Management of Inverted Papilloma During Holmium Laser Enucleation of the Prostate.

Inverted papilloma of the prostatic urethra is an especially rare finding. A 75-year-old man with urinary retention wished to proceed with a holmium laser enucleation of the prostate (HoLEP) and was found to have a mass arising from his prostate vs bladder on preoperative imaging. Cystourethroscopy revealed the mass arising from the median lobe of the prostate. After transurethral resection and frozen analysis confirmed the benign pathology of an inverted papilloma, the patient subsequently underwent a successful HoLEP during the same surgical setting. Images of this rare prostatic mass are presented to increase urologist recognition and to assist management during HoLEP.

Primary mucin-producing urothelial-type adenocarcinoma of the prostatic urethra diagnosed on TURP: a case report and review of literature.

BACKGROUND: Mucin-producing urothelial-type adenocarcinoma of the prostatic urethra is extremely rare. These lesions must be differentiated from other mucinous tumors including mucin-producing prostatic adenocarcinoma and metastases from either colonic or bladder primaries. CASE PRESENTATION: We report here a case of urothelial-type adenocarcinoma arising from the prostatic urethra. The patient is an 81 year-old man with a history of pT1 urothelial cell carcinoma of the bladder status post trans-urethral resection of bladder tumor (TURBT) who initially presented with irritative lower urinary tract symptoms and mucosuria refractory to Flomax and finasteride. A shared decision was made for the patient to undergo trans-urethral resection of prostate (TURP). At the time of surgery, a papillary tumor emanating from the prostatic urethra was found and no urothelial lesions were noted in the bladder. Pathology of the resected prostatic chips revealed an invasive adenocarcinoma with intestinal-type differentiation that stained positive for CK7, CK20, and villin, but negative for PSA, PSAP, uroplakin, and CDX-2. Colonoscopy was normal and CT scan did not show any evidence of colonic lesions nor visceral or lymph node metastases. Thus, the patient was diagnosed with a primary urothelial-type adenocarcinoma of the prostatic urethra. CONCLUSION: Herein we review the literature regarding this unusual entity, and discuss the differential diagnosis, immunohistochemistry, and the importance of correctly identifying this rare tumor.

A novel p53 mutant found in iatrogenic urothelial cancers is dysfunctional and can be rescued by a second-site global suppressor mutation.

Exposure to herbal remedies containing the carcinogen aristolochic acid (AA) has been widespread in some regions of the world. Rare A→T TP53 mutations were recently discovered in AA-associated urothelial cancers. The near absence of these mutations among all other sequenced human tumors suggests that they could be biologically silent. There are no cell banks with established lines derived from human tumors with which to explore the influence of the novel mutants on p53 function and cellular behavior. To investigate their impact, we generated isogenic mutant clones by integrase-mediated cassette exchange at the p53 locus of platform (null) murine embryonic fibroblasts and kidney epithelial cells. Common tumor mutants (R248W, R273C) were compared with the AA-associated mutants N131Y, R249W, and Q104L. Assays of cell proliferation, migration, growth in soft agar, apoptosis, senescence, and gene expression revealed contrasting outcomes on cellular behavior following introduction of N131Y or Q104L. The N131Y mutant demonstrated a phenotype akin to common tumor mutants, whereas Q104L clone behavior resembled that of cells with wild-type p53. Wild-type p53 responses were restored in double-mutant cells harboring N131Y and N239Y, a second-site rescue mutation, suggesting that pharmaceutical reactivation of p53 function in tumors expressing N131Y could have therapeutic benefit. N131Y is likely to contribute directly to tumor phenotype and is a promising candidate biomarker of AA exposure and disease. Rare mutations thus do not necessarily point to sites where amino acid exchanges are phenotypically neutral. Encounter with mutagenic insults targeting cryptic sites can reveal specific signature hotspots.

Prostatic nephrogenic adenoma. Case report.

OBJECTIVE: We present a case of prostatic urethra nephrogenic adenoma as an incidental finding following transurethral resection of the prostate. METHOD/RESULT: It is an incidental diagnosis of nephrogenic adenoma of prostatic urethra in a 50-year-old male operated for benign prostatic hyperplasia by means of transurethral resection. CONCLUSIONS: Nephrogenic adenoma is an infrequent and benign lesion of the urinary tract, associated with a previous history of trauma or irritation on the urothelium. Predisposing factors include infections, calculi, surgery, trauma and kidney transplantation.

