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PubMed1994

[Our experience with mitomycin C in the prophylaxis of superficial bladder tumors; retrospective study].

From 1984 to 1991, fifty-one patients completed prophylactic endovesical treatment with mitomycin C after transurethral resection of a bladder carcinoma Ta, Tl. The mean disease-free period was 31.2 months; twenty patients had recurrences (39.2%) and five (9.8%) had a progression in tumor stage. No statistically significant differences were found relative to the recurrences and tumor number, stage and size. The patients with prior tumors had recurrences before (p < 0.05) and more times (p < 0.01) than the primary group.

Female↗
PubMed2026

Determinants of nucleic acid quality in formalin-fixed paraffin-embedded bladder urothelial carcinoma specimens: effects of specimen type, fixation conditions, and storage time.

Formalin-fixed paraffin-embedded (FFPE) tissue is the principal substrate for cancer genomic profiling, yet pre-analytical factors affect nucleic acid quality. In our workflow, transurethral resection (TUR) specimens of bladder urothelial carcinoma are fixed promptly but exposed to electrocautery, whereas robot-assisted radical cystectomy specimens are refrigerated overnight before fixation; we compared nucleic acid quality between these specimen types. We analyzed 56 FFPE primary bladder urothelial carcinoma specimens (33 TUR, 23 cystectomy). DNA quality was assessed by the DNA Integrity Number (DIN) and short-to-long cycle threshold ratio (S/L Ct ratio), and RNA quality by the RNA Integrity Number (RIN) and percentage of RNA fragments &#x2265;200 nucleotides (DV200), with group comparisons, Spearman correlations, and multivariable regression (specimen type, fixation duration, storage time). The median DIN (4.4 vs. 3.8, p&#xa0;=&#xa0;0.004) and S/L Ct ratio (0.943 vs. 0.894, p&#xa0;<&#xa0;0.001) were higher in TUR than cystectomy specimens; the RIN was also higher (1.9 vs. 1.7, p&#xa0;=&#xa0;0.040), though low in both groups, and DV200 did not differ (50.3% vs. 47.7%, p&#xa0;=&#xa0;0.934). In multivariable analysis, TUR specimen type independently predicted higher DIN (&#x3b2;&#xa0;=&#xa0;+0.460, p&#xa0;=&#xa0;0.040) and S/L Ct ratio (&#x3b2;&#xa0;=&#xa0;+0.442, p&#xa0;=&#xa0;0.009), whereas longer storage time independently decreased the S/L Ct ratio (&#x3b2;&#xa0;=&#xa0;-0.513, p&#xa0;<&#xa0;0.001) and RIN (&#x3b2;&#xa0;=&#xa0;-0.352, p&#xa0;=&#xa0;0.010). In our institutional workflow, TUR specimens showed higher DNA quality metrics than robot-assisted radical cystectomy specimens subjected to overnight refrigerated pre-fixation delay, whereas this workflow-associated advantage did not clearly extend to DV200-defined RNA fragment-length quality. Storage time was associated with selected aspects of nucleic acid deterioration.

Humans↗
PubMed2003

Distal ureteral stenosis after early adjuvant intravesical mitomycin C application for superficial bladder cancer.

We report a case of distal ureteral stenosis after transurethral resection of a small bladder tumor near the left ureteral orifice and early postoperative mitomycin C instillation for prevention of recurrence. The patient developed late recurrent stenosis of the ureteral orifice with histologic evidence of localized, severe benign inflammatory reaction. The recurrent stenosis was successfully managed by transurethral resection of the scar tissue and ureteric stenting. Although ureteral stenosis does occur after transurethral resection, the severity and time course of the stenosis in this case suggest an influence of the intravesical chemoprophylaxis used.

Administration, Intravesical↗
PubMed2004

Phase I pharmacokinetic study of a single intravesical instillation of gemcitabine administered immediately after transurethral resection plus multiple random biopsies in patients with superficial bladder cancer.

