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Objectives. To present a novel assay for determining DNA organization in fertile human spermatozoa and establish morphometric parameters for these samples. The three-dimensional organization of DNA within a cell nucleus is intimately related to cellular function. For example, it has recently been demonstrated that normal sperm DNA organization may be necessary for successful in vitro fertilization in the mouse. Methods. Semen from 12 fertile volunteers was tested for sperm DNA organization using our nuclear matrix stability assay. Sperm DNA then underwent computerized digital image analysis and standards of normal were established. Results. Sperm DNA organization was constant in all samples tested. Normal parameters established included mean nuclear matrix diameter (9.17 ± 1.59 μm), mean DNA halo diameter (20.56 ± 2.53 μm), mean halo area (66.88 ± 7.92 μm2), and mean nuclear matrix area (32.98 ± 4.3 μm2). Conclusions. This assay may be used to determine DNA organization in a semen sample. Defining sperm DNA organization may be important clinically, because normal DNA organization is necessary for normal cellular function.

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.

Objectives : The P-30 protein (P30), a novel RNase, in combination with tamoxifen (TAM) has anti-tumor activity in vitro and in patients with pancreatic cancer. Proposed mechanisms of TAM activity include the induction of the inhibitory growth factor transforming growth factor-β1 (TGF-β1) and reduction of the tumor mitogen insulin like growth factor-1 (IGF-1). This study was designed to determine if P30 and TAM reduced prostate specific antigen (PSA) in patients with early prostate cancer recurrence. Given the limitation of using PSA alone as marker of anti-tumor activity, plasma TGF-β1 and IGF-1 were measured as potential markers of drug activity. Methods : Thirteen patients with rising PSA after local therapy for cancer of the prostate were enrolled and 11 patients were treated with Tamoxifen 20mg BID daily and P30, 480 μg/m 2 IV weekly. Patients were followed clinically. Serum PSA, Plasma TGF-β1 and plasma IGF-1 were measured by ELISA. Results : One of 5 patients who completed 3 months of therapy had stabilization of PSA. Six patients discontinued therapy secondary to toxicity before completing 3 cycles. Despite minimal effect on PSA, this therapy decreased plasma IGF-1 in 7/8 patients (p=0.02). There was no significant increase in TGF-β1 in 6/8 patients over the first month (p=0.15). Conclusions : P30 and TAM had minimal effect on PSA levels and was limited secondary to toxicity. The combination increased levels of TGF-β1 and decreased IGF-1 in most patients. Further studies are warranted to determine if these measurements correlate to anti-tumor activity better than PSA in patients with prostate cancer treated with TAM or other agents capable of modulating TGF-β1 or IGF-1.

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/m2 of mitoxantrone initially, followed by 12 mg/m2 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. Cancer 2001;92:2065–71. © 2001 American Cancer Society.

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.

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.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.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 p0.05). 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.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.

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...

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.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.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.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.

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.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.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.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.

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.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.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 p0.001). 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 p0.0001) 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 p0.001). 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.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.

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.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.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.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.

To assess how radiologic intervention altered the hospital course of patients undergoing continent urinary diversion.Thirty-seven consecutive patients with bladder cancer invading the muscular layer were treated with total cystectomy and construction of a continent urinary reservoir. Eleven of 37 patients suffered early and late anastomotic leakage; six had prolonged extraperitoneal leakage at the urethroenteric anastomosis, three had prolonged intraperitoneal pouch leaks, and two had delayed ureteroenteric leaks. Seven of these patients required radiologic intervention.Intervention in the form of drainage catheter manipulation (n = 4), percutaneous nephrostomy (n = 4), or ureteral stent placement (n = 2) resulted in cessation of leakage without surgical intervention in all seven patients. Intraperitoneal pouch leaks were more difficult to control than extraperitoneal leakage and required longer drainage intervals.Interventional radiologic procedures played a key role in the management of continent urinary diversion complications, obviating the need for repeat surgical intervention in all instances.

Patients with metastatic transitional-cell carcinoma of the bladder have a poor prognosis with brief survival. Controversy exists as to the clonality of bladder cancer, as well as the natural history of muscle-invasive disease that subsequently becomes metastatic. Newer molecular biologic techniques may help us identify and understand the molecular changes involved in transforming normal urothelium into the malignant phenotype. In addition, newer chromosomal markers may enable us to determine the prognosis and the potential for progression to invasion and metastases. Additional work to find the optimum doses and dosing schedules and combinations of chemotherapeutic agents for metastatic transitional-cell carcinoma will be necessary before we can improve survival for all patients with this disease.

