Fuat Demirelli

Serum erythropoietin level in anemic cancer patients

Anemia is a frequent complication of cancer and its treatment. A defect in erythropoietin production has been advocated as being the main cause of anemia in cancer patients. We studied serum erythropoietin levels in 74 patients with solid tumors and in a control group consisting of 20 otherwise healthy individuals without any malignancy, who have only iron deficiency anemia. Serum erythropoietin levels were measured by enzyme immunoassay in cancer patients without anemia (n=34), and in anemic cancer patients (n=40); either receiving chemotherapy (n=21) or not (n=19). Anemic cancer patients were found to have decreased response of erythropoietin for a given hemoglobin level (mean, 40.1±34.7 u/ml), compared with the patients having only iron deficiency anemia (mean, 69.7±68.6 u/ml) (P<0.05). In patients with iron deficiency anemia having no malignancy, erythropoietin response was remarkably high and inversely correlated with the level of hemoglobin (r=−0.69;P=0.05). Although there was no correlation between hemoglobin and erythropoietin response in cancer anemia (r=−0.07), serum levels of erythropoietin were found to be higher in anemic cancer patients (mean, 40.1±34.7 u/ml), compared with cancer patients with normal hemoglobin values (mean, 19.96±18.4 u/ml). There was not any statistically significant difference between erythropoietin levels in anemic cancer patients with or without chemotherapy (mean, 43.7±37.7 u/ml and 41.9±30.08 u/ml respectively;P>0.05). No difference in serum erythropoietin levels were noted in patients treated with cisplatin or non-cisplatin containing regimens (mean, 48.36±33.12 u/ml and 38.55±43.52 u/ml, respectively;P>0.05). In this study, we demonstrated that anemia in cancer patients was caused by blunted erythropoietin response, rather than its quantitative deficiency. Serial measurements, however, should be considered in patients receiving chemotherapy.

The importance of multifocal/multicentric tumor on the disease-free survival of breast cancer patients: single center experience.

Objectives:Multifocal/multicentric breast cancers have been comprehensively studied and their outcomes have been compared with unifocal tumors. We evaluated the impact of multifocality and multicentricity on the disease-free survival (DFS) and overall survival of breast cancer patients and tried to analyze the correlation between multifocality/multicentricity (M/M) and other prognostic factors. Material and Methods:Between 1994 and 2009, we analyzed retrospectively 697 breast cancer patients. Multicentric and multifocal breast cancer were defined as the presence of 2 or more invasive tumor foci within the different quadrants of the same breast or within a same quadrant of the breast, respectively. M/M and other prognostic factors were evaluated using univariate and multivariate analyses. Results:Multifocal/multicentric tumors were seen in 107 (15.4%) of the 697 breast cancer patients. pT and pN stage were related with the presence of multifocal/multicentric tumors. As tumor size increased and the number of axillary lymph nodes metastasis increased, the incidence of M/M increased significantly (P=0.003 vs. P=0.02, respectively). Overall, the median DFS time of patients with multifocal/multicentric tumors was significantly worse than that of the unifocal tumors (55 vs. 137 mo, P<0.001). Multivariate analysis showed that the presence of M/M was the most important prognostic factor for DFS (P=0.001, hazard ratio (HR): 0.33; 95% confidence interval (CI), 0.18-0.58), as were pN stage and extracapsular extension of the tumor (P=0.01, HR: 1.74; 95% CI, 1.13-2.69) (P=0.03, HR: 1.9; 95% CI, 1.04-3.47, respectively). M/M were not also statistically significant prognostic factors in breast cancer for overall survival (P=0.06). Conclusions:M/M imparts an unfavorable prognosis on the DFS of breast cancer patients in comparison to unifocal tumors and the presence of multifocal/multicentric tumors were associated with advanced pT and pN stages.

Usefulness of the epithelial tumor marker CA-125 in Non-Hodgkin's lymphoma

CA-125, a commonly used tumor marker for epithelial ovarian cancer, is a glycoprotein found in normal tissues derived from coelomic epithelia. Increased serum levels of CA-125 have also been found in nongynecologic tumors and nonmalignant diseases involving the peritoneum. A few recent studies and sporadic case reports have reported increased CA-125 levels in patients with non-Hodgkins lymphoma (NHL). In our study, we aimed to evaluate the serum levels of CA-125 in patients with NHL and determine its potential role to show disease activity in NHL. Serum levels of CA-125 were measured in 61 patients with NHL and were found to be correlated with clinical stage, site of involvement, and disease activity.