PURPOSE: In this phase I study we determined the pharmacokinetic and toxicity profiles of a single intravesical instillation of gemcitabine administered immediately after complete transurethral resection (TUR) plus multiple random biopsies. MATERIALS AND METHODS: Ten patients with superficial bladder cancer clinically staged as Ta/T1 with no carcinoma in situ were included. A single dose of gemcitabine was administered intra-vesically immediately after TUR plus 6 random biopsies. Five patients received 1,500 mg and 5 received 2,000 mg diluted in 100 ml saline. Retention time in the bladder was 60 minutes. Concentrations of gemcitabine and dFdU (2',2'-difluoro-2'-deoxyuridine) were determined by high pressure liquid chromatography assay. RESULTS: Treatment was clinically well tolerated in all patients. Two patients in the 1,500 mg group had minimal hipogastric discomfort and 1 in the 2,000 mg group had grade 1 bladder spasms. There was no remarkable systemic toxicity on hematology or biochemistry at any dose level on day 12 or 30. One patient per dose level showed tumor recurrence on 3-month repeat cystourethroscopy. Mean maximum gemcitabine concentration was 1.8 microg/ml and the mean last AUC was 158 microg/ml*minute. There was large interpatient variability but no significant differences between the 2 dose levels. CONCLUSIONS: Single intravesical instillation of gemcitabine immediately after TUR and multiple random biopsies for superficial bladder cancer are a safe and well tolerated treatment. The favorable toxicity and pharmacokinetic profiles of intravesical gemcitabine support future phase II studies with this agent.

Administration, Intravesical↗
PubMed2004

Bladder-conserving surgery and interstitial brachytherapy for lymph node negative transitional cell carcinoma of the urinary bladder: results of a 28-year single institution experience.

BACKGROUND AND PURPOSE: We retrospectively analyzed results for lymph node negative transitional cell carcinoma of the bladder treated with brachytherapy. PATIENTS AND METHODS: From 1975-2002, 58 patients received preoperative external irradiation, partial cystectomy (in 69%), iliac node dissection, and iridium-192. Pathologic stage was: 10 pT1, 41 pT2, and 7 pT3. A median total brachytherapy dose of 60 Gy was delivered to the tumor bed. RESULTS: Mean follow-up was 76 months (range, 0.5-296). Tumor stage significantly impacted cause-specific and disease-free survival (P=0.02). Eight pT1 patients were free of disease and 2 died of other cause. For pT2 patients, 5-year cause-specific and overall survival rates were, respectively, 70% (CI 95%: 53-87) and 60% (CI 95%: 43-77). Three pT3 patients died of cancer. For the pT2 patients, the probability of 5-year local control was 65% (CI 95%: 47-83) and being alive without disease with a functional bladder, 50% (CI 95%: 33-67). Previous transurethral resection (TUR) increased the bladder relapse risk among pT2 patients (P=0.03). Twelve patients had severe acute complications and 5 had severe late effects. A high dose of external irradiation increased risk of late complications (P=0.01). Most complications occurred in patients treated before 1985. CONCLUSIONS: Highly select patients presenting with pT2 tumors less than 5 cm with no history of previous TUR may be successfully treated with low-dose external irradiation, limited partial cystectomy, and interstitial brachytherapy. High-risk pT1 patients may also benefit. Postoperative complications and late side effects are minimized with modern management. We recommend lifelong cystoscopic surveillance, with prompt surgical salvage for recurrence.

Aged↗
PubMed1986

The effect of prior transurethral resection of the prostate on post radiation urethral strictures and bladder neck contractures.

Patients treated for prostate cancer from 1975-1982 were reviewed to assess if pre-irradiation transurethral resection of the prostate (TURP) predisposed to the formation of post treatment urethral strictures or bladder neck contractures. A total of 368 patients were treated with external beam irradiation delivered by a linear accelerator or 125I interstitial implants. Of the 253 patients treated by external beam, 138 patients had a history of at least one TURP before treatment. Implants were performed in 115 patients and 57 had a history of TURP before treatment. A total of 40 patients from both groups developed post treatment complications of urethral strictures or bladder neck contractures. Three patients developed both complications. An analysis of the 40 patients revealed that 29 (72.5%) patients had a TURP performed within a median time of 33 days prior to their initiation of radiation therapy. Of 195 patients in the prior TURP group, 29 (15%) developed one or both complications. Only 11 (6%) of the 173 patients in the non-TURP group developed one or both complications. This comparison was statistically significant with a p value of .025. Various factors analyzed including the treatment regimen, histologic grade, stage of disease, and volume of prostatic tissue removed at surgery did not show any positive correlation. Multiple TURP's were evaluated for greater distribution to the incidence of post treatment complications. The prior TURP group of 195 patients contained 60 with a history of at least two TURPs before radiation therapy. Eleven (18.3%) developed one or both complications. Of the 135 patients in the single TURP group, 18 (13.3%) developed complications. This was not statistically significant. Therefore, we concluded that the initial TURP was its mechanical description of mucosa and resultant scarring is a predisposing risk for development of urethral strictures or bladder neck contractures. Review of the literature concerning time sequence for healing of the urethra shows 4-6 weeks to be appropriate interval between surgery and radiation.