SUMMARY The need for prompt diagnosis and accurate staging of bladder cancer cannot be overemphasized, as delays in diagnosing the tumor are clearly associated with a poor prognosis. Accurate staging using the American Joint Committee system is essential if clinicians are to compare the results of different therapies.

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 cysto-urethrography. From these results, we believe that VUDS should be considered for children with UTI and voiding dysfunction.

Purpose: We analyzed 26 cases of malignant fibrous histiocytoma and report our conclusions regarding the diagnosis, pathology and treatment of this unusual tumor.Materials and Methods: We reviewed 25 previously reported cases of malignant fibrous histiocytoma of the spermatic cord and report 1 additional case. Further data on patient survival and tumor recurrence rates were obtained from some of the previous authors.Results: Of 26 patients 5 are long-term survivors (more than 5 years). Longest reported followup is 14 years. However, malignant fibrous histiocytoma has recurred as late as 6 years after surgery. To date 4 deaths have been reported, including 1 unrelated to the tumor and 3 from metastatic tumor. Disease recurred in 5 patients. In no case was there local lymph node involvement at surgery.Conclusions: Malignant fibrous histiocytoma presents earlier in the spermatic cord than at other sites and seems to have a more favorable prognosis. Ultrasound may aid in the diagnosis. Definitive trea...

Anatomic Radical Prostatectomy. Conformal Radiation Therapy. Brachytherapy: Patient Selection and Clinical Outcome. Brachytherapy Followed by Conformal 3D External Beam Therapy. PSA Progression after Radical Prostatectomy: Role for Radiation Therapy. Timing of Hormone Deprivation for PSA Progression Following Local Therapy. Novel Therapy for PSA Progression in Absence of Imagable Disease Following Local Therapy. Alternative Medicine in the Management of PSA Progression Following Local Therapy. Future Prospectives: Vaccines and Gene Therapy in Prostate Cancer.

Purpose A phase I trial was conducted to determine the maximally tolerated dose (MTD) of concurrent weekly docetaxel and three-dimensional conformal radiation therapy (3-D CRT) in unfavorable localized adenocarcinoma of the prostate. Patients and Methods Patients with unfavorable localized adenocarcinoma of the prostate underwent daily 3-D CRT to a total dose of 70.2 Gy at 1.8 Gy/fraction and concurrent docetaxel given once a week for 8 to 9 weeks. The initial weekly docetaxel dose level was 5 mg/m2 and the docetaxel doses were escalated as follows: 8, 12, 16, 20, and 25 mg/m2. Results Between January 2000 and August 2002, 22 men completed the chemoradiation therapy protocol. The dose-limiting toxicity was grade 3 diarrhea, which occurred in the first two patients treated at the 25 mg/m2 docetaxel dose level. The MTD of weekly docetaxel was determined to be 20 mg/m2. The overall incidence of grade 2 diarrhea and grade 2 dysuria was 36% and 23%, respectively. Seven (32%) and 15 (68%) patients did not experience any diarrhea or dysuria, respectively. No neutropenia or thrombocytopenia was observed. One patient required intermittent urinary catherization 10 months postcompletion of therapy, which resolved without any surgical intervention. Seventeen patients remain in prostate-specific antigen remission. At a median follow-up interval of 8 months (range, 2 to 27 months), all patients are alive. Conclusion Concurrent weekly docetaxel in conjunction with 3-D CRT is well tolerated with acceptable toxicity. The MTD of weekly docetaxel was determined to be 20 mg/m2 with concurrent 3-D CRT.

Circumcision is one of the commonly performed procedures on males in the United States, Canada, Australia, and the United Kingdom. The association of minor anatomic variations of the newborn genitalia in patients with minor circumcision complications has not been previously examined. In this study, we looked for an association between subtle genital anatomic variations and newborn circumcision complications.Over an 18-month period, children presenting for circumcision revision were examined for minor variations in genital anatomy. Children referred for other urological problems during the same period comprised the control group. The same physician evaluated all of the children.During this period, 68 children were evaluated for possible circumcision complications. A confirmed complication was present in 57 infants. Patients with a minor circumcision complication were found to have a 9-fold higher incidence of a prominent suprapubic fat pad, penoscrotal webbing, or being a premature infant as compared to the control group.Subtle anatomic variations may be associated with a higher incidence of circumcision complications. Physicians performing newborn circumcisions should thoroughly examine the genitalia for these anatomic variations prior to the procedure in order to reduce potential complications.

