Purpose: New markers that enable the percentage of transitional cell carcinomas (TCC) of the bladder that are diagnosed before invasion of the bladder muscle layers to be increased would reduce the morbidity and mortality associated with this disease. The purpose of this study was to develop a simple, accurate urine test based on mRNA markers and simple gene signatures that (a) could detect TCC before muscle invasion while maintaining high specificity in patients with hematuria or urinary tract infections and (b) identify patients most likely to have grade 3 or stage zT1disease. Experimental Design: RNA markers with high overexpression in stage Ta tumors and/or T1 to T4 tumors but low expression in blood or inflammatory cells were characterized by quantitative reverse transcription-PCR using 2 mL of voided urine from 75 TCC patients and 77 control patients with other urological diseases. Results: A combination of the RNAs CDC2, MDK, IGFBP5, and HOXA13 detected 48%, 90%, and 100% of stage Ta, T1, and >T1 TCCs, respectively, at a specificity of 85%. Detection of Ta tumors increased to 60% for primary (non-recurrent) Ta tumors and 76% forTa tumors z1cm in diameter. Test specificity was 80% for the 20 control patients with urinary tract infections. The combination of CDC2 and HOXA13 distinguished between grade 1 to 2 TCCs and grade 3 or stage zT1TCCs with f80% specificity and sensitivity. Conclusions: Simple gene expression signatures can be used as urine markers for the accurate detection and characterization of bladder cancer.There are f360,000 new cases of bladder cancer worldwide annually and f145,000 deaths from the disease (1). About 30% of tumors have invaded into or beyond the muscularis propria at the time of diagnosis. Patients with these muscleinvasive tumors (stages T2-T4) have 10-year recurrence-free survival rates ranging from >80% for organ-confined tumors to f30% for tumors with regional lymph node metastases (2). Muscle-invasive tumors are generally treated by radical cystectomy with bilateral pelvic lymph node dissection followed by urinary diversion. In contrast, tumors that have not invaded the muscularis propria (stage Ta, T1, and in situ carcinomas) are usually resected by organ-preserving transurethral resection and present 10-year survival rates of 70% to 85% (2). Screening high-risk groups, such as the elderly, cigarette smokers, and certain occupational groups including truck drivers, painters, and workers in the textile dye and rubber tire industries (3, 4), would be predicted to lead to a higher proportion of tumors being identified at the pre -muscle-invasive stage and an overall decrease in the bladder cancer burden.Recent studies using high-throughput microarray analysis have shown that mRNA expression profiles are a powerful method for discriminating between bladder tumors and normal urothelium and defining subgroups of bladder tumors (5-8). The informativeness of these expression profiles and the high frequency of tumor cell exfoliation into urine have raised the prospect of...
Background: Dedifferentiated chondrosarcoma (DDC) accounts for a small proportion of chondrosarcomas. They demonstrate aggressive behaviour with a high rate of local recurrence and systemic progression resulting in poor long-term survival rates. Due to its relatively low incidence, previous studies have grouped different histiotypes together to achieve adequate study numbers for analysis. Methods: This retrospective study examines the clinical course and the role of chemotherapy in the subgroup of patients with DDC where osteosarcoma is the predominant dedifferentiated component. Between 2000-2010, 21 patients were identified. Results: The mean age at presentation was 64 years (range 35-80 years). 12 patients were considered unfit for chemotherapy, whilst 2 patients declined chemotherapy. 5 patients received neoadjuvant chemotherapy, with less than 90% necrosis demonstrated in all these cases. 3 patients received post-operative chemotherapy. The median survival for the entire group was 9.5 months. In the 7 patients who received chemotherapy, the median survival was 17 months, and those who had chemotherapy had a greater median time to local recurrence. Conclusion: This study demonstrates that cytotoxic chemotherapy may be offered to appropriately selected patients.
Bone metastasis is a common problem affecting a significant proportion of patients with metastatic cancer. Bone metastasis can present in a number of ways and the patients may need surgical stabilisation of their lesions. There are many important considerations in the care of these patients that need to be borne in mind including their increased anesthetic risks and potential risk of complications. There are continuous developments in the prevention, diagnosis and treatment with advances in imaging, orthopaedic technique and medication, particularly radiopharmaceuticals and cytotoxic, endocrine treatments with newer treatments based around the tumour cell-osteoclast interaction. Having a better understanding of these considerations and developments is important in allowing the optimisation of the care of the patient with bone metastasis.
The authors regret the publication of table 1, table 3 and figure 5 owing to a coding error in the covariate 'depth'. The revised tables are attached in the following. All conclusions remained unchanged.
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