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Prostatic adenocarcinoma with urothelial (transitional cell) carcinoma features.

Prostatic adenocarcinoma and urothelial carcinoma (transitional cell carcinoma) may coexist in the prostate. However, a carcinoma with mixed features has not been recognized. Four cases, three surgical pathology cases and one autopsy case of prostatic adenocarcinoma with urothelial carcinoma features, were retrospectively found in a urological pathology teaching file maintained from 1984 to 1993. Subsequently, 181 consecutive cases of radical prostatectomy from 1994 to 1999 were reviewed, and two prostatic adenocarcinoma areas with features of urothelial carcinoma were identified. Areas with urothelial carcinoma features were identified in the intraductal component of the carcinoma in five cases and in the invasive component in three cases. The intraductal carcinoma with urothelial carcinoma areas usually merged with regions of prostatic adenocarcinoma with a papillary or cribriform pattern. All prostatic adenocarcinomas having areas with urothelial carcinoma features were of high stage, and five of six cases had ductal features. The urothelial carcinoma component displayed a positive reactivity for thrombomodulin and negative or weaker reactivity for PAP and PSA than the prostatic adenocarcinoma component in the same tumor. Excluding the case noted at autopsy, all patients died of the disease within 3 years. Urothelial carcinoma features were usually associated with ductal carcinoma of high stage. Areas of prostatic adenocarcinoma with urothelial carcinoma features should be considered histopathologically as areas of mixed carcinoma of the prostate. Prostatic adenocarcinoma with areas of urothelial carcinoma features may pose a difficult differential diagnosis problem with urothelial carcinoma, especially with small biopsies with focal weak immunoreactivity for PAP, PSA, and thrombomodulin.

Acid Phosphatase↗

Autocrine IL-6 production by human transitional carcinoma cells upregulates expression of the alpha5beta1 firbonectin receptor.

PURPOSE: Studies have demonstrated elevated expression and secretion of IL-6 by transitional cell carcinomas (TCC) following bacillus Calmette-Guerin (BCG) therapy. At present, the role of IL-6 on the biology of TCC is poorly understood. This study evaluated the influence of IL-6 expression on a critical variable regulating BCG-tumor interaction, the tumor expression of alpha5beta1 integrin. MATERIALS AND METHODS: A human TCC cell line (253J) was transfected with an expression vector containing the full-length IL-6 cDNA sequence. Overexpression of IL-6 mRNA and protein was confirmed by Northern analysis and ELISA, respectively. Clones found to overexpress IL-6 were then assayed for alpha5beta1 expression using Northern analysis and flow cytometry. The effect of alterations in alpha5beta1 expression on tumor adherence to fibronectin (FN), and BCG adherence to tumor cells was determined using specific adherence assays. RESULTS: mRNAs for both the alpha5 and beta1 subunits of the FN receptor were increased an average of 9.4 fold and 125.7 fold respectively in the IL-6 overexpressing transfectants relative to the parental 253J cells. Increased mRNA of alpha5 and beta1 was associated with increased cell surface expression of both proteins. Increased protein expression resulted in greater FN substrate binding affinity and increased adherence of BCG to tumor cells. CONCLUSIONS: Autocrine expression of IL-6 upregulates the expression of FN receptor subunits in TCC. Increased alpha5beta1 expression increases cellular adherence to FN, and BCG adherence to tumor cells. These results suggest a role for IL-6 in mediating the antitumor activity of BCG by influencing BCG's adherence to TCC.

Autocrine Communication↗

A second-look TUR in T1 transitional cell carcinoma: why?

T1 transitional cell cancer of the urinary bladder is associated with a significant risk of tumor progression when transurethral resection (TUR) is the only treatment. Additional intravesical immunotherapy can reduce this risk; however, long-term results of more than 15 years of follow-up indicate that almost half of the patients may lose their bladder or even die due to recurrent tumor. The alternative to TUR is cystectomy at either the initial presentation or time of first recurrence. However, although the results of this treatment strategy are encouraging, an unknown percentage of patients will lose their bladder and go on to experience all possible complications of urinary diversion unnecessarily. The central issue of conservative treatment but also the indication for cystectomy is the quality of TUR. From the present literature, it is evident that a 'textbook TUR' cannot be performed on every patient, i.e. macroscopical clearance of the bladder from tumor, separate thorough resection of the tumor base and separate biopsies of the borders of the resection area. Moreover, even in cases of a so-called 'correct TUR', a significant percentage of residual tumor is left behind and will be the source of local recurrence or progression. In addition, TUR specimens may be difficult to diagnose accurately, especially in respect to grade and stage. Recent publications demonstrate that the routinely performed second TUR detects residual tumors of similar or higher stage in a significant percentage of patients. The clinical implications of these findings can be considerable as the absence or presence of tumor may determine whether patients undergo conservative or aggressive treatment. Moreover, results of retrospective studies support this suggestion. Currently, there is no standard appropriate treatment of T1 tumors. However, we strongly recommend that future studies on the conservative treatment of T1 tumors include a second TUR within 2 to 4 weeks after the first one.

