In vitro trial of the pilot prototype of the prostate mechanical imaging system.

OBJECTIVES: To compare the sensitivity and accuracy of the mechanical imaging system (MI system) to that of the simulated digital rectal examination (DRE) in detecting nodules within fabricated rubber prostate phantoms. Mechanical imaging is a new technology for visualizing and characterizing tissues using mechanical strain and stress data. METHODS: Twelve rubber phantoms were designed to simulate human prostates. Ten phantoms contained hard nodules in various locations. Two phantoms contained no nodules. Each model was examined with the MI system by a urologist (R.E.W.) and research student. Three-dimensional images of the examined prostate phantoms with and without nodules were generated by the MI system software. Blind DRE was performed on each phantom independently by the urologist and student. The results of the MI examinations and DREs were compared for sensitivity in detecting the presence and location of nodules within the prostate phantoms. RESULTS: Three-dimensional MI images reconstructed from both the student and the urologist examination data demonstrated 100% of the nodules in the appropriate locations. The DREs by the urologist detected 83% of the nodules in the appropriate locations. The DREs by the student detected 67% of the nodules in the appropriate locations. CONCLUSIONS: The prostate MI system allowed the detection of nodules in the prostate phantoms with sensitivity exceeding that of an experienced urologist. In contrast to the DRE, the results of the MI examination appear to be independent of the operator's experience. Therefore, the MI system is a promising means of accurate, sensitive, objective, and recordable detection of hard nodules within the prostate.

Mitoxantrone in patients with prostate specific antigen progression after local therapy for prostate carcinoma.

BACKGROUND: Molecular mechanisms of chemotherapy resistance are present in prostate carcinoma, some of which increase after androgen ablation (AA) therapy. Therefore, the authors hypothesized that chemotherapy in patients with prostate specific antigen (PSA) progression after local therapy, before androgen ablation therapy, will have greater antitumor activity. METHODS: Twenty-three hormone-naive patients with PSA progression after prostatectomy or radiation therapy were registered in this study. Twenty-two were treated with 10 mg/m(2) of mitoxantrone initially, followed by 12 mg/m(2) every 3 weeks for a maximum of 8 cycles. Prostatectomy specimens were assessed, when possible, for topoisomerase II alpha, multidrug resistance protein MRP, and bcl-2 by immunohistochemistry. RESULTS: Twenty-two patients received a total of 131 cycles of therapy. Three patients had transient Grade 3 or 4 neutropenia without fever. During treatment, 10 of 22 patients showed a decrease in PSA, without an associated decrease in testosterone. In this group of 10 patients, the mean PSA decrease was 29% at 3 months and 43% at 6 months. Overall, 4 of 22 patients had a decrease in PSA of greater than or equal to 50%. The PSA decreased in three of seven patients whose cancer overexpressed MRP and in three of seven patients who overexpressed bcl-2. No patient with overexpression of topoisomerase II alpha (n = 4) had a decrease in PSA during the study. CONCLUSIONS: To the authors' knowledge, this is the first reported study of mitoxantrone in patients with hormone-naive prostate carcinoma and PSA progression after local therapy; mitoxantrone was safe and biochemically active, similar to prior studies in hormone refractory prostate carcinoma, suggesting that critical molecular mechanisms of chemotherapy resistance are present independent of AA. Further studies are warranted to determine whether pharmacogenomic assessment of topoisomerase II, MRP, or bcl-2 may predict for response to mitoxantrone.

Metastatic renal cell carcinoma presenting as an oral tumor.

Metastatic cancer presenting as an oral lesion is exceedingly uncommon. To the best of our knowledge this is the first reported instance of renal cell carcinoma presenting initially as an oral lesion.

Lymphatic mapping and intraoperative lymphoscintigraphy for identifying the sentinel node in penile tumors.

Lymph node mapping has become an integral part of the management of melanoma and breast cancer with regard to both staging and treatment. We report our technique for lymphatic mapping and intraoperative lymphoscintigraphy applied to a patient with penile melanoma. This technique may improve the sensitivity of identifying the sentinel lymph node in patients with malignant penile lesions.

Total pelvic exenteration and reconstruction for locally invasive recurrent sarcoma of the perineum.

Extensive primary tumors and locally recurrent tumors of the pelvis or perineum are difficult to manage. We describe the techniques necessary to perform total pelvic exenteration with en bloc resection of the perineum and genitalia for treatment of recurrent sarcoma of the perineum. Wide excision of the sarcoma with negative margins can be achieved by resecting the inferior portion of the pubic symphysis. An absorbable mesh sling may be used to suspend the small bowel above the pelvis, facilitating postoperative radiation. A catheterizable continent urinary reservoir avoids the necessity of two stomas and improves quality of life. Adequate tissue coverage can be attained by myocutaneous gracilis flaps that promote wound healing.

