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Traditional teaching has held that urinary diversion should be performed following cystectomy in the treatment of muscle invasive bladder cancer. We have found that performing the diversion prior to removal of the bladder is an acceptable modification of the standard radical cystectomy. The advantages of performing the diversion first include having a fresh operative team to perform the most technically challenging portion of the procedure, avoidance of blood loss until later in the case, and the ability to mature the stoma during abdominal wall closure.

Purpose: We determined if black men with clinically localized adenocarcinoma of the prostate have the same recurrence-free outcome following radical prostatectomy, and whether they have similar preoperative, operative and pathological characteristics as white men in an equal access health care environment., Materials and Methods: We studied consecutive single hospital case series of 366 white and 107 black patients who underwent radical prostatectomy between 1975 and February 29, 1995. Evaluation included comprehensive retrospective chart review, prospective data collection and proactive followup. Univariate and multivariate statistical analyses were done of preoperative, operative, pathological and recurrence data by race., Results: Although the incidences of hypertension and diabetes, pretreatment prostate specific antigen (PSA) and serum creatinine measurements, elevated PSA as an indication for biopsy and clinical stage were greater in black men, the operative variables of blood loss, operative time and performance of a nerve sparing procedure were not different. The incidence of margin positivity was greater in black patients but pathological stage, Gleason score and seminal vesicle or nodal involvement were not different. Black race was an adverse prognostic factor for recurrence following radical prostatectomy after multivariate adjustment for pretreatment PSA and acid phosphatase, organ confinement status and tumor grade., Conclusions: The poorer recurrence-free outcome for black patients even after multivariate adjustment suggests a potentially more aggressive variant of prostate cancer in this population, the etiology of which is unknown. Race should be a stratification factor in clinical trials, especially those including radical prostatectomy and using recurrence-free outcome as an end point.

Background: More than 50,000 male patients received hormonal therapy for metastatic prostate carcinoma in 1995. Nonsteroidal antiandrogens, such as flutamide, when used in conjunction with castration, are effective in prolonging the time to progression of disease and survival. Only one-third of newly diagnosed patients with metastatic prostate carcinoma receive flutamide. Physicians may be reluctant to prescribe flutamide because of quality of life, toxicity, and cost considerations., Methods: Physician focus groups evaluated quality of life factors for metastatic prostate cancer., Results: Using quality of life estimates with the National Cancer Institute's (NCI) 0036 clinical trial results, our revised model of flutamide use predicted that, for minimal disease, survival increased by 4.33 quality adjusted months (QAMs) at an incremental cost of $25,000 per quality adjusted life year (QALY) saved and for severe disease, survival increased by 4.11 QAM at a cost of $18,000 per QALY saved. However, if quality of life estimates are used in conjunction with the Prostate Cancer Trialists' Collaborative Group (PCTCG) meta-analysis estimates, survival increased by 2.1 QAM at an incremental cost of $41,000 per QALY saved for persons with severe disease and increased by 2.6 QAM at an incremental cost of $53,700 per QALY saved for persons with minimal disease., Conclusions: Using NCI 0036 trial data, flutamide has an incremental cost-effectiveness more favorable than most therapies, while estimates based on the PCTCG found a less favorable outcome for the drug. Concerns about out-of-pocket expenditures and efficacy limit flutamide utilization; quality of life considerations are less cogent.

Background: Prostate-specific antigen (PSA) is a most valuable tool for the early detection of prostate cancer; however, it has a high false-positive rate as presently used in prostate cancer screening programs. Patients with persistent PSA elevations, normal digital rectal examinations, and multiple negative biopsies present a clinical dilemma. We prospectively evaluated whether free PSA improves the specificity of PSA and can be useful as a clinical guide to avoid repeat prostate biopsies in a group of such patients., Methods: Sixty-seven men with persistent PSA elevations (mean 9.6 ng/mL; range 4.1-24.8 ng/mL), normal digital rectal examinations, and two or more prior sextant biopsies (mean 2.8), had serum collected for measurement of total and free PSA. All patients were rebiopsied to determine the receiver-operating characteristics (ROC) of total PSA vs. percent free PSA for prostate cancer detection., Results: This study by biopsy identified 11 new prostate cancer cases. The median percent free PSA was significantly higher at 18.1% among men without prostate cancer, compared to 6.4% in men with prostate cancer (P < 0.00005). When sensitivity was plotted against I-specificity, the area under the receiver-operating curve (ROC) for percent free PSA was 0.95, compared to 0.75 for free PSA density, 0.59 for PSA density, and 0.54 for PSA. In patients with elevated total PSA levels, normal digital rectal examinations, and two prior sets of negative sextant prostate biopsies, a cutoff of 10% free PSA would maintain sensitivity at 91% with a corresponding specificity of 86%., Conclusions: Selective measurement of percent free PSA in cases of uncertain diagnosis can significantly improve the specificity of prostate cancer detection compared to total PSA alone. A low percent free PSA (< 10%) appears to be a significant predictor of prostate cancer even after two or more negative prostate biopsies.

