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Bladder cancer
Prof, Dr Donald S Kaufman MD,Prof William U Shipley MD and Adam S Feldman
Summary(已认领)
Bladder cancer is a heterogeneous disease, with 70% of patients presenting with superficial tumours, which tend to recur but are generally not life threatening, and 30% presenting as muscle-invasive disease associated with a high risk of death from distant metastases. The main presenting symptom of all bladder cancers is painless haematuria, and the diagnosis is established by urinary cytology and transurethral tumour resection. Intravesical treatment is used for carcinoma in situ and other high grade non-muscle-invasive tumours. The standard of care for muscle-invasive disease is radical cystoprostatectomy, and several types of urinary diversions are offered to patients, with quality of life as an important consideration. Bladder preservation with transurethral tumour resection, rad iation, and chemotherapy can in some cases be equally curative. Several chemotherapeutic agents have proven to be useful as neoadjuvant or adjuvant treatment and in patients with metastatic disease. We discuss bladder preserving approaches, combination chemotherapy including new agents, targeted therapies, and advances in molecular biology.
Article Outline
Epidemiology
Pathophysiology and diagnosis
Management
Superficial bladder cancer
Muscularis propria invasive disease
Selective bladder-preserving approaches
Neoadjuvant chemotherapy
Adjuvant chemotherapy
Chemotherapy for metastatic disease
Molecular biology and targeted therapies
Search strategy and selection criteria
Epidemiology(已认领)
Bladder cancer is the second most common genitourinary malignant disease in the USA, with an expected 69 000 newly diagnosed cases in 2008, and 14 000 deaths. The incidence of bladder cancer rises with age, peaking between age 50 years and 70 years, and is three times more common in men than in women.1 Risk factors for the development of bladder cancer can be classified into three subsets; genetic and molecular abnormalities, chemical or environmental exposures, and chronic irritation. Genetic and molecular factors include oncogenes, such as TP63,[2] and [3] the epidermal growth factor receptors (EGFR),[4] and [5] and Ras p21 proteins.6 Tumour suppressor genes, including TP53 and RB1,[7] and [8] and those newly implicated such as the fragile histidine triad gene,[9] and [10] probably play a part in the genetic pathogenesis of bladder cancer. Furthermore, molecular factors are cell cycle regulatory proteins, such as CABLES, Ki67, and cyclin D1.[11], [12] and [13] Chemical and environmental exposures include aromatic amines, aniline dyes, nitrites and nitrates, acrolein, coal, and arsenic,[14] and [15] but the most important environmental factor is cigarette smoking. Other causal factors include chronic irritation, indwelling catheters, Schistosoma haematobium infestation, and pelvic irradiation.16
Pathophysiology and diagnosis(已认领)
More than 90% of bladder cancers are transitional cell carcinomas, 5% are squamous cell carcinomas, and less than 2% are adenocarcinomas. The histopathological grading of transitional cell carcinoma of the bladder has historically been grade 1–3 as per the 1973 WHO classification system,17 but in 1998 a WHO and International Society of Urological Pathology consensus classified urothelial tumours into four categories; papilloma, papillary urothelial neoplasm of low malignant potential, low grade carcinoma, and high grade carcinoma.18 Histological staging is by the tumour-node-metastasis TNM staging system, in which the tumour (T) stage of the primary tumour is based on the extent of penetration or invasion into the bladder wall.19
Of all newly diagnosed cases of transitional cell carcinomas, about 70% present as superficial tumours (stages Ta, T1, or tumours in situ [Tis]), but as many as 50–70% of those superficial tumours will recur and roughly 10–20% will progress to muscularis propria invasive disease (T2–4).20 To predict which patients will progress from superficial to musclaris propria invasive disease remains a challenge. In patients with low grade Ta disease, the 15-year progression-free survival is 95% with no cancer-specific mortality. Patients with high grade Ta tumours had a progression-free survival of 61% and a disease-specific survival of 74%, whereas patients with T1 disease had a progression-free survival of 44% and a disease-specific survival of 62%, lending support to the view that invasion of the lamina propria is a prognostic indicator for risk of disease progression and reduced survival.
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作者:admin@医学,生命科学 2011-02-09 00:55
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