Metachronous Synovial Sarcoma After Treatment of Mixed Germ Cell Tumor in a Child with Complete Gonadal Dysgenesis.

Patients with complete XY gonadal dysgenesis (GD) show a high predisposition to germ cell tumors (GCT). Patients with coexistence of GCT and GD have been reported previously. Here we present a 15-year-old girl with mixed GCT and GD who also developed an intra-abdominal synovial sarcoma one year after the treatment. This is the first report, to our knowledge, of synovial sarcoma associated with XY GD.

Malignant epitheloid angiomyolipoma of the kidney in a child treated with sunitinib, everolimus and axitinib.

The malignant variant of epithelioid angiomyolipoma (EAML) of the kidney is uncommon, extremely aggressive and behaves like a renal cell carcinoma. We present a case of a 12-year-old male with malignant EAML who was treated according to adult treatment protocols. To our knowledge, axitinib has not been used before in children. We conclude that adult protocols, in this rare case, could be safely used in rare childhood malignancies.

Metastatic Basal cell carcinoma accompanying gorlin syndrome.

Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

Prognostic factors in gastrointestinal stromal tumors: multicenter experience of 333 cases from Turkey.

BACKGROUND/AIMS: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract. In an attempt to survey the approximate incidence, clinicopathological characteristics, and immunophenotypic features of GISTs in Turkey, we conducted a clinicopathological and immunohistochemical analysis of GISTs. METHODOLOGY: Three hundred and thirty-three patients with GIST from nine institutions in Turkey were retrospectively evaluated. RESULTS: Between January 2001 and March 2011, a total of 333 patients with GISTs were included; of these, 204 (61.2%) were male and 129 (38.8%) were female. The median age was 55 years (range; 22-102 years). At the median follow-up of 26 months (range; 4-166 months), the 1-, 3- and 5-year OS rates of the 333 patients were 96.9%, 85.8% and 78.5%, respectively. The 5-year DFS rate was 40%. The 5-year OS rate and median OS time for the patients with R0 resection were significantly higher than for patients with metastatic diseases (79.7 vs. 75.7% and not reached vs. 115 months, respectively, p=0.04). CONCLUSION: Although our results should be confirmed by prospective studies, we believe that they contribute to the literature because the study included both resectable and metastatic or unresectable GIST patients and multicenter findings from Turkey.

Cisplatin plus docetaxel combination in the first-line treatment of metastatic non-small cell lung cancer.

AIMS: To evaluate activity and toxicity of cisplatin plus docetaxel combination in the first-line treatment of chemotherapy-naive patients with metastatic non-small cell lung cancer. PATIENTS AND METHODS: Between October 2004 and July 2008, 186 patients with metastatic non-small cell lung cancer treated with first-line cisplatin plus docetaxel were retrospectively evaluated in 7 centers. The chemotherapy schedule consisted of cisplatin, 75 mg/m(2) iv infusion, and docetaxel, 75 mg/m(2) iv infusion on day 1, every 3 weeks. RESULTS: Median age was 56 years (range, 28-75). Eighteen patients (9.7%) were females and 168 (90.3%) were males, with a median ECOG performance status of 1 (range, 0-2). A total of 833 cycles of chemotherapy was administered (median, 4 cycles; range, 1-6). Two patients (1.1%) achieved clinical complete response, 77 patients (41.4%) partial response, and 66 patients (35.5%) stable disease. Median time to disease progression was 6 months (95% CI, 5.54-6.46). Median overall survival was 14.6 months (95% CI, 11.47-17.73). One- and 2-year overall survival was 55.2% and 19.7%, respectively. The most common grade 3-4 hematological toxicities were neutropenia (n = 32, 17.2%) and anemia (n = 4, 2.2%). CONCLUSIONS: The cisplatin plus docetaxel combination was effective and safe in the first-line treatment of patients with metastatic non-small cell lung cancer.

Radiation induced early necrosis in patients with malignant gliomas receiving temozolomide.

