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[Inverted papilloma of the bladder: observation of 3 clinical cases and discussion on their clinico-pathologic characteristics].

Three cases of urothelial inverted papilloma, detected in two female patients aged 32 and 31 years, respectively and in one 67-year-old male patient, are described. Inverted papilloma is a benign lesion which occurs in the urinary epithelium with a 20% incidence in comparison with other urothelial tumours. The male:female ratio is 3:1. The histological structure of urothelial inverted papilloma is similar to that of inverted papilloma of the nasal and paranasal sinuses. It presents interanastomosed epithelial cords, with transitional cells, which develop in the tunica propria connective tissue. Some cells are distributed in such a way as to constitute vacuolated glandular-like structures. The histogenetic origin of the lesion from Home subtrigonal or Albarran subcervical glands is debatable. Recent aetiological hypotheses have claimed that the origin of the lesion may be related to Brunn's nest hyperplasia and/or to chronic urothelial inflammation. The latter hypothesis would currently appear to be the most accredited: immunostaining for cytokeratins would tend to support a urothelial inflammatory aetiology. In our cases, we achieved a definitive diagnosis of inverted papilloma only at histology, because of the specificity of the echotomography and cystoscopy findings. Urinary cytology revealed only a large number of inflammatory cells with anaplastic elements, but without any more detailed morphological description. We performed a transurethral resection of the bladder (TURB) in all three patients: routine follow-up showed the absence of inverted papilloma relapses. On the basis of the above-mentioned data and a thorough review of the literature, we attempt to assess and classify the clinico-pathological findings and the aetiological hypotheses of urothelial inverted papilloma. In addition, the benign nature of the lesion and any malignant transformation factors are discussed.

Adenocarcinoma↗

Phase II study of a new combined primary chemotherapy regimen, intravenous methotrexate and vincristine and intraarterial adriamycin and cisplatin, for locally advanced urinary bladder cancer: preliminary results.

A phase II study of a new combination therapy was performed using intraarterial (i.a.) cisplatin and Adriamycin in combination with i.v. methotrexate and vincristine for 27 patients with invasive urinary bladder carcinoma of stages T2-3NOMO, and the therapeutic effects were assessed. Methotrexate (20 mg/m2) was given i.v. on days 1,15, and 22, and vincristine (0.7 mg/m2) was injected i.v. on day 2 before i.a. infusion therapy and on days 15 and 22. The i.a. chemotherapy was performed after both superior gluteal arteries had been embolized using 3- or 5-mm stainless-steel coils. A mixture of cisplatin (50-70 mg/m2) and Adriamycin (20 mg/m2) was infused i.a. via both internal iliac arteries over a period of 20-30 min. Angiotensin II (mean dose, 21 micrograms) was simultaneously infused i.a. in 15 of 27 patients. In 24 of the 27 patients, at least 2 cycles of full-dose chemotherapy were completed. The dose was decreased in the remaining 3 patients because of their poor health status and advanced age. Among the 27 patients, 9 and 14 had complete (CR) and partial responses (PR), respectively; 3 manifested no change (NC), and 1 had progressive disease (PD). The objective response rate (CR+PR) was 85.2%. Among the 27 patients staged T2-3 NOMO, 6 (CR, 1; PR, 5) underwent total cystectomies and 18 (CR, 8; PR, 8; NC, 2) had transurethral resection of a bladder tumor (TUR-Bt) or partial resections following chemotherapy. The remaining 3 diminished-dose patients had no surgery. Of the 27 patients, 22 were alive after a median follow-up period of 21+ (range, 7-48+) months. No significant side effect was observed except for lower extremity paresthesias in 5 patients (18.5%). These results point to the effectiveness of this therapy and to the possibility of urinary bladder preservation in patients with invasive, advanced urinary bladder cancers.

Adult↗

New prostatectomy technique: transurethral electrovaporization of the prostate.

Major health and economic concerns have caused urologists to seek alternative forms of treatment for benign prostatic hypertrophy (BPH). The goal of these newer treatments is to decrease morbidity, reduce health care cost, and improve overall outcome for the patients with symptomatic bladder outlet obstruction. Transurethral resection of the prostate (TURP) is the gold standard treatment for BPH. One factor associated with the relative higher cost of a TURP is the average 4-day postoperative stay needed to clear the hematuria. Techniques have evolved that have allowed immediate tissue removal through "vaporization" of the prostate with a decrease in the postoperative stay. These techniques have primarily relied upon the use of lasers to vaporize tissue. A new transurethral prostatectomy technique called transurethral electrovaporization of the prostate (TVP) has been recently introduced. This relies upon a newly developed resectoscope electrode (VaporTrode) that allows vaporization of the prostate tissue in the "cutting" mode. The potential advantage of TVP is the reduction in postoperative hematuria and the utilization of equipment and techniques that are already familiar to the practicing urologist.

