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New advances in technology to directly target specific molecular events in the proliferation of cancer have led to promising results in renal cell carcinoma. Response rates in excess of 70% and complete responses in advanced (metastatic) renal cell carcinoma have caused a change in the paradigm of treatment from immunotherapy. Toxicities are significant, but manageable and pushing the toxicity to tolerability may increase the response rate.

Rhabdomyosarcoma is a malignant tumor well known to urologists. These tumors arise from the genitourinary system in 20% to 25% of cases, most commonly from the bladder, prostate, vagina, and paratesticular region. This is the first reported case of a rhabdomyosarcoma arising from the ureter. The radiographic findings and ureteroscopic appearance of this tumor suggested a benign fibroepithelial polyp; however, a ureteroscopic biopsy and subsequent nephroureterectomy revealed an embryonal rhabdomyosarcoma.

Objectives: To prospectively evaluate a clinical algorithm that predicts nodal status in patients with prostate cancer and to assess the impact on the outcome., Methods: Between September 1988 and December 1994, 192 patients with organ-confined prostate cancer and considered surgical candidates for radical perineal prostatectomy (RPP) were stratified using the algorithm: prostate-specific antigen (PSA) 20 ng/mL or less, Gleason score 7 or lower, and clinical Stage T2a or lower. Patients failing any of these criteria were placed in the high-risk group and underwent a pelvic lymphadenectomy. Patients who satisfied all the criteria were placed in the low-risk group and underwent RPP without evaluation of the pelvic lymph nodes. Another contemporaneous cohort of patients (n = 65) underwent pelvic lymphadenectomy and radical retropubic prostatectomy (RRP) without use of the algorithm and were used as a control group. Patients were monitored for at least 24 months., Results: In the RPP group, 177 patients were considered low risk according to the algorithm and were not offered staging lymphadenectomy before surgery, whereas 15 patients were categorized as high risk for metastasis and underwent staging lymphadenectomy. In the RRP and lymphadenectomy group, 41 patients were considered at low risk and 24 at high risk of disease spread according to the algorithm. In the RPP group, low-risk patients (no lymphadenectomy) had a PSA recurrence rate (27%) similar to that of low-risk patients in the RRP group with negative lymph nodes (29%), P = 0.8. Similarly, high-risk patients with negative lymph nodes in both groups had a similar recurrence rate (53% for RPP and 50% for RRP). Univariate logistic regression analysis showed that PSA was the most significant predictor for disease recurrence (P = 0.0004) followed by preoperative Gleason scores (P = 0.02) and clinical stages (P = 0.03). Multivariate stepwise analysis demonstrated that Gleason score and clinical stage did not add to the prediction of recurrence over PSA alone., Conclusions: Staging lymphadenectomy can be omitted in low-risk patients without deleterious effects on the outcome as measured by PSA recurrence.

Objective: To evaluate the impact of the camptothecin analogs on human TCC xenograft, both as monotherapy and in combination with cisplatin (CDDP)., Materials and Methods: Human transitional cell carcinoma (TCC) xenograft tumor line (DU4184) tested by subrenal capsule assay in 112 nude mice(NM-SRCA). CDDP and the camptothecin analogs irinotecan (CPT-11) and 9-aminocamptothecin(9-AC) were evaluated., Results: Both of the camptothecin analogs showed significant short term tumor inhibition which translated into enhanced survival. Maximal tumor inhibition (>95%) was achieved when either of the camptothecin analogs was combined with CDDP with minimal host toxicity. This translated into 400% increase in median survival. While all controls were dead 39 days following tumor implantation, none of the combination treated animals had died., Conclusion: The combination of CDDP with these camptothecin analogs is an effective therapy against this model of advanced TCC. These observations suggest potential clinical value.

Objectives: To compare four assays-the Abbott IMx, the Tosoh, the Chiron ACS PSA, and the Chiron ACS PSA2-in their ability to detect prostate-specific antigen (PSA) after radical prostatectomy., Methods: Serum samples were drawn on all men who had had a previous radical prostatectomy and who were seen in the urology clinic in March 1995. The results of each assay were compared using linear regression., Results: Twenty-two patients had an undetectable PSA by the IMx assay. The PSA was over the residual cancer detection limit (RCDL) of the Tosoh assay in 5 of these patients. The PSA was over the RCDL of the ACS PSA assay in 15 of these patients and over the RCDL of the PSA2 assay in 2 patients. There were no patients whose PSA was less than the RCDL of the ACS PSA assay who had a measurable PSA level by any of the other assays., Conclusions: There is a difference among PSA assays in their ability to detect low levels of PSA after radical prostatectomy. The ACS PSA assay is the most sensitive, and the IMx assay is the least sensitive.

