Cigdem Usul Afsar

Risk factors for developing cardiotoxicity of trastuzumab in breast cancer patients: An observational single-centre study

Background Trastuzumab is a recombinant humanized monoclonal antibody used to treat human epidermal growth factor receptor 2 positive breast cancer, with recognized associated cardiotoxicity. In this retrospective observational study, we investigated associated cardiotoxicity on clinical outcomes using trastuzumab in women referred to our clinic. Materials and methods The study was made up of 111 women with human epidermal growth factor receptor 2-overexpressing breast cancer who received trastuzumab in the Medical Oncology Department, between 2010 and 2013. Results A > 10% reduction of the baseline fraction of the left ventricular ejection fraction was observed in 18 (16.21%) women. Two individuals (1.8%) suffered from symptomatic heart failure, seven women showed cardiac symptoms and nine women showed asymptomatic decline of left ventricular ejection fraction. Risk factors for cardiotoxicity in the group included: postmenopausal status (p = 0.01), hypertension (p = 0.002), obesity (p = 0.0001), previously diagnosed coronary artery disease (p = 0.0001) and smoking (p = 0.03). Conclusion The aforementioned factors pose a risk for cardiotoxicity. We found postmenopausal status, hypertension, obesity, previous coronary artery disease and smoking to be associated with an increased risk of cardiac dysfunction in women using trastuzumab. While administering trastuzumab to women who have these conditions, one must be aware of the risk of cardiotoxicity of trastuzumab.

Pancreatic Carcinoma, Thrombosis and Mean Platelet Volume: Single Center Experience from the Southeast Region of Turkey

BACKGROUND The aim of this study was to investigate the general characteristics of patients with deep vein thrombosis (DVT) and pancreatic cancer as well as evaluate the relationship between mean platelet volume (MPV), DVT and survival. MATERIALS AND METHODS Seventy-seven patients with pancreatic cancer, who were admitted to Cukurova University Medical Faculty, Department of Medical Oncology, were enrolled in the study RESULTS The mean age was 59±20. Forty-nine (63.6%) were men and 28 women (36.4%) . Sixty-eight (88.3%) patients had adenocarcinoma and 9 (11.7%) had a malignant epithelial tumor. Thirty-six (46.7%) had liver metastasis at diagnosis. Twenty-six (33.8%) patients were alive, 20 (26%) were dead and in 31 (40.2%) the status was unknown. Only 14 (18.1%) patients had DVT. In 42 (54.5%) patients MPV values were normal, in 28 (36.4%) patients they were above normal, and in 7 (9.1%) patients they were below normal. There was no statistically significant difference between gender, tumour localization, chemotherapy and survival rates (p:0.56, p:0.11, p:0.21). There was no significant difference between DVT, gender, localisation, histological subtype, the presence of metastasis, stage and if the patient had been treated with chemotherapy (p:0.5, p:0.6, p:0.2, p:0.32, p:0.1, p:0.84). There was also no significant difference between MPV and DVT (p:0.57) but there was a significant difference between liver metastasis and DVT (p:0.02). Age, stage, the presence of metastasis and DVT were prognostic in pancreatic cancer patients. CONCLUSIONS Cases of pancreatic cancer with liver metastasis should be studied more carefully as thrombosis is more common in these patients.

Neurofibromatosis type 1, gastrointestinal stromal tumor, leiomyosarcoma and osteosarcoma: Four cases of rare tumors and a review of the literature