Objectives Pouchograms are routinely performed before catheter removal after continent urinary diversion at our institution. Our aim was to determine the necessity of pouchograms based on a review of our experience. Methods A retrospective review of patient records and radiographic studies was done for patients undergoing radical cystectomy and continent urinary diversions between 1991 and 2001. Results Seventy-two patients underwent continent urinary diversion (orthotopic, n=59; cutaneous, n=13) during the study period. All underwent pouchogram postoperatively (median 22 days; range 20 to 27). Six patients (8.3%) had a demonstrable radiographic leak; in 5 of the 6 patients, the urine leak was suspected on clinical grounds. Three patients (4.7%) developed urosepsis after pouchogram . Conclusions Our findings indicate that routine pouchograms before pouch activation after continent urinary diversion may not be necessary.

Werdnig-Hoffman Disease (WHD) is a rare type of spinal muscular atrophy which causes progressive deterioration of the lower motor neurons of the spinal cord and the brainstem. To our knowledge we report the first case of neurogenic bladder documented on urodynamic studies of a patient with WHD.

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.

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.

We describe 2 infants who presented with autosomal dominant-like polycystic kidney disease. Evaluation revealed that both children had tuberous sclerosis, with resulting cystic kidney disease. This diagnosis should be suspected in infants who present with bilateral, large renal cysts, and no family history of autosomal dominant polycystic kidney disease.

To the Editor. —Drs Collins and Barry 1 raise a number of important concerns about the use of screening for prostate cancer. Because the way in which questions are framed helps determine the techniques used to develop answers, we feel their concerns should be refocused. We believe 2 separate major questions need to be addressed: (1) Will screening for prostate cancer reduce morbidity, mortality, or both? (2) How aggressively should diagnosed prostate cancer be treated? Answers to the first question hinge on issues of cost-effectiveness. Answers to the second question hinge on issues of risk and effectiveness of treatment. Collins and Barry conclude that caution is necessary "regarding widespread dissemination of prostate cancer screening without the experimental evidence that such screening does more good than harm." 1 We believe this statement confounds the 2 questions and could therefore impede the search for answers. Whether to screen for prostate cancer is

A new technique for inferior vena caval tumor thrombectomy is described. Vascular isolation of the cava from the right atrium to the pelvis is achieved by temporary circulatory arrest of the lower torso. Removal of the neoplastic thrombus under direct vision with minimal blood loss was accomplished in a patient with renal cell carcinoma, whose tumor extended into the intrapericardial vena cava.

We assigned randomly 90 patients treated previously for superficial transitional cell carcinoma to conventional followup or prophylactic treatment. This followup study details the late incidence of recurrence (29 of 45 patients in the prophylactic group and 34 of 45 controls), the progression of tumor grade and stage, the deaths and causes (24 patients), and the influence of initial stage, grade, carcinoma in situ and positive cytology on the outcome of treatment.

Since 1959, 10 patients with primary adenocarcinoma of the bladder were treated at the Virginia Mason Medical Center for an incidence of 1.5 per cent of all bladder cancers. This retrospective study shows that histologic grade and tumor location had a variable influence on survival whereas clinical stage appeared to have a direct effect on survival. The only long-term survivors were the 4 low-stage patients who underwent radical cystectomy.

Mitomycin C 40 mg in 40 ml water was administered intravesically every week for 8 consecutive weeks to 60 patients with superficial bladder cancer. All patients had failed treatment with intravesical thiotepa and had evaluable disease. An objective response of 50% or greater reduction in measured tumor mucosal involvement was obtained in 68% of patients. Forty-two percent of the patients achieved a complete response, and this included 50% of patients with Grade III disease and 70% of patients with a T1 tumor. Median response duration in complete responders was 12.2 months with a range of 3.5 to 24.3 + months. Fifty-five percent of patients are still responding. Therapy was generally well tolerated, and in contrast to thiotepa, myelosuppression was not the dose-limiting effect. One third of all patients experienced symptoms of local irritation, and skin reactions were seen in 12% of patients.

