Celalettin Camci

How to Interpret Serum CA 125 Levels in Patients with Serosal Involvement? A Clinical Dilemma

The clinical utility of tumor markers is limited due to their low specificity. CA 125, an ovarian tumor marker, is a sensitive but nonspecific tumor marker used especially in the follow-up of ovarian cancer for monitoring the efficacy of therapy and for early detection of recurrence. The use of the CA 125 serum assay as a single diagnostic tool is restricted by the fact that the antigen to CA 125 is also produced by normal epithelia (peritoneum, pleura, and pericardium). Since an elevated serum CA 125 level is a marker of ovarian cancer, a laparotomy is the final tool of the physician to clarify the etiology. However, unnecessary operations have been reported in the literature revealing no ovarian pathology (e.g. cirrhosis, tuberculous peritonitis or pancreatic cancer) in such patients. Elevated serum CA 125 levels require a cautious operative planning in patients without a notable tumor mass. A secondary interpretation is needed in case of elevated CA 125 levels whenever serosal (peritoneal, pleural, or pericardial) fluid is present.

Serum CA 125 Levels in Patients with Chronic Heart Failure and Accompanying Pleural Fluid

Malignant and nonmalignant serosal fluids have been found to be associated with high serum levels of CA 125, suggesting that the presence of fluid in the serosal cavities may stimulate its release. In this study, we investigated the relationship between serum CA 125 levels and the presence of pleural fluid in patients with chronic heart failure (CHF). We performed a clinical study in 36 patients with CHF with and without pleural fluid. Patients with CHF were divided into two groups based on the presence of fluid in the pleural cavity. Group 1 included 18 CHF patients (6 females, 12 males) with pleural fluid. Group 2 consisted of 18 CHF patients (7 females, 11 males) without pleural fluid. The control group consisted of 30 healthy volunteers (12 females, 18 males). The serum CA 125 level was determined in all groups. Serum CA 125 levels were found to be 100.0 ± 129.4 U/ml in CHF patients with pleural fluids, whereas they were 36.5 ± 35.2 U/ml in CHF patients without pleural fluid and 8.9 ± 6.1 U/ml in the control group. Significantly high serum CA 125 levels were found in CHF patients with pleural fluids (p < 0.05) when compared with both CHF patients without pleural fluid and the control group. There was also a statistically significant difference in CA 125 levels between patients without pleural fluid and the control group (p < 0.05). We concluded that serum CA 125 levels should be interpreted with caution in patients with CHF in the presence of pleural fluid. Invasive procedures to define the etiology of elevated serum CA 125 levels may be unnecessary in this patient group.

Bevacizumab + Capecitabine as Maintenance Therapy after Initial Bevacizumab + XELOX Treatment in Previously Untreated Patients with Metastatic Colorectal Cancer: Phase III ‘Stop and Go' Study Results - A Turkish Oncology Group Trial

Objective: It was the aim of this study to evaluate maintenance therapy with bevacizumab + capecitabine following induction with bevacizumab + capecitabine + oxaliplatin (XELOX) versus bevacizumab + XELOX until progression as first-line therapy in metastatic colorectal cancer (mCRC). Methods: Patients received either bevacizumab (7.5 mg/kg) + XELOX (capecitabine 1,000 mg/m2 twice daily on days 1-14 + oxaliplatin 130 mg/m2 on day 1 every 3 weeks) until disease progression (arm A) or the same doses of bevacizumab + XELOX for 6 cycles followed by bevacizumab + capecitabine until disease progression (arm B). The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. Results: One hundred and twenty-three patients were randomized. Treatment compliance was similar in both groups. Median PFS was significantly longer for arm B than for arm A (11.0 vs. 8.3 months; p = 0.002). There was no significant difference between the two arms for ORR (66.7 vs. 59.0%; p = 0.861) or median OS (23.8 vs. 20.2 months; p = 0.100). Tolerability was acceptable in both treatment arms; the most frequent grade 3/4 treatment-related adverse events (arm B vs. arm A) were fatigue (6.6 vs. 16.1%), diarrhoea (3.3 vs. 11.3%), anorexia (3.3 vs. 11.3%), and neuropathy (1.6 vs. 8.1%). Conclusions: Maintenance therapy with bevacizumab + capecitabine can be considered an appropriate option following induction bevacizumab + XELOX in patients with mCRC instead of continuation of bevacizumab + XELOX.