Immunohistochemical (IHC) staining for p53 protein nuclear expression was evaluated in archival paraffin-embedded radical prostatectomy specimens from 139 patients with clinically localized prostate cancer followed up from 1 to 8 (mean, 4) years. Elevated nuclear p53 protein expression was detected in 85 (61%) of 139 patients, being heterogeneous and focal in the majority of specimens. Only four specimens displayed homogeneous nuclear accumulation of p53 protein. Disease progression, most commonly prostate-specific antigen elevation, was noted in 46 (33%) patients, with 39 (85%) having positive p53 protein IHC stains. Conversely, 93 (67%) of 139 have not recurred, with 46 (49%) having positive p53. Of all 54 p53-negative patients, 47 (87%) have had no disease recurrence. An increased p53 protein IHC stain was associated with a higher pathological stage (T1 and T2, 51% versus >/=T3, 69%) and Gleason score 2-4, 17%; 5-7, 72%; and 8-10, 87.5%). Despite these associations, p53 IHC staining was an independent predictor of disease-free survival in a multivariate analysis of p53, age, race, stage, and grade. This study revealed that a majority of clinically localized prostate cancers heterogeneously express elevated nuclear levels of p53 protein in at least a subset of malignant cells, and that this expression is an independent predictor of disease progression in prostate cancer patients after radical prostatectomy.

Objective: To determine if African-American men with newly diagnosed prostate cancer (PC) have higher pretreatment serum prostate-specific antigen (PSA) values after adjustment for clinical stage, age, and tumor grade, and to determine if any difference detected is related to tumor volume difference., Design: Consecutive case series of newly diagnosed PC patients between January 1990 and September 1994 and cohort analytic study of PC patients treated by radical prostatectomy (RP) and who had whole-mount pathologic tumor volume assessment between May 1993 December 1994., Setting: Tertiary care military medical center., Patients: A total of 541 evaluable newly diagnosed PC patients (408 white and 133 black) having pretreatment PSA assessment at one laboratory; 91 patients undergoing RP had whole-mount tumor volume analysis., Interventions: Medical record review for pretreatment PSA value, race, tumor grade, clinical stage, and age, as well as whole-mount pathologic assessment of RP specimen and measurement of tumor volume., Main Outcome Measures: The PSA differences between black and white PC patients with adjustments for age, biopsy tumor grade (Gleason score), and clinical stage (TNM stage); PSA differences between black and white PC patients undergoing RP with adjustment for age, RP grade, clinical stage, and tumor volume., Results: The mean (geometric) PSA value for 133 black men was 14.00 ng/mL compared with 8.29 ng/mL for 408 white men (P < .001). The black patients had higher PSA values across all stage, grade, and age categories. The racial difference in PSA levels remained statistically significant when stage, grade, and age were simultaneously controlled for (P < .001). Multivariable odds ratio testing revealed that even after adjustment for stage, grade, and age, black patients were 2.2 times as likely as white patients to have a PSA value greater than 10.0 ng/mL (95% confidence interval, 1.3 to 3.6). Tumor volume (geometric mean) was 5.42 cm3 and 2.10 cm3 for black and white RP patients, respectively (P = .002). Across all clinical stages (T1a to T3), black men had tumor volumes 1.3 to 2.5 times greater than those of white men. Multivariable analysis of covariance revealed that tumor volume and stage of disease were important predictors of PSA level, but race, grade, and age were not. (The percentage of white and black patients whose cancer was detected by screening [75.4% vs 70.4%] or who had symptoms [37.7% vs 29.6%] was not significantly different.), Conclusions: As a group, African-American men with newly diagnosed PC have higher PSA values at initial diagnosis than white men. This PSA difference appears to be due to larger tumor volumes within clinical (TNM) stage categories among black patients. Elevated PSA value was a surrogate for larger tumor volume in this cohort of black men. This stage-for-stage tumor volume disparity even in an equal-access health care environment should prompt further study of screening behavior and/or biological differences of PC in the black population.