Bilateral inflammatory breast metastases of epithelial ovarian cancer.

Metastases to the breast are rare. Secondary breast involvement from an epithelial ovarian cancer heralds widespread dissemination and a very poor prognosis. We report an unusual case of a patient who had epithelial ovarian cancer and who showed signs of recurrence with inflammatory metastases to both breasts, 2 years after her diagnosis of ovarian cancer. She died within 3 months of breast involvement. Our case has unique features, with both bilateral breast metastases and also with its inflammatory pattern of metastasis, which is extremely rare.

Serum Cardiolipin Antibodies in Cancer Patients with Thromboembolic Events

This study was undertaken to investigate a pos sible association of anticardiolipin antibodies (ACLAs) in can cer patients with thromboembolic events. Twenty-five patients with solid tumors complicated with acute thrombosis, 36 cancer patients without any thrombotic events, and a group of 20 healthy volunteers without thrombosis or malignancy were in cluded. The mean age of the cancer patients with and without thrombosis and healthy subjects were 50 years (range 20-75), 45 years (range 23-66), and 40 years (range 20-68), respec tively. Deep venous thrombosis (n = 16) and thrombosis of the central venous port-catheter systems (n = 9) were confirmed by Doppler sonography in all patients. IgG and IgM isotypes of ACLAs were quantitated by enzyme-linked immunosorbent as say with normal levels of <23 GPL and <11 MPL, respectively. Mean values of IgG ACLAs were found similar in cancer pa tients with acute thrombosis (13.8 ± 4.9 GPL), without throm bosis (12.8 ± 5.4 GPL) or in healthy subjects (14.8 ± 5.5 GPL). Although the mean values of IgM ACLAs were within normal limits in all groups, cancer patients with thrombotic events had higher levels of IgM ACLAs (mean = 10.5 ± 2.2 MPL) than cancer patients without thrombosis (mean = 4.6 ± 2.4 MPL) (p = .01). Healthy subjects also had lower levels of IgM ACLAs (mean = 7.1 ± 3.2 MPL) than cancer patients with thrombosis (p = .16). In addition, a higher percentage of cancer patients with or without thrombosis had IgM and IgG ACLA levels above normal limits compared with healthy controls. In con clusion, our study suggests an association between ACLAs or IgG and particularly IgM isotypes and venous thrombosis in malignancy. Identification of cancer patients who are at higher risk for developing thromboembolic events might lead to a better selection of patients for prophylactic anticoagulant therapy.

Toxicity and Survival Results of a Phase II Study Investigating the Role of Postoperative Chemo-radioimmunotherapy for Gastric Adenocarcinoma