Carcinoma, Transitional Cell↗

Suramin inhibits proliferation and DNA synthesis in transitional carcinoma cell lines.

Suramin is polysulfonated naphthylurea which has a broad range of antitumor activity. The mechanism of action of suramin is not completely understood, although it is known to inhibit enzymes in all cellular compartments, inhibit steroidogenesis and interfere with ligand-receptor binding. Suramin's large molecular size and negative charge should make it poorly absorbed through the bladder mucosa, a desired characteristic for an intravesical chemotherapeutic agent. We examined the ability of suramin to inhibit thymidine uptake and decrease cellular proliferation in 4 transitional cell carcinoma cell lines grown in vitro to determine if suramin might be a new candidate drug of treatment for patients with superficial bladder cancer. Suramin inhibited cellular proliferation of all cell lines tested (MBT2, T24, RT4 and TCCSUP) in a dose-dependent fashion. Fifty per cent inhibition of cellular proliferation compared with controls was seen with suramin concentrations of 250 to 400 micrograms/ml. by, at most, 5 to 9 days of exposure. The cell line RT4 was the cell line most sensitive to the growth inhibitory effect of suramin, with 50% growth inhibition compared with controls achieved after 3 days' exposure to a suramin concentration of 100 micrograms/ml. Suramin inhibited DNA synthesis in a dose-dependent fashion, as measured by thymidine uptake, in 3 of the 4 cell lines tested (MBT2, T24, and RT4). Suramin inhibited thymidine uptake by TCCSUP in a dose-dependent fashion, but did not achieve statistical significance.

Animals↗

The incidence of squamous and transitional cell carcinomas of the urinary bladder in northern Tanzania in areas of high and low levels of endemic Schistosoma haematobium infection.

Squamous cell carcinoma is the commonest type of bladder malignancy in most areas of northern Tanzania. Of 172 cases of bladder cancer recorded in 9 years, 72% were squamous cell carcinomas. Of these, 46% had Schistosoma haematobium eggs in sections taken from tumour tissue. The geographical distribution of this tumour closely corresponded to the prevalence of S. haematobium infection. The Mt Kilimanjaro area is free of schistosomiasis and virtually lacks squamous cell carcinoma. Although transitional cell carcinoma is rare in all regions of northern Tanzania, the relative frequency of bladder cancer in the Mt Kilimanjaro area was only one-third of that seen in other regions; population-based incidence rates were also very low in this area.

Adult↗

[Transitional cell carcinoma and renal cell adenocarcinoma: unusual case of association in the same kidney].

Presentation of one patient with a highly infrequent association of transitional cells carcinoma and renal cells adenocarcinoma synchronically developed in the same renal unit. There has been very few cases diagnosed up to now, and only around 25 have been described in the literature. There is a clear predominance of males versus females, with haematuria being the most frequent sign present in 90% cases. Elective complementary examination is CT and the choice treatment can be either nephroureterectomy or extended nephrectomy based on early suspicion of transitional cells carcinoma or renal cells adenocarcinoma.

Aged↗

[Combined small cell and transitional cell carcinoma of renal pelvis: a case report].

Primary small cell carcinoma of the renal pelvis is rare. We report a case of combined small cell and transitional cell carcinoma of the renal pelvis. The patient was a 78-year-old man with macrohematuria. He was diagnosed with right pelvic tumor by right retrograde pyelography and computerized tomography. A right radical nephroureterectomy was performed. Histological sections of the tumor showed a mixture of small cell and grade 2 transitional cell carcinoma. Positivity for Grimelius was noted in the small cell component. Masson-Fontana, chromogranin A, serotonin, keratin, leucocyte common antigen (LCA), neuron specific enolase (NSE), adrenocorticotropic hormone (ACTH), growth hormone (GH) and somatostatin were negative. Ultrastructurally, the tumor cells were tightly packed and attached together by scattered desmosomes. There were no neurosecretory granules. Seven months after operation, the patient died with peritonitis carcinomatosa. At autopsy, a metastatic tumor was found in the liver and retroperitoneal lymph node. Other organs were not involved. Especially, there were no abnormalities in the lungs.

Aged↗

Primary transitional cell carcinoma of spleen.

Transitional cell carcinoma arises from the lining of the urogenital tract and ovary. We report a 39-year-old lady with transitional cell carcinoma of the spleen that presented as a complex cystic lesion. Exhaustive search for another primary was negative. She is doing well 18 months after splenectomy was performed.

Adult↗

Possibility of spontaneous seeding of transitional cell carcinoma of the ureter in renal tubules: another mechanism of transitional cell carcinoma dissemination.

Cancer cell seeding inside the urinary tract always has been considered one possible mechanism of the multicentric origin of transitional cell carcinoma (TCC). However, there is still no direct clinical evidence to prove that the natural seeding of TCC is a real event. To our knowledge, we report the first case of spontaneous seeding of TCC of the ureter in the renal tubules of a hydronephrotic kidney. The TCC nature of the intratubular tumor cells has been confirmed by the morphological appearance of them after hematoxylin and eosin staining and positive p53 immunohistochemical staining.

