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Annular constriction of the rectum secondary to transitional cell carcinoma of the bladder.

Recurrent transitional cell carcinoma of the bladder is often a locally progressive disease. Regional lymph node metastasis is a frequent finding and may be the first sign of recurrence. Involvement of the gastrointestinal tract is rare, but metastasis to the colon, small intestine, and stomach have been reported. Herein, we present a case of recurrent transitional cell carcinoma of the bladder manifesting as an annular constricting mass of the rectum, and review the literature regarding this unusual lesion.

Aged↗

Giant cell tumor of the bladder associated with transitional cell carcinoma.

We report in detail the first giant cell tumor associated with transitional cell carcinoma of the bladder. The giant cell tumor was composed of multinucleated giant and mononuclear stromal cells, and was morphologically indistinguishable from giant cell tumor of the bone. The giant and transitional cell carcinomas showed no evidence of recurrence or metastasis 8 months after transurethral resection. No histogenetic correlation between the cancers was found.

Aged↗

Expression of squamous cell carcinoma-associated antigen in grade 3 pT1 transitional cell carcinoma of the bladder and prediction of its progression and intravesical recurrence.

BACKGROUND: Among superficial transitional cell carcinomas (TCC) of the bladder, Grade 3 pT1 disease is associated with a higher risk of progression and intravesical recurrence. The authors determined whether or not squamous cell carcinoma-associated antigen (SCC antigen) could predict clinical behavior of Grade 3 pT1 disease. METHODS: SCC antigen was immunohistochemically stained in Grade 3 pT1 TCC of the bladder that had been fixed in formaldehyde solution and embedded in paraffin. Patients were followed up, and disease progression and recurrence were identified. Disease progression was defined as histologically verified muscle invasion or clinically detectable distant metastasis, including pelvic lymph node metastasis. RESULTS: SCC antigen in the cytoplasm was positively identified with immunohistochemical staining in 21 of 55 patients with the disease. Of 21 patients with positive SCC antigen in the cytoplasm, 8 experienced disease progression, whereas there was progression in 5 of 34 patients with negative antigen. The nonprogression rate of Grade 3 pT1 carcinomas with positive antigen in the cytoplasm was significantly lower than that for those with negative antigen. The disease-free rate also was clearly lower in the positive carcinoma than in the negative. Multivariate analysis confirmed that SCC antigen in the cytoplasm was the only significant variable independently affecting progression and intravesical recurrence of the disease. CONCLUSIONS: The results suggested that immunohistochemical expression of SCC antigen in the cytoplasm is closely linked with a higher risk for progression and intravesical recurrence of Grade 3 pT1 disease. Detection of the antigen can help to more accurately predict the clinical course of the disease.

Adult↗

Contemporary management of stage T1 transitional cell carcinoma of the bladder.

PURPOSE: Transitional cell carcinoma involving the lamina propria (stage T1) is associated with a high recurrence and progression rate with implications for patient survival and quality of life. A better understanding of the natural history of and treatment alternatives for this tumor may improve the outcome in patients with this stage of bladder cancer. MATERIALS AND METHODS: Literature of the last decade was comprehensively reviewed in regard to clinical and pathological diagnosis, adjuvant treatments, prognosis, and the role and timing of cystectomy. The information was gathered from MEDLINE, current urology journals, abstracts from recent urological meetings and personal experience. RESULTS: High grade and the depth of lamina propria invasion are important prognostic factors. Early diagnosis and accurate pathological assessment are essential for determining the most adequate treatment pathway. Initial treatment consists of complete transurethral resection and adjuvant treatment with intravesical instillation of bacillus Calmette-Guerin (BCG). Immediate postoperative instillation of mitomycin C decreases the risk of recurrence possibly related to tumor implantation. Intravesical treatment does not substantially decrease the chance of progression. Lack of a complete response to BCG at 3 to 6 months, high grade, the depth of lamina propria invasion, the association of carcinoma in situ and prostate mucosa or duct involvement represent significant predictors for progression. Cystectomy should be suggested for recurrent stage T1 tumor after BCG, new onset or persistent carcinoma in situ, tumor located at a difficult site for resection, prostatic duct or stromal involvement and muscle invasion. CONCLUSIONS: High grade stage T1 transitional cell carcinoma is a highly malignant tumor. Complete resection followed by immediate mitomycin C instillation and 6 weekly BCG instillations results in an acceptably low recurrence and progression rate. Rigorous long-term surveillance and continuous reconsideration of radical cystectomy in concordance with the evolution of the disease are essential.

