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Purpose: We determine outcomes after 5 years of followup for men who were randomized to receive transurethral resection or watchful waiting for moderate symptoms of benign prostatic hyperplasia., Materials and Methods: A total of 556 patients were evaluated up to 60 months after randomization providing 966 patient-years of followup for transurethral prostatic resection and 990 for watchful waiting. Patients randomized to watchful waiting were evaluated according to whether they remained on treatment or crossed over to surgery. Outcomes included treatment failure, a genitourinary symptom score, peak flow rate, post-void residual urine volume and the degree of bother from genitourinary symptoms., Results: All outcomes were significantly better for transurethral prostatic resection than for watchful waiting. Treatment failure rates were 10% for transurethral prostatic resection versus 21% for watchful waiting (p = 0.0004). The crossover rate at 5 years was 36% and was positively associated with the degree of bother. Men with low pretreatment peak flow rates who were randomized to transurethral prostatic resection had 85% greater improvement in peak flow rate than comparable men who were randomized to watchful waiting and eventually crossed over to resection. However, after crossover, bother from genitourinary symptoms was similar to that of the resection group., Conclusions: For men with moderate symptoms of benign prostatic hyperplasia transurethral prostatic resection has more favorable outcomes up to 5 years of followup compared to watchful waiting. While many men do well on watchful waiting, those who undergo transurethral prostatic resection after a trial of watchful waiting have less improvement in measures of bladder function than men randomized to resection, although there is no difference in serious adverse outcomes or bother from genitourinary symptoms.

Context: The percentage of free prostate-specific antigen (PSA) in serum has been shown to enhance the specificity of PSA testing for prostate cancer detection, but earlier studies provided only preliminary cutoffs for clinical use., Objective: To develop risk assessment guidelines and a cutoff value for defining abnormal percentage of free PSA in a population of men to whom the test would be applied., Design: Prospective blinded study using the Tandem PSA and free PSA assays (Hybritech Inc, San Diego, Calif)., Setting: Seven nationwide university medical centers., Participants: A total of 773 men (379 with prostate cancer, 394 with benign prostatic disease) 50 to 75 years of age with a palpably benign prostate gland, PSA level of 4.0 to 10.0 ng/mL, and histologically confirmed diagnosis., Main Outcome Measures: A percentage of free PSA cutoff that maintained 95% sensitivity for prostate cancer detection, and probability of cancer for individual patients., Results: The percentage of free PSA may be used in 2 ways: as a single cut-off (ie, perform a biopsy for all patients at or below a cutoff of 25% free PSA) or as an individual patient risk assessment (ie, base biopsy decisions on each patient's risk of cancer). The 25% free PSA cutoff detected 95% of cancers while avoiding 20% of unnecessary biopsies. The cancers associated with greater than 25% free PSA were more prevalent in older patients, and generally were less threatening in terms of tumor grade and volume. For individual patients, a lower percentage of free PSA was associated with a higher risk of cancer (range, 8%-56%). In the multivariate model used, the percentage of free PSA was an independent predictor of prostate cancer (odds ratio [OR], 3.2; 95% confidence interval [CI], 2.5-4.1; P < .001) and contributed significantly more than age (OR, 1.2; 95% CI, 0.92-1.55) or total PSA level (OR, 1.0; 95% CI, 0.92-1.11) in this cohort of subjects with total PSA values between 4.0 and 10.0 ng/mL., Conclusions: Use of the percentage of free PSA can reduce unnecessary biopsies in patients undergoing evaluation for prostate cancer, with a minimal loss in sensitivity in detecting cancer. A cutoff of 25% or less free PSA is recommended for patients with PSA values between 4.0 and 10.0 ng/mL and a palpably benign gland, regardless of patient age or prostate size. To our knowledge, this study is the largest series to date evaluating the percentage of free PSA in a population representative of patients in whom the test would be used in clinical practice.

Purpose: The radiological evaluation of ureteroenteric anastomoses following cystectomy and diversion is standard practice at our institution. To our knowledge there are no data that demonstrate the efficacy of retrograde "stentograms" following cystectomy., Materials and Methods: A retrospective analysis of the retrograde stentograms of 73 patients who underwent cystectomy and diversion was reviewed., Results: Of 135 ureteroenteric anastomoses 3 (2.2%) demonstrated a leak by retrograde stentogram. No patients had evidence of obstruction., Conclusions: The 2.2% incidence of ureteroenteric leak in our series does not support the routine use of retrograde stentogram following cystectomy and diversion.

The role of surgery in metastatic renal cancer continues to evolve. Although of documented benefit in patients with significant symptoms from their primary tumor and in patients with solitary (or resectable) metastatic disease, the clinical usefulness of nephrectomy in patients with unresectable metastases remains to be proved. Important clinical trials are under way to answer this question.

