Aytug Uner

Evaluation of nutritional status in cancer patients receiving radiotherapy: a prospective study.

Objectives:The purpose of the present study was to evaluate the nutritional status of cancer patients receiving radiotherapy (RT) and to assess the possible contributions of nutritional support to patients with malnutrition. Methods:Prospectively, 207 patients referred to our outpatient radiotherapy department were included. The patients were classified according to tumor site (head/neck, breast, lung, stomach, or colorectal). Nutritional status at the onset, at the end of RT, and 3 and 6 months after irradiation was evaluated with the subjective global assessment (SGA). All of the patients were supported with additional portions of meal or standard enteral feeding formula during and after the irradiation period as long as they were in the moderately or severely malnourished groups, respectively. Results:At the onset, malnutrition was present in 31% of all patients, and it increased to 43% at the end of RT. This difference predominated in head/neck cancer patients. Malnutrition ratios in head/neck cancer patients at the onset and after RT were 24% and 88%, respectively. By a 6-month follow-up, the ratio of patients with malnutrition decreased to 8%. Nutritional status of all groups was found to improve during the 6-month follow-up period, except for the breast cancer group, which included no patients with severe malnutrition at any time. Conclusion:The results of the present study may be helpful in planning an appropriate nutritional support for cancer patients undergoing radiotherapy according to the irradiation site.

Interdigitating dendritic cell tumor with breast and cervical lymph-node involvement: a case report and review of the literature

Interdigitating dendritic cell tumor (IDCT) is an extremely rare malignancy. It occurs primarily in lymph nodes, but extranodal involvement has also been reported. A 38-year-old woman with IDCT with breast and cervical lymph-node involvement is reported in this paper. To our knowledge, this is the first case of IDCT originating from the breast. In the breast and lymph node, the tumor displayed diffuse sheets, fascicles and storiform growth pattern. It was composed of oval to spindle cells with pale to eosinophilic cytoplasm, ill-defined cell outlines, oval nuclei with vesicular chromatin and prominent eosinophilic nucleoli. Mitotic activity was three per ten high-power fields. The neoplastic cells were intermingled with small mature lymphocytes and plasma cells. Immunohistochemical studies showed that the tumor cells were strongly and diffusely positive for vimentin, CD68, S-100 protein, CD45/leukocyte common antigen and fascin and focally positive for lysozyme, alpha-1 antitrypsin and CD4. Ki-67 labeling index was 10%. The patient was treated with combined therapeutic approaches, including surgery, radiotherapy and chemotherapy. IDCT has the potential for an aggressive clinical course. However, 32 months after the initial diagnosis, the patient is still alive and being followed with a stable tumor burden.

Mutation analysis of BRCA1 and BRCA2 in Turkish cancer families: a novel mutation BRCA2 3414del4 found in male breast cancer.

Since the identification of the BRCA1 and BRCA2 breast-ovarian cancer susceptibility genes, mutation analyses have been carried out in different populations. Here we screened 15 Turkish breast and breast-ovarian cancer families for mutations in both genes by conformation-sensitive gel electrophoresis (CSGE) and the protein truncation test (PTT), followed by DNA sequencing. Three families included a male breast cancer case, one without family history. Three germline mutations were identified, two in BRCA1 and one in BRCA2. The two BRCA1 mutations, 5382insC and 5622C-->T, were found in breast-ovarian cancer families. The BRCA2 3414delTCAG is a novel mutation detected in a site-specific breast cancer family that included 1 case of male breast cancer. These first results of Turkish families show that the frequency of germline BRCA1 or BRCA2 mutations appears to be high in families with at least 3 breast and/or ovarian cancer cases.

Gemcitabine plus capecitabine combination in metastatic breast cancer patients previously treated with anthracyclines and taxanes.

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.

Doppler Sonographic Evaluation of Hemodynamic Changes in Colorectal Liver Metastases Relative to Liver Size

Objective. The mechanisms of hemodynamic alterations in colorectal liver metastases are not clearly understood yet. Considering that an increase in liver size in patients with metastases could also result in an alteration in total liver flow, we aimed to analyze hemodynamic changes relative to the liver volume and to search for the possibility of any intrinsic factors affecting blood flow in patients with metastases. Methods. Twenty‐eight patients with colorectal liver metastases and 20 control subjects with no liver disease were evaluated sonographically. All patients were examined prospectively by Doppler sonography and helical computed tomography. Hepatic hemodynamic parameters, including blood flow in the hepatic artery and portal vein, total blood flow to the liver, and Doppler perfusion index, were calculated, and values relative to liver volume were obtained. Hepatic perfusion changes in liver metastases were then compared with those in a control group. Results. The liver volume of the patients with liver metastases was greater than that of the control group (P = .003). Hepatic arterial blood flow rates were higher, whereas portal flow rates were lower, in patients with liver metastases compared with control subjects (P < .05). Total liver blood flow was not significantly different between the two groups. However, total blood flow relative to liver volume was significantly lower in the metastatic group (P < .001). Doppler perfusion index values in the patients with metastasis were significantly higher than in the control group (P = .000). Conclusions. Our findings may support the hypothesis that a humoral mediator‐induced portal venous flow reduction causes perfusion changes in liver metastases from colorectal disease. However, an additional intrinsic hepatic hemodynamic event should also be present. Doppler perfusion index measurements can provide additional information in the evaluation of patients with colorectal liver metastases.