Long-term follow-up of intravesical bacillus Calmette-Guérin treatment for superficial transitional-cell carcinoma of the bladder involving the prostatic urethra.

BACKGROUND: Intravesical bacillus Calmette-Guérin (BCG) is a treatment option for superficial (5-year follow-up. PATIENTS AND METHODS: Twenty-eight patients with high-risk superficial bladder cancer and prostatic urethral involvement were treated with once-weekly BCG for 6 weeks. Patients with prostatic stromal involvement were excluded. Maintenance was not used before 1995. Currently, we use maintenance BCG after induction. Patients were followed by cystoscopy/cytology and repeat biopsy to detect persistent and/or progressive disease. RESULTS: After 1 or 2 courses of once-weekly BCG for 6 weeks, 64.3% (18 of 28 of patients) exhibited a complete response in the bladder and prostate at their 6-month followup. Of those obtaining a complete response, 55.6% (10 of 18) experienced recurrence. Three recurrences were in the prostate: 1 isolated and 2 associated with multifocal bladder involvement. Twenty-eight percent (8 of 28 patients) underwent cystectomy because of failure of treatment to eradicate superficial disease or disease progression. Disease-specific survival was 89% (25 of 28 patients) at a median follow-up of 7.5 years. CONCLUSION: Our long-term data support the durability of intravesical BCG in select patients with superficial bladder transitional cell carcinoma with prostatic urethral involvement. Follow-up biopsy of the prostatic urethra is mandatory and, if positive, cystectomy is indicated. One third of patients will require cystectomy for persistent or progressive disease; therefore, careful surveillance is critical.

Urothelial carcinoma in the prostatic urethra and prostate: current controversies.

We reviewed the literature on urothelial carcinoma in the prostatic urethra and prostate. We concluded that the incidence of urothelial carcinoma in the prostatic urethra and prostate is probably underestimated. This fact warrants thorough follow-up of patients with high-risk bladder cancers and also whole-mount examination of the prostate after cystectomy to recognize the true incidence and extent of such tumor involvement. Resectoscope loop biopsy is the method of choice to detect urothelial carcinoma in the prostatic urethra/prostate and such biopsies should include the area around the verumontanum to ensure optimal sensitivity. Carcinoma in situ in the prostatic urethra should be treated with intravesical Bacillus Calmette-Guérin and a transurethral resection of the prostate prior to that treatment might increase the contact of Bacillus Calmette-Guérin with the prostatic urethra, improve staging and in itself treat the prostatic involvement. Conservative treatment of carcinoma in situ in the prostatic ducts is an option, although radical surgery is probably best for treating extensive intraductal involvement, since data on the former strategy are inconclusive. Patients with stromal invasion should undergo radical surgery. It is necessary to take the route of prostatic involvement into account when estimating prognosis in each individual patient, since contiguous growth into the prostate is associated with worse prognosis. Prospective studies using a whole-mount technique to investigate the prostate are needed to clarify both the role of different routes of prostate invasion and the prognostic significance of different degrees of prostate invasion. At cystectomy, when urothelial carcinoma is present in the prostatic urethra and/or prostate, it is necessary to balance the risk of urethral recurrence and decreased sexual function against opinion and expectations expressed by the patient during preoperative counseling regarding urinary diversion and primary urethrectomy.

Prognostic factors for metastatic urothelial carcinoma treated with cisplatin and 5-fluorouracil-based regimens.

