Vehbi Erçolak

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.

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.

Retrospective Analysis of Neoadjuvant Chemotherapy for Breast Cancer in Turkish Patients

BACKGROUND Neoadjuvant systemic chemotherapy is the accepted approach for women with locally advanced breast cancer. Anthracycline- and taxane-based regimens have been extensively studied in clinical trials and consequently are widely used. In this study aimed to research the complete response (pCR) rates in different regimens for neoadjuvant setting and determine associated clinical and biological factors. METHODS This study included 63 patients diagnosed with breast carcinoma among 95 patients that had been treated with neoadjuvant chemotherapy between 2007 and 2010. TNM staging system was used for staging. The histologic response to neoadjuvant chemotherapy was characterized as a pCR when there was no evidence of residual invasive tumor in the breast or axillary lymph nodes. Biologic subclassification using estrogen receptor (ER), progesterone receptor (PR), HER2 were performed. Luminal A was defined as ER+, PR+, HER2-; Luminal B tumor was defined as ER+, PR-, HER2-; ER+, PR-, HER2+; ER-, PR+, HER2-; ER+, PR+, HER2+, HER2 like tumor ER-, PR+, HER2+; and triple negative tumor ER, PR, HER2 negative. RESULTS Patients median age was 54.14 (min-max: 30-75). Thirty-two patients (50.8%) were premenopausal and 31 (49.2%) were postmenopausal. Staging was performed postoperatively based on the pathology report and appropriated imaging modalities The TNM (tumor, lymph node, metastasis) system was used for clinical and pathological staging. Fifty-seven (90.5%) were invasive ductal carcinomas, 6 (9.5%) were other subtypes. Thirty nine (61.9%) were grade II and 24 (38.1%) were grade III. Seven (11.1%) patients were stage II and 56 (88.9) patients were stage III. The patients were classified for ER, PR receptor and HER2 positivity. Seventeen patients had complete response to chemotherapy. Forty patients (63.5%) were treated with dose dense regimen (cyclophosphamide 600 mg/m2 and doxorubicine 60 mg/m every two weeks than paclitaxel 175 mg/m2 every two weeks with filgrastim support) 40 patients (48%) were treated anthracycline and taxane containing regimens. Thirteen patients (76%) from 17 patients with pCR were treated with the dose dense regimen but without statistical significance (p=0.06). pCR was higher in HER2(-), ER(-), grade III, premenopausal patients. CONCLUSION pCR rate was higher in the group that treated with dose dense regimen, which should thus be the selected regimen in neoadjuvant setting. Some other factors can predict pCR in Turkish patients, like grade, menopausal status, triple negativity, percentage of ER positivity, and HER2 expression.

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.

Primary Intracerebral Myeloid Sarcoma

Background: Myeloid sarcoma rarely presents in the absence of systemic myeloid disease. Case Report: In this study, we present a case of intracerebral myeloid sarcoma with no diagnosis of any hematological disease in a 22-year-old male patient in whom brain magnetic resonance image revealed a meningioma. However, biopsy showed myeloid sarcoma. No myeloid disease was determined. The mass disappeared following 8 cycles of chemotherapy. In the literature, we determined only 8 similar cases cited between 1970 and 2011. Conclusion: Intracerebral myeloid sarcoma has currently no standard treatment and may be confused with a primary brain disease. Chemotherapy and/or radiotherapy are the most viable and widely used treatment modalities. Potential occurrence of hematological disease should also be closely followed due to conversion risks.

Bilateral primary adrenal non-hodgkin lymphoma.

Vehbi Erçolak1, Oğuz Kara2, Meral Günaldı2, Çiğdem Usul Afşar2, Berna Bozkurt Duman3, Arbil Açıkalın4, Melek Ergin4, Şeyda Erdoğan4 1Harran University Faculty of Medicine, Department of Medical Oncology, Şanlıurfa, Turkey 2Çukurova University Faculty of Medicine, Department of Medical Oncology Adana, Turkey 3Adana Training and Research Hospital, Department of Medical Oncology, Adana, Turkey 4Çukurova University Faculty of Medicine, Department of Pathology, Adana, Turkey

Evaluation of endometrial thickness and bone mineral density based on CYP2D6 polymorphisms in Turkish breast cancer patients receiving tamoxifen treatment.