The distribution of circulating microRNA and their relation to coronary disease.

Background: MicroRNAs (miRNAs) are small RNAs that regulate gene expression by suppressing protein translation and may influence RNA expression. MicroRNAs are detected in extracellular locations such as plasma; however, the extent of miRNA expression in plasma its relation to cardiovascular disease is not clear and many clinical studies have utilized array-based platforms with poor reproducibility. Methods and Results: Initially, to define distribution of miRNA in human blood; whole blood, platelets, mononuclear cells, plasma, and serum from 5 normal individuals were screened for 852 miRNAs using high-throughput micro-fluidic quantitative RT-PCR (qRT-PCR). In total; 609, 448, 658, 147, and 178 miRNAs were found to be expressed in moderate to high levels in whole blood, platelets, mononuclear cells, plasma, and serum, respectively, with some miRNAs uniquely expressed. To determine the cardiovascular relevance of blood miRNA expression, plasma miRNA (n=852) levels were measured in 83 patients presenting for cardiac catheterization. Eight plasma miRNAs were found to have over 2-fold increased expression in patients with significant coronary disease (≥70% stenosis) as compared to those with minimal coronary disease (less than 70% stenosis) or normal coronary arteries. Expression of miR-494, miR-490-3p, and miR-769-3p were found to have significantly different levels of expression. Using a multivariable regression model including cardiovascular risk factors and medications, hsa-miR-769-3p was found to be significantly correlated with the presence of significant coronary atherosclerosis. Conclusions: This study utilized a superior high-throughput qRT-PCR based method and found that miRNAs are found to be widely expressed in human blood with differences expressed between cellular and extracellular fractions. Importantly, specific miRNAs from circulating plasma are associated with the presence of significant coronary disease.

The Use of Complementary Therapies in Cancer Patients : A Questionnaire-Based Descriptive Survey From Southeastern Turkey

Objectives:A study was designed to measure the frequency of complementary therapy (CT) usage in cancer patients in southeastern Turkey. The demographic characteristics associated with the use of CT are sought in patients undergoing or following conventional treatment. Methods:A descriptive survey was performed in a total of 560 cancer patients. Questionnaire-based measures of demographics, expectations, and effects of using different types of CT and perceived benefits were recorded. Result:Demographic characteristics (age, gender, education status, etc.) did not differ among CT users and non-CT users. Three hundred ten patients (55.4%) had used at least one type of CT since the time of the initial diagnosis of cancer. The most frequently used CT method was herbal therapy, and the most commonly used herb was the stinging nettle. The source of information about CT was mainly from friends/family, whereas physicians and nurses played a small part in providing CT-related information. The majority of the patients used CT to benefit more from medical treatment. Only 20.7% of the patients considered themselves not benefiting from using CT. Conclusions:Currently more than half of Turkish patients with cancer use CT in addition to the standard medical approaches. CT usage is not associated with any specific demographic variables. Health professionals should not disregard the reality of CT usage in cancer patients. Because the majority of cancer patients use CT regardless of the medical advice, randomized clinical trials are needed to explore risks and benefits associated with CT modalities in cancer.

Colon carcinoma with synchronous subcutaneous and osseous metastasis: a case report.

Colon cancer usually metastasizes initially to regional lymphatics and later through the bloodstream. Hematogenous metastasis usually includes the liver, lungs, and brain. In colorectal cancer, osseous and/or subcutaneous metastasis without liver metastasis is a very uncommon event. We present here a case of colon adenocarcinoma, which synchronously metastasized to facial and other subcutaneous tissue and to bone within a short period after definitive therapy. Although such a pattern is uncommon, diagnostic biopsy for any new or suspicious lesion of the skin and bone scintigraphy for symptomatic patients should be done for patients with a colorectal cancer history.

The diagnosis of C-kit negative GIST by PDGFRA staining: clinical, pathological, and nuclear medicine perspective.