Background: Renal cell carcinoma is a common neoplasm that is often refractory to treatment. It is occasionally responsive to immunomodulating agents including interferon-alpha, which enhances the effects of 5-fluorouracil upon cells. Combinations of these two drugs have been most frequently tested in patients with gastrointestinal cancers, with some promising results. Because interferon-alpha has activity for renal cell carcinoma, a trial of this combination in patients with this malignancy was undertaken., Methods: The Southwest Oncology Group performed a Phase II clinical trial of the combination of 5-fluorouracil and interferon-alpha for recurrent or metastatic renal cell carcinoma. Eligibility criteria included no prior treatment with medications for cancer, a performance status of 2 or better, and bidimensionally measurable disease. The regimen studied consisted of 5-fluorouracil, 750 mg/M2/day, by continuous intravenous infusion on Days 1-5, and interferon-alpha-2b (Intron A), 5 x 10(6)U/M2/day, subcutaneously on Days 1, 3, and 5, repeated every 21 days., Results: Forty eligible patients were treated; twenty of the 40 underwent a nephrectomy. The regimen was tolerable: 3 patients had Grade 4, and 17 had Grade 3 toxicity. There were 5 partial responses (13% with 95% confidence limits of 4-27%). Median progression free survival for all 40 patients was 4 months and median overall survival was 15 months from the time of registration., Conclusions: The combination of 5-fluorouracil and interferon-alpha given by this schedule, although tolerable and occasionally yielding responses, is not an improvement over existing therapies.

Objective: Transurethral injection of collagen (TCI) may be used to treat urinary incontinence following radical prostatectomy for prostate cancer. The transrectal ultrasound (TRUS) findings after TCI are described in this report., Materials and Methods: TRUS exams of four postprostatectomy patients who had undergone TCI were reviewed. Findings were correlated with pathologic specimens obtained at TRUS-guided core biopsy. These histologic specimens were compared with others from postprostatectomy patients who had not undergone TCI., Results: Well defined bladder apex masses of uniform echogenicity, hypoechoic to adjacent fat and muscle, were identified sonographically in all TCI patients. Masses from which positive biopsies were obtained were similar in appearance to those with no malignancy. Hypocellular fibrous tissue and foci of acellular loose connective tissue were identified in the biopsies of those patients who had undergone TCI. No acellular areas were identified in specimens from patients who had not had TCI., Conclusion: Sequelae of TCI should be included in the differential diagnosis of perianastomotic masses in postprostatectomy patients. However, the need for biopsy is not obviated as residual or recurrent prostate carcinoma may coexist.

There are multiple surgical approaches or techniques for nephron-sparing surgery. These include simple nucleation, segmental polar nephrectomy, wedge resection, major transverse resection, and extracorporeal partial nephrectomy with autotransplant. This article discusses the indications and follow-up for nephron-sparing surgery, focusing specifically on the surgical techniques for wedge resection and segmental polar nephrectomy.

DNA ploidy determinations have been shown to have clinical application in predicting disease progression, survival, or response to anti-androgen therapies in prostate carcinomas. Since intra-tumor heterogeneity may have a profound effect on DNA measurements, we determined the frequency of DNA ploidy and proliferation (here S-phase fraction) heterogeneity in early prostatic carcinomas, and estimated the potential impact of heterogeneity on predicting disease course, survival, or response to therapy. Using image and flow cytometric analysis of archival, paraffin-embedded prostate tumors, we measured DNA ploidy in individual foci of prostatic carcinoma in stage T1a, T1b and T1c disease. Image analysis studies included the use of Feulgen stained tissue sections, and a comparison of these results with flow cytometric DNA ploidy determinations on nuclei isolated from the same tumor foci. Flow cytometry was also used to measure DNA Index and tumor S-phase fraction, in some cases using multiparameter analysis of isolated nuclei to determine DNA content and the level of the proliferation-associated antigen, p105. Our results indicate that DNA aneuploid foci of prostate carcinoma are infrequently seen in stage T1a disease (13% of the individuals studied), and that the presence of both DNA diploid and aneuploid foci in the same sample is seen in less than 10% of these individuals. Stage T1b and T1c tumors containing only DNA diploid nuclei are seen, though these are likely most common in low volume, low Gleason grade tumors. By using flow cytometry to compare these results with those using image analysis of the same tumor foci, we demonstrated that the majority (> 75%) of these aneuploid tumors are DNA tetraploid. Our data on prostate tumor S-phase fractions indicate that DNA diploid tumors generally have a lower S-phase than DNA aneuploid foci (including comparisons of DNA diploid and aneuploid foci in the same prostate tumor). These results support the model that early prostate tumors are DNA diploid and have a low S-phase, and that these tumors likely evolve to DNA tetraploid tumors with a similar low S-phase fraction.

