Prognosis Of Bladder Cancer Patients Research Articles

Genetic and epigenetic aspects of bladder cancer

Transitional cell carcinoma of the urinary bladder has a diverse collection of biologic and functional characteristics. This is reflected in differing clinical courses. The diagnosis of bladder cancer is based on the information provided by cystoscopy, the gold standard in combination with urinary cytology findings. Many tumor markers have been evaluated for detecting and monitoring the disease in serum, bladder washes, and urinary specimens. However, none of these biomarkers reported to date has shown sufficient sensitivity and specificity for the detection of the whole spectrum of bladder cancer diseases in routine clinical practice. The limited value of established prognostic markers requires the analysis of new molecular parameters of interest in predicting the prognosis of bladder cancer patients; in particular, the high-risk patient groups at risk of progression and recurrence. Over the past decade, there has been major progress elucidating of the molecular genetic and epigenetic changes leading to the development of transitional cell carcinoma. This review focuses on the recent advances of genetic and epigenetic aspects in bladder cancer, and emphasizes how molecular biology would be likely to affect the future therapies.

The Clinical Significance of Molecular Markers to Bladder Cancer

Stage and grade of transitional cell carcinoma are currently the most useful tools for taking therapeutic decisions and evaluating the prognosis of bladder cancer patients. However, as there are remarkable differences in biological behavior and "biological potential" of tumors classified in the same stage, it is very difficult to predict which superficial tumors will recur and which tumors will give distant metastases. During the last two decades, the better understanding of the molecular mechanisms involved in carcinogenesis and tumor progression has provided a large number of molecular markers of bladder cancer, with a potential diagnostic and prognostic value. This article reviews comprehensively the molecular role and evaluates the clinical significance and the perspectives of these molecular markers. We concluded that, although at the moment there is not a single marker able to predict with accuracy the biological potential of bladder cancer, the most promising markers, at this point, are deletions of chromosome 9, and the tumor suppressor gene p53. Clinical studies are in progress for the assessment of other biological molecules with prognostic potential, such as the E-cadherin, the protein p120, and the telomerase.

Association of positive serum anti‐p53 antibodies with poor prognosis in bladder cancer patients

To assess the association of serum anti-p53 antibodies and overexpression of tumor p53 protein with survival and prognostic factors in patients with urinary bladder tumors. Seventy-six patients with transitional cell carcinoma of the urinary bladder were assessed prospectively (Ta, 18; T(1), 30; > or =T(2), 28). Serum anti-p53 antibodies were detected by enzyme-linked immunosorbent assay. Tumor p53 gene overexpression was assessed by immunohistochemical staining. The mean follow-up time was 34 months. Serum anti-p53 antibodies were positive in 25 patients (33%). Overexpression of tumor p53 protein was positive in 41 patients (54%). There was an association between the presence of serum anti-p53 antibodies and tumor p53 gene overexpression (P = 0.001). The total survival of the patients with positive serum anti-p53 antibodies was shorter than the patients with positive tumor p53 gene overexpression (P < 0.001, P = 0.344, respectively). In the multivariate survival analysis, both tumor stage and serum-p53 antibodies were found to be independent survival predictors (P = 0.004, P = 0.006, respectively). Serum anti-p53 antibody positive tumors had a worse prognosis than those with negative serum levels, regardless of the p53 status of the tumor.

Activated Leukocyte Cell Adhesion Molecule (ALCAM) Expression is Associated with a Poor Prognosis for Bladder Cancer Patients

Objectives: Functional E-cadherin adhesion complexes are necessary to maintain the normal differentiated phenotype in bladder epithelial cells and dysfunction of molecules in this complex is associated with an invasive phenotype. Moreover, loss of functioning of E-cadherin and/or α-catenin in cancer cells is associated with a poor prognosis for bladder cancer patients. Clearly, other adhesion molecules are also involved in the process of invasion and/or metastasis. For example the expression of activated leukocyte cell adhesion molecule, ALCAM, an adhesion molecule belonging to the immunoglobulin superfamily, appeared to be correlated with malignant potential in human melanoma. *Present address. Department of Urology, Faculty of Medicine, University of Tokyo, Japan. Methods: The expression of ALCAM in human bladder cancer specimens was studied by immunohistochemistry and correlated with E-cadherin and α-catenin expression. Results: In normal bladder tissue, only the umbrella cells showed positive membrane...

Epidemiology and biology of human urinary bladder cancer.