The natural history of carcinoma of the bladder is unpredictable. In some patients, invasive (potentially lethal) carcinomas represent their initial clinical presentation, whereas in others, a protracted clinical course characterized by multiple recurrent tumors is witnessed. This latter population of patients is the most vexing to the urologist. The prediction of the patient's "state of risk" from the tumor has historically been based on clinical pathologic staging employing grade and stage. Predictive clinical evidence for the development of invasive (potentially lethal) carcinoma has been gleaned from observations of the rapidity and pattern of tumor recurrence (single vs. multiple), tumor characteristics (grade, shape, and presence of lymphatic or venous invasion) and the presence of carcinoma in situ at preselected endoscopically normal biopsy sites. Currently available "objective" predictors such as blood group isoantigen deletion from bladder urothelium of patients with invasive bladder carcinoma are provocative. Presently, this technique cannot pinpoint when tumor invasion will occur in a particular patient. However, the application of this methodology in a prospective study (including examination of preselected endoscopically normal mucosal biopsies) is well as resected tumor tissue may prove valuable. At the ultrastructure level as studied with the electron microscope and immunofluorescent probes, alterations in the plasma membrane have been defined that are associated with malignant transformation and abnormal growth patterns (potentially predictive of tumor invasion). Certain Of these techniques appropriately applied to a population at high risk may ultimately assist the surgeon in timing extirpative surgery.

A sheathed (coaxial) ureteral catheter has been designed for use in fluoroscopically guided retrograde procedures. Once the catheter has been inserted into the ureter the inner section is removed, leaving a semiflexible sheath as a conduit for biopsy forceps, curved catheters and other instruments. The sheath facilitates ureteral stenting, forceps biopsy of the renal pelvis and brush biopsy of all calices. The sheath also helps in percutaneous stone extraction by allowing retrograde passage and removal of balloon catheters with the patient in the prone position. Cystoscopy is needed initially to insert the catheter but not to pass instruments through the sheath. Thus, procedures can be completed in a standard fluoroscopy room.

The activities of three antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase, were monitored in isolated human renal adenocarcinoma tissues and in cultured human renal adenocarcinoma cells. The results were compared to the activities of these enzymes in the proposed cell of origin, isolated human proximal tubular tissues, and cultured proximal tubular epithelial cells. Strong modulation of these enzymes by culture conditions was observed in normal cells but not in carcinoma cells. Low levels of cellular lipid peroxidation, as assessed by levels of malondialdehyde (MDA), were observed in adenocarcinoma cells under the culture conditions tested with one exception: greatly elevated MDA was observed in renal adenocarcinoma cells growth on plastic in serum-free, chemically defined medium. This increased lipid peroxidation correlated with a loss of cell viability under these conditions.

Iododeoxyuridine (IdUrd) potentiated the lethal but not the growth inhibitory properties of fluorouracil (FUra) and fluorodeoxyuridine (FdUrd) in human bladder cancer cells (T24). The rate of incorporation of IdUrd into DNA was enhanced by both fluoropyrimidines, but to a significantly greater extent by FdUrd. Both inhibition of iododeoxyridylate dehalogenation and the depletion of thymidine triphosphate pools contributed to the increased incorporation rate. Inhibition of dehalogenation accounted for 67% of the observed stimulation in the case of FUra, but only 37% of the increase produced by FdUrd. The depletion of dTTP pools, both in the presence and absence of IdUrd, was greater after FdUrd than FUra exposure. The observed increase in the rate of incorporation of IdUrd appears to account for the enhanced toxicity seen with FdUrd, but other factors may be involved in the case of FUra. Since FUra and IdUrd appear to be mutually potentiating and do not share a dependence on thymidine kinase activity, this drug combination warrants further investigation.

We analyzed the case histories of 31 patients who initially had a diagnosis of seminoma and elevated serum levels of alpha-fetoprotein or human chorionic gonadotropin. We concluded that an elevated alpha-fetoprotein level is firm evidence of the presence of non-seminomatous germ cell tumor and that the patient should be treated accordingly. However, if the level of human chorionic gonadotropin alone is elevated the diagnosis may be either non-seminomatous tumor or seminoma. Patients with seminoma and an elevated level of human chorionic gonadotropin do respond well to radiation therapy if they have low stage disease but if metastatic seminoma is present an elevated human chorionic gonadotropin level appears to be a poor prognostic sign if conventional treatment is given. A plan of treatment is proposed for these patients.

We are investigating IFN activity for human renal cell carcinoma (RCC) in conjunction with other forms of therapy in vitro. Our investigations employed IFN alpha and beta generated by recombinant DNA technology. We employed IFN species in conjunction with vinblastine or elevated temperature of incubation for RCC cells. Recombinant IFNs alpha and beta were provided by Triton/Cetus IFN program. RCC cells grown at 37°C with 1,000 IU/ml IFN alpha for seven days produced significant inhibition in growth kinetics (p