BACKGROUND Neurofibromatosis type 1 (NF1) is a genetic syndrome that predisposes patients to benign and malignant tumor development. Patients with NF1 develop multiple neurofibromas that can transform into aggressive sarcomas known as malignant peripheral nerve sheath tumors. In contrast, malignant tumors unrelated to the nervous system rarely coexist with neurofibromatosis. The aim of this article was to present four cases of adult NF1 patients with malignant tumors unrelated to the nervous system as well as a bibliographic search for papers describing these tumors in NF1, focusing on osteosarcomas, gastrointestinal stromal tumors (GISTs), leiomyosarcomas and somatostatinomas and their genetic alterations in NF1. METHODS Search engines such as PubMed and MEDLINE were browsed for English-language articles since 1989 using a list of keywords, as well as references from review articles. Search terms were NF1, osteosarcoma, leiomyosarcoma, somatostatinoma and GIST. Data were summarized in a table at the end of the Results section. RESULTS In our four NF1 cases, there were one osteosarcoma, one leiomyosarcoma, one somatostatinoma and GIST and one GIST. NF1 was diagnosed at an adult age when these patients were admitted to our oncology department. The results generated by the literature search yielded 75 articles about NF and GIST. We summarized the clinical characteristics of 43 patients with NF1 and somatostatinoma. Forty-five articles involving NF and osteosarcoma were found, and of these, 26 involved NF1; from these articles, we identified the clinical features of 8 patients. Twenty-five articles were found concerning NF1 and leiomyosarcoma, and of those, we summarized the clinical features of 15 patients. CONCLUSIONS Here we reviewed somatostatinomas, GISTs, osteosarcomas and leiomyosarcomas occurring in NF1 patients. Patients with NF1 who present with gastrointestinal symptoms, should be carefully evaluated carefully with a high index of suspicion of potential GISTs, periampullary and duodenal tumors. Patients with pathological fractures or bone pain along with NF1 should be carefully screened for malignant bone tumors. Patients with NF1 can develop leiomyosarcoma less frequently than other malignancies, but the association of uterine leiomyoma and NF1 may not be fortuitous. Somatic mutations were defined for frequent tumors, including neurogenic tumors and GISTs but not for sarcomas due to the complexity of underlying mechanisms of the disease and tumorigenesis. Based on the findings; all NF patients can develop malignant tumors, including the less frequently observed ones. Therefore, we recommend that new genetic studies should be performed for rare malignancies in cases of NF1.

Retrospective Analysis of 498 Primary Soft Tissue Sarcomas in a Single Turkish Centre

BACKGROUND Soft tissue sarcomas (STS) must be managed with a team involving pathologists, radiologists, surgeons, radiation therapists and medical oncologists. Treatment modalities and demographic characteristics of Turkish STS were analysed in the current study. MATERIAL-METHODS Primary adult STS followed between 1999- 2010 in Cukurova University Medical Faculty Department of Medical Oncology were analyzed retrospectively. RESULTS Of the total of 498 patients, 238 were male and 260 female. The most seen adult sarcomas were leomyosarcoma (23%). Localization of disease was upper extremity (8.8%), lower extremity (24.7%), head-neck 8.2%, thoracic 8%, retroperitoneal 5.6%, uterine 12.4%, abdominal 10%, pelvic region 3.6 and other regions 10%. Some 13.1% were early stage, 10.2% locally advanced, 8.2% metastatic and 12.2% recurrent disease. Patients were treated with neoadjuvant/adjuvant (12%) or palliative chemotherapy (7.2%) and 11.4% patients did not receive chemotherapy. Surgery was performed as radical or conservative. The most preferred regimen was MAID combination chemotherapy in the rate of 17.6%. The most common metastatic site was lung (18.1%). The overall survival was 45 months (95%CI 30-59), 36 months in men and 55 months in women, with no statistically significant difference (p=0.5). The survival rates were not different between the group of adjuvant and palliative chemotherapy (respectively 28 versus 18 months) (p=0.06), but radical surgery at 37 months was better than 22 months for conservative surgery (p=0.0001). No differences were evident for localization (p=0.152). Locally advanced group had higher overall survival rates (72 months) than other stages (p=0.0001). CONCLUSION STS can be treated successfully with surgery, chemotherapy and radiotherapy. The survival rates of Turkish people were higher in locally advanced group; these results show the importance of multimodality treatment approach and radical surgery.

