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Aim: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment. Method: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. Findings: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3–4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%). Discussion: The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC. © 2021 Taylor & Francis Group, LLC.

Introduction To investigate the level of psychological resilience and the impact of attachment styles on the degree of resilience to distress in patients with cancer receiving chemotherapy. Methods Patients with cancer receiving chemotherapy were included in the study. Participants were requested to complete the Relationship Scales Questionnaire (RSQ), Resilience Scale for Adults (RSA), and a personal information form during the data collection phase. One-way analysis of variance (ANOVA) was used to compare that parameter among the attachment styles. Logistic regression analysis was carried out to identify independent factors affecting resilience. Results A total of 384 individuals were included in this study (mean age 53.5 ± 12.1, 27.1 % male). The RSQ results showed that the attachment styles of 190 (49.5%) participants were secure, whereas 194 (50.5%) subjects had an insecure attachment. The median RSA score of participants with a secure attachment was significantly higher than that of patients with insecure attachment (133.15 ± 16.6 vs. 127.0 ± 20.0, p=0.001). Patients with the RSA score of >130 were more educated, were in better economic condition, had better perceived social support, and had a higher frequency of secure attachment than those defined as low resilient. Logistic regression analysis revealed that poor and medium perceived social support and insecure attachment style independently predicted low resilience (RSA≤130). Conclusion This study demonstrates that the secure attachment style in patients with cancer improves stress resilience as compared to the insecure attachment style. Our findings also show that insufficient perceived social support is likely a negative factor in resilience.

Background Cancer is considered a traumatic event that can lead to post-traumatic stress disorder. Significant changes are taking place in the life, body image, lifestyle and social life of the individual diagnosed with cancer. Therefore, they are faced with a psychological and physiological difficult process. In the researches, it was found that the attachment styles that individuals will experience in their lifelong relationships are one of the important predictors of psychological resilience. The aim of our study is to examine the relationship between psychological resilience and adult attachment styles among cancer patient individuals receiving chemotherapy. Methods A total of 391 volunteer patients receiving chemotherapy were included from Dr. A.Y. Ankara Oncology Research and Training Hospital and Ankara Guven Hospital in the study. The inventories used in the data collection phase of the study are Relationship Scales Questionnaire, Resilience Scale for Adults and a personal information form that is produced by researcher. Datasare analyzed with SPSS 23.00. Results In our results, 285 (73%) of the patients were female and the median age was 53 (20-83). The median endurance score was 130 (49-165). The patients were divided into median values to be less resistant and resistant. The age, gender, marital status, working status, educational status, economic status, who they experienced, who they grew up with, their social support, trust in chemotherapy and dominant attachment styles were compared with univariate analysis. there were four style of attachments; secure, avoidant, fearful, preoccupied. Secure attachment was at half of patients (n = 191,48.8%) while avoidant attachment was at 159 (40.6%) patients. The other attachment styles were seen significantly less. As a result of multivariate analysis, the patient’s social support is moderate or bad; lack of confidence in chemotherapy, the presence of avoidant or fearful attachment was found to be independent negative factors affecting the resilience of the patient. Conclusions Avoidant and fearful attachment have a significant negative impact on the resilience of the patients receiving chemotherapy. Legal entity responsible for the study Fatma Bugdayci Basal. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

This study aimed to reveal the habits of using internet by cancer patients and their relatives to access health-related information and services in Turkey.An 18-item questionnaire survey was applied in cancer patients and their relatives.A total of 1106 patients (male, 37.3%, and female, 62.7%) and their relatives were included in the study. The responders had been using internet to obtain health information about oncological diseases, once a month (34.2%), 1-2 times a week (27.4%) or 2-3 times a month (21.9%). After diagnosis of cancer was made, participants more frequently (64.4%) investigated health-related issues, while 64.9% of them considered internet as an important search tool, and 16.7% of them had thought to give up cancer therapy under the influence of internet information. Some (33.1%) participants had used herbal medicine, and 16.7% of them had learnt these herbal products from internet. Still 12.7% of them had not questioned the accuracy of internet information, while 26.9% of them indicated that they had not shared the internet information about cancer with their physicians, and 13 % of them searched information in internet without asking their physicians.Cancer patients and their relatives showed a higher tendency to use health-related internet information which may mislead them, and can result in treatment incompliance. Health professionals should offer evidence-based information to the patients and their relatives through internet.

Trastuzumab is known to be effective for early and advanced stages of breast cancer but optimal duration for early-stage breast cancer (EBC) is not well known. We evaluated the efficacy and toxicity of 9- and 52-week trastuzumab therapy for EBC retrospectively.In this multicenter study, the medical records of all patients with EBC were analyzed in 8 centers retrospectively. Totally consecutive, 479 female patients who received trastuzumab in the adjuvant treatment were evaluated for disease-free survival (DFS), overall survival (OS), efficacy, and toxicity.There were 181 (37.8 %) and 298 (62.2 %) patients in the 9- and 52-week trastuzumab groups, respectively. Median follow-up was 30.6 months (5.7-68.9) in the 9-week trastuzumab group and 29.3 months (5.9-59.6) in the 52-week trastuzumab group. Thirty-six month DFS was 90 and 85 % (P = 0.132) in the 9- and 52-week trastuzumab treatment groups, respectively, and 36-month OS was 96 and 97 % in the 9- and 52-week trastuzumab groups, respectively (P = 0.779). Symptomatic cardiotoxicity was observed in 1 (0.6 %) patient in the 9-week trastuzumab group and in 4 (1.3 %) patients in the 52-week trastuzumab group.In this study, similar outcomes were found in the 9- and 52-week trastuzumab treatment groups.