Ureteroenteric anastomosis in continent urinary diversion: long-term results and complications of direct versus nonrefluxing techniques.

PURPOSE: Controversy exists over the importance of antireflux mechanisms in large volume, low pressure intestinal bladder substitutions. Despite the theoretical benefits of reflux prevention, antirefluxing ureteral reimplantations may have a greater risk of anastomotic stricture. We hypothesize that this inherent stricture rate may outweigh the potential benefits associated with reflux prevention. To assess this question critically we compare our results to those of direct and nonrefluxing techniques of ureterointestinal anastomosis during continent diversion. MATERIALS AND METHODS: Between 1990 and 1998, 58 patients underwent continent urinary diversion using an Indiana pouch or ileal orthotopic neobladder following cystectomy for muscle invasive bladder cancer. A total of 56 renal units were implanted using an end-to-side Nesbit direct anastomosis and 60 were implanted in a nonrefluxing manner. Clinical end points included anastomotic stricture formation, hydronephrosis, pyelonephritis, upper tract stone formation and renal deterioration, and were assessed with a mean followup of 41 months. RESULTS: Of 60 nonrefluxing ureteroenteric anastomoses 8 (13%) resulted in nonneoplastic stricture formation compared to 1 of 56 (1.7%) direct anastomoses, which was statistically significant (Fisher's exact test p <0.05). Strictures occurred up to 6 years following the original surgery. There was no significant difference between the 2 groups in regard to hydronephrosis, pyelonephritis, upper tract stone formation or azotemia. CONCLUSIONS: Nonrefluxing methods of ureterointestinal reimplantation resulted in a statistically significant higher rate of anastomotic stricture than the end-to-side direct anastomosis. This finding appears to outweigh any theoretical benefits of preventing pyelonephritis, stones or azotemia. For patients undergoing large volume, low pressure continent diversion the refluxing ureterointestinal anastomosis may be the technique of choice since it preserves renal function as well as the nonrefluxing method, is technically easier to perform and poses less risk of stricture. Delayed stricture formation years after surgery underscores the necessity for long-term radiological followup in patients following continent diversion.

Endovascular stent graft for management of ureteroarterial fistula after orthotopic bladder substitution.

We describe the first case of an ureteroarterial fistula developing after orthotopic neobladder substitution and its minimally invasive management using endovascular stent grafting. We outline the risk factors for the development of ureteroarterial fistulae and trace the evolution of diagnostic and therapeutic modalities used in the management of these life-threatening complications. Minimally invasive management with endovascular stent grafting and exclusion of two pseudoaneurysms in the iliac artery system was performed successfully. After successful endovascular exclusion of two pseudoaneurysms, the patient's hematuria resolved and he recovered fully. Three-dimensional computed tomography performed 3 months later documented a patent aortoiliac arterial system without evidence of pseudoaneurysm or endovascular leak. Ureteroarterial fistula after orthotopic bladder substitution was managed with an endovascular stent graft without the need for extra-anatomical vascular bypass. Early recognition, stabilization, and angiographic evaluation followed by this minimally invasive technique may avoid open operative repair and attendant morbidity.

Prospective evaluation of endorectal magnetic resonance imaging to detect tumor foci in men with prior negative prostastic biopsy: a pilot study.

PURPOSE: Prostate cancer foci have a characteristic appearance on endorectal magnetic resonance imaging (MRI) which might be useful for prostate cancer detection. In this pilot study the ability of endorectal MRI to detect prostate cancer foci prospectively in men at risk for a malignant prostatic neoplasm is assessed. MATERIALS AND METHODS: Endorectal MRI was performed in 33 consecutive men with 1 or more prior negative prostatic biopsies. All studies were read by 2 MRI dedicated study radiologists in consensus before and after receiving patient clinical data. Areas of interest on endorectal MRI were mapped as low, moderate or high suspicion for carcinoma on a prostate model. Directed needle biopsy cores of the prostate were obtained based on this model, and the histopathological findings were compared with MRI results. RESULTS: Carcinoma was detected in 7 of 33 men (21.2%) on post-MRI biopsy, including 1 of 18 (5.6%) with low, 1 of 8 (12.5%) with moderate and 5 of 7 (71.4%) with high suspicion MRI. The site of positive biopsy correlated correctly with the area of suspicion on MRI in 85.7% of cases. Overall, endorectal MRI had 40% positive predictive value (moderate or high suspicion), 94.4% negative predictive value (low suspicion) and 69.7% accuracy. On multivariate analysis positive endorectal MRI was associated with an 11.3-fold risk of positive biopsy. CONCLUSIONS: Endorectal MRI may effectively stratify patients with prior negative prostatic biopsy into low, moderate and high risk groups for a malignant prostatic neoplasm, and may improve our ability to identify prostatic tumor foci prospectively.

