Ewing's sarcoma of the urinary bladder - the urologic and pathologic differential diagnosis and current therapeutic options.

BACKGROUND: Bladder cancer is 11th most common cancer worldwide. Histologically, most of the tumors are classified as urothelial carcinomas. Less common variants (squamous cell or adenocarcinomas) usually comprise up to 10% of cases. Other types of tumors are exceptional. The finding of Ewing's sarcoma in the bladder is considered extremely rare. CASE: We present the case of a 54-year-old female patient examined for painless hematuria. During the follow-up examination, a bulky tumor of the bladder was detected, but considering the extent of the bladder tumor, only a diagnostic transurethral resection was possible. According to the primary staging, the disease was already advanced at the time of admission with metastatic spread, anemia and present obstruction of the upper urinary tract. RESULTS: Histologically, Ewing's sarcoma was surprisingly demonstrated in the urinary bladder. Anemia caused by hematuria and advanced disease was corrected by blood transfusions and obstruction of the right kidney by puncture nephrostomy. However, despite a very quick diagnosis, completion of staging and preparation of the patient for further treatment, the patient had died before the planned systemic treatment began. CONCLUSION: The diagnosis of Ewing's sarcoma is identical to that of the other bladder tumors, i.e. transurethral resection. In the case of confirmation of this histological type, it is necessary to complete staging examinations and start multimodal treatment. Early systemic chemotherapy plays a key role and if metastatic spread is excluded, radical cystectomy or radiotherapy are included, too. The aim of our communication is to present a rare case of this disease, discuss the differential diagnosis and point out the principles and possibilities of its treatment.

Cabozantinib in the treatment of metastatic renal cell carcinoma - final data analysis from four oncology centers in the Czech Republic.

BACKGROUND: Current standard treatments for patients with metastatic renal cell carcinoma (mRCC) involve tyrosine kinase inhibitors (TKI) that inhibit angiogenesis. Cabozantinib is a multi TKI used for the treatment of mRCC in the first- and second-line setting. PURPOSE: The aim of this study was the final analysis of treatment outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with cabozantinib after previous targeted therapy. PATIENTS AND METHODS: A total of 54 patients with mRCC from four oncology centers in the Czech Republic were evaluated retrospectively; the median follow-up was 18.5 months. Cabozantinib was administered in a dose of 60mg/day, a subset of patients received an initial dose of 40mg/day. The treatment was administered until the progression. The Kaplan-Meier analysis was used to calculate progression free survival (PFS) and overall survival (OS). We performed a multivariate analysis of risk factors for treatment outcomes (PFS, OS) by regression analysis. All statistics were evaluated at the significance level α = 0.05. RESULTS: The median PFS in all patients was 9.3 months (95% CI 7.2 - 11.4). The median OS in all patients was 21.9 months (95% CI 15.5 - 28.4). The median PFS in patients with bone metastases was not statistically significantly different compared with patients without bone metastases (9.3 vs 8.7 months, P = 0.53). The median OS in patients with bone metastases was statistically significantly shorter compared with patients without bone metastases (17.7 vs 26.8 months, P = 0.021). A treatment response was observed in 40.7 % of cases, including one complete remission. The regression analysis demonstrated a significant effect on OS in patients with the presence of subsequent treatment (P = 0.001), patients with treatment duration of first line therapy 6 months (P = 0.019) and 12 months (P = 0.003) and in patients without bone metastases (P = 0.021). CONCLUSION: Our final analysis of patients with mRCC treated with cabozantinib after previous targeted therapy confirmed its effectiveness.

Changes in expression of lysosomal membrane proteins in leucocytes of cancer patients treated with tyrosine kinase inhibitors.