Previous studies have suggested that serum prostate-specific antigen (PSA) levels are under androgenic influence, especially in patients with adenocarcinoma of the prostate. PSMA (prostate-specific membrane antigen) is thought to reflect hormonal or clonal resistance or an independence with respect to testosterone regulation. The influence of testosterone on serum PSA expression in normal men is not clear. We studied the effect of exogenous testosterone administration on the serum levels of PSA and PSMA in hypogonadal men. Serial serum PSA, serum PSMA by Western blot, and serum total testosterone levels were obtained at intervals of every 2-4 weeks in 10 hypogonadal men undergoing treatment with exogenous testosterone, delivered as testosterone enanthate injection or by testosterone patch. Linear and quadratic orthogonal polynomial scores were calculated for PSMA, PSA, and testosterone. A 2-tailed, paired t-test failed to demonstrate a significant correlation between serum PSA (linear P = 0.432, quadratic P = 0.290) or PSMA (linear P = 0.162, quadratic P = 0.973) and serum testosterone levels. This study suggests that in hypogonadal men, neither PSMA nor PSA expression is testosterone-dependent.

We tested and proved the safety of recombinant human tumor necrosis factor given intravesically weekly for 11 weeks (dwell time 2 hours) for the treatment of superficial bladder cancer in 8 men and 1 woman 46 to 87 years old (mean age 69 years). Cohorts of 3 patients received 200, 400 and 1,000 micrograms. recombinant human tumor necrosis factor. The maximal tolerated dose was not achieved. There were 9 episodes of urological symptoms, 8 of flu-like symptoms, 4 of headache and 3 of chest tightness. Hematological and gastrointestinal toxicities were minor, and no renal toxicity was encountered. Recombinant human tumor necrosis factor was safe to administer at doses up to 1,000 micrograms. We hope that recombinant human tumor necrosis factor in conjunction with other antitumor agents will lead to a new, effective treatment for superficial bladder cancer.

We report a dramatic decrease in prostate specific antigen in response to the discontinuation of megestrol acetate in a patient with progressive metastatic prostate cancer. Our case demonstrates that withdrawal responses may occur with steroidal and nonsteroidal antiandrogens.

The concept of maximal androgen deprivation (MAD) has become the accepted therapy for metastatic prostate cancer. MAD is also under investigation as neoadjuvant therapy prior to radical prostatectomy and radiation therapy. Innovative new approaches, such as intermittent androgen deprivation and new combination therapies, will emerge over the next decade.

Thymic hyperplasia has been reported as a rebound phenomenon in children and young people, most commonly following chemotherapy for cancer. Although thymic hyperplasia has been documented in testis cancer patients after chemotherapy, to our knowledge it has not previously been reported in newly diagnosed cases before systemic therapy. A retrospective review of 362 testicular germ cell tumor patients treated at a single tertiary care center between January 1, 1980 and August 1, 1993 was performed, with special review of 221 who underwent computerized tomography staging of the chest. Thymic hyperplasia was detected in 4 of the 221 patients (1.8%) including 3 of 100 (3.0%) with seminoma and 1 of 121 (0.8%) with nonseminoma. All 4 patients had low stage (I or IIa) disease with a delay in diagnosis (5 to 24 weeks) and thymic hyperplasia was discovered at staging evaluation 18 to 37 days after orchiectomy but before other cancer therapy was administered. Of the 4 patients 2 underwent thymectomy, revealing histological thymic rebound hyperplasia. All 4 patients had no evidence of recurrence at 1 to 54 months after treatment. In addition to the well known post-chemotherapy phenomenon, thymic hyperplasia may also occur in nonsystemically treated, newly diagnosed testicular cancer patients. An anterior mediastinal mass in an otherwise low stage newly diagnosed testicular cancer patient may represent thymic hyperplasia and not necessarily metastatic disease.

Objectives: To examine the accuracy rate of abdominal staging using third and fourth generation computed tomography (CT) scanning in clinical Stage I testicular nonseminoma patients., Methods: Between January 1985 and August 1993, 57 patients presented to our center with clinical Stage I testicular nonseminoma. Retroperitoneal computed tomographic staging studies were interpreted to be normal preoperatively in the entire group. In addition, tumor marker values were normal or returned to normal postorchiectomy within the appropriate half-life intervals. All patients were subjected to radical or modified retroperitoneal lymph node dissection (19% and 72%, respectively). Original abdominal CT scans (preretroperitoneal lymph node dissection) were available for blinded retrospective re-review in 16 cases (7 pathologic Stage II, 9 pathologic Stage I)., Results: Nineteen of 57 (33%) patients were upstaged at surgery including 6 patients (11%) who demonstrated II B volume disease. Third and fourth generation CT scanning of the retroperitoneum yielded a 66% accuracy rate in this population. Six out of 7 pathologic Stage II pre-lymph node dissection abdominal CT scans that were available for blinded re-review revealed nonpathologic nodes by size criteria in the primary landing zone for the corresponding original tumor., Conclusions: Our data suggests that for clinical Stage I nonseminoma in the 1985 to 1993 era, undue reliance was placed on a less than ideal staging test. The 33% false-negative rate reported showed no improvement over earlier reports and reaffirms concern for relying solely on third or fourth generation CT imaging of the retroperitoneum in the staging of clinical Stage I nonseminomatous germ cell tumor (NSGCT) patients. The presence of any number of lymph nodes in the expected primary landing zone, regardless of size, should raise serious suspicion for occult nodal disease.