BACKGROUND: Temozolomide is the major drug in the treatment of malignant gliomas. Radiation induced necrosis can behave radiologically and clinically like a recurrent tumor. The major problem is the differentiation between recurrence and radiation injury especially in early phases of treatment. The aim of this study was to evaluate the patients receiving temozolomide showing early clinical or radiological progression and impact of early necrosis on follow-up. PATIENTS AND METHODS: We retrospectively evaluated medical records of 67 patients with malignant glioma receiving temozolomide. All patients received concomitant radiotherapy and temozolomide followed by adjuvant temozolomide. In case of any radiological or clinical progression, MRI spectroscopy evaluation was used to confirm tumoral progression. RESULTS: Radiological or clinical progression was observed in 17 (25.4%) patients. Early radiation induced necrosis was diagnosed in 4 of 17 patients (23.5%) by surgery (n=3) and MRI spectroscopy (n=1). The observed incidence of pseudoprogression was 4 in 67 (6%) patients. Patients with diagnosis of early radiation injury had median progression-free survival of 7 months compared to 5 months in patients without radiation damage (p=0.004). However, there was no statistically significant difference in terms of overall survival between groups. CONCLUSION: Temozolomide can cause early radiation induced injury which can mimic progressive tumor. Although the discrimination between two entities results in the accurate evaluation of response to therapy and benefits those patients, it did not affect overall survival. MRI spectroscopy is a valuable tool to define early radiation necrosis and should be further evaluated in larger prospective studies.

Synchronous bilateral breast cancer in an aged male patient.

BACKGROUND: Male breast cancer is an uncommon disease. Moreover, synchronous bilateral breast cancer is extremely rare in men. The management is still undefined, although it shows similarities to breast cancers in women. CASE REPORT: We report the case of a 66-year-old male patient who presented with palpable bilateral breast masses. Synchronous bilateral breast cancer was diagnosed with imaging studies and tru-cut biopsy. Histopathological examination revealed bilateral early-stage breast cancer. None of the possible predisposing factors, including hormonal and hereditary history, could be detected. Following bilateral modified radical mastectomy, the patient received adjuvant chemotherapy with tamoxifen. The pertinent literature is reviewed. CONCLUSION: More studies are warranted to better identify possible risk factors for male breast cancers.

Serum M30 levels are associated with survival in advanced gastric carcinoma patients.

BACKGROUND: Cytokeratin 18 (CK-18) is a cytoskeleton protein of epithelial cells which are released into the circulation during necrotic or apoptotic cell death. M30 detects caspase-cleaved neo-epitope of CK-18; whereas M 65 measures whole length intact protein. We aimed to evaluate the prognostic significance of serum M65 and M30 levels in patients with gastric carcinoma. METHODS: Thirty eight patients with advanced disease were included in the study. Thirty-two healthy people were chosen as control group. Serum M65 and M30 levels were measured by quantitative ELISA method. RESULTS: Serum M65 levels were found significantly elevated in patients compared to control group (385.7+/-280.6 vs. 200.2+/-164.5, p=0.002). Serum M30 levels were significantly increased in patients compared to the control group (204.6+/-245 vs. 106.5+/-17.5, p=0.03). Patients with metastatic disease had significantly higher levels of serum M30 compared to patients with locally advanced disease (267.1+/-296.1 vs. 102.3+/-53.2, p=0.03). Serum M30 and M65 levels were evaluated in respect to survival. Best cut-off value for the prediction of death for M30 antigen level was 83.8U/L. Patients with higher M30 levels had significantly shorter median survival compared to patients' lower serum M30 levels. However, there was no impact of serum M65 levels on survival. Serum M30 levels and clinical stage were found as the strongest variables with independent prognostic value for overall survival. DISCUSSION: These results suggest that serum M65 and M30 levels were elevated in patients with advanced gastric carcinoma patients. Serum M30 levels can be helpful to predict tumor load and also survival.

The effect of bevacizumab on serum soluble FAS/FASL and TRAIL and its receptors (DR4 and DR5) in metastatic colorectal cancer.

PURPOSE: Bevacizumab-based chemotherapy has become the standard of care in metastatic colorectal cancer (MCRC). We aimed to measure the levels of serum soluble FAS, FASL, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and its death receptors DR4 and DR5 in MCRC patients and to define prognostic significance of these parameters in response to bevacizumab in these patients. PATIENTS AND METHODS: The levels of these parameters in serum samples were quantified by a commercially available ELISA kit in 31 MCRC patients before and after 2 cycles of therapy and 25 healthy controls. RESULTS: Pretreatment sFAS levels in MCRC patients was significantly lower than the levels of controls (p = 0.043). There was no significant difference in sFAS and sFASL levels in MCRC patients before and after bevacizumab-based treatment. There was no significant difference in sFAS/sFASL ratio in MCRC patients before and after treatment and controls. Soluble DR5 levels were significantly higher in pretreatment serum samples compared with controls (p = 0.008). However, pretreatment sTRAIL and sDR4 levels were similar to the levels of controls. There was no significant difference in sTRAIL, sDR4, and sDR5 levels in MCRC patients before and after treatment. When patients were grouped according to treatment response (responders vs. non-responders), post-treatment sFAS/sFASL ratio was significantly lower in responding patients compared with non-responders (p = 0.029). Significant correlations were observed between post-treatment sFASL and sDR4, sFAS and sTRAIL, sTRAIL and sFAS/sFASL ratio, and sFASL and sDR5. CONCLUSION: Non-significant changes in apoptotic markers with bevacizumab-based chemotherapy showed that they have no prognostic significance in MCRC patients. Significant change in sFAS/sFASL ratio according to treatment response could be an indicator of chemosensitivity.

