Mehmet Metin Seker

Survival analysis and prognostic factors for neuroendocrine tumors in Turkey.

BACKGROUND This study aimed to determine the demographical distribution, survival and prognostic factors for neuroendocrine tumors monitored in our clinic. MATERIALS AND METHODS Data for 52 patients who were admitted to Cumhuriyet University Medical Faculty Training Research and Practice Hospital Oncology Center between 2006 and 2012 and were diagnosed and treated for neuroendocrine tumors were investigated. RESULTS Of the total, 30 (58%) were females and 22 (42%) were males. The localization of the disease was gastroenteropancreatic in 29 (56%) patients and other sites in 23 (44%). The most frequently involved organ in the gastroenteropancreatic system was the stomach (n=10, 19%) and the most frequently involved organ in other regions was the lungs (n=10, 19%). No correlation was found between immunohistochemical staining for proteins such as chromogranin A, synaptophysin, and NSE and the grade of the tumor. The patients were followed-up at a median of 24 months (1-90 months). The three-year overall survival rate was 71%: 100% in stage I, 88% in stage II, 80% in stage III, and 40% in stage IV. The three-year survival rate was 78% in tumors localized in the gastroenteropancreatic region, and 54% in tumors localized in other organs. In the univariate analysis, gender, age, performance status of the patients, grade, localization, surgical treatment, and neutrophil/ lymphocyte ratio (≤ 5 versus >5) affected the prognosis of the patients. CONCLUSIONS Most of the tumors were localized in the gastroenteropancreatic region, and the three-year survival rate in tumors localized in this region was better than the tumors localized in other sites. Surgical treatment was a positive independent prognostic factor, whereas Grade 3 and a neutrophil/lymphocyte ratio of >5 were negative independent prognostic factors.

Predictive Role of Neutrophil Gelatinase-Associated Lipocalin in Early Diagnosis of Platin-Induced Renal Injury

BACKGROUND Acute kidney injury is an important issue in chemotherapy receiving patients an neutrophil gelatinase-associated lipocalin has been proposed as a novel marker. We here aimed to assess the role of urinary levels for assessment after platin exposure. MATERIALS AND METHODS Patients who had treated with cisplatin or carboplatin or oxaliplatin containg regimens were included in this study. Baseline and postchemotherapy serum urea, creatinine, urine neutrophil gelatinase-associated lipocalin and urine creatinine levels were determined. To avoid the effects of hydration during chemotherapy infusion the urinary neutrophil gelatinase-associated lipocalin/urine creatinine ratio was used to determine acute kidney injury. RESULTS Of a total of 42 patients receiving platin compounds,14 (33.3%) received cisplatin containing regimens, 14 (33.3%) received carboplatin and 14 (33.3%) oxaliplatin. The median age was 60 (37-76) years. Nineteen of the patients (45.2%) had lung cancer, 12 (28.6%) colorectal cancer and 11 (26.2%) others. The median pre and post chemotherapy urine neutrophil gelatinase-associated lipocalin/urine creatinin ratio was 15.6 ng/mg and 35.8 ng/mg (p=0.041) in the cisplatin group, 32.5 ng/mg and 86.3 ng/mg (p=0.004) in the carboplatin group and 40.9 ng/mg and 62.3 ng/ mg (p=0.243) in the oxaliplatin group. CONCLUSIONS Nephrotoxicity is a serious side effect of chemotherapeutic agentslike cisplatin and carbopaltin, but only to a lower extent oxaliplatin. All platin compounds must be used carefully and urine neutrophil gelatinase-associated lipocalin measurement seems to be promising in detecting acute kidney injury earlier than with creatinine.

Treatment and Outcomes of Ewing Sarcoma in Turkish Adults: A Single Centre Experience

BACKGROUND Ewing sarcoma is a small round cell tumor arising from soft tissue and bone that predominantly affects children and adolescents. The most unfavorable prognostic factor is the presence of distant metastasis at the time of diagnosis. MATERIALS AND METHODS The records of 26 Ewing sarcoma patients (14 male, 12 female) were re-evaluated retrospectively. RESULTS The median age was 26.5 (19-42) years. Eight patients (31%) showed a primary tumor in their extremities, 8 (31%) in the thorax, 4 (15%) at the vertebra, 4 (15%) in the head and neck, and 2 (8%) in the abdomen. Five patients (19%) had distant metastasis at diagnosis. The median progression-free survival was 72 months and 10 months in localized and metastatic disease, respectively (p=0.005). The overall survival rate was 19 months in metastatic disease, and the 5-year overall survival rate was 64% in localized disease (p=0.006). Patients who had localized disease in the extremities and were under age 30 had a favorable prognosis. CONCLUSIONS Although Ewing sarcoma is a tumor affecting children and adolescents, it may be seen in adults, where the prognosis is generally worse. Although it is a highly malignant tumor, it is possible to achieve improved survival with combined modality treatments.

Do neutrophil gelatinase-associated lipocalin and interleukin-18 predict renal dysfunction in patients with familial Mediterranean fever and amyloidosis?