Elevated Serum Levels of Heat Shock Protein 70 Are Associated with Breast Cancer

Breast cancer (BC) is the most frequent cause of cancer death in women throughout the world. Thus, it is necessary to establish sensitive screening, diagnosis and treatment methods for BC. Heat shock protein 70 (HSP70) is an important cellular stress response protein that protects cells from apoptosis. Recent studies have shown that serum HSP70 levels may provide clinically important information in various types of cancer. HSP70 is also overexpressed in BC, which is known to be associated with cancer progression, apoptosis and cell proliferation. However, the serum level of HSP70 and its diagnostic and prognostic potential in BC have not been investigated yet. The aim of this study was to determine the usefulness of serum HSP70 level as a diagnostic test and its predictive value in patients with BC. This prospective study consisted of 45 female patients diagnosed with BC and 16 healthy women who were matched for age and body mass index (BMI). Enzyme-linked immunosorbent assay (ELISA) technique was used to measure the serum level of HSP70. The serum level of HSP70 was significantly higher in patients with BC than in the healthy control group (5.98 ± 2.05 vs. 1.49 ± 0.47 ng/ml, p = 0.001). HSP70 level > 2.41 ng/ml was the best cutoff value to predict BC (97.78% sensitivity and 93.75% specificity). This study shows that HSP70 can be used as an adjunct to other diagnostic tests for BC and may be helpful for identifying patients at increased risk of BC.

Clinical significance of serum omentin-1 levels in patients with pancreatic adenocarcinoma.

Background Omentin is related with metabolic syndrome and obesity. Pancreatic adenocarcinoma (PA) is a lethal and obesity-linked malignancy. This study was conducted to investigate the serum levels of omentin in patients with PA and the relationship with tumor progression and known prognostic parameters. Material and methods Serum samples were obtained from thirty-three patients on first admission before any treatment. Age, sex and body mass index (BMI) matched 30 healthy controls were included in the analysis. Both serum omentin levels were measured using enzyme-linked immunosorbent assay (ELISA). Results The median age at diagnosis was 59 years (32–84 years). Twenty (61%) patients were men and the remaining were women. The most common metastatic site was liver in 23 patients with metastasis (n = 19, 83%). Thirty-nine percent of 23 metastatic patients who received palliative chemotherapy (CTx) were CTx–responsive. Median overall survival of the whole group was 41.3 ± 8.3 weeks [95% confidence interval (CI) = 25–58 weeks]. The baseline serum omentin levels were significantly higher in patients with PA than in the control group (p < 0.001). Serum omentin levels were significantly higher in patients with larger pathologic tumor size compared with smaller size (p = 0.03). Conversely, serum omentin concentration was found to have no prognostic role on survival (p = 0.54). Conclusion Serum levels of omentin may have a good diagnostic role in patients with PA.

Capecitabine-Induced Hypertriglyceridemia and Hyperglycemia: Two Cases

Capecitabine has shown significant antitumor activity against anthracycline/taxane refractory breast cancer and advanced colorectal carcinoma. The main drug-related adverse effects are palmar-plantar erythrodysesthesia (hand-foot syndrome), diarrhea and stomatitis. Dyslipidemia is a rare but important side effect of this drug. The mechanism of capecitabine-induced hypertriglyceridemia (CI-HTG) is unclear. It may be due to the decreased activities of lipoprotein lipase and hepatic triglyceride lipase. This report is associated with 2 patients who developed severe HTG when receiving capecitabine. Capecitabine was discountinued and antilipemic treatments were given and both cases are in follow-up with normal lipid levels. This report describes CI-HTG and possible pathogenetic mechanisms and the literature is reviewed.

Clinical significance of serum claudin-1 and claudin-7 levels in patients with colorectal cancer.