Objective: To derive age-specific upper limits for prostate specific antigen (PSA) level in men 50-74 years of age with no clinical evidence of prostatic carcinoma, and to test the sensitivity and specificity for cancer detection of these upper limits., Subjects and Methods: A total of 6166 men were recruited for a multicentre study of prostate cancer detection and underwent a serum PSA determination and digital rectal examination (DRE). Men considered to be clinically free of prostatic carcinoma were those with a normal DRE and a PSA level < or = 4.0 ng/mL, and men with an abnormality in either parameter who underwent ultrasonography-guided prostate biopsy that revealed no evidence of carcinoma. By these criteria, 5469 men had no evidence of prostatic carcinoma. Dividing the population into 5-year age increments, three statistical methods were assessed to derive upper limits for serum PSA level by age; the mean +2 SD, the 99th percentile, and a 97.5% prediction interval based on linear regression., Results: Newly-derived upper limits calculated by each method in the 50-54 and the 70-74 age group were 3.9 ng/mL and 7.6 ng/mL (mean +2 SD), 5.2 ng/mL and 14.0 ng/mL (99th percentile), and 4.7 ng/mL and 8.2 ng/mL (97.5% prediction interval). The sensitivity of the newly-derived upper limits was tested using receiver operating characteristic curves derived from men with no suspicious findings on DRE and a serum PSA concentration > 4.0 ng/mL. Although the specificity of the test increased with increasing PSA upper limits, no upper limits derived from these three methods yielded adequate sensitivity to detect cancer; sensitivities by age range were from 53 to 94%, using mean +2 SD, from 25 to 50% with the 99th percentile, and from 47 to 64% with the 97.5% prediction interval., Conclusion: We do not recommend age-referenced adjustments in upper limits for serum PSA concentration, but recommend that an upper limit of 4.0 ng/mL be used in all men 50-74 years of age.

A multicenter, phase II trial of continuous-infusion interleukin 2 (IL-2) was done in the Southwest Oncology Group to evaluate the efficacy and safety of this treatment in a broad-based population of patients with metastatic renal-cell carcinoma. Forty-seven patients from 11 different institutions were entered in this study, with 43 eligible. Two technically ineligible patients who received treatment and for whom records are available are included in the data analysis. Thus, there are 45 analyzable patients. Of these patients, performance status was 0 in 58% and 1 in 42%. Thirty-one patients had a prior nephrectomy, and 12 patients had received prior therapy. IL-2 was initially given at a dose of 4.5 x 10(6) Roche U/m2/day, 4 days a week, for 4 weeks in a row, followed by a 3-week rest period. Because of the difficulty in obtaining reimbursement for the hospitalization required on the days of IL-2 administration, after 10 patients had been entered, the treatment regimen was changed to 6 x 10(6) Roche U/m2/day for 4 days as an inpatient, followed by 2 weeks of potential outpatient treatment at a dose of 3 x 10(6) Roche U/m2/day for 4 days each week. This was followed by a 2-week rest period. Within the 45 analyzable patients, there were 0 complete responses and 6 partial responses, for a response rate of 13% (95% confidence interval 5.1-27%). Responses occurred in lung metastases, nodal disease, and in one patient with bone metastases and the primary kidney tumor. Response durations were 1 month, 1 month, 14+ months, 19 months, 26+ months, and 27 months. Of 12 patients with a nephrectomy and only lung metastases, 4 showed partial responses. Medial survival for all analyzable patients is 15 months (95% confidence interval 8-20 months). Toxicity was significant, with nausea and vomiting, diarrhea, fever and chills, dermatologic changes, and fatigue the most frequent. There were 18 instances of grade 4 toxicity, with the most common grade 4 toxicity, respiratory, found in 8 patients. There were two early deaths of probable heart-related causes while receiving treatment. A continuous-infusion IL-2 regimen that allows some potential outpatient treatment shows effectiveness and toxicity similar to that in other multicenter IL-2 infusion trials and high-dose intravenous bolus regimens.

With the advent of more-routine prostate-specific antigen (PSA) blood testing, many more patients are being identified in whom the only clinical sign of their underlying disease is an elevated PSA level. Most evidence to date suggests that such patients do harbor clinically significant cancers and thus should be treated in a fashion similar to patients with T1b, T2a, and T2b disease.