Aged↗

A randomized trial comparing intravesical instillations of mitoxantrone and doxorubicin in patients with superficial bladder cancer.

BACKGROUND: This randomized trial was conducted to compare the efficacy and side effects of intravesical mitoxantrone instillation with those of doxorubicin in superficial bladder cancer following transurethral resection. METHODS: Sixty-three patients were randomized into mitoxantrone and doxorubicin groups. Most of the patients enrolled were elderly people (mean age, 71 years). The instilled doses of doxorubicin and mitoxantrone were 30 and 14 mg, respectively. Disease recurrence and side effects were compared using Fisher's exact test. The interval to recurrence was shown by Kaplan-Meier survivorship curves, and the log-rank test was used to compare the time to recurrence. RESULTS: The median follow-up period was 36 months. Thirty-three patients received mitoxantrone, whereas 30 patients used doxorubicin. The recurrence rate in the doxorubicin group was 30% (95% CI: 19.8%-38.8%), while it was 27.3% (95% CI: 17.5%-36.8%) in the mitoxantrone group. The median recurrence-free survival in the mitoxantrone group and in the doxorubicin group was 22 and 20 months, respectively (p=0.580). Higher recurrence rates were found for Grade III and multiple primary tumors. There was no significant difference in response rates (p=0.784). The incidence of side effects was 20% in the doxorubicin group and 21.2% in the mitoxantrone group. However, the difference was not significant (p>0.99). CONCLUSIONS: The results revealed that the efficacy and side effects of mitoxantrone were similar to those of doxorubicin. Especially for patients with pulmonary tuberculosis or aged patients with primary bladder tumors, mitoxantrone and doxorubicin may be the tolerable and effective intravesical agents.

Administration, Intravesical↗

Recurrences and progression of superficial bladder cancer following long-term intravesical prophylactic therapy with mitomycin C: 48-month follow-up.

A total of 208 patients with superficial transitional-cell carcinoma of the bladder (STCC) after transurethral resection were treated with 30 mg intravesical instillations of mitomycin C (MMC) weekly for 8 weeks, followed by monthly maintenance doses for 12 months. All patients were controlled with a urinary cytological examination every 2 months and with cystoscopy every 3 months. Mean follow-up was 47.8 and 49.3 months in the prophylaxis and control groups, respectively. The incidence of tumor recurrences at the 12th and 48th months was 29 and 44%, respectively, in the MMC group and 45 and 58%, respectively, in the control group. Progression evaluated by grade and stage was significantly higher in the control group. These data indicate that MMC appears to be effective in the prophylaxis of STCC, but the possibility of long-term relapse suggests maintenance of a longer therapy.

Administration, Intravesical↗

Prostatic occurrence of transitional cell carcinoma after intravesical chemotherapy.

Thirteen patients with Stage Tis, Ta, or T1 transitional cell carcinoma (TCC) of the bladder treated by transurethral resections and intravesical chemotherapy developed TCC of the prostate. Among the 13 cases, cytology specimens were obtained from 10 at the time prostatic disease was diagnosed; 9 demonstrated TCC. One was treated successfully by transurethral resection of a Ta lesion involving the prostatic urethra only. One of 2 patients declining radical surgery is alive with residual disease at twenty-four months, and the other died of progressive disease at nineteen months. Of the 10 patients who underwent radical cystoprostatectomy, 7 are alive with no evidence of disease eight to forty-two months postoperatively, with 2 of these 7 having received 4 courses of systemic methotrexate, vincristine, Adriamycin, and cisplatinum (MVAC) for metastatic disease. Two of the 10 died of metastatic disease six and thirteen months postoperatively, and one frail patient died of surgical complications. When treating patients with intravesical chemotherapy for superficial TCC, biopsy of the prostate should be done during follow-up examinations, especially in the presence of cytologic or palpable prostatic abnormalities.

Administration, Intravesical↗

[Clinical investigation for recurrence and progression in Ta grades 1 and 2 bladder cancer].

