Prognostic factors in gastrointestinal stromal tumors: multicenter experience of 333 cases from Turkey.

BACKGROUND/AIMS: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract. In an attempt to survey the approximate incidence, clinicopathological characteristics, and immunophenotypic features of GISTs in Turkey, we conducted a clinicopathological and immunohistochemical analysis of GISTs. METHODOLOGY: Three hundred and thirty-three patients with GIST from nine institutions in Turkey were retrospectively evaluated. RESULTS: Between January 2001 and March 2011, a total of 333 patients with GISTs were included; of these, 204 (61.2%) were male and 129 (38.8%) were female. The median age was 55 years (range; 22-102 years). At the median follow-up of 26 months (range; 4-166 months), the 1-, 3- and 5-year OS rates of the 333 patients were 96.9%, 85.8% and 78.5%, respectively. The 5-year DFS rate was 40%. The 5-year OS rate and median OS time for the patients with R0 resection were significantly higher than for patients with metastatic diseases (79.7 vs. 75.7% and not reached vs. 115 months, respectively, p=0.04). CONCLUSION: Although our results should be confirmed by prospective studies, we believe that they contribute to the literature because the study included both resectable and metastatic or unresectable GIST patients and multicenter findings from Turkey.

Tissue and serum adiponectin levels in patients with gastric cancer: are there any correlations between adiponectin levels and histopathological variables?

BACKGROUND/AIMS: Adiponectin is secreted from adipose tissue and is characterized by hyperinsulinemia, which is related with obesity. Adiponectin levels are significantly lower in gastric cancer patients than in healthy controls. The aim of this study was to investigate the relationship between adiponectin levels in serum, tumor tissue and normal tissue with some other insulin resistance parameters. METHODOLOGY: A total of 35 patients with gastric cancer who had undergone curative gastrectomy by standard lymph node dissection were enrolled in this study. Their serum adiponectin levels, tumor tissue and normal breast tissue adiponectin levels were compared. RESULTS: The mean adiponectin levels of the tumor tissue, normal gastric tissue and serum were 48.6±2.9 (range, 39.7-50.6), 48.3±4.2 (range, 34.4-50.69) and 49.4±0.83 (range, 48.2-50.2), respectively. There was no relationship between the adiponectin levels in serum, normal tissue and tumor tissue (p=0.08). There was an inverse relationship between normal tissue adiponectin levels and insulin levels (p=0.002, r=-0.5), but this association was not detected with adiponectin levels in tumor and serum (p>0.05). CONCLUSIONS: Relationships between adiponectin levels in serum, normal tissue and tumor tissue for gastric cancer patients were not found. The small sample size in this study may have influenced the results. However, we believe that our results constitute a first in evaluating the tissue adiponectin levels in gastric cancer tissue.

Pulmonary BALT lymphoma successfully treated with eight cycles weekly rituximab: report of first case and F-18 FDG PET/CT images.

Extra marginal-zone lymphomas of the lung is a very rare tumor and it originates from bronchial-associated lymphoid tissue. A 68-yr-old woman presented with productive cough and dyspnea. A thorax computed tomography scan showed a 9 × 10 cm in size mass in the left lung and pleural effusion in the lower lobe of left lung. Positron emission tomography/computed tomography (PET/CT) revealed intense uptake foci at the upper and middle sites of left lung and slight uptake foci at the mediastinal lymph nodes which showed malignant involvement. After bronchoscopic biopsy, the diagnosis of pulmonary bronchial-associated lymphoid tissue (BALT) lymphoma was confirmed. At the end of the eight cycles weekly rituximab treatment, complete response was obtained by PET/CT findings. It is concluded that extended rituximab schedule is more effective and it would be beneficial to investigate the use of PET/CT in the diagnosis and evaluating of the treatment response of pulmonary BALT lymphoma.

Is there any impact of plasma M30 and M65 levels on progression-free survival of patients with advanced gastric cancer?