Prostate cancer is rare in young adults and when clinically detected it has been invariably locally or distantly advanced, undifferentiated and exhibiting aggressive behavior. To our knowledge no previous report documents clinically detected and localized disease amenable to curative surgery in a young adult. We report on a 29-year-old man with clinically detected, moderately differentiated adenocarcinoma of the prostate who was treated by nerve sparing radical retropubic prostatectomy. The patient was disease-free and morbidity-free 30 months after treatment.

Prostatic tissue specimens derived from transurethral resections of patients with metastatic prostate cancer were analyzed for genetic alterations in the hormone-binding domain of the androgen receptor (AR) gene. Direct sequencing of the polymerase chain reaction-derived DNAs of 6 of 24 specimens revealed a codon 877 mutation (ACT-->GCT, Thr-->Ala) in the hormone-binding domain of the AR gene. This same AR mutation has been reported previously in a metastatic prostate cancer cell line, LNCaP, where this mutation confers upon the AR an altered ligand-binding specificity which is stimulated by estrogens, progestagens, and antiandrogens. It is possible that analogous to an activated/altered growth factor receptor oncogene, codon 877 mutant AR with altered ligand binding may provide a selective growth advantage in the genesis of a subset of advanced prostate cancer. Although estrogens are used infrequently, antiandrogens are used increasingly in hormonal therapy for patients with advanced prostate cancer. The stimulatory effect of these therapeutic agents on the codon 877 mutant AR further suggests that this frequently observed AR mutation may contribute to the treatment refractory disease.

Objective: To test the hypothesis that prostate cancer lymph node (LN) micrometastases, undetected by standard histology, might be found using sensitive immunohistologic methods and may correlate to preoperative prostate-specific antigen (PSA) levels., Method: Archival paraffin blocks of pelvic lymphadenectomy specimens from radical prostatectomy were blindly submitted for immunostaining using pan-cytokeratin monoclonal antibody SB-3, as well as antibodies directed against PSA. Automated immunostaining was performed on a Ventana Medical Systems 320 immunostainer. As a positive control, 7 cases with known nodal metastases by standard histology were blindly analyzed and all has detectable micrometastases by this methodology., Results: For 13 patients with PSA < 10.1 (8%) had LN micrometastases detected. For 10 patients with PSA between 10 and 20 and for 9 patients with PSA > 20, no occult metastases were detected. We did find previously undetected prostate cancer (CaP) LN micrometastases in 1 of 32 (3%) clinically localized prostate cancer patients who had undergone radical prostatectomy. In many LNs, cytokeratin stains cross-reacted and stained individual plasma cells, whereas in the positive metastatic case, a cluster/nest of CaP cells were reactive. To the unfamiliar observer, the pitfall of false-positive results because of nonspecific cytokeratin staining must be considered. These results are in exact agreement with another recent study which also found only a 3 percent incidence of unsuspected pelvic lymph node micrometastases in clinically localized CaP utilizing similar methods., Conclusions: Our hypothesis was not substantiated: LN micrometastases were uncommon and did not correlate to serum PSA. Unlike studies with breast cancer, occult micrometastatic nodal disease not appreciated by standard methods appears to be uncommon in clinically localized prostatic carcinoma.

In a recent intergroup study under the auspices of the National Cancer Institute, 603 eligible patients with newly diagnosed disseminated adenocarcinoma of the prostate were prospectively randomized in a double-blinded clinical trial to receive either a gonadotropin-releasing hormone analogue (leuprolide) and a nonsteroidal antiandrogen (flutamide) or leuprolide and placebo. Of the 603 eligible patients, 300 were in the leuprolide and placebo arm and 303 were in the leuprolide and flutamide arm. At the time of disease progression, the code was broken: Those patients in the placebo arm were given the opportunity to receive flutamide, and the patients in the flutamide arm were treated at their physician's discretion. There was no survival time distribution difference, based on survival measured from the progression data, between the patients who were received flutamide after progression and those who were treated at their physician's discretion after progression. Furthermore, the addition of flutamide to leuprolide at the time of disease progression resulted in a survival-time distribution that is similar to other treatments of hormone-refractory prostate cancer.