Combined Modality Therapy↗
PubMed1991

Stage T1 bladder cancer: grade is the primary determinant for risk of muscle invasion.

Tumor characteristics believed to predict for deep muscle invasion after transurethral resection of superficial bladder cancer alone were analyzed in 51 patients with stage T1 (stage A) transitional cell carcinoma of the bladder. All patients were treated at Stanford University Medical Center and none had intravesical chemotherapy at any time during the median followup of 78 months. No patient had carcinoma in situ. A total of 14 patients (27%) had deep muscle invasion. None of the patients with grade 1, 5 (22%) with grade 2 and 9 (50%) with grade 3 to 4 tumors had deep muscle invasion. Comparison of the risk of muscle invasion using pathological tumor grade at diagnosis, highest grade at any cystoscopic biopsy before the diagnosis of muscle invasion or highest grade at cystoscopic biopsy immediately antecedent to the cystoscopy at which muscle invasion was diagnosed all showed similar probability of muscle invasion. Mean interval to development of muscle invasion was 6 and 12 months in the grades 2 and 3 to 4 groups, respectively. At 36 months the cumulative probability of invasion-free survival was 62% for grade 2, compared to 50% for grades 3 to 4 cancer patients (p less than 0.005, Gehan). Univariate regression analysis demonstrated grade to be the only significant factor in predicting for invasive disease (p = 0.005), with tumors in the bladder neck to be of borderline significance (p = 0.159). On multivariate logistic regression analysis, grade remained the single tumor variable predicting for invasive bladder cancer (p = 0.004). These data suggest that of routinely available data at diagnosis and during subsequent followup cystoscopic examinations, tumor grade is the most important biological predictor of progression to muscle invasive cancer.

Aged↗
PubMed2001

Risk factors for multiple intravesical recurrences of superficial bladder cancer.

OBJECTIVES: To elucidate the risk factors for a second or third intravesical recurrence in patients with superficial bladder cancer. METHODS: Of 84 consecutive patients newly diagnosed as having superficial bladder cancer in Sapporo Medical University Hospital, 30 patients who had at least one recurrent superficial bladder cancer and were followed up for more than 3 years were included in this study. Multivariate analysis by Cox's proportional hazards model was used to determine which clinical and pathologic variables significantly affected the second and third recurrences. Stepwise regression analysis was used to determine which clinical and pathologic variables significantly affected multiple recurrences of bladder cancer. RESULTS: The 1, 2, and 5-year recurrence-free rates as determined by the Kaplan-Meier method were 66.1%, 43.8%, and 29.8% for a second recurrence and 67.4%, 61.8%, and 39.2% for a third recurrence, respectively. Multivariate analysis revealed that only the interval between the initial transurethral resection of the bladder cancer and the first recurrence was a significant and independent factor affecting the second recurrence. In the study of the third recurrence, the interval between the first and second recurrences was the only definite risk factor for the third one. When multiple recurrences were considered, stepwise regression analysis revealed that a time of 6 months or less from the initial transurethral resection until the first recurrence was a significant factor that affected the total frequency of bladder cancer recurrence (R(2) = 0.220, P = 0.0078). CONCLUSIONS: The results of our study indicate that patients will have the potential for frequent recurrences if they have the disease with recurrence after a short interval. This result may contribute to the selection of patients with superficial bladder cancer to receive aggressive adjuvant treatments to prevent frequent recurrences.

Adult↗
PubMed2000

Urolume stent placement for the treatment of postbrachytherapy bladder outlet obstruction.