Background and Purpose:To investigate the role of postoperative concomitant chemoradioimmunotherapy in gastric adenocarcinoma patients.Patients and Methods:59 patients, who underwent total or subtotal gastrectomy, with lymph node involvement, positive microscopic surgical margins or serosal involvement were included in the study. Radiotherapy started concomitantly with chemotherapy and levamisole. Extended-field radiotherapy was given to gastric bed and regional lymphatics via two anterior-posterior/posterior-anterior fields. A total dose of 45 Gy in 25 fractions with a fraction size of 1.8 Gy was planned. In 28 patients (48%) with positive surgical margins a 10-Gy boost dose was given to the anastomosis site. An adjuvant i.v. bolus of 450 mg/m2/day 5-fluorouracil (5-FU) was administered concomitantly during the first 3 days and at the 20th day of irradiation. After completion of radiotherapy, i.v. boluses of 450 mg/m2/day 5-FU and 25 mg/m2/day rescuvorin were continued for 6 months once a week. Levamisole 40 mg/day orally was started at the 1st day of radiotherapy and also continued for 6 months. Median follow-up was 37 months (7–112 months).Results:Median survival was 23 months. Overall 3- and 5-year survival rates amounted to 35% and 14%, respectively. Median survival of the patients with positive surgical margins was 22 months. The 3- and 5-year locoregional control rates were 59% and 55%, respectively. The most common toxicity was upper gastrointestinal system toxicity, which was observed in 42 patients (71%). Four patients (7%) died on account of early toxic effects, and six (10%) could not complete treatment.Conclusion:Although 48% of the study population involved patients with microscopic residual disease, the survival results as a whole were satisfactory. However, due to high toxicity, radiotherapy must be delivered with the most proper techniques along with adequate nutrition and supportive care.Hintergrund und Ziel:Untersuchung der Rolle der postoperativen Radiochemotherapie bei Patienten mit Adenokarzinom des Magens.Patienten und Methodik:59 total oder subtotal operierte Patienten mit Adenokarzinom des Magens, die eine Invasion der Serosaoberfläche, einen Befall der regionären Lymphknoten oder positive Resektionsränder aufwiesen, wurden in die Studie eingeschlossen. Postoperativ wurde eine simultane Radiochemotherapie begonnen. Die Bestrahlung wurde in „Extended-field“-Technik über zwei Felder (anterior-posterior und posterior-anterior) mit einer Gesamtdosis von 45 Gy in 25 Fraktionen zu 1,8 Gy appliziert. 28 Patienten (48%) mit positiven Resektionsrändern erhielten zusätzlich einen 10-Gy-Boost auf den Anastomosenbereich. Die adjuvante Chemotherapie mit einem 450-mg/m2-Bolus 5-Fluorouracil (5-FU) wurde an den ersten 3 Tagen verabreicht und am 20. Tag wiederholt. Nach der Strahlentherapie erhielten die Patienten 450 mg/m2 5-FU i.v. und 25 mg/m2 Leukovorin i.v. wöchentlich für weitere 6 Monate. Die Immunmodulation mit 40 mg Levamisol p.o. wurde am 1. Bestrahlungstag begonnen und für 6 Monate weitergeführt. Der mediane Nachuntersuchungszeitraum lag bei 37 Monaten (7–112 Monate).Ergebnisse:Die mediane Überlebenszeit betrug 23 Monate. Die 3- und 5-Jahres-Gesamtüberlebensraten lagen bei 35% und 14%. Patienten mit positiven Resektionsrändern wiesen eine mediane Überlebenszeit von 22 Monaten auf. Die lokoregionale Kontrollrate betrug 59% nach 3 Jahren und 55% nach 5 Jahren. Die häufigsten Nebenwirkungen der Behandlung waren gastrointestinale Beschwerden bei 42 Patienten (71%). Vier Patienten (7%) starben infolge der Nebenwirkungen. Sechs Patienten konnten die Behandlung aufgrund von Nebenwirkungen nicht beenden.Schlussfolgerung:Obwohl 48% der Patienten in dieser Studie einen mikroskopisch nachweisbaren Resttumor aufwiesen, war die beobachtete Überlebenszeit verhältnismäßig gut. Aufgrund der hohen Toxizität sollte die Behandlung jedoch sehr sorgfältig unter Einsatz angemessener supportiver Maßnahmen durchgeführt werden.

Clinicopathological features and outcomes of patients with gastric cancer: a single-center experience.

AIM To evaluate the location, histopathology, stages, and treatment of gastric cancer and to conduct survival analysis on prognostic factors. METHODS Patients diagnosed with of stomach cancer in our clinic between 2000 and 2011, with follow-up or a treatment decision, were evaluated retrospectively. They were followed up by no treatment, adjuvant therapy, or metastatic therapy. We excluded from the study any patients whose laboratory records lacked the operating parameters. The type of surgery in patients diagnosed with gastric cancer was total gastrectomy, subtotal gastrectomy or palliative surgery. Patients with indications for adjuvant treatment were treated with adjuvant and/or radio-chemotherapy. Prognostic evaluation was made based on the parameters of the patient, tumor and treatment. RESULTS In this study, outpatient clinic records of patients with gastric cancer diagnosis were analyzed retrospectively. A total of 796 patients were evaluated (552 male, 244 female). The median age was 58 years (22-90 years). The median follow-up period was 12 mo (1-276 mo), and median survival time was 12 mo (11.5-12.4 mo). Increased T stage and N stage resulted in a decrease in survival. Other prognostic factors related to the disease were positive surgical margins, lymphovascular invasion, perineural invasion, cardio-esophageal settlement, and the levels of tumor markers in metastatic disease. No prognostic significance of the patients age, sex or tumor histopathology was detected. CONCLUSION The prognostic factors identified in all groups and the proposed treatments according to stage should be applied, and innovations in the new targeted therapies should be followed.