Bevacizumab plus irinotecan-based therapy in metastatic colorectal cancer patients previously treated with oxaliplatin-based regimens.

BACKGROUND: Treatment of patients with metastatic colorectal cancer (MCRC) previously exposed to oxaliplatin-based regimen is challenging. Efficacy and toxicity of bevacizumab plus irinotecan-based regimens were assessed in the second-line treatment of MCRC patients. PATIENTS AND METHODS: Forty patients with a median age of 53 years (range, 31-75) were retrospectively evaluated. Patients progressing or relapsing after treatment with oxaliplatin-based regimens were given bevacizumab 5 mg/kg every 2 weeks in combination with irinotecan-based regimens. All patients had previously received oxaliplatin either in the adjuvant setting (n = 8) or for metastatic disease (n = 32). RESULTS: Three patients achieved a complete response (7.5%), 5 partial responses (12.5%) and 14 (35%) stable disease resulting in an overall response rate of 20%. Median progression-free survival was 6 months (95% CI, 4.0-8.0) with a median overall survival of 14 months (95% CI, 10.2-17.8). One-year survival rate was 55.9%. Grade 3-4 toxicities were as follows: neutropenia (n = 15, 37.5%), febrile neutropenia (n = 2, 5%), diarrhea (n = 11, 27.5%), nausea and vomiting (n = 3, 7.5%), gastrointestinal perforation (n = 2, 5%), and thromboembolism (n = 2, 5%). CONCLUSION: Bevacizumab plus irinotecan-based combination chemotherapy is an active and safe treatment option in patients failing oxaliplatin-based therapy.

Concomitant chemoradiotherapy with cisplatin and docetaxel followed by surgery and consolidation chemotherapy in patients with unresectable locally advanced non-small cell lung cancer.

AIMS: To evaluate preoperative concomitant chemoradiation using cisplatin plus docetaxel followed by consolidation chemotherapy in patients with unresectable locally advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Medical records of patients with locally advanced unresectable NSCLC (stage IIIA and IIIB) treated with concomitant chemoradiotherapy using cisplatin + docetaxel combination followed by consolidation chemotherapy were retrospectively evaluated. All the patients were consecutively treated. Chemotherapy consisted of weekly cisplatin 20 mg/m(2) and docetaxel 20 mg/m(2) during radiotherapy. Radiotherapy dose was 58-66 Gy given in 2 Gy fractions, 5 days per week. The patients were subsequently referred to surgery if adequately downstaged. Consolidation chemotherapy using cisplatin and docetaxel both at doses 75 mg/m(2) every 3 weeks followed local therapy in all patients. RESULTS: A total of 54 patients were evaluated (49 males, 5 females with a median age of 58 years; 41 [75.9%] stage IIIB and 13 [24.1%] IIIA). Twelve patients (22.2%) achieved pathologic complete response and 20 (37%) partial response. Downstaging was possible in 32 patients (59.3%). Twenty-six patients (48.1%) were operated after concomitant chemoradiotherapy (pneumonectomy [n = 2], lobectomy [n = 12], and wedge resection [n = 12]). Toxicity was tolerable. Median progression-free survival and overall survival (OS) for the entire cohort were 14 and 22 months, respectively. In resected patients (n = 26), median PFS and OS have not been reached with a median follow-up duration of 24 months. CONCLUSION: Preoperative concomitant chemoradiation using weekly cisplatin and docetaxel followed by surgery and consolidation chemotherapy is effective and well tolerated in patients with unresectable locally advanced NSCLC.

Docetaxel combined with oral etoposide as second-line treatment for advanced gastric carcinoma after failure of platinum- and fluoropyrimidine-based regimens.