Female urethral adenocarcinoma: immunohistochemical evidence of more than 1 tissue of origin.

PURPOSE: Urethral adenocarcinoma is a rare malignancy whose origin remains controversial. The monoclonal antibody mAbDas1 (formerly 7E12H12) was developed against a unique colonic epithelial epitope and is reactive in areas of intestinal metaplasia. Recently the antibody was shown to react in cystitis glandularis as well as adenocarcinoma of the bladder, suggesting that cystitis glandularis may be the precursor of bladder adenocarcinoma. We examined urethral adenocarcinomas and benign urethral specimens using mAbDas1 to determine whether it could provide insight into their histogenesis. MATERIALS AND METHODS: Archival tissue from 12 cases of primary female urethral adenocarcinoma and urethral specimens of inflamed urethral mucosa, urethritis glandularis and transitional cell carcinoma was studied. Immunohistochemical analysis of formalin fixed, paraffin embedded archival tissue was done using the monoclonal antibody mAbDas1. Tumors were also evaluated with a prostate specific antigen (PSA) polyclonal antibody as previous studies have noted PSA reactivity in these tumors. RESULTS: Of the 12 cases 9 were columnar/mucinous adenocarcinoma, 2 clear cell adenocarcinoma and 1 a cribriform pattern resembling adenocarcinoma of the prostate. All columnar/mucinous adenocarcinomas reacted positively (6 strongly and 3 focally) with the mAbDas1 antibody but did not react with the PSA antibody. The tumor with a cribriform pattern reacted strongly with PSA but did not react with mAbDas1. The 2 clear cell adenocarcinomas did not react with either antibody. The benign urethral specimens demonstrated strong reactivity to the mAbDas1 antibody in areas of urethritis glandularis but normal and inflamed urethral mucosa and transitional cell carcinoma did not react. CONCLUSIONS: Primary adenocarcinoma of the female urethra arises from more than 1 tissue of origin. Columnar/mucinous adenocarcinomas of the female urethra and urethritis glandularis demonstrate consistent reactivity with the mAbDas1 antibody, suggesting that these tumors arise from glandular metaplasia analogous to the potential histogenesis previously demonstrated in the bladder. PSA reactivity occurred in 1 tumor with a cribriform pattern and likely represents origin from Skene's glands. Clear cell adenocarcinomas did not react with either antibody, suggesting a third possible pathway in the development of this rare subset of adenocarcinomas.

The monoclonal antibody 7E12H12 can differentiate primary adenocarcinoma of the bladder and prostate.

OBJECTIVE: To determine if the monoclonal antibody 7E12H12, which reacts with a 40 kDa protein in normal human enterocytes and has been shown to be a marker for intestinal metaplasia and adenocarcinoma arising in the bladder, could assist in distinguishing prostatic, urachal and vesical adenocarcinoma, using a sensitive immunohistochemical assay. MATERIALS AND METHODS: Fifteen primary prostatic adenocarcinomas and five adenocarcinomas of the urinary bladder were selected for a retrospective evaluation. The monoclonal antibody 7E12H12 (IgM isotype) was used in an immunoperoxidase assay to survey formalin-fixed, paraffin-embedded archival tissue specimens. RESULTS: All vesical adenocarcinomas reacted positively with the antibody, regardless of grade; none of the 15 prostatic specimens reacted positively in either the benign or malignant glandular epithelium. CONCLUSION: The monoclonal antibody 7E12H12 can differentiate primary adenocarcinoma of the bladder from secondary adenocarcinoma arising in the prostate and may be a useful tool in diagnostic pathology.

National trends in the epidemiology of prostate cancer, 1973 to 1994: evidence for the effectiveness of prostate-specific antigen screening.