PURPOSE: M30 and M65 are different circulating fragments of cytokeratin 18. They release during apoptotic cell death, so it is believed that they reflect cell death of epithelial tumors. The aim of this study was to determine the prognostic value of plasma M30 and M65 levels in predicting of survival for patients with advanced gastric cancer compare with healthy controls. METHODS: Thirty-four patients with advanced gastric cancer and thirty-two healthy controls were included. Plasma M30 and M65 values were measured by quantitative ELISA method. RESULTS: The median age of patients and control groups was 60 and 56 years, respectively. No difference was detected between patient and control groups with respect to plasma median M30 values (390.4 vs. 270.7 U/l, respectively, P = 0.10). The median plasma M65 values of patients were significantly higher than those of control group (1232.1 vs. 580.1 U/l, P < 0.001). The best cut-off values for plasma M30 and M65 for predicting progression-free survival (PFS) were 277.7 and 1434.9 U/l in ROC analysis. The patients whose plasma M30 values were higher than 277.7 U/l had worse PFS than patients with plasma M30 value <277.7 U/l (8.9 vs. 11.2, respectively, P = 0.01). The median PFS of patients whose M65 levels lower than or equal to 1434.9 U/l was better than that of patients whose M65 levels were >1434.9 U/l (12.4 vs. 10.4, respectively, P = 0.04). But plasma M30 and M65 level in patient group were not found to be an important prognostic factor for PFS in the multivariate analysis. CONCLUSIONS: These results showed that plasma M65 values were significantly elevated in patients with advanced gastric cancer compared to healthy people. Moreover, both increased plasma M30 and M65 levels can predict PFS in patients with gastric cancer.

The role of PET-CT in the differential diagnosis of thymic mass after treatment of patients with lymphoma.

Thymic hyperplasia is a common phenomenon in both children and young adults after chemotherapy and may explain the finding of a mediastinal mass in patients with malignant lymphoma after complete remission. In the present study, we report 5 cases with malignant lymphoma presenting with a mediastinal mass on CT scan after completion of chemotherapy diagnosed as thymic hyperplasia by PET-CT imaging. We retrospectively analyzed 5 patients who presented with anterior mediastinal masses a median of 4 months (range 3-6) after achieving complete remission following successful treatment for malignant lymphoma. Three patients were diagnosed with Hodgkin's lymphoma (HL) and the others with non-Hodgkin's lymphoma (NHL). The median age of the patients was 23 (range of 18-47). PET-CT was performed on these patients to determine the characteristics of a mass which had been detected on CT. PET-CT was performed for all patients, and the thymic masses demonstrated only mild FDG uptake considered to be consistent with thymic hyperplasia. During a median of 24 months of follow-up, all patients were recurrence-free with a median survival of 15 months (range 10-26 months). It is important to be aware of the possibility of thymic hyperplasia after chemotherapy to avoid misdiagnosis or over-staging of disease, as well as unnecessary biopsies, especially when the presenting anterior mediastinal mass was originally located near the thymus on CT scan. Mild FDG PET uptake was sufficient for the diagnosis of benign disease in the cases in this study.

Investigation of human papillomavirus DNA in colorectal carcinomas and adenomas.

Human papillomavirus (HPV) has been considered to be an etiological agent for anogenital cancers, such as cervical cancer and possibly a subset of cancers of the aerodigestive tract. The aim of the study was to evaluate the presence of human papillomavirus DNA in colorectal carcinomas and adenomas. Formalin-fixed and paraffin-embedded archival tissue samples were used for DNA extraction. One hundred and six colorectal carcinomas and 62 adenomas were screened by nested polymerase chain reaction (PCR) for HPV DNA with a control group of 49 cervical tissues with invasive cervical carcinoma and cervical intraepithelial neoplasia (CIN). In the study group, we did not find HPV DNA positivity in any of all the colorectal carcinomas and adenomas. In the control group with cervical lesions, 34 out of 49 (69.4%) samples were positive for the HPV DNA. These results indicated that there was no correlation between HPV infection and colorectal carcinomas and adenomas.

Role of human papillomavirus in the development of urothelial carcinoma.