Background: Gastrointestinal stromal tumors (GIST) comprise a majority of tumors previously diagnosed as gastrointestinal leiomyomas, leiomyoblastomas, and leiomyosarcomas. Although GIST may be identified by light microscopy, pathologists commonly employ a panel of immunohistochemical markers to confirm the morphological impression including anti-CD34, smoothmuscle actin, desmin, S100, and CD-117. However, in CD- 117 negative cases, it becomes difficult to diagnose GIST. This is of great importance, since the use of imatinib mesylate has led to a dramatic improvement in survival rates of GIST patients besides improved quality of life. Case Report: We report the case of a 67-year-old male patient diagnosed as having chemotherapy-resistant metastatic leiomyosarcoma. We reviewed the specimen for a possible diagnosis of c-kit negative GIST. Plateletderived growth factor receptor-alpha (PDGFRA) immunohistochemical stain was recommended. The specimen was positively stained for PDGFRA. Imatinib mesylate (400 mg/d) was started. The patient showed an excellent response after receiving imatinib treatment which was documented with 18 fluoro-deoxyglucose positron emission tomography and computed tomography (18F-FDGPET/ CT) prior to and after treatment. Conclusion: The importance of diagnosis of c-kit negative GIST is emphasized while stressing the importance of PDGFRA staining besides PET/CT response evaluation.

Association between the Thr431Asn polymorphism of the ROCK2 gene and risk of developing metastases of breast cancer.

The objective of this study was to analyze the genotype distributions and allele frequencies for ROCK2 Thr431Asn and Arg83Lys polymorphisms among breast cancer patients. In this case-control study, 223 patients with breast cancer were recruited and divided into two groups according to metastases (n = 128) and without metastases (n = 95). Genomic DNA from the patients and the control cases (n = 150) was analyzed by real-time PCR using a Light-Cycler. Neither genotype distributions nor the allele frequencies for the Arg83Lys polymorphism showed a significant difference between the groups. Although no marked changes were observed with nonmetastatic group, a statistically significant association was found between the control and metastatic group for the Thr431Asn polymorphism. Although homozygous carriers of the Thr431Thr genotype were more frequent, heterozygous carriers of the Thr431Asn genotype were less frequent among the metastatic patients than among controls. There was also an increase in Thr431 allele (60.5% in patients vs. 51.7% in controls) and decrease in Asn431 allele frequencies (48.3% in control vs. 39.5% in metastatic patients) in metastatic groups (p = 0.036). Our results demonstrate that Thr431Asn polymorphism of the ROCK2 gene could be a risk factor for the metastases of the breast cancer, and may help in predicting the prognosis.

Cytokine concentrations are not predictive of bacteremia in febrile neutropenic patients.

Assay of cytokines and C reactive protein (CRP) in different periods of febrile neutropenia may be helpful for early defining the risk in severe infections. We determined serum interleukin-6 (IL-6), interleukin-8 (IL-8), soluble interleukin-2 receptor (sIL-2R), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and CRP in 22 previously untreated patients with various malignancies. Samples were obtained in four different clinical periods of febrile neutropenia; prior to chemotherapy, afebrile neutropenic period after chemotherapy, febrile neutropenic period, and recovery period. When compared to sex-and age-matched group of healthy subjects, IL-6, IL-8, sIL-2R, and CRP levels were found to be elevated in all periods. The highest levels were encountered in the febrile neutropenic period. For predictivity purposes, the afebrile neutropenic period was the most important period. Serum sIL-2R, IL-6, IL-8 and CRP levels were elevated in this period. IL-8 levels showed the most stable elevation through different stages of febrile neutropenia. Serum IL-8 levels were found to have the most reliable and stable elevation in different clinical stages of febrile neutropenia. Nevertheless, IL-8 is not able to discriminate among risk groups and cannot be used as a predictive factor.

Detection of complete response to imatinib mesylate (Glivec ® /Gleevec ® ) with 18F-FDG PET/CT for low-grade endometrial stromal sarcoma

Malignant mesenchymal tumors consist of approximately 10% of uterine tumors. The majority of uterine sarcomas are leiomyosarcoma and endometrial stromal sarcoma (ESS). Surgery, radiotherapy, chemotherapy, and hormonal therapy are used for the treatment of ESS. Imatinib mesylate is indicated in the management of gastrointestinal stromal tumor and chronic myelogeneus leukemia. There is an interest to use imatinib mesylate in the treatment of c-kit positive ESS. We reported a case of 42-year-old female low-grade ESS progressed on chemotherapy and presented with objective response to imatinib mesylate. The treatment response was evaluated with FDG PET/CT. Complete metabolic response was detected. FDG PET, a sensitive method for tumor response evaluation on the basis of tumor metabolism changes, is useful for the evaluation of imatinib treatment in low-grade ESS.