Carcinoma, Transitional Cell↗

Exposure to alkyllysophospholipids inhibits in vitro invasion of transitional cell carcinoma.

Alkyllysophospholipids (ALP) are a group of synthetic analogs of a naturally occurring 2-lysophosphocholine. They are directly cytotoxic to a variety of neoplastic cell lines and can modulate the activation of macrophages against tumor cells. Moreover, recent reports have demonstrated the ability of racemic 1-octadecyl-2-methyl-sn-glycero-3-phosphocholine (ET-18-O-CH3) to prevent tumor cell invasion when given in noncytotoxic concentrations. Using an in vitro model, we studied the ability of ET-18-O-CH3 to prevent transitional cell carcinoma invasion. Cytostatic activity was determined by clonal growth assay (25,000 cells per plate). Suppression of colony growth was found at concentrations greater than 4 micrograms/ml. of ET-18-O-CH3 in rat and mouse transitional cell carcinoma (TCC) cell lines and greater than 2 micrograms/ml. in a human TCC line. Inhibition of tumor cell invasion was assessed by the effects on cell migration through Matrigel-coated 8 microns-pore polycarbonate filters (using 1 x 10(5) cells per chamber). Invasion was reduced to 50 to 70% of controls in both the mouse and rat TCC lines at the highest concentration (4.0 micrograms/ml.). In the human TCC line, invasion was reduced to less than 30% of controls at concentrations as low as 0.5 micrograms/ml. Motility (without invasion) of the human TCC line, as measured by cell migration through the micropore filter without the Matrigel coating, was inhibited at the same concentration of ET-18-O-CH3 found to inhibit invasion. The anti-invasive effect seen with noncytotoxic concentrations of ALP may prove useful in the treatment of transitional cell carcinoma.

Animals↗

Thrombomodulin expression in transitional cell carcinoma.

Thrombomodulin (TM) is a surface glycoprotein reported to be expressed in a variety of tumors, including mesotheliomas, endothelial vascular tumors, squamous carcinomas, and various adenocarcinomas. This study evaluated TM expression in transitional cell carcinomas (TCCs) and determined whether immunostaining for TM has practical value in the diagnosis of TCCs. TM expression was observed in 96 of 106 primary tumors (bladder, 64/72; renal pelvis, 12/14; ureter, 3/3; prostate, 17/17) and in 21 of 23 metastatic TCCs. Among the adenocarcinomas, only 3 of 18 originating in the bladder, 7 of 46 in the lung, 4 of 21 in the breast, 2 of 24 in the ovary, and 2 of 4 in the pancreas expressed this marker. No staining was observed in the 22 renal cell carcinomas or the 35 adenocarcinomas of the prostate, 13 of the endometrium, or 12 of the colon. Nearly all squamous cell carcinomas (lung, 21/27; skin, 7/7; uterine cervix, 6/6; esophagus, 2/2; bladder, 2/2) reacted for TM. TM is a sensitive marker for TCC. TM immunostaining can assist in distinguishing this tumor from others, especially renal cell carcinomas and adenocarcinomas of the prostate, colon, and bladder, but it has no value in separating TCC from squamous cell carcinomas.

Adenocarcinoma↗

Lymphocyte antibody interaction in cytotoxicity against human transitional cell carcinoma.

The interaction of antibodies and lymphocytes in their immune reaction against human transitional cell carcinomas was studied using the in vitro microcytotoxicity assay. A non-complement dependent, IgG antibody was detected in the serum of occasional transitional cell carcinoma patients, which induced cytotoxicity against transitional cell carcinoma target cells by lymphocytes from donors with and without transitional cell carcinoma. The observation that lymphocytes from transitional cell carcinoma donors were more sensitive to activation by this anti-transitional cell carcinoma, lymphocyte dependent antibody is compatible with the hypothesis that the surface of lymphocytes from some transitional cell carcinoma donors is coated in vivo with an anti-transitional cell carcinoma lymphocyte dependent antibody and that this antibody may be a significant factor in immunity to transitional cell carcinomas of the urinary tract.