Background Lymphangiogenesis and angiogenesis are critical processes for tumor growth, invasion, and metastasis, and are crucial for therapeutic strategies. The aim of the present study was to evaluate the clinical significance of lymphangiogenesis and its regulation in gastric carcinomas. Methods The lymphatic vessel density (LVD) in 65 gastric carcinoma cases was investigated by immunohistochemistry using D2-40 antibody, and evaluated with prognostic parameters. The intratumoral microvessel density (MVD), using CD31 antibody, was assessed and correlated with LVD. Results D2-40 identified peritumoral lymphatics in all cases, and lymphatic vessel density (LVD) ranged from 3 to 19 (median, 5; mean ± SD, 7.69 ± 4.67). The peritumoral LVD significantly correlated with large tumor size ( P = 0.0001), lymph node metastasis ( P = 0.004), visceral organ metastasis ( P = 0.0001), and TNM stage ( P = 0.001). Survival was also significantly lower in patients with high LVD tumors than in patients with low LVD tumors ( P = 0.04). Among various clinicopathologic characteristics, CD31 expression was associated only with lymph node metastasis ( P = 0.001). However, there was no significant correlation between CD31 and D2-40. Conclusion Our study showed that lymphangiogenesis plays an important role in the progression of gastric carcinoma. Therefore, D2-40, as an indicator for tumor lymphangiogenesis, may serve as a prognostic marker in gastric carcinoma.

Bevacizumab-based chemotherapy has become the standard of care in metastatic colorectal cancer (MCRC). We aimed to measure the levels of serum soluble FAS, FASL, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and its death receptors DR4 and DR5 in MCRC patients and to define prognostic significance of these parameters in response to bevacizumab in these patients.The levels of these parameters in serum samples were quantified by a commercially available ELISA kit in 31 MCRC patients before and after 2 cycles of therapy and 25 healthy controls.Pretreatment sFAS levels in MCRC patients was significantly lower than the levels of controls (p = 0.043). There was no significant difference in sFAS and sFASL levels in MCRC patients before and after bevacizumab-based treatment. There was no significant difference in sFAS/sFASL ratio in MCRC patients before and after treatment and controls. Soluble DR5 levels were significantly higher in pretreatment serum samples compared with controls (p = 0.008). However, pretreatment sTRAIL and sDR4 levels were similar to the levels of controls. There was no significant difference in sTRAIL, sDR4, and sDR5 levels in MCRC patients before and after treatment. When patients were grouped according to treatment response (responders vs. non-responders), post-treatment sFAS/sFASL ratio was significantly lower in responding patients compared with non-responders (p = 0.029). Significant correlations were observed between post-treatment sFASL and sDR4, sFAS and sTRAIL, sTRAIL and sFAS/sFASL ratio, and sFASL and sDR5.Non-significant changes in apoptotic markers with bevacizumab-based chemotherapy showed that they have no prognostic significance in MCRC patients. Significant change in sFAS/sFASL ratio according to treatment response could be an indicator of chemosensitivity.

Diet and lifestyle related to socioeconomic status emerged as risk factors for gastric cancer in several studies. However, the results were not always consistent with the socioeconomic status. The aim of this study was to evaluate the risk factors independent from education as a measure of socioeconomic status. Two hundred and fifty-three patients with gastric cancer diagnosed in 2005 and equal number of control subjects were interviewed for several characteristics and diet. Matching was done for age, gender, city of residence and also for the level of education. Despite these matching preferences, patients had significantly lower income when compared to the control subjects (P = 0.0001). Higher rate of patients were smoking more than 2 packs/day of cigarettes (P = 0.018). Also significantly higher rate of control subjects were using antibiotics (P = 0.002). Coffee (P < 0.0001), salad (P = 0.006), bread (P = 0.005), vegetable-derived cooking oil (P = 0.003) consumptions appeared as highly protective factors against gastric cancer in univariate analysis in the present trial. In multivariate analysis, significant risk reducing factors were bread (P = 0.005) and coffee consumption (P = 0.0001) other than the level income (P = 0.002). In conclusion, the goal of obtaining comparable socioeconomic status by including the level of education in the matching criteria was not met in our study because of the difference in income level. The only risk reducing factor that was not in accordance with income level was the unexpectedly higher rate of bread consumption in control group.