BACKGROUND: Platinum, antracyline, and fluoropyrimidine combination chemotherapy has been widely used as a first-line treatment for advanced gastric cancer (AGC). In the present study, we determined the efficacy and the safety of docetaxel and oral etoposide as second-line combination chemotherapy after failure of commonly used combination regimens in AGC. METHODS: Patients with histologically proven gastric cancer and measurable metastatic disease received docetaxel 75 mg/m(2) as a 1-h intravenous infusion on day 1, and oral etoposide 50 mg/m(2) once daily on days 1-5, every 3 weeks until disease progression or unacceptable toxicities. RESULTS: Between June 2006 and September 2008, 32 patients, of median age 60 years (range 32-77 years) were included in the study. Overall response rate was 9.4% and 31.3% of patients achieved a stable disease. Median progression-free survival was 3 months (95% CI, 2.5-3.5). Median overall survival was 6 months (95% CI, 3.8-8.2) with 16.9% 1-year survival rate. Grade 3-4 toxicities included neutropenia (28.8%), febrile neutropenia (18.8%), thrombocytopenia (3.1%), nausea and vomiting (15.6%), diarrhea (9.4%), and mucositis (6.2%). CONCLUSION: Docetaxel and oral etoposide combination was moderately effective and safe in appropriately selected AGC patients after failure of platinum- and fluoropyrimidine-based combination regimens.

Outcome of newly diagnosed glioblastoma patients treated by radiotherapy plus concomitant and adjuvant temozolomide: a long-term analysis.

AIMS AND BACKGROUND: Glioblastoma is the most common primary brain tumor in adults. The standard treatment is surgery and radiotherapy. In this study, the results of radiotherapy plus concomitant and adjuvant temozolomide are reported. In addition, the efficiency of adjuvant temozolomide is evaluated. METHODS AND STUDY DESIGN: Forty-one patients were analyzed. All patients received radiotherapy (2 Gy daily fractionation dose, median 60 Gy total doses) and concomitant temozolomide (at a daily dose of 75 mg/m2/day, 7 days per week) after surgery. Thirty-one patients received an average of 6 cycles (range, 1-8 cycles) of adjuvant temozolomide after radiotherapy, every 28 days for 5 days at a dose of 200 mg/m2/day. The primary end point was overall survival. RESULTS: The median overall survival was 16.7 months. The overall survival significantly increased in the adjuvant temozolomide group compared to the group with no adjuvant therapy (18.9 vs 9.8 months). The difference in overall survival between adjuvant temozolomide cycles of < or = and > 3 was significant (8.7 vs 20 months). On multivariate analyses, the important prognostic factors were type of surgery and application of adjuvant temozolomide for at least 4 cycles. Grade III/IV toxicity was seen in 4% and 6.5% of patients during concomitant and adjuvant therapy, respectively. CONCLUSIONS: The study confirmed the effectiveness of radiotherapy plus temozolomide in newly diagnosed glioblastoma. It was established that the application of adjuvant temozolomide for at least 4 cycles is required to obtain a benefit from adjuvant therapy. However, further studies are needed to confirm these data.

Non-gestational uterine choriocarcinoma in a postmenopausal woman.

BACKGROUND: Gestational trophoblastic disease occurs rarely in postmenopausal women. CASE REPORT: We report on a 65-year-old woman with uterine choriocarcinoma developing 16 years after menopause and 25 years after her last pregnancy. She was found to have a uterine tumor on laparotomy after presenting with uterine bleeding and abdominal pain. Histopathological examination demonstrated malignant syncytiotrophoblastic and cytotrophoblastic cells with extensive necrosis and hemorrhage, consistent with pure choriocarcinoma. Chemotherapy consisting of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) was started. The treatment was changed to methotrexate and folinic acid because of severe hypersensitivity reaction after etoposide infusion. After 4 cycles, the serum beta-human chorionic gonadotropin (beta-hCG) level had decreased to normal. The patient remains disease free 20 months after the treatment. CONCLUSIONS: This case further illustrates that choriocarcinoma may be seen in older women after a long menopausal period. Accurate diagnosis and treatment are essential, because the tumor is very chemosensitive and curable even in advanced stages.

Normal CA 19-9 levels in Hashimoto's thyroiditis.