Serum leptin levels are associated with tamoxifen-induced hepatic steatosis.

Summary Purpose: Tamoxifen, used in breast cancer treatment, may induce hepatic steatosis. It has been suggested that leptin, which has a relationship with body fat stores, may be involved in the pathogenesis of hepatic steatosis. In this study, we compared serum leptin levels in tamoxifen-treated patients with and without hepatic steatosis. Methods: Thirty-four women with breast cancer receiving tamoxifen were included in the study. Serum samples were obtained from the patients before and 3 months after tamoxifen therapy. Results: Increased hepatic steatosis was detected in 15 of 34 (44%) patients after 3 months of tamoxifen therapy. Serum leptin levels were found to be significantly elevated in patients with increased hepatic steatosis (37.3 ± 17.7 to 50.5 ± 22.4 ng/ml, p = 0.023) compared to patients without or stable hepatic steatosis (48.2 ± 20.2 to 42.6 ± 14.9 ng/ml, p > 0.05) after tamoxifen treatment. Conclusion: Leptin may play a role in tamoxifen-induced hepatic steatosis. The exact mechanism involved should be investigated in further studies.

Bevacizumab Plus Irinotecan-Based Therapy in Metastatic Colorectal Cancer Patients Previously Treated With Oxaliplatin-Based Regimens

ABSTRACT 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 53years (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 14months (95% CI, 10.2–17.8). One-year survival rate was55.9%. 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 chemotherapyis an active and safe treatment option in patients failing oxaliplatin-based therapy.

Temozolomide in Newly Diagnosed Malignant Gliomas: Administered Concomitantly with Radiotherapy, and Thereafter as Consolidation Treatment

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 ad-ministered 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/m2/day concomitantly with cranial radiotherapy. After 4 weeks of rest, patients were treated with temozolomide 200 mg/m2 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.

Gelatinase B expression as a prognostic factor in patients with stage II/III rectal carcinoma treated by postoperative adjuvant therapy.

Objective:The matrix-metalloproteinases (MMPs) are thought to be critically involved in tumor invasion and metastasis. This retrospective study was aimed both to examine the gelatinase expression status in patients with rectal cancer and to investigate their prognostic value on survival. Methods:Sixty patients who underwent postoperative adjuvant chemoradiotherapy for Stage II and III rectal carcinoma were included. Expressions of MMP-2, MMP-9, and tissue inhibitors of MMP (TIMP-1 and TIMP-2) were analyzed by immunohistochemistry in paraffin-embedded primary rectal cancers and graded for the intensity and the percentage of cells stained. The relation between the expression of the markers studied and clinicopathologic features were evaluated for the primary study endpoint. The data were also analyzed using a multivariate Cox proportional hazards model for prognosis as a secondary endpoint. Results:Positive MMP-9 expression was observed in 70% of the tumors. The ratio of tumors with positive MMP-9 expression was increased according to N stage (P = 0.005), AJCC stage (P = 0.005), and tumor differentiation (P = 0.017). Overall survival was reduced in poorly differentiated tumors and tumors with positive MMP-9 expression (P = 0.002). Disease-free survival was lower in patients with positive MMP-9 expression (P = 0.007). Multivariate analysis indicated that positive MMP-9 expression was an independent predictor of reduced overall survival (P = 0.0103) and reduced disease-free survival (P = 0.0360). The other markers studied were associated with neither any clinicopathologic feature nor any survival parameter. Conclusion:MMP-9 expression was observed in the tumors of patients with Stage II and III rectal carcinoma in comparable values and was characterized by poor overall survival and disease-free survival.

Adjuvant systemic chemotherapy with or without bevacizumab in patients with resected liver metastases from colorectal cancer.

Background: We aimed to investigate the impact of adjuvant systemic therapy with modern chemotherapy combinations on survival outcomes in patients with resected liver-confined metastases from colorectal carcinomas, and whether addition of bevacizumab (BEV) provides further benefit. Methods: A total of 229 consecutive patients who underwent resection for liver-confined colorectal liver metastases were retrospectively analyzed. Results: Of 229 patients, 204 who received chemotherapy with fluoropyrimidine-based (n = 27), irinotecan-based (n = 84) and oxaliplatin-based (n = 93) combinations were analyzed. Among these, 87 patients received BEV while 117 did not (NoBEV). With a median follow-up of 27 months after metastasectomy, the median recurrence-free survival (RFS) and overall survival (OS) were 17 and 53 months, respectively. OS rates at 3 and 5 years were 71% and 40%, respectively. No significant differences were found in the median RFS (p = 0.744) and OS (p = 0.440) among different chemotherapy regimens. The median RFS (p = 0.375) and OS (p = 0.251) were similar in BEV and NoBEV arms. In multivariate analysis, having 4 liver metastases was the only negative independent factor on both RFS and OS, while positive surgical margin was another negative independent factor for RFS. Conclusion: Chemotherapy type and addition of BEV have no impact on both RFS and OS in the adjuvant setting following complete resection of colorectal liver metastases.