ABS TRACT Objective: Hormone receptor (HR) and Her2/neu expressions may change following neoadjuvant chemotherapy. The clinical significance of this receptor alteration is unclear. We retrospectively investigated the frequency of HR and Her2/neu status change in response to neoadjuvant chemotherapy. Material and Methods: Medical records of 49 patients with locally advanced breast cancer treated with anthracyclineand/or taxane-based neoadjuvant chemotherapy were retrospectively evaluated. The median age at diagnosis was 53 years (range, 27-79). All patients were operated within 3-4 weeks of the last cycle of chemotherapy. We also analyzed the relation of tumor marker alterations with patient outcome. Results: Alterations in hormonal receptor and Her2/neu protein expression were observed in 16 (32.6%) of the 49 patients. There was no statistically significant difference in HR expressions before and after neoadjuvant chemotherapy (p=NS). In addition, two (4%) patients with positive Her2/neu became Her2/neu negative after neoadjuvant chemotherapy. Twelve (24%) patients with negative estrogen and progesteron receptor expressions were converted to positive after neoadjuvant chemotherapy. There was no effect of HR alterations on patient outcome. Conclusion: HR and Her2/neu expression alterations are not infrequent in response to neoadjuvant chemotherapy. Tumor marker status determination in the final surgical specimen is recommended.

Aims To evaluate preoperative concomitant chemoradiation using cisplatin plus docetaxel followed by consolidation chemotherapy in patients with unresectable locally advanced non-small cell lung cancer (NSCLC). Patients and methods Medical records of patients with locally advanced unresectable NSCLC (stage IIIA and IIIB) treated with concomitant chemoradiotherapy using cisplatin + docetaxel combination followed by consolidation chemotherapy were retrospectively evaluated. All the patients were consecutively treated. Chemotherapy consisted of weekly cisplatin 20 mg/m(2) and docetaxel 20 mg/m 2 during radiotherapy. Radiotherapy dose was 58-66 Gy given in 2 Gy fractions, 5 days per week. The patients were subsequently referred to surgery if adequately downstaged. Consolidation chemotherapy using cisplatin and docetaxel both at doses 75 mg/m2 every 3 weeks followed local therapy in all patients. Results A total of 54 patients were evaluated (49 males, 5 females with a median age of 58 years; 41 [75.9%] stage IIIB and 13 [24.1%] IIIA). Twelve patients (22.2%) achieved pathologic complete response and 20 (37%) partial response. Downstaging was possible in 32 patients (59.3%). Twenty-six patients (48.1%) were operated after concomitant chemoradiotherapy (pneumonectomy [n = 2], lobectomy [n = 12], and wedge resection [n = 12]). Toxicity was tolerable. Median progression-free survival and overall survival (OS) for the entire cohort were 14 and 22 months, respectively. In resected patients (n = 26), median PFS and OS have not been reached with a median follow-up duration of 24 months. Conclusion Preoperative concomitant chemoradiation using weekly cisplatin and docetaxel followed by surgery and consolidation chemotherapy is effective and well tolerated in patients with unresectable locally advanced NSCLC.

Cyclooxygenase-2 (COX-2) is upregulated in gastric carcinoma, and its increased levels were found to have a prognostic significance in some studies. Both angiogenesis and Helicobacter pylori infection have been reported to be associated with COX-2 expression of gastric cancer in recent studies. In this study, COX-2 expression and its association with CD31 staining, H.-pylori infection, and well-known clinicopathological factors were investigated in 65 gastric cancer patients. COX-2 and CD31 expression assessment was done by immunohistochemical methods. Whartin Starry stain was performed for H.-pylori infection. Of 65 patients, 32 (49%) revealed intense COX-2 immunostaining. Among various clinicopathologic characteristics, COX-2 expression was inversely correlated with tumor size, TNM stage, and lymph node status. Thirty-two (49%) patients revealed intense CD31 immunostaining. Among various clinicopathologic characteristics, CD31 expression was associated only with lymph node metastasis. COX-2 expression was not correlated with CD31 staining and H.-pylori infection. Both COX-2 and CD31 staining had no prognostic significance. In conclusion, we found that COX-2 expression was significantly higher in earlier stages of gastric cancer. It can be suggested that COX-2 expression may be important in the initial development of gastric cancer but not in progression of the disease. Other factors which may be associated with COX-2 in gastric cancer, including angiogenesis and H.-pylori infection, should be investigated in further studies.

YKL-40 is a growth factor for connective tissue cells; it also stimulates the migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum levels have been associated with poorer prognosis in metastatic breast cancer. In the present study we evaluated the prognostic role of serum YKL-40 levels in patients with locally advanced breast cancer.YKL-40 levels were measured using ELISA in serum samples obtained from 45 breast cancer patients prior to surgery and chemotherapy. The median follow-up time was 46 months (range, 10-96 months). All patients underwent surgery after chemotherapy. During the follow-up period, 21 patients relapsed and there were 17 deaths.The median serum YKL-40 concentration in patients with locally advanced breast cancer was 149.5 mug/l (range, 25.0-1021.3 microg/l). This was higher than levels observed in healthy female controls but the difference was not significant (P=0.44). Serum YKL-40 levels were also higher in patients with tumour size2 cm and node-positive disease but again the differences were not significant (P0.05). Tumour volume was correlated with serum YKL-40 levels (r=0.308, P=0.039). High serum YKL-40 levels were associated with shorter disease-free and overall survival although this trend failed to reach significance (P0.05). Multivariate analysis including tumour size, lymph node status, oestrogen and progesterone receptor status, tumour grade, and serum YKL-40 levels indicated that serum YKL-40 levels were an independent prognostic variable for overall survival (hazard ratio, 1.004; 95% confidence intervals: 1.00, 1.07; P=0.027). Tumour size, lymph node status and oestrogen receptor status were also independent prognostic variables for overall survival (P0.05).Our results show that serum levels of the growth factor YKL-40 may be a useful prognostic indicator of outcome for patients with locally advanced breast cancer. Further studies are required to fully elucidate the biological function of YKL-40 in breast cancer.