Abstract Background: The aim of this study was to evaluate whether neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) predict renal disfunction in patients with familial Mediterranean fever (FMF). Methods: This prospective study consisted of 102 patients with FMF in attack-free period, and 40 matched healthy controls. Of the patients, nine were diagnosed as amyloidosis. The patients were divided into two groups according to eGFR as below 120 mL per minute and above 120 mL per minute. Also, patients were divided into three groups according to the degree of urinary albumin excretion as normoalbuminuric, microalbuminuric, and macroalbuminuric. The serum levels of IL-18 (sIL-18) and NGAL (sNGAL), and urinary levels of IL-18 (uIL-18) and NGAL (uNGAL) were measured by using ELISA kits. Results: The levels of sIL-18, sNGAL, uIL-18, and uNGAL were detected significantly higher in FMF patients, particularly in patients with amyloidosis, when compared to controls. sNGAL, uIL-18, and uNGAL were significantly higher in patients with eGFR < 120 mL per minute than in patients with eGFR ≥ 120 mL per minute. sNGAL, uIL-18, and uNGAL were correlated significantly with urinary albumin excretion, additionally, were inverse correlated with eGFR. The most remarkable findings of this study are of the higher values of sIL-18, sNGAL, uIL-18, and uNGAL in both normoalbuminuric FMF patients and patients with eGFR ≥ 120 mL per minute. Conclusions: The results of this study suggest that sIL-18, uIL-18, sNGAL, and uNGAL are reliable markers of early renal disfunction in FMF patients, and may let us take measures from the early stage of renal involvement.

Lung cancer in women: a single institution experience with 50 patients.

BACKGROUND Lung cancer is the most common cause of cancer-related death worldwide. The incidence of lung cancer is aproximately 7-8 thousand percent in Turkish women. In this study, we aimed to evaluate the clinical, pathological properties and survival data of female patients with lung cancer who were treated in our center. MATERIALS AND METHODS From 2007 to 2012, 50 women with lung cancer were enrolled. Patient data were evaluated retrospectively. RESULTS The median age was 61 (40-81). Forty patients (80%) were diagnosed with non small cell lung cancer (NSCLC), 10 patients (20%) were small cell carcinoma (SCC). Twelve (24%) patients were smokers and 13 of 16 non-smokers had a history of exposure to asbestos. The most common histologic subtype was adenocarcinoma (46%) and this accounted for 71% in patients with exposure to asbestos. The most common initial Eastern Cooperative Oncology Group (ECOG) performance score was 1 (24 patients, 48%) and initial stage was IV (25 patients, 50%) in the study group. During the median 15 months (1-96 months) followup period: 1 year overall survival (OS) was 68%, 2year overall survival was 36% and the median survival time was 19 months. According to univariate analysis, poor ECOG performance status, advanced stage, anemia and weight loss at time of diagnosis were negative prognostic factors. However, adenocarcinoma sub-type was a positive prognostic factor. CONCLUSIONS In this study NSCLC sub-type, poor ECOG performance score, advanced stage, anemia and weight loss were prognostic factors in Turkish women with lung cancer.

Clinicopathologic Features and Prognosis of Osteosarcoma in Turkish Adults

BACKGROUND Osteosarcomas are the most common solid malignancies of bone. In the last two decades there have been no concrete developments in their systemic treatment. In this trial we aimed to present our osteosarcoma patient clinical and demographic outcomes. MATERIALS AND METHODS Patients treated and followed up for osteosarcoma in Ankara Numune Education and Research Hospital from 2002 to 2012 were reviewed retrospectively. RESULTS A total of 21 patients (15 male, 6 female) were diagnosed with osteosarcoma. The disease was located at extremities in 76% and in 14% was metastatic at the time of diagnosis. Median disease free survival (DFS) was 36 months in non-metastatic patients and median progression free survival (PFS) was 2 months in metastatic patients (p<0.0001). Median overall survival (OS) was 80 months and 4 months, respectively (p=0.012). There were no survival differences in terms of presentation with pathological fracture, tumor size, tumor grade, alkaline phosphatase and lactate dehydrogenase level and type of chemotherapy regimen. CONCLUSIONS Tumor site and stages are the most important prognostic factors for osteosarcoma. Extremity primary tumors have beter survival rates than non-extremity tumors. As a result of the use of effective chemotherapy the long term survival rates have improved from 10-20% to 60-70% in the last decades but we need more active agents, especially for metastatic cases.

The prognostic value of UHRF-1 and p53 in gastric cancer.