We treated 107 new patients with stage Ta, grades 1 and 2 transitional cell bladder carcinoma by transurethral resection during the past 23 years. The clinicopathological factors evaluated were grade, size, number and form of tumor. Fifty-five patients (51%) had recurrent tumors after initial resection and progression (muscle invasion or metastasis) occurred in four patients (3.7%). The 5-year and 10-year recurrence free rates were 47.3 and 29.8%, respectively. Seven patients (6.5%) had grade 3 tumor (grade-up) at recurrence. An increase in T category to T1 (stage-up) occurred in 13 patients (12%), only one of whom later developed an invasive tumor (pT4). The size of tumor significantly affected the rate of recurrence (p < 0.01). Sessile tumor were at a significantly greater risk for progression (p < 0.05). Stage-up did not have a significant effect on progression, but grade-up was significantly risky for progression (p < 0.01). Initial grade 2 tumors were highly related to grade-up (p < 0.05).

Adult↗

Prognostic significance of histopathological grading and immunoreactivity for p53 and p21/WAF1 in grade 2 pTa transitional cell carcinoma of the urinary bladder.

OBJECTIVE: At present, there are no predictors of tumour behaviour for grade (G) 2 pTa transitional cell carcinomas (TCC) of the bladder. Here we analyse the prognostic relevance of histopathological grading and the immunohistochemical detection of p53 and p21/WAF1. METHODS: 70 patients were newly diagnosed with G2 pTa TCC of the bladder based on transurethral resection specimens. Two pathologists, blinded with respect to the clinical outcome, confirmed the initial grade and subclassified the G2 lesions into G2a and G2b carcinomas based on the degree of nuclear atypia and the number of mitoses. Immunoreactivity for p53 and p21/WAF1 was evaluated semiquantitatively. RESULTS: There were 52 G2a and 18 G2b tumours, mean follow-up was 49.2 months. Of all patients, 31.4% remained tumour-free, 48.6% recurred with the same tumour grade and stage, and 20.0% showed tumour progression. Patients with G2a tumours developed tumour progression in 13% in contrast to 39% with G2b lesions (p = 0.037). Of 21 p53-positive tumours, 33% (7/21) developed progressive disease, whereas 14% (7/49) of p53-negative patients showed tumour progression (p = 0.102). Neither p21/WAF1 expression alone nor the combination of p53 and p21/WAF1 correlated with clinical outcome. CONCLUSION: The more detailed grading system but not p53 or p21/WAF1 immunohistochemistry was found to be an independent prognostic factor for tumour progression.

Carcinoma, Transitional Cell↗

Overview of bladder cancer trials in the Cancer and Leukemia Group B.

The Cancer and Leukemia Group B (CALGB) Genitourinary Committee has developed a broad range of clinical trials across most stages of bladder cancer. Recurrence rates of superficial bladder cancer after transurethral resection range from 50-70%. Although adjuvant bacillus Calmette-Guerin reduces the risk of disease recurrence or progression, only 30% of patients have long-term disease-free survival. Because the development of novel secondline agents is needed, the CALGB is evaluating the utility of intravesicle gemcitabine as well as an oral proapoptotic agent (CP-461). In patients with locally advanced disease with an increased risk of disease recurrence after cystectomy, a randomized trial of conventional chemotherapy versus sequential dose-dense therapy is under development. The gemcitabine/cisplatin combination has become a commonly used regimen for the treatment of advanced transitional cell carcinoma (TCC). The CALGB is undertaking a Phase II study that incorporates a fixed dose rate gemcitabine infusion in this regimen, together with a selective epidermal growth factor receptor tyrosine kinase inhibitor, Iressa (Astra Zeneca, Wilmington, DE). In patients with renal insufficiency, a regimen of carboplatin, gemcitabine, and Iressa is planned. Novel agents, including arsenic trioxide and trastuzumab (Herceptin; Genentech, Inc., South San Francisco, CA), are being evaluated as secondline therapy in patients with advanced TCC who have disease progression after frontline therapy.

Antineoplastic Combined Chemotherapy Protocols↗

[Contribution of fluorescence immunocytochemistry (uCyt+TM) in the postoperative surveillance of bladder cancer].

OBJECTIVE: To assess 1) the value of fluorescence immunocytochemistry (uCyt+ test, DiagnoCure Inc., Quebec) in the detection of recurrent bladder tumour after transurethral resection (TUR) and 2) the predictive value of a positive uCyt+ test in patients with negative cystoscopy. MATERIAL AND METHODS: This study was based on 132 patients with a mean follow-up of 21.9 weeks after TUR. The initial tumours were pTa G1-2 in 66.7% of cases, and G3 in 28.8% of cases. Cystoscopy, urine cytology (UC) and uCyt+ test data were collected on the day of the first control visit (D0), and the patients were then reviewed at 6 and 12 months. All lesions detected on cystoscopy were biopsed. RESULTS: The mean sensitivity of UC was 47.4% and the mean sensitivity of uCyt+ was 73.7% (84.2% in combination). In patients with negative cystoscopy on D0, a positive uCyt+ test has no predictive value at 6 months. At 12 months, 20.0% of patients with positive UC had relapsed, versus 16.7% of patients with negative UC (p = ns). On the other hand, at 12 months, 50.0% of patients with negative cystoscopy but positive uCyt+ test had relapsed, versus 16.4% of patients with a negative uCyt+ test (p < 0.01). CONCLUSIONS: The uCyt+ test allows assessment of the risk of recurrence at I year, while UC alone only has a diagnostic value. These results raise the possibility of combining the tests in order to decrease the frequency of follow-up cystoscopy.