Lysosomal sequestration of weak base drugs has been identified as one of the stress-related mechanisms that trigger in vitro lysosomal biogenesis controlled by transcription factor EB (TFEB). Whether such mechanism can induce lysosomal biogenesis in vivo is unknown. In this study, we addressed the question whether prolonged treatment with sunitinib (SUN) in patients with advanced renal cell carcinoma (n = 22) and with imatinib (IM) in those with gastrointestinal stromal tumor (n = 6) could induce lysosomal biogenesis in leukocytes. Lysosomal biogenesis was monitored using immunoblotting of three lysosomal membrane proteins: lysosome-associated membrane proteins 1 and 2 (LAMP1 and LAMP2) and vacuolar H+-ATPase, B2 subunit (ATP6V1B2). Present results indicate that prolonged treatment with SUN affects LAMP1 and LAMP2 expression only marginally in most patients. In contrast, changes in ATP6V1B2 expression were marked and resembled irregular oscillations. Very similar changes in the expression of lysosomal membrane proteins were also found in IM-treated patients. Conclusion: prolonged treatment of cancer patients with SUN and IM did not induce leucocyte lysosomal biogenesis but dramatically affected expression of ATP6V1B2.

Pazopanib: a new multiple tyrosine kinase inhibitor in the therapy of metastatic renal cell carcinoma and other solid tumors.

Angiogenesis plays a crucial role in tumor progression. Tumor angiogenesis is driven by host-derived circulating factors. Prominent among these factors is vascular endothelial growth factor (VEGF). Two basic approaches have been pursued in therapies targeting VEGF: neutralization of VEGF by antibodies or inhibition of VEGF receptor (VEGFR). VEGFR inhibition has relied on the use of small-molecular inhibitors. These drugs inhibit the tyrosine kinase activity of VEGFRs as well as other tyrosine kinases, and the term tyrosine kinase inhibitor (TKI) is used to describe this class of drugs. Pazopanib (GW786034), N(4)-(2,3-dimethyl-2H-indazol-6-yl]-N(4) - methyl-N(2)-(4-methyl-3-sulfnonamidophenyl)-2,4-pyrimidinediamine, is a novel orally bioavailable TKI that targets VEGFR1, VEGFR3, platelet-derived growth factor receptor (PDGFR)-alpha, PDGFR-beta and c-kit. Activity was observed in early clinical testing, specifically in patients with metastatic renal cell carcinoma (RCC). In subsequent phase II and phase III trials, the activity of pazopanib was comparable to other targeted agents used in the first-line therapy of metastatic RCC. Promising activity was reported in a number of other tumors, including metastatic carcinoma of the uterine cervix and differentiated carcinomas of the thyroid.

Endoscopic versus minimally invasive vein harvesting. Impact on leg-related morbidity in coronary artery bypass surgery: one-year follow-up of a prospective trial.

AIM: We sought to compare the impact of endoscopic and minimally invasive great saphenous vein harvesting on leg-related patient morbidity after coronary artery bypass grafting. METHODS: From February 2004 to July 2006, 120 patients underwent minimally invasive vein harvesting, and 180 patients underwent endoscopic vein harvesting for coronary artery bypass grafting. Patients were evaluated prospectively for wound-healing disturbances, residual leg edema, pain intensity and saphenous neuropathy at seven days, three months and one year after surgery. RESULTS: Both harvesting techniques were associated with a low incidence of wound-healing disturbances; nevertheless, endoscopic vein harvesting was associated with a significantly lower incidence of residual edema (12% vs 28%, P<0.05 seven days postoperative; 6% vs 19%, P<0.001 three months postoperative), pain (9% vs 20%, P<0.05; 6% vs 10%, P<0.05) and saphenous neuropathy (6% vs 23%, P<0.001; 3% vs 14%, P<0.05) during follow-ups. Endoscopic vein harvesting was also associated with a significantly lower incidence of neurological disturbances at one-year follow-up (2% vs 8%, P<0.05). Mean harvesting time (43.9+/-10.2 vs 40.6+/-15.5 min, P=0.09), conversion rate (2% vs 3%, P=0.71) and injury per conduit (0.3+/-0.1 vs 0.3+/-0.2, P=0.91) were comparable for both groups. CONCLUSION: EVH is superior to MIVH in terms of reduction in pain intensity, residual leg edema and saphenous neuropathy at seven days and again at three months postoperative. A significantly lower incidence of neurological disturbances is still presented one year after surgery.