It has been estimated that almost 10% of the worldwide cancer burden is linked to human papillomavirus (HPV) infection. Although the association between HPV and bladder carcinoma has been extensively investigated, data on the role of HPV in bladder carcinogenesis are controversial. The aim of the study was to assess the possible role of human papillomavirus in the development of urothelial bladder carcinomas. Formalin-fixed and paraffin-embedded archival tissue samples were used for DNA extraction. Seventy urothelial bladder carcinoma tissues were screened by nested-polymerase chain reaction (PCR) for HPV DNA with a control group of total 18 cervical tissues with invasive cervical carcinoma and cervical intraepithelial neoplasia III (CIN III). In the study group, we did not find HPV DNA positivity in any of the urothelial carcinomas. In the control group, 15 out of 18 (83.3%) samples were positive for the HPV DNA. These results indicated that there was no association between HPV infection and urothelial carcinomas.

The effect of tumor size on overall survival in patients with pT3 gastric cancer: experiences from 3 centers.

BACKGROUND: Although a number of studies have investigated whether tumor diameter is a prognostic factor in gastric cancer, no consensus was reached on its clinical importance. In this study, we aimed to determine the effect of tumor size on survival in patients with pT3 gastric cancer. PATIENTS AND METHODS: A total of 232 patients with pT3 gastric cancer, who underwent curative gastrectomy with D2 lymph node dissection, were retrospectively analyzed. Receiver operating characteristics analysis showed that the cutoff value for tumor size was 8 cm. On the basis of this cutoff point, patients were divided into 2 groups: small-size tumors (SST, ≤8 cm) and large-size tumors (LST, >8 cm). The prognostic significance of tumor size and the relationship between tumor size and other prognostic factors were evaluated. RESULTS: LST was detected in 44% of patients. Resection type, tumor site, lymph node metastasis, tumor differentiation, lymphatic vessel invasion, and blood vessel invasion were correlated with tumor size. The median survival of patients with SST was significantly better than that of patients with LST (107 vs. 18.2 months; p < 0.001). Multivariate analysis indicated that tumor size was an independent prognostic factor (p = 0.001; hazard ratio (HR): 0.43) as were resection type and blood vessel invasion. CONCLUSIONS: Our results show that tumor size is an important prognostic indicator in patients with pT3 gastric cancer, who underwent curative gastrectomy, and that the rate of LST increased with aggressiveness and stage of disease. Tumor size may be a useful and reliable prognostic factor for detection and staging in patients with gastric cancer, who have a poor prognosis after curative resection.

Factors that Affect Patients' Decision-Making about Mastectomy or Breast Conserving Surgery, and the Psychological Effect of this Choice on Breast Cancer Patients.

BACKGROUND: Breast cancer is the most common cancer in women. Primary treatment is surgery, with breast conserving surgery (BCS) being widely used for early-stage disease. Due to changes in body image, depressive symptoms can occur after surgery. Here, we evaluate factors that affect patients' decision on surgery, and investigate differences in the level of depression after mastectomy or BCS in a population of Turkish patients. PATIENTS AND METHODS: One hundred breast cancer patients who had undergone mastectomy or BCS and were followed up at our institution between 2007 and 2008 were included. Patients were questioned about their involvement in surgical decision-making. Depression was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) criteria via a Structural Clinical Interview for DSM (SCID). Severity of depression was evaluated by using the Beck Depression Inventory (BDI). RESULTS: Patients who were older than 50 years, had more than 1 child, a history of lactation, and a positive family history of breast cancer mostly preferred mastectomy. However, patients who sought a second opinion and further information on BCS preferred BCS (p < 0.005). There was no statistical correlation between marital status, first childbearing age, and educational status and the decision on surgery type (p > 0.005). Mastectomy patients were prone to depression, but this was not statistically significant (p = 0.099). CONCLUSION: Age, parenthood, lactation, and positive familial history, as well as thorough information about the type of surgery were important factors for the patients' decision. After breast cancer surgery, patients might experience depression affecting treatment and quality of life. Therefore, adequate information and communication are essential.

Does the metastatic lymph node ratio influence the disease-free survival of patients with breast cancer: single-center experiences.