The aim of this study was to determine the ultrastructural effects of doxorubicin (Adriblastina; Pharmacia and Upjohn, Milan, Italy), paclitaxel (Taxol; BMS, Princeton, NJ), Cremophor EL (a diluent of paclitaxel) and doxorubicin/paclitaxel combinations on normal lung tissues.In the experimental protocol, 50 Wistar albino rats were used, divided into five different groups: the control group (n=10), the doxorubicin group (1 mg/kg) (n=10), the paclitaxel group (2 mg/kg) (n=10), the Cremophor EL group (150 mg/kg) (n=10) and the paclitaxel/doxorubicin group (2 mg/kg+ 1 mg/kg) (n=10). The drugs were administered weekly to rats via intraperitoneal injections for 14 weeks. After 3 weeks of observation, the rats were killed with thiopental sodium (30 mg/kg) and their left median lung tissues were removed and examined with a Carl Zeiss EM 900 transmission electron microscope.Our experiments showed doxorubicin to cause an increase in collagen fibre content of the alveolar wall, and paclitaxel to cause degenerations in cellular organelles. In the group in which the two agents were administered together, both effects were observed, although the effects of paclitaxel were seen to be dominant. Ultrastructural appearance was similar in the Cremophor EL group compared to the control group.It was detected that doxorubicin and paclitaxel caused ultrastructural degenerations in normal lung tissues and Cremophor EL seemed to be unaccountable for these degenerations.

The aim of the study was to evaluate the toxicity and efficacy of 62 patients with locally advanced nasopharyngeal carcinoma (NPC) (stage III, IVA, IVB) treated by three different modalities. Cisplatin was given weekly 35 mg/m(2)/day or every 3 weeks 100 mg/m(2)/day during radiotherapy (RT) in all patients. Patients were classified into following three groups: The patients in the group 1 (n = 23) were treated only with concurrent chemoradiotherapy (CCRT). In the group 2 (n = 15), before the CCRT, neoadjuvant chemotherapy, consisting of intravenous cisplatin and docetaxel on day 1, every 3 weeks treatment cycles was administered. In the group 3 (n = 24), adjuvant chemotherapy, consisting of cisplatin on day 1 and 5-flourouracil on day 1 to 5 every 3 weeks was used after CCRT. Three arms were treated with the same RT technique and dose. There was no difference for age, sex, and stage among the groups. Radiotherapy was administered in planned dose for all patients. A total of 82% patients completed planned chemotherapy concurrent with RT. The treatment related adverse effects were mild or moderate in intensity. There was no statistical difference between the groups regarding the treatment responses. Complete response rate of RT was 73.9%, 86.7%, and 87.5%, respectively. Median progression free survival (PFS) and overall survival (OS) were 13, 12, 9 months and 22, 20, 15 months for groups 1, 2, 3, respectively. No difference was observed in median OS and PFS among three groups. In our study, the efficacy and toxicity of neoadjuvant and/or adjuvant chemotherapy with CCRT and CCRT alone were found similar.

Meeting of the Society-for-Ultrastructural-Pathology/Annual Session of the United-States-and-Canadian-Academy-of-Pathology -- FEB, 2005 -- San Antonio, TX WOS: 000238155000012 PubMed: 16517476 Endothelium is the first physiological barrier between blood and tissues and can be injured by physical or chemical stress, particularly by the drugs used in the cancer therapy. Paclitaxel and doxorubicin are frequently used anticancer drugs and their cardiac side effects are well observed in clinical setting. Their side effects on the endothelium are still not clear enough. There are few investigations assessing the damages elicited by the combination use of chemotherapy agents in animal experimental models. The purpose of this study was to examine and compare the side effects of doxorubicin and paclitaxel on endothelium in vivo. The drugs were administered weekly to rats via intraperitoneal injections singly or in combinations. Lastly, aorta endothelium was examined. The most familiar parts of the aorta endothelium are the nucleus, free ribosomes, Weibel-Palada granules, plasmalemmal vesicles, and clear basement membrane. Examination of the endothelium and the related structures revealed some clear degenerative findings. Notably, administration of a paclitaxel and doxorubicin combinations caused the most dramatic change in ultrastructure, which may disrupt many functions of the endothelium. Soc Ultrastructural Pathol, US Canadian Acad Pathol

A relationship between cyclooxygenase-2 (COX-2) expression and the pathogenesis of colorectal cancer has been reported in recent studies. Moreover, it has been indicated that COX-2 expression may have a prognostic role in colorectal cancer patients. In this study, we investigated the prognostic significance of COX-2 expression in 83 patients with colorectal cancer. COX-2 expression was assessed using immunohistochemical methods and was evaluated by grading both staining intensity and staining extension. The relationships between COX-2 expression and clinicopathological features of the patients and patient survival were evaluated. There was no relationships between COX-2 expression and tumor size (tm < 3cm or tm >= 3cm), tumor histopathological differentiation (poorly differentiated or moderately+well differentiated), number of metastatic lymph nodes (< 4 or >= 4), histopathology of the tumor, localization of the tumor (colon or rectum), distant metastasis, and vascular invasion of the tumor. In the multivariate analysis, COX-2 expression was not found as an independent prognostic factor. We demonstrated that COX-2 expression was not correlated with clinicopathological characteristics of colon carcinoma and disease outcome. (c) 2005 Elsevier GmbH. All rights reserved.