Objective: We studied the usefulness of transrectal sonography, prostate-specific antigen levels, and prostate-specific antigen density as indications for directed and random biopsies of the prostate in patients with possible prostatic cancer., Materials and Methods: A total of 141 patients with increased levels of prostate-specific antigen or abnormal findings on digital rectal examination had transrectal sonography of the prostate and determination of prostate-specific antigen density. Through sonographic visualization, all patients had biopsies of possible cancerous lesions and random biopsies of regions of the prostate that appeared normal. Histologic results were correlated with sonographic findings and determinations of prostate-specific antigen levels and prostate-specific antigen density., Results: Adenocarcinoma was detected in 40 (28%) of the 141 patients. Transrectal sonography showed an abnormality that was determined by directed biopsy to be a carcinoma in 27 (68%) of the 40 patients. Transrectal sonography showed no carcinoma in 13 patients (32%) for whom random biopsy revealed a tumor. The sensitivity of sonography was 68%, and the specificity was 49%. The combination of sonographic findings suggestive of cancer and increased prostate-specific antigen density had a sensitivity of 75% and a specificity of 75%; we calculated a sensitivity of 72% and a specificity of 56% for the combination of sonographic findings suggestive of tumor and increased levels of prostate-specific antigen. Thirty-nine (97%) of 40 patients with cancer had either sonographic findings suggestive of tumor or increased prostate-specific antigen density, and one (3%) had no evidence of tumor on sonography and a normal prostate-specific antigen density., Conclusion: Directed and random sonographic biopsies of the prostate are indicated in patients with sonographic findings suggestive of tumor and increased prostate-specific antigen density and in patients with abnormal sonographic findings and normal prostate-specific antigen density. Random biopsies are indicated in patients with normal sonographic findings and increased prostate-specific antigen density. In our series, random biopsies were not indicated in 25 of 26 patients with normal sonographic findings and normal prostate-specific antigen density. Further research on the need for random biopsies when there are no sonographic abnormalities and when prostate-specific antigen densities are not elevated is warranted.

The Southwest Oncology Group (SWOG) studied the response rate and toxicity of merbarone (1,000 mg/m2 IV continuous infusion days 1-5, q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 36 eligible patients, there was one partial response for a response rate of 3% (95% C.I. 0.1-15%). There were no mixed responses. There were no treatment related deaths or adverse drug reactions. Significant anemia, diarrhea, and hypercalcemia were observed. Mild to moderate degrees of malaise/fatigue/lethargy, dizziness/vertigo, hyperglycemia, creatinine increase, nausea, vomiting, weight loss, pedal edema, dyspnea, and granulocytopenia were noted. Merbarone does not have significant activity as a single agent in advanced renal cell carcinoma.

The case records of 2 patients recently treated at our medical centers with prostatic cystic epithelial-stromal tumor (ages 22 and 62 years), as well as 14 cases previously reported in the literature were reviewed to obtain a consensus as to the therapy for this uncommon malignancy. Patients with prostatic cystic epithelial-stromal tumor often present with obstructive voiding symptoms and a palpable suprapubic mass. Computerized tomography typically reveals a huge, complex retrovesical mass with displacement of surrounding pelvic and abdominal structures, which may invade locally into the bladder, ureters or rectal wall. Our experience with immunohistochemical staining of these tumors suggests an epithelial component that is positive for prostate specific antigen, prostatic acid phosphatase, epithelial membrane antigen, chorioembryonic antigen and cytokeratin, and a stromal component that is positive for vimentin, desmin, cytokeratin and myosin. Rapid recurrences are the rule in patients in whom the tumor is incompletely resected. Histological evidence of malignant transformation and distant metastases has been reported in these neoplasms. An aggressive surgical approach aimed at total removal of this pelvic tumor will be discussed.

Serum concentrations of tryptophan (TRP) and kynurenine (KYN) were determined in renal allograft recipients (RAR) as an index of interferon-gamma-induced, indoleamine-dioxygenase-catalysed TRP degradation. Serum TRP and KYN in RAR during periods of stable graft function were typically within the normal range, however, the median values for serum KYN demonstrated significant increases 5-7 days prior to biopsy-confirmed acute rejection (1.6-fold, P less than 0.01) and on the day of biopsy (1.7-fold, P less than 0.001). Serum KYN was also markedly elevated in patients who contracted viral or Gram-negative bacterial infections in the absence of graft rejection. Serum KYN was not correlated with serum creatinine in RAR nor were serum TRP or KYN affected by antirejection therapy with high dose steroids. Retrospective analysis of intra-patient changes in serum KYN demonstrated that KYN monitoring was a useful adjunct to serum creatinine in the early detection of first acute rejection episodes. The first course of OKT3 therapy was associated with low serum TRP and significant increases in serum KYN (two- to three-fold) following the first three doses. The time course of these abnormalities corresponded to that over which many of the side effects of the OKT3 'first dose reaction' have been reported to occur. Significant changes in serum KYN were not observed in patients receiving repeat courses of OKT3 therapy. Significant decreases in serum TRP and significant increases in serum KYN were both prevalent and frequent in RAR during the first two postoperative months.(ABSTRACT TRUNCATED AT 250 WORDS)

Clear cell adenocarcinoma in a urethral diverticulum in the female is a very rare and unusual tumor. We recently treated two patients with this tumor. Their presentation, histologic evaluation, and management are reviewed in light of the limited experience in the literature.