Adult↗

Does intravesical chemotherapy prevent invasive bladder cancer?

Intravesical chemotherapy has been shown to prolong the interval free of disease and to reduce the tumor recurrence rates in patients with superficial bladder cancer. These observations led us to consider whether a course of intravesical chemotherapy might provide a long-term decrease in the recurrent tumor rate or reduce the incidence of progression to invasive carcinoma. The records of 123 patients entered into a randomized multicenter protocol between 1975 and 1978 were examined. Patients had received a 1-year course of thiotepa or VM26, or transurethral resection alone. Mean followup was 47 months. Patients receiving thiotepa or VM26 had a lower rate of tumor recurrence, expressed as recurrences per 100 patient-months, than those undergoing transurethral resection only (5.25 versus 5.71 versus 7.98) but this was not statistically significant. However, 28 per cent of the controls required therapy besides transurethral resection to control the bladder cancer and 19 per cent died of advanced bladder cancer during followup. Only 15 per cent of the patients undergoing intravesical chemotherapy required therapy other than transurethral resection and only 3 per cent died of advanced carcinoma of the bladder. This finding suggests that intravesical chemotherapy given for 1 year is associated with a significant decrease in the incidence of tumor progression, and provides the justification to conduct future trials with extended followup.

Administration, Topical↗

[Clinical statistics on inpatients and operations at Mishina Urological Office between July, 1984 to December, 1990].

The total number of inpatients was 1,309. There were 1020 males and 289 females, the male to female ratio being 3.5: 1. The major diseases seen in inpatients were benign prostatic hypertrophy, bladder tumor, prostatic carcinoma, ureteral stone, urethral diverticulum, bladder neck contracture, inguinal hernia and renal tumor. The total number of patients operated on was 1,211; 953 males and 258 females. These operations were performed at 11 hospitals using a semi-open system. Major operations were transurethral resections of prostatic and bladder tumor, subcapsular prostatectomy, castration, urethral diverticulectomy, nephrectomy, inguinal hernioplasty, ureterolithotomy, radical cystectomy and transurethral ureterolithotripsy. New operation methods were radical prostatectomy by Walsh's method, Kock pouch, penis prosthesis implantation, transurethral incision of bladder diverticular orifice, Gil-Vernet method for VUR and Stamey's method for stress incontinence. Major small operations and examinations for outpatients were transperineal prostatic needle biopsies, transurethral urethral and bladder mucosal biopsies, phimotomy, transurethral intravesical surgery and percutaneous renal cyst puncture.

Adolescent↗

Transurethral resection with perioperative instilation on interferon-alpha or epirubicin for the prophylaxis of recurrent primary superficial bladder cancer: a prospective randomized multicenter study--Finnbladder III.

PURPOSE: We evaluated the efficacy of single dose of interferon or epirubicin administered immediately after transurethral resection compared with transurethral resection only on the recurrence of primary (not recurrent) superficial bladder cancer. MATERIALS AND METHODS: A total of 283 patients with stages Ta to T1 primary superficial, grades 1 to 3 bladder cancer was randomized into study groups 1-transurethral resection only, 2-transurethral resection plus 50 million units interferon-a2b and 3-transurethral resection plus 100 mg. epirubicin. Eligible for final analysis were 200 patients, including 66 in group 1, 66 in group 2 and 68 in group 3. Patients were followed with cystoscopy every 3 months for 2 years or until the initial recurrence. RESULTS: Group 3 had the most favorable outcome, since 45 of the 68 patients (66%) were without recurrence after 2 years compared to 24 of the 66 (37%) in group 2 and 26 of the 66 (40%) in group 1 (log rank test p <0.001). Side effects were mostly mild and transient, and no differences were found among the groups. CONCLUSIONS: A single 100 mg. dose of epirubicin given intravesically immediately after transurethral resection is safe, and significantly decreases the recurrence of primary superficial bladder cancer. A 50 million unit dose of interferon-alpha2b is well tolerated but it has no effect on recurrence as a single dose. The long-term effect of this treatment remains to be studied.