Background: Prostate cancer is the most frequent cancer diagnosed in American men today. Currently, about half of all patients with newly diagnosed prostate cancer present with metastatic diseases., Methods: Antiandrogenic drugs, or more appropriately androgen-receptor antagonists, represent a group of compounds that currently have played a limited role in the treatment of metastatic prostate cancer. Their method of action is primarily one of blocking androgens at their receptor sites in target tissues. They generally are classified as steroidal or nonsteroidal compounds. Cyproterone acetate and megestrol acetate are synthetic steroidal antiandrogenic drugs that, not only compete with testosterone and dihydrotestosterone for androgen receptors, but also have progestational activity and reduce pituitary luteinizing hormone and subsequently plasma testosterone. Nonsteroidal antiandrogenic agents (flutamide, Casodex [ICI Pharmaceuticals, England], and nilutamide) block cellular binding of androgens only, and there is no reduction of testosterone levels., Results: Antiandrogenics have been used in numerous trials both in Europe and the United States. This group of compounds have been used as monotherapy and in combination therapy, ie, with orchiectomy or with LHRH agonists., Conclusions: Currently, antiandrogens are used primarily in conjunction with conventional medical or surgical castration to achieve maximal androgen deprivation; however, ongoing clinical studies are comparing these compounds alone against standard hormonal therapy. It seems probable that antiandrogens will play an expanding role in the treatment of metastatic prostate cancer as well as having a role in the treatment of prostate cancer.

Background: Prostate cancer is the most common cancer in American men today. Unfortunately, at the time of diagnosis, most men will have either regional or distant metastatic disease., Methods: Six hundred three patients with advanced prostate cancer who could be examined were randomized in a double-blind, placebo-controlled trial to receive the luteinizing hormone-releasing hormone (LHRH) agonist leuprolide with either flutamide or placebo., Results: Patients receiving the combined therapy arm of leuprolide and flutamide had an increased progression-free survival time of 16.9 versus 13.8 months and a survival advantage of 35.1 versus 20.3 months. A more striking difference was found in the subset of patients receiving combination therapy who had good performance and minimal disease., Conclusions: There appears to be a definite advantage of combination therapy over leuprolide alone, especially in patients with minimal disease and good performance. Another larger intergroup study using orchiectomy and flutamide versus orchiectomy and placebo is currently underway.

We report an 18-month prospective study of 90 patients undergoing penile prosthesis implantation to evaluate a possible cause-and-effect relationship between degree of diabetic control and the risk of infection complicating the operation. Long-term diabetic control was objectively evaluated by measurement of the glycosylated hemoglobin of the patient, which is known to provide an objective value for degree of control for the preceding 60 to 90 days. Of 90 patients 5 (5.5%) had a periprosthetic infection requiring explantation and all infections occurred in the 32 diabetics (36%) in the population (p less than 0.009). Of the 32 diabetics 13 (41.1%) were poorly controlled with time as demonstrated by a glycosylated hemoglobin level of greater than 11.5% and 4 of the infections occurred in this group. Of the 19 remaining controlled diabetics (glycosylated hemoglobin level less than 11.5%) only 1 infection occurred. Therefore, infection occurred in 31% of the poorly controlled versus 5% of the adequately controlled patients (p less than 0.0003). Measurement of glycosylated hemoglobin values appears to be a useful tool to evaluate diabetic patients before implantation of a penile prosthesis. Patients with a glycosylated hemoglobin level of 11.5% or greater should be more optimally controlled before undergoing implantation in an effort to avoid infectious complications.

The authors describe a rare case of primary scrotal neoplasm. The necessity of a prompt diagnosis is emphasized.

Fifteen patients with previously untreated metastatic prostate cancer were treated on a pilot trial with a combination of maximal androgen blockade plus intermittent cytotoxic therapy after androgen priming to stimulate cell division. Androgen blockage was carried out using a gonadotropin-releasing hormone analog (leuprolide) plus a nonsteroidal antiandrogen (flutamide). Carboplatin (CBDCA) (800 mg/m2) was given intravenously every 28 days, preceded for 3 days and followed for 3 days by androgen treatment with fluoxymesterone (5 mg orally twice a day), during which time flutamide was discontinued. Three patients (20%) achieved a complete response (CR), and eight patients (53.3%) achieved a partial response (PR). Four patients (26.7%) had stable disease (SD). The median progression-free survival (PFS) time was 31 months. Nine of 15 patients (60%) remain alive with a median follow-up time of 42+ months (range, 22 to 54 months). Grade 4 thrombocytopenia and Grades 3 or 4 leukopenia were experienced in 87% and 80% of patients, respectively, requiring dose reductions of CBDCA in 85% of the cycles. Six of 15 patients experienced a flare in bone pain with androgen priming. There were no associated spinal cord compressions; however, exclusion of impending spinal cord compression was required before entrance on study.

