Bladder carcinoma as a systemic disease

Abstract

One hundred and fifty-one patients with transitional cell carcinoma of the bladder who were evaluated by conventional means preoperatively underwent a radical cystectomy. They were then classified according to the highest known pathological stage, first site of postoperative metastasis and the temporal relationship of the cystectomy to the appearance of the metastasis. Fifty patients developed metastases, 80% of which were proven histologically. Thirty-nine of fifty patients (78%) who developed metastases did so within a year of cys-tectomy. Extent of local tumor was directly related to the incidence of positive pelvic nodes. Metastases occurred most commonly in lung and bone. Soft tissues of the pelvis were involved in thirteen (16%) of the patients who developed metastatic carcinoma and those patients with positive pelvic nodes were more likely to have these kinds of recurrent disease. These evaluations suggest that the metastases must be present at cystectomy or as a result of it. The data imply the existence of appreciable heterogeneity among patients andor their invasive bladder carcinoma. Disseminated but silent metastases suggest that a relationship between the primary tumor and the Occurrence of metastatic disease may exist. Knowledge of this relationship is very important in planning subsequent therapeutic strategies.

Loss of heterozygosity on chromosome 18q is associated with muscle-invasive transitional cell carcinoma of the bladder

“…The theory of multistep carcinogenesis (Nordling. 1953) was given a molecular basis by the demonstration of an accumulation of genetic events resulting in the activation of oncogenes and the loss of TSGs in colorectal tumours of increasing grade and stage (Fearon & Vogelstein, 1990 (Prout et al. 1979).…”

Activation of matrix metalloproteinase-9 by TNF-α in human urinary bladder cancer HT1376 cells: The role of MAP kinase signaling pathways

“…Bladder tumors can be divided into two broad categories-superficial and invasive-based on growth patterns and biological behavior (2,3). The majority of bladder cancers (90%) are transitional cell carcinomas (TCC), which result from neoplastic lesions with environmental and occupational causal factors (4).…”

Expression of angiogenesis inhibitors in human bladder cancer may explain rapid metastatic progression after radical cystectomy

“…For many different tumor types a rapid progression of metastasis after surgical resection of the primary tumor has been described. Several different hypotheses have been proposed to explain this phenomenon: i) production and secretion of antimitotic factors by the cells of the primary tumor that inhibit the proliferation of metastatic cells at distant sites (20), ii) induction of an immunologic response against the metastasis by the primary tumor -concomitant immunity (21), iii) depletion of available nutrition by the primary tumor that leads to malnutrition and growth inhibition of metastatic cells (22) and iv) surgically induced tumor cell dissemination and postoperative immunosuppression leading to rapid metastatic growth after extensive surgical procedures (5). While none of these proposed mechanisms have been confirmed by a molecular mechanism, O'Reilly et al in 1993 proposed another hypothesis, that: '…a primary tumor, while capable of stimulating angiogenesis in its own vascular bed, can inhibit angiogenesis in the vascular bed of a metastasis or other secondary tumor' (23).…”

“…In 1979, Prout and colleagues recognized this clinical phenomenon and stated: '...either metastases are a direct cause of the operation or have been present before the procedure' (5). It is our hypothesis that these metastases have already been seeded prior to surgery and that a factor secreted by the primary tumor is responsible for maintaining a dormant state, as long as the primary tumor is in place.…”