OBJECTIVES: Transurethral resection (TURP) or incision of the prostate is generally not effective for treating bladder outlet obstruction after transperineal brachytherapy for prostate cancer. Furthermore, TURP could compromise full-dose effective radiation delivery to the prostate. We analyzed the efficacy of the UroLume stent in treating the urinary outflow obstruction in such patients. METHODS: Five patients who had undergone brachytherapy (3 with (192)Ir high-dose radiation and 2 with (125)I) subsequently developed one or more episodes of urinary retention 2 weeks to 4 years after treatment. The patients failed or could not tolerate alpha-blockers or clean intermittent catheterization. Three patients subsequently underwent urethral dilation/optical internal urethrotomy for strictures, and 1 patient underwent suprapubic tube placement. Following the failure of these interventions, each of these patients had a UroLume stent placement. A single UroLume stent (2 cm in 3 patients and 2.5 cm in 2 patients) was placed under local/spinal anesthesia. RESULTS: All patients were able to void spontaneously immediately after stent placement. Of the patients with previous urethral strictures, 1 remained continent and 1 had persistent incontinence. Neither of the patients with early postbrachytherapy retention developed incontinence after stent placement. The main complaints following stent placement were referred pain to the head of the penis and dysuria. Stent-related symptoms necessitated stent removal in 2 of 5 patients, 4 to 6 weeks after placement. CONCLUSIONS: The UroLume stent can be used as an alternative form of therapy for managing postbrachytherapy bladder outlet obstruction. The treatment is easily reversible by removing the stent when obstruction resolves.

Aged↗
PubMed2003

Can patient selection for bladder preservation be based on response to chemotherapy?

BACKGROUND: Neoadjuvant chemotherapy for patients with muscle-invasive bladder carcinoma is given to treat micrometastases and to preserve the bladder. The objective of this study was to evaluate the possibility of bladder preservation in patients with muscle-invasive bladder carcinoma who were treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) chemotherapy. METHODS: One hundred four consecutive patients with T2-T4,N0,M0 transitional cell carcinoma of the bladder were treated with 3 cycles of neoadjuvant M-VAC chemotherapy. After clinical restaging, 52 patients underwent transurethral resection of the bladder (TURB) alone, 13 patients underwent partial cystectomy, and 39 patients underwent radical cystectomy. RESULTS: The median survival for the entire group was 7.49 years (95% confidence interval, 4.86-10.0 years). Forty-nine patients (49%) were T0 at the time of TURB after receiving M-VAC. Thirty-one of 52 patients (60%) who received chemotherapy and underwent TURB alone were alive at a median follow-up of 56 + months (range, 10-160 + months): Twenty-three patients (44%) in that TURB group maintained an intact bladder. Of 13 responding patients with monofocal lesions who underwent partial cystectomy, only 1 patient required salvage cystectomy, and survival generally was good. The 5-year survival rate for this group was 69%. With a long median follow-up of 88 + months (range, 16-158 months), 4 patients (31%) were alive with a functioning bladder. In the radical cystectomy group, the median follow-up was 45 months (range, 4-172 + months), and 15 of 39 patients (38%) patients remained alive. In 77 patients who had their tumors down-staged to T0 or superficial disease, the median follow-up was 63 months (range, 4-172 + months), and the 5-year rate survival was 69%. This is in contrast to a 5-year survival rate of only 26% in 27 patients who failed to respond and had a status >/= T2 after receiving chemotherapy (median follow-up, 31 months; range, 7-156 + months). The median survival for 27 elderly patients (age >/= 70 years; median age, 73 years; range, 70-82 years) was 90 months (7.5 years). For elderly patients who underwent TURB and partial cystectomy, the 5-year survival rate was 67% with a 109-month (9-year) median survival; 47% of patients preserved their bladders intact. The median follow-up of the living elderly patients was 61 months (range, 20-120 + months). CONCLUSIONS: Bladder sparing in selected patients on the basis of response to neoadjuvant chemotherapy is a feasible approach that should be confirmed in prospective, randomized trials. Selected elderly patients are candidates for this approach.

Adult↗
PubMed1996

Endocervical type glands in urinary bladder: a clinicopathologic study of six cases.

The authors report six cases of glandular lesions made up of endocervical type glands in the urinary bladders of women aged 34 to 65 years (mean, 39 years). Two patients presented with dysuria, one with painless hematuria, one with complaints of pelvic discomfort and hematuria, and one with vaginal discharge. The sixth patient was asymptomatic, but on a routine gynecologic examination, a pelvic mass was found. On physical examination, three women had masses between the bladder and uterus. Four lesions were located in the posterior wall of the urinary bladder, one in the dome, and one in the trigone. Four patients underwent biopsy of the bladder lesion. One of these patients had undergone a hysterectomy 10 years earlier. One woman with a pelvic mass between the bladder and uterus underwent a hysterectomy, bilateral salpingo-oophorectomy, and partial cystectomy. The sixth patient had a transurethral resection of the bladder tumor and left oophorectomy. Histologically, all cases showed intermediate to large-sized irregularly shaped endocervical type glands in the muscularis propria of the urinary bladder. Some glands exhibited cystic dilatation and contained mucinous secretions. The glands elicited no desmoplastic tissue reaction. The intraluminal mucin frequently contained polymorphonuclear leukocytes. In all cases, the glands were lined by mucinous, tall, columnar cells and less commonly by flattened to cuboidal cells. Rare admixed ciliated cells were also observed. The lining epithelium was bland in five cases, but moderate nuclear atypia was seen in one case. Mitoses were not observed in any case. Associated lesions included endometrial type glands surrounded by elastotic stroma in one case, exuberant cystitis glandularis in one case, and a pseudodiverticulum of the bladder in one case. Review of the slides from the patient who had had a hysterectomy 10 years previously revealed endocervical adenocarcinoma in situ. Follow-up (mean = 30 months; range = 6 to 60 months) shows that all patients are alive and well, suggesting that the lesion is benign.