OBJECTIVES: We have previously shown that a combination of infusion cisplatin and high-dose 5-fluorouracil/leucovorin (P-HDFL) has moderate activity and acceptable toxicity in patients with metastatic urothelial carcinoma. The present study sought to identify factors that predict for patient survival after treatment with P-HDFL-based regimens. METHODS: The outcomes of 79 patients (median age 69 years) with metastatic urothelial cancer treated in two Phase II trials, including P-HDFL and paclitaxel plus P-HDFL, were updated. The log-rank test and multivariate Cox proportional hazard models were used to identify the prognostic factors predicting for survival. RESULTS: The median follow-up duration was 38.9 months (range 10.2 to 89.0). A Karnofsky performance status scale of less than 80% (hazard ratio 2.6, 95% confidence interval 1.5 to 4.6), presence of visceral metastasis (hazard ratio 2.3, 95% confidence interval 1.3 to 4.1), and alkaline phosphatase level of 220 U/L or greater (hazard ratio 2.5, 95% confidence interval 1.3 to 4.5) were three significant risk factors predicting for poor survival in the Cox proportional hazard model. The three factors weighted approximately the same and were independent of each other. The median survival for patients with three, one or two, and no risk factors was 4.6, 13.2, and greater than 81.8 months, respectively (P <0.001). CONCLUSIONS: The Karnofsky performance status scale, presence of visceral metastasis, and alkaline phosphatase level were independent risk factors for survival in patients with metastatic urothelial carcinoma treated with cisplatin and 5-fluorouracil-based regimens.

Phase II trial of pemetrexed as second-line therapy in patients with metastatic urothelial carcinoma.

PURPOSE: The purpose of this single-center phase II study was to determine the activity of pemetrexed administered as second-line therapy in patients with advanced urothelial carcinoma. METHODS: Patients with advanced urothelial carcinoma that had relapsed after receiving perioperative chemotherapy, or progressed on first-line chemotherapy for metastatic disease, were eligible for enrollment. Patients received pemetrexed 500 mg/m(2) every 21 days along with folic acid and vitamin B12 supplementation. RESULTS: A total of 13 patients were enrolled. An objective response was achieved in 1/12 evaluable patients for an overall response rate of 8% (90% upper limit 29%). This level of activity did not meet criteria for expansion based on the pre-defined optimal 2-stage Simon design and the trial was concluded. Treatment was generally well tolerated, however, 2/13 patients developed febrile neutropenia. Non-hematologic grade > or = 3 toxicity was rare. CONCLUSIONS: Pemetrexed as second-line therapy in advanced urothelial carcinoma is associated with modest activity. The role of this novel antifolate in chemotherapy-naïve patients warrants further investigation.

Intravesical instillations with bacillus calmette-guérin for the treatment of carcinoma in situ involving prostatic ducts.

OBJECTIVES: Bacillus Calmette-Guérin (BCG) has proven its efficacy in the treatment of carcinoma in situ (CIS) of the prostatic urethra. We performed a retrospective study to evaluate the use of intravesical instillations of BCG in patients with carcinoma in situ involving prostatic ducts after complete transurethral resection (TUR). MATERIAL AND METHODS: Eligibility for the study was CIS of the prostatic urethra involving prostatic ducts. Previous instillation with BCG was an exclusion criterion. Patients were treated with intravesical BCG Connaught (81 mg) administered once a week, over a 6-wk period. TUR loop biopsies of the prostate were performed only when a macroscopic tumor was present. RESULTS: In this retrospective study of 11 patients, 8 (73%) presented with macroscopic tumor in the prostatic urethra. Ten patients (91%) had a simultaneous superficial bladder carcinoma. Eight patients (73%) had tumoral involvement of the bladder neck region. After a median follow-up of 27 mo (n=10 patients), the response in the prostatic urethra was 82%, and the response in the bladder due to superficial tumor recurrence was 64%. Two patients with residual ductal disease in the prostatic urethra were subsequently treated with cystoprostatectomy and are currently free of disease. In one of those patients, the cystoprostatectomy specimen did show prostatic stromal invasion. Another patient developed distant metastatic disease and died a few months after diagnosis. Thus, progression was encountered in two patients (18%). Currently, 90% of patients are alive without evidence of disease and 72.7% have benefitted from this bladder preservation strategy. CONCLUSION: Intravesical BCG is a feasible treatment option for patients with CIS involving prostatic ducts. In this retrospective study, bladder preservation was successful in 8 of 11 patients (70%) and there was only one oncologic death. Obviously, these patients need a careful follow-up with cystoscopy and cytology to detect either recurrence or progression and in those with persistent disease after the initial BCG induction therapy, prompt cystectomy is indicated.