A total of 34 patients with measurable superficial transitional cell cancer of the bladder entered into a phase 1, nonrandomized, noncomparative trial to assess the toxicity of the oral interferon inducer bropirimine. Of the patients 26 were also evaluable for response. The toxicity of bropirimine was minimal. At the 3-month evaluation 6 patients had experienced complete regression of tumor and had negative cytology studies, and 2 had partial responses. The majority of complete responses were in patients with carcinoma in situ only, with most responses seen at higher dose levels. One patient with papillary tumor and carcinoma in situ had a complete response. Some early responses appear to be durable. Most importantly, a high rate of complete response was noted at higher dose levels among patients who had failed prior therapy with bacillus Calmette-Guerin. Further clinical trials of bropirimine in bladder cancer appear warranted.

The effects of 40 days of treatment with Cyclosporine A (CSA) on plasma and urine free amino acids were investigated in sham-operated (C) and partially nephrectomized (Pnx) female Fischer 344 rats. High Dose CSA (30 mg/kg/day ip) was associated with reduced weight gain, increased plasma urea nitrogen, and hypoproteinemia in C and Pnx animals. These animals also demonstrated increased plasma levels of alanine, markedly reduced levels of tryptophan, and an increase in urinary excretion of methylhistidines. C but not Pnx animals also showed a significant increase in plasma serine and a decrease in plasma taurine. CSA treatment of group C resulted in a progressive aminoaciduria involving substrates of the neutral and acidic renal amino acid transport systems; however, the renal excretion of taurine and beta-alanine by these animals was markedly reduced as compared to vehicle treated controls. High dose CSA exacerbated aminoaciduria in Pnx animals, but in this group, the excretion of beta amino acids was also increased. Our findings demonstrate that chronic CSA toxicity in rodents with normal renal function is characterized by increased muscle protein catabolism, significant reductions in plasma tryptophan, and an apparent decrease in whole body taurine pools. With the exception of the taurine abnormalities. CSA treatment had similar effects on Pnx animals; however, in this group, CSA-induced pathological changes were superimposed on the changes due to renal insufficiency per se. CSA toxicity as identified by the parameters investigated in this study was no more severe in Pnx animals with moderate chronic renal insufficiency than in controls with intact renal function.

Definitive treatment of localized carcinoma of the prostate has included radical surgery, external beam radiation therapy, and interstitial radiation therapy. The interstitial agent most commonly used is Iodine-125. Forty-eight patients were treated with interstitial radiation therapy using Iodine-125 implants with a median follow-up of 55 months. Forty-three percent of the evaluable patients had progressive disease with approximately 50% progressing at 5 years by Kaplan-Meier analysis. Overall actuarial survival in the group was 80% at 5 years. This and several other studies suggest that control of prostate cancer with Iodine-125 seeds may be suboptimal as compared with other treatment modalities, especially the radical retropubic prostatectomy. Analysis of treatment parameters is presented along with a discussion of the current status and future prospects for treatment of localized carcinoma of the prostate with interstitial radiation therapy.

We report on a sixty-five-year-old man with hematuria secondary to superficial bladder cancer. Because of previous urethral trauma, a complete transurethral resection of his bladder tumor could not be done. He, therefore, underwent cystectomy, at which time we incidentally found a transitional cell carcinoma of the left ureteral stump that had been left from a previous left nephrectomy for a World War II-related injury. This case underscores the importance of a thorough investigation of the complete urinary tract in a patient with hematuria or other urinary tract symptoms even if an obvious cause is found for his symptoms.

Despite cyclosporine's efficacy in preventing rejection, its use has been hampered by nephrotoxicity. Questions remain concerning its application in patients with decreased renal function. The purpose of this study was to 1) establish a reliable animal model with chronic renal insufficiency (CRI) to study cyclosporine (CyA) nephrotoxicity, and 2) compare the long-term (50 day) severity of CyA nephrotoxicity in CRI versus normal animals. Fischer 344 rats were divided into six groups (15 to 22 each). In three groups, CRI was induced by a 5/6th nephrectomy (three groups were sham operated). After three wks., daily i.p. injections of olive oil, CyA at five mg./kg., or CyA at 30 mg./kg. daily were administered. Serum and urine were collected at 10 day intervals for the determination of biochemical indices of renal function. Animals were sacrificed after 50 days of treatment and renal histology was evaluated by light and electron microscopy. Chronic CyA treatment was well tolerated by both intact and CRI rats, suggesting that this is a reliable model for long-term CyA toxicity studies. CyA decreased renal function at day 50 in both CRI and intact animals. CRI of mild to moderate degree had little effect on the biochemical and histological indices of CyA induced nephrotoxicity. CRI does appear to potentiate the metabolic toxicity that occurs after chronic treatment with high dose CyA.