Adenocarcinoma↗

Nonrandom chromosomal changes in transitional cell carcinoma of the bladder.

Nine cases of transitional cell carcinoma (eight from the urinary bladder and one from the ureter; six noninvasive and three invasive) were subjected to detailed cytogenetic analysis with a G-banding method. The synchronization of primary cultures with methotrexate for high-resolution banding was performed in five cases. In the remaining four cases, the chromosomes were obtained from short-term cultures after prolonged (16 hr) exposure to Colcemid. Two cases were near-tetraploid, one was hypotriploid, and six were near-diploid (three hyperdiploid and three hypodiploid). All but one case showed various structural abnormalities in the karyotype. The chromosomal changes ranged from the presence of only two abnormal chromosomes (markers) to complex karyotypes with as many as 15 markers. In most tumors, the origin of the marker chromosomes could be readily deciphered. The nonrandom chromosomal aberrations included: (a) an isochrosome of the short arm of chromosome 5 (three cases); (b) monosomy of chromosome 9 found in four cases (this was the sole abnormality in one case); (c) involvement of chromosome 8 as an isochromosome of the long arm (two cases) or loss of the short arm due to deletion (one case) or translocation (one case); and (d) interstitial deletion of chromosome 13 (three cases). Our results indicate that the formation of i(5p) and monosomy 9 may be the primary karyotypic changes in two subgroups of transitional cell carcinoma. Involvement of chromosomes 8 and 13, on the other hand, seems to be a result of secondary karyotypic evolution. Two invasive tumors showed the presence of secondary clones, with additional structural chromosome aberrations superimposed on those already existing in the main cell population. In both cases, the additional aberrations involved the short arm of chromosome 11, resulting in loss of genetic material from the short arm. The short arm of chromosome 11, is the putative site of an oncogene which has been isolated from human bladder carcinoma cell lines. Deletion of the 11p was also seen in one case of noninvasive transitional cell carcinoma localized in the ureter; the material from 11p was probably translocated to chromosome 13. These findings suggest that the loss of genetic material from the short arm of chromosome 11 is a secondary event in the karyotypic evolution of transitional cell carcinoma, probably related to the invasive behavior of the tumor.

Aged↗

The value of DNA cytometry in transitional cell carcinoma of the urinary bladder.

Transitional cell carcinomas are tumors with a high tendency of local recurrence. The extent of the primary tumor and histopathologic grade incompletely predict the individual outcome. In several studies, measurement of nuclear DNA content has been found to be of prognostic value in bladder cancer. We performed static DNA cytometry on transitional cell carcinomas of 130 patients. DNA parameters were correlated with stage and grade. There was a good correlation between local tumor extent (T category), grading, and DNA parameters. Ta and T1 tumors had significantly lower levels of 5c exceeding rate and DNA grade of malignancy than muscle invasive carcinoma. Well-differentiated carcinoma (G1) also had lower levels than G2 and G3 tumors. As a result of earlier studies, a DNA-based risk-adapted concept for treatment has been developed for superficial tumors. First preliminary results of a clinical study are given in the present paper.

Adult↗

[Transitional cell carcinoma involvement of the prostate].

Transitional cell carcinoma of the prostate (PTCC) has become a well recognized entity and is increasing in incidence due to the growing awareness of and search for. PTCC is part of the well known pan-urothelial disease: particularly the urologist must always consider the prostate in the management of superficial and invasive bladder cancer. Most cases are diagnosed in association with bladder cancer (secondary PTCC): primary prostatic transitional cell carcinoma arises "de novo" as the first tumor of the prostate urothelium and is rare. Prognosis depends on the prostate invasion degree. No reliable staging system is presently available. Non-invasive PTCC can be successfully treated with conservative means (TUR +/- BCG) whereas stromal invasive PTCC must be aggressively treated with radical cystectomy. PTCC can interphere with surgeon's decisions about urinary diversion in patients undergoing radical cystectomy for urothelial cancer.