Adult↗
PubMed2002

Idiopathic myelofibrosis with extramedullary haemopoiesis involving the urinary bladder in a Chinese lady.

Extramedullary haemopoiesis (EMH) associated with idiopathic myelofibrosis most commonly involves the reticuloendothelial organs, such as the spleen and liver, although ectopic haemopoietic tissue has also been described rarely in the lymph nodes, skin, gastrointestinal tract, pleura, peritoneum, central nervous system, and genital and urinary tracts. We report on a 54-year-old Chinese lady with a long history of idiopathic myelofibrosis who presented with gross haematuria and left hydronephrosis due to EMH in the bladder trigone. Cystoscopic examination revealed a sessile necrotic papillary growth at the trigone, obstructing the left ureteric orifice. Transurethral resection of the bladder tumour was performed, and microscopic examination of the tumour chips demonstrated atypical megakaryocytes, immature granulocytes and normoblasts, confirming the presence of EMH. The residual bladder tumour responded well to low dose radiotherapy, with subsequent disappearance of haematuria and normalization of ultrasonogram findings.

Cell Lineage↗
PubMed1993

Influence of fibrin clot inhibitors on the efficacy of intravesical Bacillus Calmette-Guérin in the treatment of superficial bladder cancer. The Dutch Southeast Cooperative Urological Group.

After transurethral resection (TUR) of superficial bladder tumors, intravesical instillations with BCG are successfully used to lower the recurrence rate. The mechanism of the antitumor activity of BCG is not completely understood. After TUR, a fibrin clot is formed on the damaged urothelium. Fibronectin (FN) is part of the clot. It has been demonstrated that binding of BCG to the bladder wall is mediated by FN, and therefore FN seems necessary for the antitumor activity of BCG. This binding can be inhibited by fibrin clot inhibitors, like aspirin and coumarin. A reduced efficacy of BCG in patients with superficial bladder cancer using these drugs has been described. We studied 183 patients with superficial bladder cancer, treated with one or two 6-week courses of intravesical BCG instillations. Of the 42 patients that used fibrin clot inhibitors, 13 (31%) experienced a recurrent tumor, as compared to 56 (40%) of 141 patients who did not use these drugs (p = 0.28). The mean time to recurrence was the same in both groups. These results did not depend on the BCG strain used (Tice or RIVM, p = 0.92) and were not influenced by the use of antibiotics against urinary tract infections. We conclude that in our study fibrin clot inhibitors have no adverse effect on the efficacy of BCG therapy for superficial bladder cancer.

Administration, Intravesical↗
PubMed1983

Prognostic factors in superficial bladder tumors. A study of the European Organization for Research on Treatment of Cancer: Genitourinary Tract Cancer Cooperative Group.

A randomized clinical trial was performed on 308 patients with stage T1 carcinoma of the bladder to compare the efficacy of transurethral resection alone or followed by bladder instillations of thiotepa or VM-26 (teniposide) for 1 year. With the recurrence rate as the primary end point of interest the data from this trial were used to assess the prognostic importance of the following factors at entry into the study: number of tumors, prior recurrence rate, tumor size, grade, age, treatment group assigned and, finally, the interval between transurethral resection at entry into the study and the start of intravesical treatment. Using multivariate statistical techniques we found that the number of tumors at presentation was the most important prognostic factor followed by, in order of importance, the recurrence rate at entry and the size of the largest tumor. Of particular note was the discovery that patients with less than 1 recurrence per year at entry had a prognosis similar to patients with primary tumors, while those with a higher recurrence rate did uniformly poorly. These results show that patients with stage T1 carcinoma of the bladder form a heterogeneous group and that more aggressive therapy should be considered for patients with a poor prognosis.