Background: Several previous studies have examined the effect of CYP2D6 gene polymorphism on the efficacy and metabolism of tamoxifen (Tamoxifen Teva, Nolvadex) in the treatment of breast cancer. In the present study, the metabolic profiles associated with various CYP2D6 genotypes were evaluated. Method: In the present study 92 Turkish breast cancer patients with early-stage hormone receptor-positive tumors treated with adjuvant tamoxifen (20 mg) were evaluated for CYP2D6 genotype and metabolic profiles. Known side effects of tamoxifen treatment, including endometrial thickening, changes in serum lipid levels and bone density, and hepatosteatosis, were evaluated according to the CYP2D6 polymorphism. Result: The distribution of metabolic characteristics in the Turkish population was as follows: 77.1% normal metabolism, 11.5% intermediate metabolism, 5.2% ultrarapid metabolism, and 2.1% poor metabolism. The CYP2D6 genotypes associated with rapid metabolism were CYP2D6 3X*1/*1 duplication (DUP) and CYP2D6 2X*1/*2, while poor metabolism was associated with the genotypes CYP2D6 *3/*4 and CYP2D6 *6/*6. There was no statistically significant relationship between metabolic characteristics and bone density or hepatosteatosis. A statistically significant difference in total cholesterol and triglycerides was detected in lipid profile analysis (p = 0.003, p = 0.02). Assessment of endometrial thickness revealed a significant association of hyperplasia and poor metabolism, and an association between atrophy and ultrarapid metabolism (p = 0.01). Conclusion: Significant development of endometrial hyperplasia was identified among individuals with poor tamoxifen metabolism. As a result, tamoxifen may be a significant predictor of endometrial thickening among individuals with poor metabolic characteristics.

Carbamazepine and multiple myeloma: possible interaction.

To the Editor Epilepsy is the most common chronic neurological disease and patients are treated by various classes of antiepileptic drugs [1]. In addition to their acute side effects, there are long-term adverse effects of antiepileptic drugs [2]. Hemopoietic neoplasias such as lymphoma, multiple myeloma, and some solid cancers including lung, liver, pancreas, and gastrointestinal cancers are the malignant disorders most frequently discussed in relation to use of antiepileptic drugs [3,4]. The carcinogenic effect of carbamazepine is very limited. However, there are some case reports and series containing a limited number of cases of hypogammaglobulinemia, monoclonal gammopathy of undetermined significance (MGUS), and multiple myeloma [3,4,5,6,7,8,9,10,11]. We present here a 54-year-old woman with multiple myeloma with long exposure to carbamazepine. Vertebral fracture was detected and vertebroplasty was done urgently. There was no evidence of neurologic deficit. She had a history of 400 mg carbamazepine usage for more than 20 years due to idiopathic epilepsy. Laboratory examination showed total protein/albumin of 8.85/3.41 g/dL and calcium of 10.77 mg/dL (8.4-9.2); she had macrocytic anemia. Bence-Jones protein in the urine was not demonstrated. Protein electrophoresis showed an M-peak (Figure 1) with an elevated serum level of immunoglobulin G (IgG) of 2740 mg/dL. Immunoelectrophoresis revealed M-protein composed with a kappa chain. Bone marrow aspiration and biopsy showed 90% plasma cell infiltration and CD38 and kappa were positive. Cytogenetic analysis of bone marrow showed 17 p deletion (+), 13 q deletion (+), t (11;14), t (4;14). Histopathological examination of a vertebroplasty specimen revealed plasma infiltration. Carbamazepine usage was stopped and treatment was continued with valproic acid. A regimen containing bortezomib (1.3 g/m2), dexamethasone (40 mg), and zoledronic acid was prescribed. After 4 courses of chemotherapy, blood and bone marrow exams were normal. Stem cell transplantation was planned for consolidation. Carbamazepine-related multiple myeloma has been reported in a few case reports. It has been suggested that carbamazepine may cause the IgG type of M-protein multiple myeloma, MGUS, and hypogammaglobulinemia [5,6,9,11,12]. Our patient was younger than is usual for multiple myeloma. We can speculate that the exposure to an extrinsic factor may be associated with younger age in this case. The relationships among the duration of use of antiepileptic drugs, cumulative dose of antiepileptic drugs, and development of multiple myeloma are not known completely. In our case, multiple myeloma developed after 20 years of carbamazepine use. In conclusion, carbamazepine may be a potential drug in the development of multiple myeloma. For this reason, periodical evaluation of serum levels of immunoglobulin is necessary in patients receiving carbamazepine. Figure 1 Abnormal serum protein electrophoresis pattern in a patient with multiple myeloma. Note the large spike in the early gamma region. Conflict of Interest Statement The authors of this paper have no conflicts of interest, including specific financial interests, relationships, and/ or affiliations relevant to the subject matter or materials included.

Primary cutaneous small-cell carcinoma: a case report

Most commonly arising in the gastrointestinal and genitourinary tracts, extrapulmonary small-cell carcinoma is quite rare. Although its prognosis is very poor, complete remission or even cure can be achieved by combination of different treatment modalities. We report here a 32-year-old woman with a cutaneous gluteal mass diagnosed as small-cell carcinoma of the skin. Combination chemotherapy containing cisplatin and etoposide was started. Radiotherapy was administered after two courses of chemotherapy. Following radiotherapy, additional 4 courses of chemotherapy were given. She has been in remission for three years with no evidence of tumor recurrence.