Prolapso de uretra / Urethral prolapse

El prolapso uretral en la mujer es infrecuente. Se define como la completa eversión de la mucosa uretral a través del meato. Ocurre frecuentemente en mujeres negras prepúperes y en mujeres blancas posmenopáusicas. El tratamiento recomendado incluye desde la terapia conservadora hasta múltiples intervenciones quirúrgicas (AU)

Prolapse of the urethra in female patients is a rare events. It is defined as the complete eversion of the urethral mucosa through the external meatus. It occurs most often in pre-puberal black girls and in postmenopausal white women. Recommended treatment ranges from conservative therapy to a diversity of operative techniques (AU)

[A case report: an urethral tumor with cavernous structure developed after optical urethrotomy].

A 70-year-old man underwent transurethral resection of the prostate (TURP) in February 1999 and he received optical urethrotomy because of urethral stricture in May. In May 2000, a distal urethral tumor was found by urethroscopy. Endoscopic resection of the urethral tumor was performed. The tumor consisted of normal urethral epithelial tissue and had a cavernous structure. We conclude that the tumor was vegetation of the corpus spongiosum penis.

Clear cell adenocarcinoma in a female urethral diverticulum.

Primary urethral carcinoma is an uncommon diagnosis, and carcinomas arising from within a urethral diverticulum are rare. Because of the limited number of diagnosed cases, optimal treatment guidelines are not available. However, patients require an aggressive treatment approach to provide the best chance for cure.

Tumorigenicity of sodium ascorbate in male rats.

Sodium ascorbate, like other sodium salts such as saccharin, glutamate, and bicarbonate, produces urinary alterations when fed at high doses to rats, which results in mild superficial urothelial cytotoxicity and regeneration but not tumors in a standard 2-year bioassay. Sodium saccharin was shown to produce a low incidence of bladder tumors in rats if administered in a two-generation bioassay. In the present study, we evaluated sodium ascorbate in a two-generation bioassay that involved feeding to the male and female parental F344 rats for 4 weeks before mating, feeding the dams during gestation and lactation, and then feeding the weaned (at 28 days of age) male F1 generation rats for the remainder of their lifetime (up to 128 weeks of the experiment). Dietary levels of 1.0, 5.0, and 7.0% sodium ascorbate were tested. At 5.0 and 7.0% sodium ascorbate, there was an increase in urinary bladder urothelial papillary and nodular hyperplasia and the induction of a few papillomas and carcinomas. There was a dose-responsive increase in renal pelvic calcification and hyperplasia and inhibition of the aging nephropathy of rats even at the level of 1% sodium ascorbate. Because the short-term urothelial effects of sodium ascorbate in rats are inhibited by treatments producing urinary acidification to pH < 6.0, we coadministered high doses of long-term NH4Cl to groups of rats with 5.0 or 7.0% sodium ascorbate to evaluate the long-term effects. The combination of 7.0% sodium ascorbate plus 2.78% NH4Cl in the diet was toxic, and the group was terminated early during the course of the experiment. The group fed 5.0% sodium ascorbate plus 2.04% NH4Cl showed complete inhibition of the urothelial effects of sodium ascorbate and significant inhibition of its renal effects. We also demonstrated the presence of a calcium phosphate-containing urinary precipitate in rats fed sodium ascorbate at all doses, in a dose-responsive manner. The formation of the precipitate was inhibited by coadministration with NH4Cl. The proliferative effects of sodium ascorbate on the male rat urinary tract in this study are similar to those seen with sodium saccharin when administered in a two-generation bioassay. Mechanistic information suggests that this is a high-dose, rat-specific phenomenon.

[Local anesthesia in CO2 laser treatment of disseminated therapy-resistant condylomata]. / Lokalanaestesi ved CO2-laserbehandling af udbredte terapiresistente kondylomer.

In an open prospective study 67 patients with refractory genital warts, irrespective of anatomic localization, received CO2-laser vaporization in local anaesthesia, using lidocaine 2% as the local anaesthetic. Sufficient anaesthesia was obtained in all treated patients, with minor pain as the only side effect observed. A single CO2-laser treatment resulted in disappearance of the lesions in 37 (55%) of the patients. Repeated CO2-laser vaporizations in patients with recurrent disease increased the cure rate to 85%. The response rate seemed unaffected by the localization of the warts. It is concluded, that local anaesthesia might replace general anaesthesia in the treatment of patients with multiple refractory genital warts.