Humans↗
PubMed1993

Analysis of the immunologic mechanism of intravesical bacillus Calmette-Guerin therapy for superficial bladder tumors: distribution and function of immune cells.

Intravesical bacillus Calmette-Guerin (BCG) administration has been used as an adjuvant therapy after transurethral resection for superficial bladder cancer, but the exact mechanisms of its antitumor activity are not yet known. The aim of this study was to characterize the immunologic aspects of antitumor activity of BCG using an animal model. C3H/He inbred mice and murine bladder tumor cell line, MBT-2 were used. The changes in immune cells such as helper T cells, suppressor T cells, macrophages and natural killer cells in the bladder and spleen were analysed by immunohistochemical method in intravesical BCG instilled in normal bladder, MBT-2 implanted after electrocauterization of the bladder mucosa and MBT-2 implanted and intravesical BCG treated group. The changes in natural killer cell activity of the splenocytes and peritoneal lymphocytes were evaluated using 51chromium release assay at regular time intervals following intraperitoneal BCG instillation. The prophylactic anticancer effect was evaluated by observing the tumor growth in the intravesically BCG treated group after intravesical MBT-2 implantation. In immunohistochemical examination, a remarkable infiltration of macrophage and helper T cell was observed in the lamina propria of the bladder, and the helper and suppressor T cells ratio (Th/Ts ratio) was increased after intravesical BCG therapy. In 51chromium release assay, enhanced natural killer cell activity of the splenocytes and peritoneal lymphocytes was observed after intraperitoneal BCG inoculation. The growth of implanted tumor was suppressed following intravesical instillation of BCG. These results suggest that the antitumor activity of BCG is not related to the simple inflammatory reaction but to the local and systemic immune response in which helper T lymphocytes and mononuclear cells play an important role.

Animals↗
PubMed2002

[Treatment of bladder neck obstruction (sclerosis): personal experience and literature review].

The goal of this article is a description of bladder neck obstruction (sclerosis) treatment results at the Department of Urology at Kaunas University of Medicine Hospital and the review of current literature on this subject. Sixty seven patients treated for bladder neck obstruction (sclerosis) in the period of 1995-2000 years were analyzed retrospectively. On admission to the hospital, 31 patient had undergone open prostatectomy for benign prostatic hyperplasy, 14 had undergone thransurethral prostate resection and 22 had no previous prostatic surgery. The usual diagnostic procedure for bladder neck obstruction (sclerosis) in Kaunas University of Medicine Hospital is retrograde uretherocystography. According to current literature the videourodynamics is the most effective diagnostic procedure, however, still not available at Kaunas University of Medicine Hospital. The transurethral bladder neck incision or/and resection is effectively used for bladder neck obstruction (sclerosis) treatment at Kaunas University of Medicine Hospital. The near postoperative results are good for 73.4% of patients. This method is the most widely used for bladder neck obstruction (sclerosis) treatment around the world.

Adult↗
PubMed1997

In vitro modulation of implantation and intraepithelial expansion of bladder tumor cells by epidermal growth factor.

A major problem in the management of bladder cancer is the high risk for recurrence of bladder tumors after transurethral resection. This has generally been attributed to the attachment and subsequent expansion of exfoliated tumor cells to the traumatized bladder wall. An in vitro cocultivation model was used to study the implantation and growth of human tumor cells in traumatized murine urothelium. Furthermore, we investigated in a time-course experiment whether stimulation of the regenerative activity of the normal urothelium by a growth factor could affect implantation and subsequent growth of bladder tumor cells. After inoculation on injured confluent cultures of murine urothelium, human T24 and SD bladder carcinoma cells preferentially attached to the denuded areas. SD cells expanded into the normal urothelium as a sharply demarcated tumor, while T24 cells infiltrated as single cells. Treatment of the primary urothelium with epidermal growth factor (EGF) stimulated the proliferation of the primary urothelium and reduced the implantation and growth of T24 considerably. EGF reduced the implantation of the SD tumor cells but could not prevent the further expansion at the expense of surrounding normal urothelium. Since EGF had no effect on migration or proliferation of SD or T24 cells, its modulation of expansive growth is most probably due to an increase in the regeneration of normal urothelium. This study suggests that recurrence of transitional cell carcinomas might in some instances be inhibited by stimulation of the regeneration of traumatized urothelium. The reported in vitro cocultivation model may be useful for studying additional factors involved in intraepithelial expansion of carcinoma cells.

Animals↗