Chronic pain syndromes are well known to the medical community. The incidence of chronic pain syndromes and cost of evaluating these patients are rapidly increasing. Chronic testicular pain is a fairly common manifestation of a chronic pain syndrome. Retrospectively, we reviewed the records of 48 patients with chronic testicular or scrotal pain (greater than 6 months) evaluated at our institution during the last 7 years. These patients had multiple diagnostic and interventional procedures with few positive findings. There was little improvement in these patients after multiple surgical procedures. Based on the paucity of objective clinical findings a carefully directed diagnostic evaluation for orchialgia is outlined. The treatment of these patients is best managed by a multidisciplinary approach involving the urologist and a pain clinic environment. We believe that extensive diagnostic testing is not indicated in the absence of clinical findings and may serve to worsen the condition or lead to iatrogenic injury. Surgical intervention should be limited to cases when a clear indication is present.

A randomized, double-blind trial in patients with disseminated, previously untreated prostate cancer (stage D2) was designed to test the hypothesis that maximal androgen blockade improves the effectiveness of the treatment of prostatic cancer. Six hundred three men received leuprolide in combination with either placebo or flutamide, and were followed for a minimum of 5 years. The 303 patients randomly assigned to receive leuprolide and flutamide had a longer progression-free survival and an increase in the median length of survival compared with the 300 patients receiving leuprolide plus placebo. Differences between the treatments were particularly evident for men with minimal disease and good performance status.

The superior mesenteric artery and celiac axis were inadvertently ligated during left radical nephrectomy for a large upper pole renal carcinoma with massive perihilar and periaortic adenopathy. Computer-generated 3-dimensional illustrations created from the computerized tomography scan demonstrated the close proximity between these visceral branches and the adenopathy mass complex, and showed how this bulky disease may interfere with surgical anatomy. When left radical nephrectomy is performed for locally advanced and/or bulky node-positive renal neoplasms, surgeons must be cognizant of the location of the major visceral arterial branches and possible anatomical distortions.

We believe this is the fifteenth case report of adrenal cortical carcinoma with tumor thrombus to the vena cava, and the fourth reported case of a left-side tumor propagating thrombus to the vena cava. The patient underwent successful resection which required cardiopulmonary bypass. The caval tumor thrombus was very friable and gelatinous, unlike many renal cell thrombi, and required special surgical considerations.

The Testicular Cancer Center Intergroup Study entered surgically staged patients with nonseminomatous tumor and metastases limited to the regional lymph nodes into a previously reported cooperative trial of immediate versus delayed therapy for positive retroperitoneal node disease. Patients with negative nodes (stage I) were placed in an observation registry with specified treatment strategy upon relapse. Of 264 stage I cancer patients 27 (10.2%) had recurrence: 5 of these 27 patients died after recurrence of the testicular malignancies, while 4 other nontumor-related deaths have occurred. Pre-lymphadenectomy staging characteristics observed to predict significantly node positivity are the results of radiological examinations, presence of tumor invasion, vascular invasion and tumor histology. In a multiple logistic regression analysis with these variables, misclassification still occurs in more than a fourth of the patients. Future refinements in diagnosis may allow for better prediction of these patients at risk to have positive lymph nodes and ultimately recurrence. Presently, if assessment of nodal involvement is the objective, noninvasive procedures are not an adequate substitute for surgical staging with modified lymphadenectomy.

The M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimen has been utilized at our two institutions to treat 17 patients with advanced stage transitional cell carcinoma of the bladder. We report 2 cases of carcinomatous meningitis resulting from metastatic transitional cell carcinoma which occurred in patients treated with M-VAC. Review of the literature suggests that our experience with central nervous system metastases is not unique, and that treatment of advanced stage transitional cell carcinoma of the bladder with M-VAC may enhance the incidence of meningeal metastases. Carcinomatous meningitis, although rare, is a rapidly fatal manifestation of metastatic transitional cell carcinoma if left untreated. However, prompt diagnosis and early aggressive therapy may result in palliation and stabilization of neurologic status. We review the pathophysiology, diagnosis, and treatment of transitional cell carcinomatous meningitis.