Is Her-2 Status in the Primary Tumor Correlated with Matched Lymph Node Metastases in Patients with Gastric Cancer Undergoing Curative Gastrectomy?

BACKGROUND HER2 expression in the primary tumor and its lymph node metastases vary in gastric cancer, reflecting intratumoral heterogeneity. This finding also suggests that proliferation of a different clone in metastatic nodes is possible. In the current study, we aimed to determine the cause of discordance in HER-2 expression in the primary tumor and lymph node metastases for patients with gastric cancer. MATERIALS AND METHODS Eighty-one patients with gastric cancer who had undergone radical gastrectomy and were found to have lymph node metastasis upon pathological examination were included. Histopathological samples were obtained from biopsies obtained during patient gastrectomies and lymph node dissection. HER2 status was evaluated by both immunohistochemistry (IHC) and silver in situ hybridization (SISH). RESULTS Sixty-four (79%) patients were SISH (-), while 17 (21%) were SISH (+) in the primary tumor. However, in metastatic lymph nodes, HER2 status was SISH positive in 5 (28.3%) of the 64 SISH (-) primary tumor specimens. One of the 17 SISH (+) primary tumors was SISH (-) in the metastatic lymph nodes. Thus, SISH results for HER2 in both primary tumors and lymph node metastases were comparable, showing a concordance of 92.5%. In total, six patients demonstrated discordance between the primary tumor and lymph node metastases. The prevalence of HER2 discordance was significantly higher for patients in the pN2 and N3 stages (p=0.007). Although discordant patients had worse survival rates than concordant patients, the differences were not significant (p>0.05). CONCLUSIONS Our study indicates that the frequency of concordance in HER2 status, as determined by IHC or SISH, is high in primary tumors and their corresponding lymph node metastases for patients with gastric cancer. If there is a discrepancy in HER2 status, its evaluation by both IHC and SISH may be useful for detecting patients who would benefit from trastuzumab, and it would therefore help guide decision-making processes in administering treatment.

Primary splenic tuberculosis in a patient with nasal angiocentric lymphoma: mimicking metastatic tumor on abdominal CT.

Tuberculosis may be difficult to diagnose when it presents in an uncommon extrapulmonary site. The authors report a case of splenic tuberculosis mimicking metastatic tumor on computed tomography in a 60-year-old woman who had been treated with combination chemotherapy for nasal angiocentric lymphoma. Diagnostic splenectomy revealed multiple necrotic masses in the spleen, which were consistent with caseating granulomas microscopically. Diagnosis was confirmed by positive cultures in Lowenstein medium, which grew typical Mycobacterium tuberculosis organisms. Following splenectomy, the patient was also treated with a triple-drug antituberculosis regimen with no recurrence of her symptoms.

Clinicopathological Features and Localization of Gastric Cancers and their Effects on Survival in Turkey

BACKGROUND This study was designed to examine changing trends in localization of gastric cancer in Turkey in recent years. MATERIALS AND METHODS A total of 796 adult patients with newly diagnosed, histologically proven adenocarcinomas, treated and followed up at our oncology center between 2000-2011, were examined retrospectively. In all cases tumor localization were identified and recorded with clinicopathological features. RESULTS The median age was 58 with a range between 22-90 for the 552 men and 244 women. Median follow up was 12 months (1-276) and median overall survival was also 12 months (11.5-12.4). There was a trend for a change in tumor localization from distal to proximal. Survival of patients was low with advanced T and N stage tumours. Positive surgical margins, lymphovascular invasion, perineural invasion, cardioesophageal localization were predisposition factors for metastatic disease in gastric cancer. There was no relation between age or sex and histopathological type of gastric cancer. CONCLUSIONS There is a trend in our country for a change in gastric tumour localization from distal to proximal, with clear significance for treatment choices.