Objective: To present a rare case of breast cancer associated with both inflammatory muscle disease and liver disease as a paraneoplastic syndrome. Clinical Presentation and Intervention: A woman with breast cancer presented with elevated liver enzymes and progressive proximal muscle weakness. Liver biopsy was consistent with hepatitis and muscle biopsy revealed myositis. The start of corticosteroid therapy was followed by relief of the myopathic symptoms and regression of hepatitis histopathologically. Conclusion: A case of polymyositis and hepatitis associated with breast cancer and their flare-up with recurrence of malignancy is presented. In this case, the temporal relation with malignancy following its concurrent remission and relapse suggests a paraneoplastic mechanism.

Background/aim Colorectal cancer is seen mostly among patients older than 50 years of age. An aggressive behavior is a frequently cited as characteristic of colorectal cancer in young patients. The purpose of the present study was to reveal the clinicopathologic characteristics of colorectal cancer among patients under 50 years of age. Methods Two hundred and seventy-one patients with colorectal cancer admitted to our oncology center were evaluated, and clinicopathologic findings of the young and old patients were compared. Patient gender, site distribution, tumor stage classification, lymph node involvement, metastatic site, histologic classification, histologic differentiation, family history of malignant tumors, presenting symptoms and survival rates were compared. Results One hundred patients were 50 years of age or under. Clinical, histopathologic characteristics and overall survival of the two groups did not differ. A higher rate of familial cancer syndromes was detected among young patients. Conclusions The presentation and outcome of the disease in young patients do not differ from those of older patients. A significant family history of colorectal cancer in the young patients showed the need for screening whereas the outcome of metastatic disease was poor. In order to anticipate long survival, early detection and aggressive treatment is necessary.

Background: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal system. The rectum is a rare location for GIST. Prostate adenocarcinoma is the most common malignancy in geriatric men. Rarely, rectal GIST mimics prostate pathologies. Case Report: We describe a 58-year-old male patient who was admitted with signs and symptoms of prostatism. A presumptive diagnosis of primary prostate sarcoma was made based on imaging studies and a trucut biopsy. Removal of the mass compressing both the prostate and the rectum revealed the final diagnosis of synchronous prostate adenocarcinoma and high-grade GIST originating from the rectum. The patient also had a family history of GIST. Conclusion: According to our knowledge, there are 5 more reported cases of rectal GIST, which were misdiagnosed as prostate malignancy. Rectal GIST may simulate prostate carcinoma clinically, and should always be kept in mind in the differential diagnosis of prostate pathologies.

e12007 Background: Breast cancer is the most common cancer among women in Turkey. The risk factors and characteristics of breast cancer patients have not been widely studied in Turkish population. ...

e18535 Background: 18F-FDG-PET is a functional imaging method and widely used for initial diagnosis, staging and response evaluation in the treatment of malignant lymphomas. We evaluated the FDG-PE...

Distribution and prevalence of germline mutations in BRCA1 and BRCA2 differ among different populations. For the Turkish population, several studies have addressed high-risk breast cancer and ovarian cancer (BC-OC) patients. In most studies, both genes were analyzed in part, and a quite heterogeneous mutation spectrum was observed. For high-risk Turkish prostate cancer (PCa) patients, however, there are no data available about mutations of germline BRCA genes. To accurately determine the contribution of germline mutations in BRCA1 and BRCA2 in Turkish BC, OC, and PCa high-risk patients, 106 high-risk BC-OC patients, 50 high-risk PCa patients, and 50 control subjects were recruited. The study represents the only full screening, to date, of a large series of Turkish high-risk BC-OC patients and the only study in Turkish high-risk PCa patients. Mutation screenings were performed on coding exons of both genes with either denaturing gradient gel electrophoresis or denaturing high performance liquid chromatography, or with both techniques. Three deleterious mutations in BRCA1 and three deleterious mutations in BRCA2 were detected in different BC-OC patients, and one truncating mutation was detected in a high-risk PCa patient. In addition, 28 different unclassified and mostly novel variants were detected in both genes, as well as several silent polymorphisms. These findings reflect the genetic heterogeneity of the Turkish population and are relevant to genetic counseling and clinical management. (C) 2010 Elsevier Inc. All rights reserved.