BACKGROUND: Axillary lymph nodes (ALNs) are the most important prognostic factor for survival in breast cancer. Pathological evaluation can affect the number of involved lymph nodes. In the current study, we evaluated whether the metastatic lymph node ratio (n ratio) is important in predicting disease-free survival (DFS) for breast cancer patients. MATERIAL AND METHODS: From 802 breast cancer cases, 427 patients with ALN metastasis were analyzed retrospectively. The n ratio was categorized as n ratio 1 (1-10%), n ratio 2 (10.01-50%) and n ratio 3 (>50%). DFS was established according to the Kaplan-Meier method. Predicting risk factors for relapse were analyzed using the Cox proportional hazards model. RESULTS: The n ratio was significantly higher in breast cancer patients with advanced pathologic pT, pN and clinical stage, undifferentiated histology, lymphovascular and extracapsular invasion, more resected ALNs and positive progesterone receptor. In the univariate analysis, multicentricity, necrosis, grade, pN stage, estrogen receptor and progesterone receptor positivity, trastuzumab and neoadjuvant chemotherapy usage, the presence of inflammatory breast cancer and n ratio were found to be important factors in predicting DFS. Multivariate analysis indicated that multicentricity, neoadjuvant chemotherapy, trastuzumab usage and n ratio were significantly associated with prognosis. CONCLUSIONS: The n ratio is inexpensive, easily available and a simple prognostic factor for breast cancer patients with positive ALNs.

Is metastatic lymph node ratio superior to the number of metastatic lymph nodes to assess outcome and survival of gastric cancer?

BACKGROUND: The aim of this study was to determine the prognostic value of metastatic lymph node ratio (n ratio). PATIENTS AND METHODS: We retrospectively analyzed 202 patients who had undergone curative gastrectomy. The prognostic factors including UICC/AJCC TNM classification and n ratio were evaluated by univariate and multivariate analysis. RESULTS: The n ratio was significantly higher in patients with gastric tumors with undifferentiated histology, greater size, lymphatic vessel, blood vessel and perineural invasion (PNI), and advanced stage. Multivariate analysis indicated that n ratio and pN classification were independent prognostic factors, as were age, tumor size, Borrmann classification, PNI, and tumor differentiation. The receiver operating characteristics (ROC) analysis showed that the sensitivity and the specificity of the presence of lymph node metastasis with 16 lymph nodes resected - which was required to assess the presence of lymph node involvement - were 67.1 and 66.6%, respectively. Three-year overall survival (OS) rates and the median OS time were lower in patients with <16 lymph nodes resected compared to the patients who had >16 lymph nodes resected (p = 0.04). CONCLUSIONS: Our results showed that n ratio and pN classification were independent prognostic indicators for OS of patients with radically resected gastric cancer, but the superiority of n ratio to pN stage could not be proved.

Prognostic significance of perineural invasion in patients with gastric cancer who underwent curative resection.

BACKGROUND: The prognostic significance of perineural invasion (PNI) in gastric cancer has been previously investigated in a few studies, but had not reached a consensus. The aim of this study was to determine the prognostic value of PNI in patients with gastric cancer who underwent curative resection. MATERIALS AND METHODS: We retrospectively analyzed 238 patients who had undergone curative gastrectomy. Paraffin sections of surgical specimens from all patients were stained with hematoxylin and eosin. PNI was defined when carcinoma cells infiltrated into the perineurium or neural fascicles. PNI and the other prognostic factors were evaluated by univariate and multivariate analysis. RESULTS: PNI was detected as positive in 180 of the 238 patients (75.6%). pT stage, tumor size, lymph node metastasis, clinical stage, tumor differentiation, Borrmann classification, histological type, lymphatic vessel invasion, and blood vessel invasion were closely associated with the presence of PNI. The PNI-positive tumors had significantly larger size and more lymph node metastasis than the PNI-negative tumors (P = .001 and P < .001, respectively). The median survival of the PNI-positive patients was significantly worse than that of the PNI-negative patients (28.1 vs. 64.9 months, P = .001). Multivariate analysis indicated that the positivity of PNI was an independent prognostic factor (P = .02, hazard ratio [HR]: 2.75; 95% confidence interval [95% CI]:1.12-3.13) as were classical clinicopathological features. CONCLUSION: Our results showed that the frequency of PNI was high in patients with gastric cancer who underwent curative gastrectomy and the proportion of PNI positivity increased with progression and clinical stage of disease. PNI may be useful in detecting patients who had poor prognosis after curative resection in gastric cancer.

