vitamin D levels were also checked on the same day of the questionnaire. The patients was divided into 2 groups, group A with normal BMD and group B with osteopenia/osteoporosis. RESULTS The median age of the study population was 58 (40-76). Thirty (30.0%) were female, whereas 79 (70.0%) were male. The median follow-up was 48 months (14-120 months). Vitamin D deficiency was found in 109 (96.5%); mild deficiency (20-30 ng/ml) in 19 (16.8%), moderate deficiency (10-20 ng/ml) in 54 (47.8%) and severe deficiency (<10 ng/ml) in 36 (31.9%). Osteopenia was evident in 58 (51.4%) patients whereas osteoporosis was noted in 17 (15.0%) . Normal BMD was observed in 38 (33.6%). No apparent effects of type of surgery, presence of stoma, chemotherapy, radiotherapy and TNM stage were found regarding the risk of osteopenia and osteoporosis. Also, the severity of the vitamin D deficiency had no effect in the risk of osteopenia and osteporosis (p=0.93). In female patients, osteopenia/osteoporosis were observed in 79.5% patients as compared to 60.7% of male patients (p=0.04). CONCLUSIONS In our study, vitamin D deficiency and osteopenia/osteoporosis was observed in 96.5% and 66.4% of colorectal cancer survivors, respectively. There is no defined absolute risk factor of osteopenia and osteoporosis in colorectal cancer survivors. To our knowledge, in the literature, our study is the first to evaluate all the risk factors of osteopenia and osteoporosis in colorectal cancer survivors.

First hematopoietic cell transplantation in Uzbekistan: Progress through education and cooperation.

HCT rates are one of the important parameters defining developmental stage of a given country. There is a steady increase in HCT activity on both sides of Atlantic. But in certain parts of the world, HCT activities have yet to begin. Here we report the history of the establishment of the first HCT center and its preliminary activity in Tashkent-Uzbekistan through close cooperation between Turkish Cooperation and Coordination Agency (TIKA) and Uzbekistan Ministry of Health. As of 2014, a total of 10 multiple myeloma patients successfully underwent autologous HCT in Uzbekistan. This encouraging project may be seen as a good example for other developing countries.

Role of obesity on the efficacy of exemestane plus ovarian suppression in hormone receptor-positive premenopausal breast cancer

10.2217/FON.15.6