Carbohydrate antigen 19-9 (CA 19-9) is a glycosphingolipid of the Lewis blood group that for years has been proposed as a useful marker for epithelial type gastrointestinal cancers. It is well known that moderately increased concentrations of CA 19-9 can be found in 15-36 % of patients with benign conditions such as pancreatic, liver, biliary diseases and benign hydronephrosis. In current study, we investigated whether there was any tendency for CA 19-9 elevation in 71 patients with Hashimoto's thyroiditis. Patients with malignancy, benign pancreas, liver, lung and biliary diseases, inflammatory bowel diseases, urinary tract infection, hydronephrosis, endometriosis, diabetes mellitus and chronic renal failure were excluded. In the Hashimoto's thyroiditis cases, mean serum CA 19-9 level was 12.5-/+10.4 (range, 2.5-55), while it was 11.9-/+ 9 (range, 2.5-29.3) and 10.3-/+ 8 (range, 2.5-28.9) in patients with Graves' and healthy volunteers respectively, without any significant intergroup differences. Although the American Society of Clinical Oncology does not recommend tumor markers like CA 19-9 in screening for malignancies, they may be used for this purpose. In contrast to case reports showing possible elevation of CA 19-9 in Hashimoto's thyroiditis, we did not detect such a relation. Moreover, there was no pointers to change in CA 19-9 levels in patients with hypo-, hyper- or eu-thyroidism.

Elevated serum levels of M30 and M65 in patients with locally advanced head and neck tumors.

BACKGROUND: M30-Apoptosense and M65 ELISAs can detect caspase cleaved and intact forms of cytokeratin 18. As biologic marker of cell death, both assays can be useful to evaluate prognosis and chemotherapy response in the patients with breast, lung, and endometrium cancer. In the present study, we measured serum M30 and M65 levels in the patients with locally advanced head and neck tumors, and compared with healthy controls. MATERIALS AND METHODS: A total of 40 consecutive patients with locally advanced head and neck tumors were included in this study. The sera were collected from the patients and 32 healthy controls. Median age was 51 years (range: 19-80) and squamous cell carcinoma of head and neck was major histopathologic subtype. Primary tumors were localized in larynx, nasopharynx, hypopharynx and tongue. The mean serum M30 concentration was 112.7+/-59 U/L in patients and this was significantly higher than healthy controls (mean 106.5+/-17.6 U/L) (p<0.05). Serum M65 levels were also higher in patients with head and neck tumors when compared to controls but not statistically significant (261.7+/-175 U/L vs 200.2+/-164.5 U/L, p=0.077). There was no statistically significant correlation among age, stage and localization of tumor and serum M30 and M65 levels. CONCLUSION: According to our knowledge, this is the first study which evaluated serum M30 and M65 levels in head and neck tumors. We found increased serum levels of M30 and M65 levels in head and neck tumors. Significantly higher levels of serum M30 may have prognostic importance in this type of tumor. Larger studies are needed to evaluate its' prognostic importance.

Opportunistic cytomegalovirus infection in a patient receiving temozolomide for treatment of malignant glioma.

Treatment of malignant gliomas has changed substantially over the last few years. An oral alkylating agent, temozolomide, has become the standard agent for glioma management. Although it is generally well tolerated, it can cause lymphopenia and may lead to opportunistic infections. We report on a patient with malignant glioma who developed opportunistic cytomegalovirus (CMV) pneumonia following the termination of temozolomide therapy. The patient was admitted with acute dyspnea, fever and hypoxia, and she was diagnosed with CMV pneumonitis using a PCR-based CMV-DNA analysis. After treatment with ganciclovir, she recovered dramatically. To our knowledge, although there have been reported cases of Pneumocystis carinii infection associated with temozolomide therapy, there has only been one other case of CMV infection. We also review this report.

Gemcitabine-induced acute coronary syndrome: a case report.

OBJECTIVES: To report a case of metastatic leiomyosarcoma, in which a patient developed chest pain accompanied by acute left bundle-branch block (LBBB) after gemcitabine infusion. CLINICAL PRESENTATION AND INTERVENTION: A 59-year-old woman admitted with bilateral pulmonary nodules had classic risk factors for coronary heart disease and coronary stenosis as demonstrated by previous coronary angiography. She was treated with gemcitabine infusion, and 30 min later she experienced severe chest pain accompanied by acute LBBB confirmed by ECG. We suspected gemcitabine-induced coronary vasospasm exacerbated by the preexisting coronary artery disease as the cause of the acute coronary syndrome. The patient was subsequently treated with antianginal therapy and percutaneous coronary intervention. Her chest pain resolved and LBBB disappeared. She was discharged 2 days later without any further cardiac events. No additional cancer therapy was given and she died 5 months later, due to disease progression. CONCLUSION: This case showed that chemotherapeutic agents must be administered with intensive cardiac monitoring especially in patients with cardiac disease and well-known risk factors to prevent the development of cardiac complications, despite an agent not being known to be 'cardiotoxic'.