Clinical value of FDG PET/CT in the diagnosis of suspected recurrent ovarian cancer: is there an impact of FDG PET/CT on patient management?

PURPOSE: The aim of this study was to evaluate the clinical value of FDG PET/CT in patients with suspected ovarian cancer recurrence as compared with diagnostic CT, and to assess the impact of the results of FDG PET/CT on treatment planning. METHODS: Included in this retrospective study were 60 patients with suspected recurrent ovarian cancer who had previously undergone primary debulking surgery and had been treated with adjuvant chemotherapy. Diagnostic CT and FDG PET/CT imaging were performed for all patients as clinically indicated. The changes in the clinical management of patients according to the results of FDG PET/CT were also analysed. RESULTS: FDG PET/CT was performed in 21 patients with a previously negative or indeterminate diagnostic CT scan, but an elevated CA-125 level, and provided a sensitivity of 95% in the detection of recurrent disease. FDG PET/CT revealed recurrent disease in 19 patients. In 17 of 60 patients, the indication for FDG PET/CT was an elevated CA-125 level and an abnormal diagnostic CT scan to localize accurately the extent of disease. FDG PET/CT scans correctly identified recurrent disease in 16 of the 17 patients, a sensitivity of 94.1%. Moreover, FDG PET/CT was performed in 18 patients with clinical symptoms of ovarian cancer recurrence, an abnormal diagnostic CT scan, but a normal CA-125 level. In this setting, FDG PET/CT correctly confirmed recurrent disease in seven patients providing a sensitivity of 100% in determining recurrence. In four patients, FDG PET/CT was carried out for the assessment of treatment response. Three of four scans were classified as true-negative indicating a complete response. In the other patient, FDG PET/CT identified progression of disease. In total, 45 (75%) of the 60 patients had recurrent disease, in 14 (31.1%) documented by histopathology and in 31 (68.9%) on clinical follow-up, while 15 (25%) had no evidence of recurrent disease. The overall sensitivity, specificity, accuracy, and positive and negative predictive value of FDG PET/CT were significantly superior to those of diagnostic CT (95.5% vs. 55.5%, 93.3% vs. 66.6%, 95% vs. 58.3%, 97.7% vs. 83.3%, 87.7% vs. 33.3%, respectively; p = 0.02) in the detection of recurrent ovarian cancer. FDG PET/CT changed the management in 31 patients (51.6%). It led to the use of previously unplanned treatment procedures in 19 patients (61.2%) and the avoidance of previously planned therapeutic procedures in 12 patients (38.8%). CONCLUSION: Our results confirm that FDG PET/CT is a superior posttherapy surveillance modality for the detection of recurrent ovarian cancer than diagnostic CT imaging. Furthermore, integrated FDG PET/CT was useful specifically in optimizing the treatment plan and it might play an important role in treatment stratification in the future.

Determining of metastatic lymph node ratio in patients who underwent D2 dissection for gastric cancer.

The purpose of this study was to determine outcome of the ratio of metastatic lymph nodes to the total number of dissected lymph nodes (MLR) in patients with gastric cancer. We retrospectively analyzed 111 patients who underwent D(2) lymph node dissection. The prognostic factors including UICC/AJCC TNM classification and MLR were evaluated by univariate and multivariate analysis. The MLR was significantly higher in patients with a larger tumor, lymphatic vessel invasion, blood vessel invasion and perineural invasion, and advanced stage. Moreover, the MLR was significantly associated with the depth of invasion and the number of lymph node metastasis. The univariate analysis revealed for overall survival (OS) that stage of disease, lymphatic vessel invasion, blood vessel invasion, perineural invasion, lymph node metastasis (UICC/AJCC pN stage) and MLR were relevant prognostic indicators. Furthermore, both UICC/AJCC pN stage and MLR were detected as prognostic factor by multivariate analysis, as was perineural invasion. Our results indicated that MLR and UICC/AJCC pN staging system were important prognostic factors for OS of patients with D(2) lymph node dissection in gastric cancer in a multivariate analysis. MLR may be useful for evaluating the status of lymph node metastasis in gastric cancer.