OBJECTIVES: The use of prostate-specific antigen (PSA) to screen for prostate cancer remains controversial. Although it is still too early to measure directly the effects of PSA screening on mortality, we examined changes in the epidemiology of prostate cancer to determine if there is other evidence of the effectiveness of PSA as a screening tool. METHODS: We examined trends in age at diagnosis, and age-adjusted trends in stage and grade at diagnosis, for 140,936 white and 15,662 African American men diagnosed with prostate cancer from 1973 to 1994 in the National Cancer Institute's Surveillance Epidemiology and End Results data base. RESULTS: We found a significant downward trend in age at diagnosis, concomitant with a downward shift in stage of disease at diagnosis, starting with the advent of the PSA era in the late 1980s. We noted most cancers detected since the PSA era to be moderately well differentiated (International Classification of Diseases of the World Health Organization grade 2; Gleason score 5, 6, 7) and organ confined. Although findings were similar for both whites and African Americans, African Americans experienced a greater increase in poorly differentiated disease than did whites. CONCLUSIONS: Changes in the epidemiology of prostate cancer since the advent of the PSA era are consistent with the introduction of an effective screening test. This is evidenced by an increase in detection of significant prostate cancer in individuals who will likely benefit from treatment.

Correlation of mechanical imaging and histopathology of radical prostatectomy specimens: a pilot study for detecting prostate cancer.

PURPOSE: A new modality termed mechanical imaging has recently been developed. We determined whether mechanical imaging could be used to detect prostate cancer in radical prostatectomy specimens. MATERIALS AND METHODS: Stress patterns on the surface of excised prostates were evaluated using the data obtained from a planar piezoelectric resistive force sensor array. Seven radical prostatectomy and 2 cystoprostatectomy specimens were manually palpated and evaluated by the mechanical imager. The prostates were histopathologically analyzed for the presence of cancer. The results of the manual palpation, mechanical imaging and pathological analysis were correlated. RESULTS: Mechanical imaging correlated closely with nodules palpated in all specimens and in 1 it revealed a suspicious area undetected by palpation, which on subsequent histological analysis demonstrated carcinoma. CONCLUSIONS: Mechanical imaging can detect areas of heterogeneity in prostate tissue which correlate with cancer. Our findings provide the basis for the development of a transrectal mechanical imaging probe for prostate cancer detection.

Trends in poorly differentiated prostate cancer 1973 to 1994: observations from the Surveillance, Epidemiology and End Results database.

PURPOSE: Using the Surveillance, Epidemiology and End Results Program, we evaluated the changing demographics of poorly differentiated prostate cancer since early detection measures, such as serum prostate specific antigen screening, were introduced into clinical practice in the United States. MATERIALS AND METHODS: Trends between 1973 and 1994 in the proportion, stage and treatment of poorly differentiated tumors (International Classification of Diseases [ICD]-O code 3, Gleason score 8, 9, 10) were assessed, and multivariate Cox proportional hazards models were used to identify independent correlates of disease specific survival. RESULTS: The number of ICD-O grade 3 tumors increased during the study period, although these comprised a decreased proportion of all diagnosed cases (24.4% of 29,588 in 1980 to 1984 versus 21.4% of 81,932 in 1990 to 1994, chi-square p < 0.001). ICD-O grade 3 tumors were less often metastatic in 1990 to 1994 compared to 1980 to 1984 (17.4% versus 33.1%, chi-square p < 0.0001) and more often treated with radical prostatectomy or radiotherapy in 1990 to 1994 compared to 1983 to 1984 (37.5 versus 15.6%, chi-square p < 0.001). Although treatment group (radiotherapy versus radical prostatectomy) among patients with clinically confined tumors was an independent correlate of disease specific survival (hazard ratio 2.3, 1983 to 1984 and 3.3, 1990 to 1994), one must recognize potential selection biases inherent to this nonrandomized tumor registry study. The observed 12-year actuarial disease specific survival rates were 67.6% for radical prostatectomy and 46.3% for radiotherapy. CONCLUSIONS: In the present era ICD-O grade 3 tumors are being detected in increasing number, are less likely to be metastatic at presentation and are more likely to be treated definitively with radical prostatectomy or radiotherapy. Disease specific survival rates observed with radical prostatectomy and radiotherapy in patients with clinically confined tumors support current efforts to detect and treat these highly aggressive tumors while clinically localized.

Adenocarcinoma arising within a testicular metastasis.

Teratoma with malignant transformation is defined as the emergence of a non-germ cell tumor from a teratoma. Although extremely rare in extraovarian sites, cases have been reported that involve primary extragonadal germ cell tumors with transformation to variants of sarcoma. We report a 54-year-old man who was found to have adenocarcinoma arising within a mature teratomatous retroperitoneal metastasis 15 years after treatment of a nonseminomatous testicular germ cell tumor. The tumor was successfully excised and he remains without evidence of disease.

Evaluation of the utility of video-urodynamics in children with urinary tract infection and voiding dysfunction.