In a randomized, double-blind trial for metastatic prostate cancer (Stage D2), 603 men received leuprolide, a gonadotropin-releasing hormone analog that inhibits the release of gonadotropins, coupled with either placebo or flutamide, a nonsteroidal antiandrogen that inhibits the binding of androgens to the cell nucleus. The 303 men receiving androgen blockade with leuprolide and flutamide demonstrated a longer progression-free survival (16.9 vs. 13.9 months, P = 0.039) and an increased median length of survival (35.0 vs. 27.9 months, P = 0.035). In the subgroup of men with minimal disease and good performance status, the advantages of maximal androgen blockade were more pronounced. It is concluded that combined androgen blockade with leuprolide and flutamide was more effective than leuprolide alone for patients with metastatic cancer of the prostate. The therapeutic benefits, although greatest in patients with minimum disease, need to be evaluated in a prospective, randomized fashion in trials specifically designed for men with minimal disease and good performance status. Exploratory analyses using the black race as an explanatory variable were also performed. Black race is associated with shorter survival times and is also associated with other prognostic factors, including recent weight loss, anemia, elevated phosphatase levels, and pain. These findings suggest the need for future studies of the relationship of black race and response to prostate cancer therapy.

The accuracy of intraoperative frozen section examination of excised lymph nodes was analyzed in 40 consecutive patients with clinical stages A2, B1 and B2 adenocarcinoma of the prostate who underwent pelvic lymphadenectomy immediately before anticipated radical prostatectomy. Lymph node metastases were observed with frozen sections and verified with paraffin sections in 5 cases (13 per cent). Among the 35 patients with negative frozen sections lymph node metastases were found with paraffin sections in 3 cases (9 per cent). Despite the potential for false negative findings we believe that intraoperative frozen sections constitute a practical method of pathologic staging prior to radical prostatectomy.

A malleable penile prosthesis incorporating a stainless steel core has been designed to provide a more rigid prosthesis while still ensuring concealability. A total of 56 patients in our initial series underwent implantation of this malleable penile prosthesis. Our experience indicates that this prosthesis provides ease of implantation, outstanding cosmetic results, and a much simplified and reduced inventory.

The predictive value of liver scans for the detection of hepatic metastases is discussed. A retrospective review was done on 104 patients with urologic malignancies who had undergone liver scans and liver function tests. Liver scans had a low predictive value, while serum alkaline phosphatase alone had a higher predictive value. The combination of low predictive value and high cost/benefit ratio indicates that the liver scan has no routine role in the urologic oncologic staging.

Radioimmunoassay for prostatic acid phosphatase and a conventional enzymatic method using alpha-naphthyl phosphate were employed to document the changes in serum levels of this enzyme following transurethral prostatectomy and prostatic massage. Thirty-four patients with histologically proved benign prostatic hyperplasia and 120 controls were studied. Consistent parallel elevations were noted after surgical trauma. A rapid clearance was observed with normal levels returning at twenty-four hours. Prostatic massage did not elicit a change by either method.

We analyzed the efficacy of radiation therapy and retroperitoneal lymphadenectomy preceded and followed by radiation therapy as curative treatment in 113 patients with clinical stages I and II nonseminomatous germ cell tumors of the testis. Radiation therapy alone was curative in 86 and 82 per cent of the patients with clinical stages I and II disease, respectively, and radiation therapy before and after retroperitoneal lymphadenectomy was curative in 89 and 73 per cent of patients with clinical stages I and II disease, respectively. Of 26 patients with clinical stage II disease in the group receiving radiation therapy before and after retroperitoneal lymphadenectomy only 13 (50 per cent) had pathologic documentation of retroperitoneal metastasis or histologic evidence of nodal metastases that had been destroyed by radiation therapy alone. When analyzed by pathologic stage radiation therapy before and after retroperitoneal lymphadenectomy was curative in 91 and 51 per cent of patients with stage I and II disease, respectively. In our series clinical overstaging may have been responsible for the favorable results of radiation therapy alone, and radiation before and after retroperitoneal lymphadenectomy in the treatment of clinical stage II nonseminomatous germ cell tumors.

Patients with advanced prostate carcinoma that had been stabilized by orchiectomy (ORCH) or hormone therapy for at least 3 months, were randomized to either diethylstilbestrol (DES) alone or DES plus Cytoxan or DES plus Emcyt. A total of 188 patients were randomized between July, 1976 and February, 1982 of which 161 were evaluable for objective response to treatment. Objective response rates, response duration, or survival experiences were not demonstrably different between treatment arms, either for all patients or within good or poor prognosis groups determined by initial pain or acid phosphatase level. Subjective improvements in performance status were small for each treatment. Pain relief was somewhat greater in the chemotherapy-hormone combinations than in the DES/ORCH, but the advantage was not statistically significant. Side effects were primarily nausea and vomiting and leukopenia, mostly in the DES + Cytoxan arm. The duration of stabilization prior to entry did not influence response overall, although there were opposing trends within each of the two chemotherapy arms. The premise for combining antitumor agents with hormones before hormone failure is still felt to be a more logical approach than waiting for the ultimate hormone failure, and a combination of hormones plus two antitumor agents is being evaluated in a subsequent ongoing trial where a more rigid design limits the duration of the preentry period of hormone stabilization.