The association of serum adiponectin levels with histopathological variables in gastric cancer patients.

Adiponectin is a peptide hormone secreted from the adipose tissue, affecting the proliferation and insulin sensitivity in different cell types. The levels of adiponectin have been found to be decreased in hyperinsulinemia and insulin resistant states, such as obesity. The previous studies have suggested that plasma adiponectin levels are decreased in patients with endometrial and breast cancer. In our study, the relationship among serum adiponectin levels, demographic features and histopathological variables was evaluated in gastric cancer patients. Forty consecutive patients with gastric cancer who underwent gastrectomy with standard lymph node dissection were included and 43 healthy controls were included in this study. The serum levels of glucose, insulin, C-peptide, HbA1c and adiponectin were measured in both groups. We analyzed the correlation among these parameters and patients' demographic features, such as age, gender, body mass index (BMI) and histopathological variables such as tumor localization, stage, nodal status, histological grade, vascular and lymphatic invasion. The mean age was 60.05+9.72 in patients, while it was 38.6+12.73 in controls. The mean serum adiponectin levels were 12.62+7.9 and 10.07+6.72 ng/ml, respectively, in groups. There was no different in terms of adiponectin, C-peptide, HOMA-R level in both groups. On the other hand, BMI, glucose and insulin levels were significantly different in gastric cancer patients in comparison with the controls. There was no correlation among the levels of adiponectin, BMI, insulin and c-peptide levels in patient group (P>0.05). The adiponectin levels of woman were significantly lower than male patients (P=0.002). No relations were detected among tumor stage, tumor localization, nodal status, lymphatic and vascular invasion, and the levels of serum adiponectin (P>0.05). Interestingly, a positive correlation was found between tumor grade and plasma adiponectin levels (r=0.372; P=0.018). Our results suggest that plasma adiponectin levels were similar in both patients with gastric cancer and the controls. In addition, no correlation was found between adiponectin levels and demographic features and histopathological variables of patients. But, in undifferentiated tumors, plasma adiponectin level was significantly higher than well-differentiated grade tumors.

Preoperative serum leptin levels in patients with breast cancer.

Leptin is an adipocyte-derived protein and plays an important role in the control of body weight by acting as a neurohormone regulating energy balance and food intake in the hypothalamus. The high serum leptin levels and the overexpression of leptin receptors have been documented in breast cancer patients, but the levels never checked preoperatively. In the present study, the relationship between preoperative serum leptin levels of the breast cancer patients and the healthy controls were evaluated. The serum leptin levels in 30 breast cancer patients were compared to 30 healthy female volunteers. In addition, the association of serum leptin levels and the various well-known risk factors were studied. Serum leptin levels of patients with breast cancer (28.55 + 19.7 ng/ml) were tended to be higher than those of controls (26.43 + 19.4 ng/ml), but it did not reach statistical difference (P = 0.712). There was significant correlation between the expression of ER, PR, and serum leptin levels (P = 0.018 and 0.037, respectively), but not with the HER-2/neu receptor expression (P = 0.067). Also association was not found between the tumor size, lymph node involvement, and the levels of serum leptin (P = 0.235, 0.34, and 0.86, respectively). The serum leptin level was also found to be similar in premenopausal (24.85 +/- 18.14 ng/ml) and postmenopausal (30.49 +/- 17.19 ng/ml) patients (P = 0.235). The preoperative serum leptin levels in breast cancer patients were similar to healthy controls. In subset analysis, the significant correlation between the leptin level and hormonal status was noted, but association with HER-2/neu was not detected. These findings should be confirmed with larger studies.