Aged↗

Cytokine-induced gene expression of interleukin-8 in human transitional cell carcinomas and renal cell carcinomas.

Chemotactic cytokines play a critical role in recruiting leukocytes to sites of tissue injury. Interleukin-8 (IL-8) is a chemotactic cytokine secreted by a variety of cells (eg, monocytes, endothelial cells, fibroblasts) during the inflammatory response. In this report, the authors demonstrate that human transitional cell carcinomas and renal cell carcinomas have the capacity to elaborate IL-8 in response to the inflammatory mediators IL-1 beta and tumor necrosis factor (TNF)-alpha. All cell lines expressed high levels of IL-8 mRNA on stimulation with either IL-1 beta or TNF-alpha, but not lipopolysaccharide; one expressed the gene constitutively. The authors selected one transitional cell carcinoma cell line (UM-UC-9) and one renal cell carcinoma cell line (UM-RC-5) for further study. Both displayed a time- and dose-dependent increase in steady-state levels of IL-8 mRNA in response to IL-1 beta and TNF-alpha. Specific mRNA was detectable by 1 hour after stimulation. Secretion of antigenic IL-8 measured by enzyme-linked immunosorbent assay into culture supernatants reflected the kinetics of mRNA expression. Because heat-inactivated TNF-alpha failed to induce synthesis of IL-8 mRNA, and cycloheximide augmented TNF-alpha-induced synthesis, IL-8 expression appears to be a stimulus-specific primary induction phenomenon. As with other inflammatory mediators whose mRNA contains a 3' AU-rich sequence (eg, IL-2, TNF-alpha), the half-life of IL-8 mRNA was short, less than 1 hour. Our data suggest that secretion of IL-8 by malignant cells may partly account for the inflammatory infiltrates associated with some malignant neoplasms.

Base Sequence↗

Maintenance bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study.

PURPOSE: Bacillus Calmette-Guerin (BCG) immunotherapy has been widely accepted as the optimal treatment for carcinoma in situ and high grade superficial transitional cell carcinoma. However, controversy remains regarding the role of maintenance therapy, and its long-term effect on recurrence and progression. MATERIALS AND METHODS: All patients in the study had transitional cell carcinoma of the bladder with carcinoma in situ or an increased risk of recurrence. The criteria for increased risk were 2 or more episodes of tumor within the most recent year, or 3 or more tumors within 6 months. At least 1 week following biopsy of carcinoma in situ and resection of any stage Ta or T1 transitional cell tumors 660 patients were started on a 6-week induction course of intravesical and percutaneous Connaught BCG. Three months following initiation of BCG induction therapy 550 consenting patients were stratified by purified protein derivative skin test and the presence of carcinoma in situ, and then randomized by central computer to receive BCG maintenance therapy (maintenance arm) or no BCG maintenance therapy (no maintenance arm). Maintenance therapy consisted of intravesical and percutaneous BCG each week for 3 weeks given 3, 6, 12, 18, 24, 30 and 36 months from initiation of induction therapy. The 384 eligible patients who were disease-free at randomization constitute the primary intent to treat analytic group because they could be followed for disease recurrence. All patients were followed for adverse effects of treatment, recurrence, disease worsening and survival. RESULTS: No toxicities above grade 3 were noted in the 243 maintenance arm patients. The policy of withholding maintenance BCG from patients with increased side effects may have diminished the opportunity to observe severe toxicity. Estimated median recurrence-free survival was 35.7 months (95% confidence interval 25.1 to 56.8) in the no maintenance and 76.8 months (64.3 to 93.2) in the maintenance arm (log rank p<0.0001). Estimated median time for worsening-free survival, defined as no evidence of progression including pathological stage T2 disease or greater, or the use of cystectomy, systemic chemotherapy or radiation therapy, was 111.5 months in the no maintenance and not estimable in the maintenance arm (log rank p = 0.04). Overall 5-year survival was 78% in the no maintenance compared to 83% in the maintenance arm. CONCLUSIONS: Compared to standard induction therapy maintenance BCG immunotherapy was beneficial in patients with carcinoma in situ and select patients with Ta, T1 bladder cancer. Median recurrence-free survival time was twice as long in the 3-week maintenance arm compared to the no maintenance arm, and patients had significantly longer worsening-free survival.

Adjuvants, Immunologic↗

[Percutaneous treatment with BCG in multiple upper tract transitional cell carcinoma].

Upper tract transitional cell carcinoma is a low prevalent tumour and frequently associated to bladder carcinoma. The antegrade endoscopic access represents a safe, efficient and minimally invasive access. The association to immunotherapy seems effective in decreasing recurrence. We present one patient with multiple upper tract carcinoma treated with percutaneous surgery and BCG.

Adjuvants, Immunologic↗