Background. Treatment of patients with metastatic colorectal cancer (MCRC) previously exposed to oxaliplatin-based regimen is challenging. Efficacy and toxicity of bevacizumab plus irinotecan-based regimens were assessed in the second-line treatment of MCRC patients. Patients and Methods: Forty patients with a median age of 53 years (range, 31-75) were retrospectively evaluated. Patients progressing or relapsing after treatment with oxaliplatin-based regimens were given bevacizumab 5 mg/kg every 2 weeks in combination with irinotecan-based regimens. All patients had previously received oxaliplatin either in the adjuvant setting (n = 8) or for metastatic disease (n = 32). Results: Three patients achieved a complete response (7.5%),5 partial responses (12.5%) and 14 (35%) stable disease resulting in an overall response rate of 20%. Median progression-free survival was 6 months (95% CI, 4.0-8.0) with a median overall survival of 14 months (95% CI, 10.2-17.8). One-year survival rate was 55.9%. Grade 3-4 toxicities were as follows: neutropenia (n = 15, 37.5%), febrile neutropenia (n = 2, 5%), diarrhea (n = 11, 27.5%), nausea and vomiting (n = 3, 7.5%), gastrointestinal perforation (n = 2, 5%), and thromboembolism (n = 2, 5%). Conclusion: Bevacizumab plus irinotecan-based combination chemotherapy is an active and safe treatment option in patients failing oxaliplatin-based therapy.

The aim of this study was to evaluate the role of whole body 18F-FDG PET/CT imaging in the detection of primary tumors in patients with a metastatic cancer from an unknown primary site.The study population consisted of 43 patients with a biopsy proven metastatic disease, negative conventional diagnostic procedures (including CT/MRI/endoscopic procedures) and a whole body 18F-FDG PET/CT examination. Patients' records were retrospectively analyzed. According to the final pathologic diagnoses, rate of detection of the primary tumor site was determined. Additionally, overall patient survival was calculated to evaluate the prognostic value of 18F-FDG PET/CT findings.A primary tumor site was shown by 18F-FDG PET/CT in 24 patients (24/43; 55.8%). In 18 patients 18F-FDG PET/CT scans were negative (18/43; 41.8%). In a patient with an adenocarcinoma metastasis 18F-FDG PET/CT was falsely positive for an inflammatory lesion in the lung. Among the 18F-FDG PET/CT positive and negative groups median overall survival was not significantly different (log-rank p=0.573).Whole body 18F-FDG PET/CT imaging has a high rate of detection of a primary tumor in patients with a carcinoma of unknown origin.

Background Temozolomide is a novel cytotoxic agent for malignant gliomas. However, treatment failure occurs approximately in half of patients, and the optimal regimen in this setting has yet to be defined. In the present study, we assessed retrospectively the efficacy and toxicity of the combination of carboplatin and oral cyclophosphamide in temozolomide-resistant patients. Methods We evaluated the medical records of 30 patients with malignant gliomas. After failure of temozolomide therapy, patients were treated with a combination of carboplatin and oral cyclophosphamide. Treatment consisted of intravenous carboplatin AUC 6 (based on the Calvert Formula) on day 1 and oral cyclophosphamide 75 mg/m2 daily on days 1 to 14, followed by 14 days of rest, with the treatment repeated every 4 weeks. Results All patients were evaluated for response and toxicity. The objective response rate was 30%, including 9 partial responses. Median time to disease progression and median overall survival was 7 months and 8 months, respectively. Clinically responsive patients had statistically significant longer progression-free survival and overall survival than unresponsive patients. Hematological side effects were commonly observed toxicities, with neutropenia the most frequent. Conclusions Our data suggest that carboplatin and oral cyclophosphamide therapy is a convenient regimen after failure of temozolomide therapy in patients with malignant gliomas because of its activity, feasibility and tolerability. Further prospective studies are needed in this setting.

Background: Surgical resection followed by radiotherapy used to be the standard treatment in malignant gliomas. Recently, temozolomide has become a cornerstone in the treatment of these patients. We evaluated retrospectively the efficacy and the toxicity of temozolomide which was administered concomitantly with radiotherapy, and thereafter as consolidation treatment. Patients and Methods: Medical records of 64 patients with malignant glioma were reviewed. Postoperatively, temozolomide was given at a dose of 75 mg/m(2)/day concomitantly with cranial radiotherapy. After 4 weeks of rest, patients were treated with temozolomide 200 mg/m(2) on days 1-5 every 28 days for 6 cycles. Results: 62 patients were evaluable for response and toxicity. Objective response rate was 38.7% including 7 (11.3%) complete responses, and 17 (27.4%) partial responses. Median progression-free survival, and overall survival have not yet been reached in the grade III astrocytoma group at a median follow-up of 19 months. In the glioblastoma multiforme group, median progression-free survival, and median overall survival were 10 and 19 months, respectively. 2-year survival rates were 80% and 19% for the grade III astrocytoma, and for the glioblastoma multiforme groups, respectively. Toxicity was mild to moderate with rare grade 4 toxicities. Conclusion: Our data suggest that temozolomide is an active regimen for malignant gliomas. It was more effective in younger patients with better performance status.