The bladder constitutes the most frequent localization of malignant tumors in the urinary tract. Further prognostic factors are molecular and cytogenetic alterations, which have been identified as key mechanisms in the carcinogenetic pathway of bladder cancer. Structural or numerical chromosomal alterations lead to the activation of a variety of cancer-inducing oncogenes as well as to the inactivation of various distinct antiproliferative tumor-suppressor genes. With regard to the biological heterogeneity in transitional cell carcinoma, which is also reflected in epidemiological data, the differing clinical course and the limited value of established prognosticators, the analysis of new molecular parameters has become of interest in predicting the prognosis of bladder cancer patients. In addition, the definition of high-risk patient groups that are at at risk of progression and recurrence is a further objective of urological research in this field.

Multivariate Analysis of Flow Cytometric Deoxyribonucleic Acid Parameters and Histological Features for Prognosis of Bladder Cancer Patients

We studied whether flow cytometry provides significant prognosticators beyond the classical histological evaluation in the patient with bladder cancer. A total of 203 patients with untreated bladder cancer was evaluated using fresh bladder tumor specimens. Tumor grading and stage were the histological prognostic parameters. Deoxyribonucleic acid (DNA) index, percentage S-phase cells, percentage G2/M-phase cells and hypertetraploid cell presence were assessed as flow cytometric prognostic parameters. Multivariate survival analysis was performed using Cox’s proportional regression model to study statistical individual prognostic values of histological and flow cytometric parameters. Hypertetraploid cell presence was the single most important prognostic factor (p <0.01), with tumor grade being nearly as important (p <0.01), followed by tetraploidy (p <0.01) and tumor stage (p <0.05). No other parameters, including the DNA index or cell phase fractions, contributed to the model. These results indicated that combined use of histological and flow cytometric parameters may provide additional information regarding the clinical outcome for bladder cancer patients.

Multivariate evaluation of prognostic determinants in bladder cancer patients.

To clarify the relative importance of factors affecting the survival of patients with bladder cancer, a multivariate analysis by Cox's proportional hazards model was performed on 264 patients initially treated from 1973 to 1984 at Nagoya University Hospital. Clinicopathological data included in the analysis were sex, age, symptoms, interval from onset of symptoms to first consultation, smoking history and tumor characteristics (location, size, number, shape, histological grade and stage). The analysis revealed that stage is the most statistically significant determinant for survival, followed by size, irritative symptoms, age and grade in this order. The model composed of the above five determinants yielded hazard ratios of: 4.6 for stage (pT2-pT4 vs. pTa-pT1); 3.1 for size (greater than 3 vs. less than or equal to 3 cm); 2.5 for irritative bladder symptoms (present vs. absent); 2.7 for age (70 years or more vs. younger), and 2.1 for grade (high grade vs. low grade tumors). We conclude that these findings quantitatively confirm previous clinical impressions that accurate staging of the tumors is most important for improving the prognosis of bladder cancer patients, and that each of the above five determinants should be considered when planning an effective initial treatment regimen.

回腸導管造設術の遠隔成績

The late results on 105 patients who underwent ileal loop diversion at the Keio University Hospital and the afiliated hospitals during the period of 1966 to 1974 were reviewed. Radical cystectomy was carried out in most of the cases together with the conduit diversion. The age varied 5 to 77 and of the 105 patients, 79 were male and 26 were female, with the sex ratio of 3 to 1.Actual survival rates from the 105 cases were 80.3% for one year, 69.4% for two years, 60.7% for three years, 54.8% for four years and 52.8% for five years.Eighty-six cases of bladder malignancies were evaluated for stage and grade classifications. Actual survival rate of the patients with low grade transitional cell carcinomas (grade 1 and 2) was 73.2% for five years, while in those with high grade transitionnal cell carcinomas (grade 3 and 4) the rate was 33.5%. The five year survival rates according to the stage were 85.5% in stage A, 62.4% in stage B-1, 35.7% in stage B-2, 25.0% in stage C and 13.5% in stage D. In TNM classification, the survival rates were 85.5% in P-1, 62.4% in P-2, 31.8% in P-3 and 13.5% in P-4.The prognosis of bladder cancer patients depends on radicality at the time of surgery. Five year survival rate in patients who underwent radical cystectomy together with ileal conduit diversion was 78.0% in stages A and B-1, and 41% in stages B-2 and C. On the other hand, the patients who underwent simple cystectomy and ileal conduit or the diversion only showed poor prognosis despite the postoperative radiation and chemotherapy.Early complications such as wound infection, fistula, intestinal obstruction were seen in 15.2% of the cases. Only one operative death (1.0%) was due to gastrointestinal bleeding. Peristomal dermatitis (9.5%) was most common as late complications. It is emphasized that postoperative rehabilitation clinic consisted of doctors, nurses and paramedical personals can eliminate the patient's distress and fear in their daily life with urinary devices.