Carcinoma, Transitional Cell↗

Ultrastructure, karyology and immunology of a cell line originated from a human transitional-cell carcinoma.

A cell line (J82) was derived from a poorly differentiated, invasive, transitional-cell carcinoma, Stage T3. The cells have been propagated in vitro for 5 years and showed 100% aneuploidy and a mixed epithelial-fibroblastic morphology. The majority of cells contained 2Y chromosomes and several distinctive markers. Peripheral-blood lymphocytes from the donor of the J82 cells were tested sequentially for cytotoxicity toward autologous and allogeneic tumour cells. Autologous cytotoxicity was detected against J82 cells in early in vitro passage. Allogeneic lymphocytes from some patients with transitional-cell carcinoma were also cytotoxic to J82 cells in primary culture. However, selective cytotoxicity by lymphoid cells from bladder-carcinoma patients was not detected against J82 cells in long-term tissue culture.

Carcinoma, Transitional Cell↗

Clinical significance of natural killer activity in patients with transitional cell carcinoma of the bladder.

We studied the relationship of natural killer activity from peripheral blood mononuclear cells with clinical stage of disease and the different modalities of treatment in 67 untreated patients with transitional cell carcinoma of the bladder and 29 normal controls. Peripheral blood mononuclear cells from 39 patients with superficial bladder tumor (stages Ta and T1) showed a natural killer cell activity similar to that of controls (p greater than 0.05), while in 28 patients with infiltrating tumors (stages T2, T3 and T4) this activity was significantly depressed (p less than 0.01). This functional phenomenon cannot be ascribed to a deficient number of natural killer cells in patients with infiltrating tumors, since the amounts of HNK-1+ (Leu 7), CD16+ (Leu 11) and CD11b+ (OKM1) cells in peripheral blood mononuclear cells were similar in the 3 groups of subjects (p greater than 0.05). Furthermore, the natural killer activity of peripheral blood mononuclear cells was normal (p greater than 0.05) in patients who underwent transurethral resection of the tumors and intracavitary cytostatic therapy with doxorubicin who remained free of disease at least 6 months after treatment. However, in patients with superficial recurrent tumor a significant decrease in the natural killer activity of peripheral blood mononuclear cells was observed (p less than 0.05), which was more pronounced in those with infiltrating recurrence. Also, in the latter patients total cystoprostatectomy was associated with a relevant increase in the spontaneous level of peripheral blood mononuclear cells. We conclude that in patients with transitional cell carcinoma of the bladder there is a correlation of the levels of natural killer activity in peripheral blood mononuclear cells with clinical evolution and pathological stage of disease. The determination of this activity is useful to monitor patients with transitional cell carcinoma of the bladder.

Aged↗

Antigen(s) on human transitional cell carcinoma detected by a xenogeneic antiserum.

In studies concerning human bladder cancer, antisera were raised in rabbits against human tumours, normal tissue, and cell lines derived from human tumours and were analysed by absorption and complement dependent microcytotoxicity tests. No significant selective cytotoxicity was discernible with any unabsorbed antisera. After absorption of A53, (an antiserum against the transitional cell carcinoma derived cell line T24) with peripheral blood cells and normal adult tissues, it was cytotoxic to two bladder cancer cell lines (T24 and J82) but not to four other cell lines. This activity was removed by absorption with each of two specimens of transitional cell carcinoma but not by normal bladder and by absorption with T24 or J82 but not with four other non-bladder cell lines. This functional specificity for transitional cell carcinomas could be due to a tumour associated antigen, a significant quantitative difference between tumour and normal cells, or an embryonic specificity re-expressed on the tumor. Further experiments are necessary to investigate these alternatives.

Absorption↗

[Study of growth fraction on fine needle aspirated prostatic tissue smear using monoclonal antibody Ki-67].