In this study, we investigated the activity of single agent gemcitabine in the second-line setting of non-small cell lung cancer (NSCLC). File records of 21 patients treated with single agent gemcitabine in advanced NSCLC who received one prior chemotherapy including a taxane and platinum combination were retrospectively evaluated. Treatment consisted of IV gemcitabine 1,250 mg/m(2) on days 1 and 8, followed by a 1-week rest repeated every 3 weeks. A partial response was achieved in four (19%) patients. The median response duration was 16 (range, 12-32) weeks. Six (29%) patients had a SD more than 3 months. The median time to progression was 16 (range, 8-32) weeks. No complete response was observed. Median overall survival was 36 weeks for second-line gemcitabine in all patients (95%: CI 5-13 months). Hematological toxicity (all grades) was reported by 9 (42.9%) patients. One (4.75%) patient experienced grade 3/4 neutropenia. Grade 3/4 nausea and vomiting and mucositis were reported in one (4.75%) patient. In conclusion, this study shows that single agent gemcitabine is active and well tolerated as a second-line therapy for advanced NSCLC.

Purpose: The aim of this article was to investigate the efficacy of ultrasonography-guided core needle biopsy and prognostic factor analysis of breast cancer to plan overall treatment strategy. Patients and Methods: A consecutive series of nonpalpable and palpable breast cancers constituted our study group (n= 201 lesions; mean size, 20.4 mm) Mean number of core samples was 3.4. Malignant lesions diagnosed with core biopsy underwent therapeutic surgical excision. Core biopsy and surgical excisions were compared for histologic type, grade, estrogen receptors (ERs), progesterone receptors (PgRs), and c-erbB2 levels. Cutoff values for ER, PgR, and c-erbB2 affecting the management strategy were selected as 10%, 10%, and 50%, respectively. Results: Eighty-five lesions (42.3%) were malignant in core biopsy (mean size, 18.4 mm). 1 Among these, 11 were inoperable and 13 were surgically excised at other institutions. In 61 lesions, core and surgical excision specimens were evaluated in the same institution (mean tumor size, 18.6 mm; range 6-60 mm). Concordance between the 2 biopsy methods was 85.2% (52 of 61) for histologic type of tumor, 1 68.8% (33 of 48) for tumor grade, 90% (27 of 30) for ER, 86.7% (26 of 30) for PgR, and 79.3% (23 of 29) for c-erbB2 levels. Appropriate site selection for sampling was indicated to be of paramount importance, I especially in determining reliable ER, PgR, and c-erbB2 levels. Conclusion: Core needle biopsy of breast cancer is equally effective compared wth surgical biopsy and can be used in overall treatment planning. However, appropriate site selection for sampling should be guaranteed using ultrasonographic guidance.

Background: Treatment of patients with metastatic breast cancer (MBC) exposed to anthracyclines and taxanes is challenging. Effective and well-tolerated regimens are required. Gemcitabine plus capecitabine combination was assessed in MBC patients pretreated with anthracyclines and taxanes. Patients and Methods: A total of 31 patients treated between November 2004 and September 2005 were retrospectively evaluated in 4 institutions. The median age was 48 years (range 29–77). The patients were given gemcitabine 1,000 mg/m2 on days 1 and 8, and capecitabine 1,500 mg/m2 twice daily on days 1–14 every 3 weeks. Results: A total of 160 cycles of chemotherapy were administered with a median of 5 cycles per patient (range 2–12). Three patients achieved a partial response (10%) and 8 patients (26%) stable disease. The median time to disease progression was 6 months (95% CI 5–7), with a median survival of 18 months (95% CI 15–21) at a median follow-up of 16 months (range 2–28). One-year and 2-year survival rates were 67 and 28%, respectively. Grade 3–4 toxicities were as follows: neutropenia (n = 11, 35%), nausea and vomiting (n = 4, 13%), hand-foot syndrome (n = 2, 6%), anemia (n = 2, 6%), thrombocytopenia (n = 2, 6%) and asthenia (n = 1, 3%). Conclusion: The combination of gemcitabine plus capecitabine was a tolerable regimen with a mild but comparable survival efficacy to similar regimens in patients with MBC after anthracyclines and taxanes.

Detection of a breast mass accompanied by a contralateral axillary lymphadenopathy presents a dilemma because of the possible presence of an occult breast cancer on the same side as the axillary lymphadenopathy. A patient presented with an axillary lymphadenopathy from an occult breast cancer and a synchronous contralateral breast cancer, for which the differential diagnosis was established through a significant difference in estrogen and progesterone receptor levels. The patient was treated with neoadjuvant chemotherapy followed by bilateral modified radical mastectomy, adjuvant chemotherapy, and adjuvant radiation therapy. She is alive and free of disease 1.5 years after the diagnosis. (c) 2004 Elsevier Ltd. All rights reserved.

Expression of nm23 has been identified as a potential metastatic suppressor. In this study, nm23-H1 expression, clinicopathological parameters and influences on clinical outcomes were investigated in colorectal carcinoma patients.Immunostaining was performed on 185 colorectal carcinomas using a polyclonal anti-nm23-H1 antibody.The nm23-H1 immunoreactivity was weak in 31 (17%), moderate in 48 (26%) and strong in 106 (57%) cases. The well differentiated adenocarcinomas showed significantly strong staining for nm23-H1 compared with the moderately and poorly differentiated adenocarcinomas (chi2 test, P0.001). Advanced tumour stages were associated with reduced nm23-H1 expression (P0.001). There was an inverse correlation with angiolymphatic invasion, nodal metastasis and liver metastasis (univariate logistic regression analysis, P0.001). In univariate analysis, patients with reduced expression of nm23-H1 had significantly shorter overall and disease-free survival than the strong expression group (log-rank test for trend, P=0.002 and P=0.003, respectively).Our results indicated that reduced nm23-H1 expression showed poor prognosis in colorectal carcinomas. As a result, nm23-H1 expression might be a useful marker to predict outcome while planning treatment.