Administration, Intravesical↗

Intravesical BCG administration in the guinea pig. A histomorphological study.

Intravesical BCG administration is used as an adjuvant therapy after transurethral resection for superficial bladder cancer in man. The mechanisms of its antitumor activity are not known. The aim of this study was to characterize the histomorphological changes in various organs of the guinea pig after intravesical BCG administration. The BCG preparation used was BCG-RIVM, a Dutch BCG preparation. Instillations were performed in previously undamaged bladders weekly for 6 consecutive weeks and lasted 30 min or 1 h. Different doses were used ranging from 10(3) culturable particles (c.p.) to 5 x 10(7) c.p. of BCG. After 6 weeks, the animals were killed and postmortem examination was performed. The bladder wall, retroperitoneal lymph nodes, spleen, liver, lungs and distant lymph nodes were examined histologically. The BCG therapy, with a dose of 10(6) culturable particles and higher, induced an inflammatory reaction consisting of mononuclear infiltrates in the subepithelial tissue of the bladder wall. In approximately 50% of the animals investigated, the infiltrates were accompanied by non-caseating granulomatous lesions indicated by the presence of epithelioid cells. In general, the epithelial layer of the bladder showed no visible alterations. Similarly, a granulomatous inflammatory reaction was observed in the first retroperitoneal (iliac) lymph nodes draining the bladder. Granulomatous lesions were occasionally also present in liver and lung. In three of the 29 animals investigated, lesions were present both in liver and lungs, and in two of these three animals a granulomatous reaction was observed in the spleen and distant lymph nodes indicating a generalized inflammatory response induced by BCG.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Airway obstruction due to late-onset angioneurotic edema from angiotensin-converting enzyme inhibition.

PURPOSE: Angioneurotic edema is a well-documented complication of angiotensin-converting enzyme inhibitors (ACEI). We report a case of acute airway obstruction from a late-onset, probable ACEI-related angioneurotic edema and its subsequent management. CLINICAL FEATURES: A 48-yr-old obese man presented for transurethral resection of a bladder tumour (TURBT). His past medical history included hypertension controlled with hydrochlorothiazide and quinapril which had been started 13 mo earlier. Previous surgery was uncomplicated. Midazolam was used for premedication and for intraoperative sedation together with fentanyl and propofol. After uneventful spinal anesthesia with bupivacaine, operation and recovery, he was transferred to the floor. Five hours later he developed severe edema of his face, tongue and neck, with drooling, that progressed into airway obstruction and respiratory arrest. Ventilation was restored via immediate cricothyroidotomy, and a subsequent tracheotomy was completed uneventfully in the operating room. His serum C1 esterase inhibitor levels at 1, 5 and 23 days later were normal. The angioneurotic edema was attributed to the ACEI treatment. The edema resolved after 48 hr, and further follow-up was unremarkable. CONCLUSION: This observation is consistent with other reports that angioneurotic edema from ACEI can occur many months after the initiation of treatment. This can involve the airway and may produce life-threatening respiratory compromise. Physicians should be aware of this association and the possible need for immediate surgical intervention for the establishment of an airway in case of worsening edema or respiratory arrest.

Airway Obstruction↗

Anesthetic assessment in an outpatient consultation clinic reduces preoperative anxiety.

PURPOSE: Preoperative anxiety in relation to anesthesia remains for many patients a major subject of concern. The aim of the present study was to compare the level of preoperative anxiety in patients assessed in an outpatient consultation clinic with the anxiety level of those having been assessed by the anesthesiologist after entering the hospital. METHOD: We studied two groups of 20 patients who underwent elective transurethral prostate or bladder resection: group A having the anesthetic assessment between one-two weeks before hospitalisation, group B having this assessment the evening before surgery, after entering the hospital. Two different methods to assess anxiety were used: the Multiple-Affect-Adjective-Check-List (MAACL) and the visual analogue scale of anxiety (VAS). RESULTS: Both anxiety provided scores, assessed by two different methods, were lower in group A, than in group B(P<0.01). CONCLUSION: The results of this study confirm that an anesthetic assessment in an outpatient consultation clinic reduces preoperative anxiety, when compared with an assessment on the evening before surgery.

Adult↗

Transurethral resection of the prostate in the outpatient setting.

Transurethral resection of the bladder neck (8 patients) or prostate (142) was performed in the outpatient setting. Of the patients 5 required hospitalization for post-prostatectomy hemorrhage. This method has proved to be safe and cost-effective in the treatment of patients with outlet obstruction.

Adenocarcinoma↗