The urodynamic results in 68 females with urinary retention were reviewed. There were two groups: 39 patients with neurologic causes for retention, and 29 patients in whom possible causes for retention included: psychological history (15 patients), gynecologic pathology, and urinary tract infection. Nine patients in the neurogenic group and 13 patients in the non-neurogenic group had undergone urethral dilatation with no improvement. Upper urinary tract evaluation was unremarkable. Detrusor failure was the prominent bladder pattern in both groups. In the neurogenic group, low pressure detrusor activity was also present in 10 patients, 3 of whom had sphincter dyssynergia. Flow rate, surface electromyography, and bethanechol supersensitivity test could not help differentiate neurogenic from non-neurogenic detrusor failure. The notation of abnormal bladder sensation did significantly differ between the groups, but was of limited accuracy as an indicator of neurogenic retention. Self-intermittent catheterization was the most effective treatment for both groups, with some patients voiding adequately in follow-up. Although no one test can accurately differentiate neurogenic from nonneurogenic female urinary retention, careful neurourologic evaluation will help guide us to more appropriate management.

We report on 13 patients undergoing flank incisions in whom the postoperative pain was managed with a patient-controlled analgesia device. An initial group of 7 patients was used to determine the optimal injection dose for each patient and to examine variability in narcotic requirement during the postoperative course. A progressive decrease in narcotic need was noted during the postoperative course with patient-controlled analgesia, resulting in excellent patient acceptance, no postoperative complications and no drug-seeking behavior. A second group of 10 patients was randomized prospectively to receive either patient-controlled analgesia or a standard regimen of intramuscular morphine sulfate. Based on nursing observations, an analgesia and sedation scale was developed that compared the 2 groups. Analysis of a questionnaire evaluating subjective perception of postoperative pain revealed significantly less pain, less sedation and greater activity among patients randomized to patient-controlled analgesia (95 per cent confidence limit).

A retrospective study of 412 consecutive hospital admissions of patients with collagen vascular disease yielded 63 patients who were admitted for abdominal complaints. Of these 63 patients, 11 died during their admission of primary intra-abdominal pathology or a complication thereof. A significantly higher incidence of abdominal complications occurred in black women (P less than 0.01). Peritoneal signs invariably were lacking in patients who eventually died. Radiographic documentation of small bowel obstruction or gastroduodenal ulceration in these patients was particularly ominous. Rapid radiologic evaluation and early surgical intervention including diagnostic peritoneal lavage should decrease the mortality rate for these difficult patients.

The parameters of age, height, weight, serum creatinine and 24-hour urinary creatinine production were measured in 101 consecutive spinal cord injury patients (79 men and 22 women, 43 quadriplegics and 58 paraplegics) admitted to a rehabilitation hospital. Creatinine production was significantly lower than that of age and sex-matched hospitalized controls, upon whom commonly used nomograms for evaluation of endogenous creatinine clearance are based. Therefore, these nomograms grossly overestimate the creatinine clearance in paralyzed patients, which often results in aminoglycoside overdosage. Regression analysis identified the interval since injury and age as important determinants of creatinine production. We propose 2 simple equations and nomograms that should allow more accurate prediction of creatinine clearance in spinal cord injury patients.

We performed urinary undiversion using ileocecocystoplasty in a patient who sustained bladder and ureteral necrosis secondary to transfemoral cardiac catheterization.

The role of nutritional assessment and support in patients with bladder carcinoma undergoing radical cystectomy is controversial. Morphometric, visceral protein and cell-mediated immune statuses were measured in 33 patients with bladder cancer treated by radical cystectomy. Malnourished patients had greater operative morbidity, operative mortality and days of intensive care than their nutritionally normal counterparts. Kaplan-Meier survival plots showed a tendency to early death of disease in the malnourished patients with convergence of survival rates after 36 months. Of the malnourished patients 7 had extensive nutritional support, and 6 had no parenteral and minimal enteral or oral support. Operative morbidity and mortality rates were higher in the nutritionally supported than in the unsupported groups. Nutritional support in the immediate perioperative period probably does little to alter operative complications.

After exposing urological tumor cells to anticancer agents in vitro, cellular esterase activity and the ability to exclude propidium iodide (PI) were examined as dual indicators of functionality or "viability." High esterase activity/PI exclusion was observed in assays in which anticancer agents failed to inhibit cellular proliferation, while low esterase activity/PI exclusion was often observed when proliferation had been significantly inhibited. In a number of instances, exposure to anticancer agents did produce significant inhibition of proliferation without lowering viability. In this setting, the recovery of proliferative capacity could be demonstrated with several transitional cell carcinoma cell lines, and this recovery was always associated with high esterase activity/PI exclusion. When the proliferation of primary urological tumor preparations was inhibited by drug exposure, estimates of elevated viability were obtained in 27 per cent of the determinations. Thus, viability estimates may be an indicator of the potential for tumor-cell recovery from exposure to anticancer agents. Moreover, the potential for recovery may explain differences between the results of chemosensitivity testing and actual clinical events by reconciling clinical failures with elevated viabilities indicative of this potential.