5-Fluorouracil induces arterial vasoconstrictions but does not increase angiotensin II levels.

Because the mechanisms of 5-Fluorouracil (5-FU) cardiotoxicity have not yet been completely identified, prophylactic options are not available. To our knowledge, there are no published data investigating the use of angiotensin converting enzyme (ACE) inhibitors for 5-Fluorouracil-associated cardiotoxicity. In this study, we aimed to evaluate the influence of 5-FU administration on the diameter of the brachial artery and the levels of angiotensin II. The patients were administered bolus 5-FU/leucovorin in the study group. Angiotensin II and troponin T assays, complete blood cell counts, hepatic and renal function tests were analyzed in five consecutive blood samples in the initiation, just after termination, and on 24, 48, and 72 h after termination of the regimen. Pre- and post-treatment angiotensin II and troponin T assays, complete blood cell counts, hepatic and renal function tests were also analyzed in the control group. Brachial arterial diameters were measured and recorded in all patients before and after the treatment. A total of 59 patients were included in this study. Thirty one out of 59 patients (52.5%) were in the 5-FU study group and the remaining 28 patients (47.5%) were in the control group. Basal and post-treatment brachial artery diameters in the 5-FU study group were 0.436 +/- 0.51 and 0.423 +/- 0.50 cm, respectively (P = 0.001). The corresponding values in the controls were 0.3954 +/- 0.50 and 0.3957 +/- 0.49 cm, basal and post-treatment, respectively (P = 0.979). Angiotensin II levels were not changed significantly at serial measurements (P = 0.496). Moreover, the corresponding measurements were not statistically different in both two groups treated with and without 5-FU (P = 0.372). The pathophysiology of 5-FU-induced cardiac toxicity has not yet been elucidated. In the present study, 5-FU-associated vasoconstriction was not dependent on angiotensin II levels, thus we suggest that the prophylactic administration of ACE inhibitors cannot prevent cardiotoxicity in these patients. The underlying mechanisms of cardiotoxicity related to 5-FU might be multifactorial; nevertheless, further prospective investigation for the toxic effects of fluoropyrimidines on the coronary endothelium and myocardium are needed.

Neoadjuvant chemotherapy for locally advanced breast cancer: a single center experience.

Neoadjuvant chemotherapy (NAC) is one of the treatment options for patients with locally advanced breast cancer (LABC). Preoperative chemotherapy potentially may reduce the extent of the surgery and offers the opportunity to assess the chemosensitivity of the tumor in vivo. Herein, we evaluated the results of NAC in Turkish LABC patients. We retrospectively analyzed 73 LABC patients. Anthracycline/taxane-based chemotherapy regimens were administered. Patients were stratified according to age, menopausal status, type of surgery, response to the treatment, histopathological properties, and survival. After 3-6 cycles of chemotherapy, patients were re-staged radiologically and surgery was performed in operable patients. Adjuvant chemotherapy was administered as needed. The median age was 45 (29-93) at the time of diagnosis. Sixteen percentage of patients were younger than 35 years of age and 45.2% were premenopausal. Median follow-up time was 20.2 months. Sixty-seven out of 73 patients responded to therapy (89%). Breast conserving surgery was possible in the 15% of the patients. In histopathological analysis, lymph node invasion was detected in 85%. The estrogen (ER) and progesterone (PR) receptor were positive in 78.1% and c-erb-B2 was positive in 17.5% of patients. The median disease-free survival (DFS) was 44 months (SE: 9; %95 CI: 27.1-60.8), overall survival (OS) was not reached at the time of analysis. Three-year DFS and OS were 58% and 91.9%, respectively. In a multivariate Cox regression analyses; no demographic or pathologic prognostic parameter predicted overall survival. In recent years, NAC in breast cancer has become a viable treatment option for patients with LABC. NAC is not commonly applied in Turkey. The response rate to NAC in Turkish breast cancer patients is encouragingly high. Broader efforts should be made to evaluate breast cancer patients preoperatively at tumor boards for proper treatment sequence.