OBJECTIVE: To assess the use of video-urodynamic studies (VUDS) in children with urinary tract infection (UTI) and symptoms of voiding dysfunction (frequency, urgency, incontinence), to ascertain whether VUDS significantly assists in diagnosis and deciding treatment. PATIENTS AND METHODS: Over a 16-month period, all children seen at our centre with a UTI in conjunction with previous symptoms suggestive of voiding dysfunction underwent free and pressure-flow VUDS. Forty-two children underwent VUDS and 38 (mean age 9 years, range 4-16, 15 male, 23 female) had sufficient information to be included in the study. RESULTS: All children had a prior history of voiding dysfunction (mean 55 months). Only five patients were found to have reflux and three of these had associated detrusor instability. In addition, 24 of 33 patients who did not have reflux had abnormalities on urodynamic study, the most common problem being detrusor instability in 17 of 24 patients. Other abnormalities included sphincter dyssynergia (five patients), poor bladder compliance (two) and hypersensitivity on bladder filling (three). CONCLUSION: VUDS can provide information about the aetiology of UTI and voiding dysfunction in children that cannot be obtained from any other source. The results of VUDS can be used to select specific treatments, to avoid inappropriate therapy and to identify children who may benefit from follow-up studies despite normal findings on voiding cystourethrography. From these results, we believe that VUDS should be considered for children with UTI and voiding dysfunction.

Adenocarcinoma of the urachus and bladder expresses a unique colonic epithelial epitope: an immunohistochemical study.

PURPOSE: Primary adenocarcinoma of the bladder is a rare neoplasm whose histogenesis is poorly understood. Current data support the concept that adenocarcinoma of the bladder and urachus evolves from zones of intestinal metaplasia that become dysplastic and invasive. To address this hypothesis further we determined the immunoreactivity of benign and malignant epithelial tissue from the bladder and urachus with a monoclonal antibody that is reactive with colonic epithelium to evaluate the presence of a common reactive epitope. MATERIALS AND METHODS: The monoclonal antibody 7E12H12 (IgM isotype), developed against a colonic epithelial protein, was used in an immunoperoxidase assay to survey formalin fixed, paraffin embedded archival tissue specimens. A total of 26 specimens obtained by endoscopic biopsy or extirpative surgery, including benign and malignant bladder and urachal epithelial abnormalities, was chosen for retrospective evaluation. RESULTS: All adenocarcinoma reacted positively regardless of the histological variant, differentiation, or bladder or urachal origin. In contrast, transitional cell and squamous cell carcinomas were nonreactive. Also, the pattern of reactivity in tissues that contained benign epithelial proliferations suggested a stepwise transition with no reactivity in normal urothelium or Brunn's epithelial nests, rare staining of cystitis cystica, and uniformly positive reactivity in cystitis glandularis and frank colonic intestinal metaplasia of the bladder and urachus. CONCLUSIONS: The shared, aberrant phenotypic expression of a unique colonic epitope in benign epithelial metaplasia, and adenocarcinoma of the bladder and urachus suggests a common underlying pathway toward adenocarcinoma in cystic and urachal adenocarcinoma. The implications for diagnostic pathology are discussed.

Routine stentograms are not necessary before stent removal following radical cystectomy.

PURPOSE: Although ureteral stents have significantly reduced perioperative complications of urinary diversion, there is no universal agreement regarding their postoperative management. As part of an effort to eliminate unnecessary studies and hospital costs for radical cystectomy, we recently reviewed our experience with postoperative radiological stent studies to determine their clinical use and cost. MATERIALS AND METHODS: A retrospective examination of medical records and radiographic studies was performed for 96 patients undergoing cystectomy and urinary reconstruction between 1989 and 1996. All patients were stented at the time of surgery. Of the patients 51 underwent bilateral retrograde "stentograms" performed under fluoroscopic guidance before stent removal to evaluate for obstruction or urine leak as dictated by the preference of the primary surgeon in each case. A total of 41 evaluable patients did not undergo stentograms. RESULTS: In this study 102 stent injections were performed on 51 patients before stent removal. No patients were found to have ureteral obstruction at the ureterointestinal anastomosis, while 1 (0.98%) had a clinically silent anastomotic leak that healed with conservative measures. Complications directly attributable to the stent studies, including episodes of urosepsis, were noted in 9 patients (17.6%). Nine additional leaks were diagnosed in this cohort by other means. Half of all leaks were evident clinically and 60% of this group required further invasive procedures. All clinically silent leaks healed with conservative measures. Of 41 evaluable patients who did not undergo stentograms leak following stent removal developed in only 2 and both healed with conservative measures. The additional cost of detecting a single anastomotic leak with routine stentograms is estimated to be $58,000. CONCLUSIONS: Routine evaluation of the ureterointestinal anastomosis with stentograms before stent removal is unnecessary, costly and may in fact increase patient morbidity.