Leiomyosarcoma of the inferior vena cava is a rare disease with protean manifestations related to the location of the tumor. Urological manifestations of the disease are rare and include renal vein thrombosis and renovascular hypertension. Approximately 63 cases have been reported in the literature, with a striking female predominance. Presentation as an isolated suprarenal mass has not been reported previously. We discuss this unusual tumor and report a case that presented as an asymptomatic suprarenal mass.

To test the hypothesis that maximal androgen blockade improves the effectiveness of the treatment of prostatic cancer, we conducted a randomized, double-blind trial in patients with disseminated, previously untreated prostate cancer (stage D2). All 603 men received leuprolide, an analogue of gonadotropin-releasing hormone that inhibits the release of gonadotropins, in combination with either placebo or flutamide, a nonsteroidal antiandrogen that inhibits the binding of androgens to the cell nucleus. As compared with the 300 patients receiving leuprolide and placebo, the 303 patients randomly assigned to receive leuprolide and flutamide had a longer progression-free survival (16.5 vs. 13.9 months; P = 0.039) and an increase in the median length of survival (35.6 vs. 28.3 months; P = 0.035). The differences between the treatments were particularly evident for men with minimal disease and good performance status; however, further studies should be conducted in this subgroup. Symptomatic improvement was greatest during the first 12 weeks of the combined androgen blockade, when leuprolide alone often produces a painful flare in the disease. We conclude that in patients with advanced prostate cancer, treatment with leuprolide and flutamide is superior to treatment with leuprolide alone.

We report a case of organ-limited amyloidosis of the distal portion of both ureters in which bilateral osseous metaplasia was present as well as radiographic evidence of ureteral wall calcification. This case represents the twenty-eighth report of localized ureteral amyloidosis and the fourth report with bilateral involvement.

Flow cytometry was used to measure the DNA content in archived paraffin-embedded human prostatic cancer tissue for 69 patients with known outcomes that presented between 1975 and 1982. Of these, 51 patients had clinically localized lesions and were surgically staged prior to radical prostatectomy, while 18 patients presented with advanced Stage D2 disease. Thirty-six of 37 (97.3%) pathologic Stage B lesions were diploid. In contrast, the majority (72.2%) of patients with metastatic disease had aneuploid tumors. The average Gleason grade for aneuploid tumors was 8.2 +/- 1.98 versus 5.5 +/- 1.89 for diploid tumors (p less than 0.01). For 51 patients with clinically localized tumors, 13.9 percent of diploid tumors with a low Gleason sum (2 to 6) had extracapsular spread of tumor or regional lymph node involvement compared with 83.3 percent of aneuploid tumors with high Gleason scores (7 to 10). The addition of DNA ploidy to degree of glandular differentiation may enhance the prognostic evaluation of prostatic tumors and eventually improve our ability to select patients who are likely to benefit from radical prostatectomy.

An unusual type of ureteral injury is described. The conventional surgical management of a penetrating ureteral injury was not utilized. Because debridement was not necessary in this case, we did not use an internal ureteral stent. A good postoperative result was obtained with this conservative treatment.

A simple method of timed urine flow measurement performed at home by the patient is compared to instrumental measurements of peak flow rate. The timed method correlates well with the peak flow rate. Timed uroflowmetry is free, can be done in the privacy of the home and provides multiple measurements. This is a valid technique to document a weak stream and is a useful screening test for patients with lower urinary tract obstruction.

Single and combination chemotherapy was compared in a clinical trial for men with advanced, metastatic prostate cancer who had received prior pelvic irradiation and had had progression of disease despite hormonal therapy. The 149 patients were randomized to receive estramustine phosphate or cis-platinum alone or in combination. Of the 149 patients 25 (17 per cent) were excluded from the study but 124 were evaluated for response and survival. Entry variables were distributed similarly among patients in each treatment arm. There were no complete or partial responders but there were nearly twice as many patients whose disease was stabilized (33 per cent) on the combination regimen compared to estramustine phosphate (18 per cent) and about a third more than for cis-platinum (21 per cent). Analysis of survival revealed some advantage for patients on combination therapy. Major toxicities for all treatments were nausea and vomiting (62 to 88 per cent) and accompanying anorexia (72 to 95 per cent). Azotemia developed in 45 per cent of the patients receiving combination therapy. In addition an elevation in serum creatinine occurred in 22 per cent of the patients receiving combination therapy and in 17 per cent of those receiving cis-platinum alone. Myelosuppression occurred infrequently.