Immunohistochemical staining using monoclonal antibody Ki-67 was performed in 30 patients with benign prostatic hypertrophy (BPH), one with prostatic tuberculosis (TB), 22 with prostatic adenocarcinoma, one with prostatic transitional cell carcinoma and one with prostatic invasion from a bladder cancer. Specimens were aspirated from the prostate transrectally and a cytological smear were made. This antibody is specific for a proliferation-associated nuclear antigen. Alkaline phosphatase anti-alkaline phosphatase stained immunopositive nuclei red making positive or negative specimens easy to recognize. In BPH and TB smears, no immunopositive cell was reactive with Ki-67. In prostatic malignancy were found many immunopositive cells ranging from 2.5 to 10.2% (mean 5.9%) in prostatic adenocarcinoma (n = 22), and from 11.9 to 24.3% (mean 18.1%) in prostatic transitional cell carcinoma. Transitional cell carcinoma may have a much greater growth fraction than adenocarcinoma in prostatic tissue. Poorly differentiated adenocarcinoma showed a higher growth fraction (from 4.2 to 10.2%, mean 6.9%) than well differentiated (from 3.1 to 8.9%, mean 5.8%) and moderately differentiated adenocarcinoma (from 2.5 to 10.1%, mean 5.6%), but this difference was not significant. There was no correlation with age, clinical stage, bone metastasis or Böcking's cytological grade. In conclusion, immunohistochemical staining using Ki-67 on aspirated prostatic smear is visualizes the growth fraction of prostatic disease well and is useful to diagnose prostate cancer.

Adenocarcinoma↗

M-VAC or MVC for the treatment of advanced transitional cell carcinoma: metastatic, induction, and adjuvant.

The cisplatin-based combination chemotherapy regimens of M-VAC (methotrexate, vinblastine, doxorubicin, cisplatin) or MVC (methotrexate, vincristine, cisplatin) were given to 25 patients with metastatic urothelial carcinoma, 13 with locally advanced bladder cancer, and 10 as adjuvant therapy after radical surgery. Toxicity was significant with two deaths. Forty-eight percent of the patients with metastatic disease had a complete (20%) or partial (28%) response. Survival was only improved if a CR was achieved. Nine of 13 patients given M-VAC/MVC as neoadjuvant therapy underwent cystectomy and six are free of disease (mean 31 months). Three of the four patients who did not have radical surgery are also free of disease. These regimens appear to be superior to cisplatin alone. In the overall response evaluation, however, toxicity is greater.

Antineoplastic Combined Chemotherapy Protocols↗

Transitional cell carcinoma in patients with spinal cord injury: a high risk malignancy?

OBJECTIVES: To study bladder cancer incidence in patients with spinal cord injury (SCI) in Germany, Switzerland, and Austria. SCI is associated with neurogenic bladder dysfunction. These patients are at an increased risk of developing bladder malignancies. METHODS: A questionnaire was mailed to all SCI centers in these countries. The number of patients with SCI treated between 1995 and 1999, and the data of all patients with SCI with bladder cancer were recorded. RESULTS: The charts of 43,561 patients were reviewed. Of these, 48 patients (0.11%) developed bladder cancer. The data of 8 female and 29 male patients were fully available. The mean age was 53.3 years. Bladder management was reflex voiding in 18 patients, intermittent catheterization in 12 patients, and an indwelling catheter in 7 patients. Twelve patients were smokers. The mean time between SCI and the first bladder cancer diagnosis was 22.6 years. Thirty-two percent had superficial cancers, 8% had carcinoma in situ, and 60% presented with muscle-infiltrating tumors; 81% had urothelial cancer and 19% squamous cell cancer. Thirteen patients rarely had urinary tract infections (UTIs), 9 had more than 10 UTIs annually, and 15 had chronic UTIs. CONCLUSIONS: The bladder cancer incidence in patients with SCI and in the general population is comparable. More than 60% of the patients with SCI, however, initially presented with muscle-infiltrating bladder cancer. Indwelling catheters and chronic UTIs were common in patients with bladder cancer. Immunologic pathologic mechanisms and a prolonged exposure to carcinogens may be involved in bladder cancer carcinogenesis in patients with SCI.

Austria↗