The present study aimed to investigate the serum levels and clinical relevance of claudin (CLDN) 1 and CLDN7 in patients with colorectal cancer (CRC). A total of 140 patients with a pathologically confirmed diagnosis of CRC were enrolled in this study. The serum levels of CLDN1 and CLDN7 were determined using the solid-phase sandwich ELISA method. A total of 40 healthy age- and gender-matched controls were included in the analysis. The median age of the patients was 60 years (range, 24–84 years). The localization of the tumor in the majority of the patients was the colon (n=81, 58%). Of the 55 metastatic patients who received palliative chemotheraphy, 31% were chemotherapy-responsive. The baseline median serum CLDN1 and CLDN7 levels were significantly lower in non-metastatic and metastatic patients compared with those in healthy controls (CLND1, P=0.008 and 0.002; and CLND7, P=0.002 and 0.002, respectively). Moreover, known clinical variables, including poor performance status and high carcinoembryonic antigen (CEA) levels were found to be associated with lower serum CLDN1 concentrations for all patients (P=0.03 and P=0.03, respectively). High T stage and high CEA levels were found to be correlated with lower serum CLDN7 concentrations for all patients (P=0.04 and 0.03, respectively). A correlation was identified between CLDN1 and CLDN7 levels in non-metastatic and metastatic CRC patients (both P-values <0.001). Our study results did not reveal any statistical significance for serum CLDN1 or CLND7 concentrations regarding progression-free and overall survival rate. Therefore, reduced serum levels of CLDN1 and CLND7 may be useful markers in the differential diagnosis of CRC.

PRAME Expression and Its Clinical Relevance in Hodgkin's Lymphoma.

Objectives: Although Hodgkins lymphoma (HL) is one of the most curable cancers in adult patients, new targets have to be defined in cases resistant to traditional chemotherapy. The preferentially expressed antigen of melanoma (PRAME) is a cancer testis antigen and its expression is very scarce or absent in normal tissues. For this reason PRAME is a promising candidate for tumor immunotherapy. The aim of this study is to understand the correlation of PRAME expression with prognostic factors in HL, to determine the utility of PRAME as a targeted molecule for immunotherapy and to compare real-time polymerase chain reaction (real-time PCR) and immunohistochemistry (IHC) for the detection of PRAME. Methods: In 82 patients, PRAME was studied using real-time PCR and IHC. Data analyses were performed using statistical methods such as t test, Mann-Whitney U test, χ2 test, Kaplan-Meier method, log-rank test and Cox regression analysis. Results: PRAME was detected in 15 (18.3%) patients using IHC and in 8 (9.8%) patients using real-time PCR. A correlation was found between PRAME positivity and higher International Prognostic Score (p = 0.039). PRAME positivity detected using real-time PCR was found to be correlated with shorter disease-free survival (DFS) and overall survival (OS, p = 0.0005). Discussion: The demonstration of PRAME especially in histiocytes and Reed-Sternberg cells may provide guidance for immunotherapy. Although PRAME positivity increases the risk for death (3.56), independent risk factors that affected DFS and OS occurred in advanced age and high-risk groups. Conclusion: Although real-time PCR is sensitive in the detection of PRAME, IHC can be another useful method. Despite the need for studies conducted on larger patient samples, PRAME expression is considered as a poor prognostic parameter in HL.

Abdominal actinomycosis with multiple myeloma: A case report.

Actinomycosis is a chronic suppurative infection, for which immune suppression is a predisposing factor. In unusual cases, this disease may present as an abdominal wall involvement simulating a soft tissue tumor as seen in the present case. The presented patient had no signs of trauma or surgical approach and the pathology was considered to be a primary abdominal wall actinomycosis. Preoperative diagnosis is difficult due to the nonspecific nature of clinical presentation, radiographic and laboratory findings. Surgery combined with antibiotic treatment is a curative approach for this relatively rare infection. Surgeons must be aware of this disease in order to ensure correct diagnosis and to prevent performing any unnecessary procedures. The present study describes a case of abdominal actinomycosis with multiple myeloma, together with a review of important points related to this disease.