Background/Aims: This study aimed to examine whether UHRF-1 and p53 overexpression is a prognostic marker for gastric cancer. Patients and Methods: Sixty-four patients with gastric cancer (study group) and 23 patients with gastritis (control group) were evaluated. Immunohistochemistry was used to examine expression of UHRF-1 and p53 in gastric cancers and a control group diagnosed with gastritis. Results: The median age was 63 years (18-83 years) in the study group. UHRF-1 was positive in 15 (23%) patients with gastric cancer and five (21.7%) patients with gastritis (P = 0.559). UHRF1 expression level in gastric cancer is more powerful than in gastritis (P = 0.046). Thirty-seven (61%) patients with gastric cancer and only one patient with gastritis were p53 positive (P < 0.001). After a median follow-up of 12 months (1–110), the 2-year overall survival rates were 55% and 30% in negative and positive p53, respectively (P = 0.084). Also, the 2-year overall survival rates were 45% and 53% in negative and positive UHRF-1, respectively (P = 0.132). Conclusion: According to this study, UHRF-1and p53 were not prognostic factors for gastric cancer, whereas they may have a diagnostic value for differantiating between gastric cancer and gastritis.

Investigation of antitumor effects of sorafenib and lapatinib alone and in combination on MCF-7 breast cancer cells.

BACKGROUND Breast cancer evolution and tumor progression are controlled by complex interactions between steroid receptors and growth factor receptor signaling. Aberrant growth factor receptor signaling can augment or suppress estrogen receptor function in hormone-dependent breast cancer cells. Thus, we aimed to investigate antitumor effects of sorafenib and lapatinib alone and in combination on MCF-7 breast cancer cells. MATERIALS AND METHODS Cytotoxicity of the sorafenib and lapatinib was tested in MCF-7 cells by XTT assays. 50, 25, 12.5 and 6.25μM concentrations of sorafenib and 200, 100, 50 and 25μM concentrations of lapatinib were administered alone and in combination. Results were evaluated as absorbance at 450nM and IC50 values are calculated according to the absorbance data RESULTS Both sorafenib and lapatinib showed concentration dependent cytotoxic effects on MCF-7 cells. Sorafenib exerted cytotoxic effects with an IC50 value of 32.0μM; in contrast with lapatinib the IC50 was 136.6μM. When sorafenib and lapatinib combined, lapatinib increased cytotoxic effects of sorafenib at its ineffective concentrations. Also at the concentrations where both drugs had cytotoxic effects, combination show strong anticancer effects and killed approximately 70 percent of breast cancer cells. CONCLUSIONS Combinations of tyrosine kinase inhibitors and cytotoxic agents or molecular targeted therapy has been successful for many types of cancer. The present study shows that both sorafenib and lapatinib alone are effective in the treatment of breast cancer. Also a combination of these two agents may be a promising therapeutic option in treatment of breast cancer.

Orbital metastasis of endocervical stromal sarcoma: a rare tumor and an uncommon metastasis

Endocervical stromal sarcoma (ECSS) is a very rare uterine sarcoma. The most common presentation is pelvic mass and vaginal bleeding. The mainstay of treatment is surgery. There is no consensus on the adjuvant treatment. Relapses are usually in the pelvic and abdominal regions. To a lesser extent, lung, liver and bone metastases may be seen. A 46-year-old woman had total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy (BSO) performed due to endometrial polyp and leiomyoma. Six months after the TAH-BSO, she was admitted to the hospital with cough and hemoptysis. A thoracic mass was detected, and a biopsy was done. The diagnosis was low-grade ECSS metastasis. One week after thoracotomy, she was admitted to the hospital with loss of vision in the left eye. An orbital mass was detected with magnetic resonance imaging. Endometrial and cervical pathology preparations were reassessed and were compatible with ECSS. We performed mammography, thorax, and abdomen and cranial imaging to rule out other malignancies that may cause lung and orbital metastasis. Partial remission was achieved with systemic chemotherapy and orbital radiotherapy. Orbital metastasis may be seen in ECSS patients. Although we have less knowledge about the choice of chemotherapeutic agents, ifosfamide and doxorubicin are effective in treating ECSS.

Anti-Ri-associated paraneoplastic neurological syndrome: Initial symptom of breast cancer with HER2 overexpression and treatment by dual HER2 blockade

Paraneoplastic neurological syndrome is associated with anti-Ri antibodies, which are typically present with opsoclonus–myoclonus–ataxia. Human epidermal growth factor receptor 2 (HER2) overexpression is present in 15%–25% of breast cancer and is associated with poor prognosis. There are a few reports of paraneoplastic neurological syndrome associated with HER2-positive breast cancer in the literature, of which most are anti-Yo-associated paraneoplastic neurological syndrome. We present herein the case of a female patient with HER2-positive breast cancer who had atypical anti-Ri antibody associated with opsoclonus–myoclonus paraneoplastic neurological syndrome. Following the diagnosis of paraneoplastic syndrome, chemotherapy with dual HER2 blockade and immunomodulating treatment including intravenous immunoglobulin and oral prednisolone were administered. Although the patient was negative for serum anti-Ri antibodies, there was partial clinical improvement and her neurological deficit persisted. To our knowledge, this is the first case report of female patient with HER2-positive breast cancer who had atypical anti-Ri antibody associated with opsoclonus–myoclonus paraneoplastic neurological syndrome and treated with dual HER2 blockade.