We evaluated the optimal means of prevention and treatment of urinary tract infections in 46 patients with an intermittently catheterized neurogenic bladder. Suppression with nightly 160 mg. trimethoprim and 800 mg. sulfamethoxazole compared to placebo showed no difference in the rate of symptomatic or total urinary tract infections. Symptomatic urinary tract infections occurred at the same rate whether routine asymptomatic infections were treated or not. Three-day antibiotic treatment of urinary tract infections showed no decrease in the frequency of symptomatic or total urinary tract infections compared to 10-day therapy. The frequency of post-treatment urinary tract infection persistence, relapse and cure was identical in both groups. Suppressive antibiotics, treatment of asymptomatic urinary tract infections and full course antibiotic therapy offered no advantage over placebo, treatment of symptomatic urinary tract infection only and short course therapy in the management of urinary tract infection in patients with an intermittently catheterized neurogenic bladder.

The analysis of data generated on a flow cytometer (FCM) is often performed on a computer obtained especially for dedicated use with the flow cytometer. This computer component can be expensive and also presents the FCM user with the added burden of mastering specialized programming language or of accepting the secret analytical processes of protected proprietary program routines. We believe that the evolution of more accurate and efficient FCM analyses that have the power to consider complex signal distributions can be assisted by the availability of analysis programs written in languages common to many users. DNA analysis routines written for a relatively inexpensive microcomputer (IBM PC/XT) in Basic and Pascal are described here. The routines can automatically process multiple FCM data files and can provide high-resolution graphic hardcopy. A foreground/background utilization is also described that allows the computer to be available for other uses in the laboratory.

The estrogenicity of coumestrol, a fluorescent phytoestrogen, has been examined in murine uteri. Coumestrol competed with 17 beta-[3H]estradiol for binding to cytoplasmic estrogen receptors, caused cytoplasmic estrogen receptors to associate with chromatin in the nucleus, and induced progesterone receptors. By use of size-exclusion high-performance liquid chromatography (SEHPLC), the interaction of coumestrol with estrogen receptors was examined directly by monitoring the fluorescence associated with macromolecules having properties characteristic of estrogen receptors. These analyses were made possible by the addition of dimethylformamide to the elution buffer, at a concentration (7.5%) which improved recoveries but did not interfere with estrogen receptor binding. It was possible to detect fluorescent coumestrol at approximately 0.5 nM. All determinations were performed with preparations in which estrogen receptor activity was 3-10 nM. Exposure of these preparations to coumestrol (50 nM) resulted in the elution of increased fluorescent activity in the regions where estrogen receptors eluted during SEHPLC. This fluorescent activity was reduced when diethylstilbestrol, 17 beta-estradiol, hexestrol, or tamoxifen was present as a competitor (2 microM) but was unaffected by testosterone or progesterone. Diethylstilbestrol reduced fluorescence below endogenous base lines and thereby displayed a fluorescence quench property which was not observed with other ligands. When hepatic and renal estrogen receptor preparations were used, the injected receptor activity was observed to be the major limiting factor in detecting the interaction of coumestrol with estrogen receptors. These observations are relevant to attempts to visualize estrogen receptors in tumor cells and demonstrate that accepted biochemical criteria for ligand-receptor interaction can be satisfied when fluorescent ligands are examined.

Although resection of the residual retroperitoneal mass after chemotherapy for nonseminomatous testicular cancer is standard practice, controversy exists as to the appropriate management of the residual mass after chemotherapy for advanced seminoma. A literature review suggests that 15 to 25 per cent of such masses will contain residual cancer, suggesting that retroperitoneal lymph node dissection is appropriate in these patients.

Because in vitro cell growth of transitional cell carcinoma explants and cell lines often fail to adequately proliferate in semisolid media, we have examined the effect of agents used to make media semisolid (methyl cellulose, Bacto-agar, Sea Plaque agarose and Sea Prep 15/45 agarose) on the in vitro growth of 11 transitional cell carcinoma cell lines. The growth of human transitional cell carcinoma lines was supported such that agents permissive for growth ranked as follows: Sea Plaque agarose approximately Sea Prep agarose greater than methyl cellulose greater than Bacto-agar. These observations have important implications for the in vitro study of transitional cell carcinoma cell lines and are relevant to the development of improved chemosensitivity determinations for human transitional cell carcinoma.