Summary Tumor angiogenesis is believed to be related to prognostic factors involved in tumor development and metastasis. Using immunohistochemical methods, we evaluated tumor angiogenesis in 42 early invasive breast cancer patients (T1-2, N0-1-2, M0). Four patients received tamoxifen, 25 patients received CAF or CA, and 15 patients received CMF as adjuvant therapy. The median follow-up was 47 (range 24–119) months. Ten patients (43.5%) in the node-positive group and 2 patients (10.5%) in the node-negative group relapsed (p = 0.019). The mean microvessel count (MVC) was 60.3 ± 3.05 per 200× field (range: 16–95). MVCs of postmenopausal and premenopausal patients were 50.13 ± 5.74 and 68.64 ± 4.11, respectively, in the axillary lymph node (ALN)-negative patient group (p = 0.04). Staining was moderate to strong in 13 (68%) ALN-negative and in 17 (74%) ALN-positive patients (p > 0.05), and was also moderate to strong in 82% of premenopausal patients and in 50% of postmenopausal patients (p = 0.037). There was no significant relationship between angiogenesis and p53, nor was angiogenesis significantly associated with the patient ER status and tumor size. No significant correlations were found between OS/DFS and Factor VIII staining or p53 (log rank test, p > 0.05). Of all ALN-negative patients with increased angiogenesis, one patient of the CMF group relapsed, but no recurrence occurred in patients undergoing anthracycline-based chemotherapy (p > 0.05). On the other hand, of all ALN-positive patients with increased angiogenesis, 5/14 patients treated with anthracylcine and 2/2 CMF-treated patients relapsed (p = 0.175). Despite the statistical insignificance, anthracycline-based adjuvant chemotherapy appears to be more effective than CMF as regards relapse prevention particularly in early ALN-positive breast cancer patients with increased angiogenesis. Additional studies are necessary to demonstrate the clinical importance of angiogenesis.

The aim of this study was to investigate the relationship between MUC1 and MUC2 mucin expressions and clinicopathologic variables in gastric carcinomas with regard to survival times. MUC1 and MUC2 expressions were revealed immunohistochemically in 143 gastric carcinomas. Of these 143 patients, follow-up data were available for 45 (median survival time of 30 months, ranging from 2 to 80 months). MUC1 was detected in 82 (58%), and MUC2 in 60 (42%) out of 143 cases. Papillary adenocarcinomas showed significantly higher MUC1 and MUC2 immunoreactivity than did signet-ring cell and mucinous tumors (p = 0.045 and p = 0.01, respectively). MUC1 was highly positive in intestinal-type carcinomas (p = 0.006), whereas intestinal and diffuse carcinomas did not differ in MUC2 expression. There was a positive correlation between tumor differentiation and MUC1 expression. However, no correlation was found between MUC1 and MUC2 expressions and angiolymphatic invasion. According to the TNM classification, stage 1A tumors have significantly lower rates of MUC1 reactivity compared to higher stages (p = 0.04). The patients with gastric carcinomas expressing MUC1 showed significantly poorer survival than those without MUC1 expression (p = 0.04). The present study suggests that MUC1 expression be a useful prognostic factor for predicting the outcome of gastric carcinoma patients, whereas the role of MUC2 expression is still unclear.

Background: Metastatic breast cancer is a common clinical entity, and its treatment is still a major clinical problem in modern oncology. Both cisplatin (CDDP) and 5-fluorouracil (5-FU) are effective agents. Patients and Methods: In this retrospective study, the therapeutic efficacy and tolerability of CDDP and continuous infusion of 5-FU were evaluated in patients with pretreated metastatic breast cancer. 16 patients were surveyed. All of them were pretreated with anthracyclines in an adjuvant and/or therapeutic setting. Eight of them also received taxanes after the failure of anthracyclines. CDDP at 80 mg/m(2) for 1 day and 5-FU at 1,000 mg/m(2) as a continuous 24-hour infusion for 5 consecutive days were administrated every 3 weeks. Results: 13 patients were included in response analysis. Because of severe toxicity, chemotherapy protocols of 3 patients were stopped after the first cycle. The objective response rate (partial response) was 46%. No complete response was observed. The median response duration was 5 (3.5-7) months in the response group. Favorable objective responses were observed more frequently in cases with skin metastasis. Five out of 6 patients who attained partial remission had skin metastasis. Response rates were similar in patients pretreated with taxanes and in those not pretreated with taxanes (75 vs. 80%). The most serious toxicity was myelosuppression (25%). Conclusions: Although this study is based on only a limited number of patients, the combination of CDDP and 5-FU can be recommended in patients refractory to both anthracyclines and taxanes and especially in cases of skin metastasis with a good performance status.

Background: Cancer is a rapidly increasing worldwide health problem and despite medical interventions success rates are not very high. Complementary approaches are commonly used by patients in conjunction with