The specific red cell adherence test as a method to detect blood group antigen deletion in urothelial malignancy has been reported to yield approximately 40 per cent false negative results in 0 blood group patients. Our study of multiple sections of 8 normal ureters from blood group 0 patients and more than 220 specimens of transitional cell cancer taken from 48 patients reveals that the immunoperoxidase technique is more specific than the specific red cell adherence method in predicting subsequent invasion in blood group O(H) patients presenting with superficial transitional cell carcinomas (71 compared to 29 per cent) but is no more specific for tumors containing A or B antigens. However, immunoperoxidase staining does improve discernment of underlying histologic detail and, thereby, facilitates recognition of false positive antigen testing associated with squamous and adenomatous metaplasia. Areas of squamous and adenomatous metaplasia in specimens we tested were frequently antigen positive in invasive tumors. Therefore, we believe that these areas must be disregarded in determining antigen deletion in transitional cell carcinomas.

The success of cancer therapy depends on the destruction of all viable cancer cells in the primary site, as well as in metastatic areas. Surgery alone can do little for the patient whose tumor has produced distant involvement except in those situations where surgical excision, radiotherapy, chemotherapy, or immunotherapy can be relied on to eradicate metastatic disease. Because of the paucity of systemic therapy for renal cell carcinoma, an aggressive surgical approach to the primary tumor is justifiable when all metastatic lesions can be excised or otherwise definitively treated and in experimental protocols in which adjuvant therapy of possible benefit can be combined with palliative nephrectomy. There is no evidence, however, in reported studies to suggest that routine palliative nephrectomy in patients who will not be offered adjuvant systemic therapy or radiation is beneficial. Such practice is also associated with a higher incidence of complications and mortality than is expected for resection of localized renal cell carcinoma. For these reasons, it is reasonable to recommend adjunctive nephrectomy only in certain selected instances, which include (1) the control of a patient's current symptoms related to the primary disease, for example, flank pain, hematuria, fever and toxicity, anemia, erythrocytosis, and hypercalcemia; (2) nephrectomy with the excision of a solitary metastasis; and (3) the patient who is willing to undergo experimental therapy, part of which involves removal of the primary tumor.

Employing technetium labeled dimercaptosuccinic acid, we predicted the inulin and p-aminohippuric acid (PAH) clearances after recovery of an obstructed kidney before relief of the obstruction. Sixteen rabbits had one renal unit obstructed for varying period of time. The animals were scanned immediately before relief of the obstruction. After 4 to 6 months recovery, inulin and PAH clearances were measured in all animals. The scans were mathematically analyzed, and accurately predicted the inulin and PAH clearances obtained after complete recovery (P less than 0.001 and P less than 0.001, respectively). Six rabbits were scanned at the time of the clearance measurements. By a different mathematical analysis, inulin and PAH clearance measured concurrently correlated with the scan (P less than 0.001 and P less than 0.01 respectively).

We report on the use of transcutaneous electrical nerve stimulation to improve bladder emptying in a multiple sclerosis patient with a hypotonic bladder. Urodynamic testing demonstrated decreased bladder capacity, earlier first sensation and increased bladder pressure during trials of stimulation.

A prospective, randomized, double-blind trial of bladder irrigation with a 0.5% solution of epsilon aminocaproic acid (EACA) versus normal saline plus placebo was undertaken in 75 patients undergoing transurethral resection of the prostate for benign or malignant disease. Systemic absorption after irrigation with EACA was not detectable. No significant advantage, however, was demonstrated for the EACA solution over normal saline irrigation in measured postoperative blood loss, irrigant volume, hours of catheterization, or length of hospital stay.

The survival of patients with Wilms tumors has improved dramatically during the last few decades. In contrast, the bilateral form of the disease, especially when the tumors are not concurrent, is still considered by many to hold a much worse prognosis. A review of 50 cases reported during the last 20 years reveals that the survival of patients with metachronous Wilms tumors has improved in parallel with survival of patients with unilateral disease and, when matched for extent of tumor spread, survivals for the last decade are almost identical to those of bilateral synchronous disease and unilateral Wilms tumors.

Herein is reported a fifth case of malignant pheochromocytoma of the urinary bladder. Pheochromocytoma represents only 0.4 per cent of bladder tumors with 5 to 10 per cent being malignant. A review of the 4 previously reported cases plus our own suggest that iliac-hypogastric lymphadenectomy should be considered in all cases of pheochromocytoma of the bladder. Early establishment of the malignant potential of these tumors coupled with aggressive surgical treatment improves prognosis.

We recently encountered 5 patients with synergistic gangrene of the genitalia secondary to colorectal disease. This number of cases suggests that there may be an increasing incidence of this entity that has been reported only several times in the past. Pseudomonas was one of the organisms cultured in all cases. Because of the high mortality rate we advocate aggressive therapy, consisting of early and repeated radical débridement into normal tissues and appropriate management of the colorectal source of contamination. Our experience indicates that the lower gastrointestinal tract should be considered as a possible cause of infection in all cases of synergistic gangrene of the scrotum and penis.