Objectives: To determine the incidence of granulomatous prostatitis and acid-fast bacilli (AFB) after intravesical bacillus Calmette-Guerin (BCG) therapy for superficial bladder transitional cell carcinoma (TCC) or carcinoma in situ (CIS)., Methods: One hundred nineteen men underwent radical cystoprostatectomy for invasive bladder cancer from January 1, 1980 through December 31, 1995. Twelve patients had received intravesical BCG therapy before undergoing cystoprostatectomy. Nine men who did not receive intravesical BCG therapy before undergoing cystoprostatectomy served as controls. The surgical specimens were examined with a Ziehl-Neelsen stain for the presence of granulomatous prostatitis and for the presence of AFB., Results: Granulomatous prostatitis was identified in 9 of 12 patients (75%) who had received intravesical BCG therapy. AFB were identified in 7 of 9 patients (77%) with granulomatous prostatitis., Conclusions: Pathologic evidence of granulomatous prostatitis with AFB is a common occurrence after intravesical BCG therapy and its incidence is far greater than the reported incidence of symptomatic granulomatous prostatitis. AFB discovered during the evaluation of either an increased level of prostate-specific antigen or prostate nodule in otherwise asymptomatic men may require no specific therapy.

Background: Luteinizing hormone-releasing hormone agonists (LHRH-a) have become an established treatment for certain patients with prostate carcinoma. LHRH-a are known to decrease bone mineral density. The purpose of this study was to determine the risk of bone fracture in men receiving LHRH-a for prostate carcinoma., Methods: A retrospective chart review and phone interviews were conducted to determine the incidence of bone fractures occurring in patients receiving LHRH-a for the treatment of prostate carcinoma. Abstracted data included the number of monthly LHRH-a injections, age, clinical stage of disease, sites of metastases, and bone fracture history., Results: Twenty of the 224 patients (9%) treated with LHRH-a for prostate carcinoma between 1988 and 1995 at 3 teaching hospitals had at least 1 bone fracture during treatment with LHRH-a. The duration of treatment to the time of fracture ranged from 1 to 96 months (mean, 22.2 months). Seven fractures (32%) were osteoporotic in nature (i.e., vertebral compression fractures or hip fractures after a fall from standing), whereas 8 fractures (36%) were associated with a significant traumatic event (i.e., a motor vehicle accident, boxing, etc.) and 5 were of mixed etiology. Two of 22 fractures (9%) were pathologic., Conclusions: This study demonstrated a 9% fracture incidence in a cohort of patients receiving LHRH-a for prostate carcinoma for up to 96 months. The incidence of osteoporotic fractures was 5%.

Two open-label, multicenter studies were conducted to evaluate the efficacy and safety of a long-acting depot formulation of leuprolide acetate (22.5 mg) administered intramuscularly every 12 weeks to patients with stage D2 prostate cancer. Clinical evaluations were performed every 12 weeks, and serum testosterone levels were monitored biweekly or weekly for 24 weeks. Onset of castrate levels (< or = 50 ng/dL) of testosterone was achieved within 30 days of the initial depot injection in 87 (95%) of the 92 assessable patients enrolled in the two studies. Mean testosterone levels remained well within the castrate range throughout each dosing interval. Two patients experienced a transient escape (testosterone levels > 50 ng/dL on two consecutive determinations). Delay of an injection of up to 2 weeks did not have an effect on testosterone suppression: in 16 patients in whom the depot injection was delayed by 3 to 14 days, testosterone values remained within the castrate range. A favorable objective tumor response (no progression) to treatment occurred in 85% of the patients. Prostate-specific antigen and prostatic acid phosphatase decreased by 50% or more in 96% and 84% of patients, respectively, with elevated pretreatment values and at least one treatment value. Assessment of local disease status and overall performance status showed improvement or stability in most patients. The most common adverse events were hot flashes (59%), pain (27%), and testicular atrophy (21%). The 22.5-mg depot formulation of leuprolide, which acts in a manner similar to the monthly 7.5-mg depot formulation, was shown to be effective and safe in treating patients with advanced prostate cancer.

Objectives: Bropirimine is an orally administered immunostimulant that has been shown to have activity against carcinoma in situ (CIS) of the bladder. To further assess this potential activity, bropirimine was administered to 42 patients for bladder CIS in a Phase II trial., Methods: Patients were treated with bropirimine 3.0 g/day by mouth for 3 consecutive days each week up to 1 year. Cystoscopy with biopsies and bladder wash cytology were performed quarterly., Results: Twenty (61%) of 33 evaluable patients converted malignant biopsies and bladder wash cytology to negative, including 6 (50%) of 12 who failed prior bacillus Calmette-Guérin (BCG) immunotherapy, 14 (67%) of 21 who had not received prior BCG therapy, and 12 (80%) of 15 with primary CIS. Median response duration exceeds 21 months. Four of the 20 responders did have a papillary tumor recurrence at 3 to 15 months, all Stage Ta or T1. Mild toxicity (grade I or II) suggestive to interferon induction or administration occurred in one third of patients. Headache, transient hepatic enzyme elevations, skin rash, and arthralgias each occurred in 5% to 14% of the patients, with nausea or emesis in 21%. Grade 1 tachycardia/palpitations or chest pain each were noted in 5%., Conclusions: Oral bropirimine can induce remission of bladder CIS with acceptable toxicity at 3.0 g/day. Bropirimine may be a valuable alternative to cystectomy for some failures of BCG therapy and may have the potential to replace BCG as front-line therapy because of its ease of administration.

The objective of this article is to determine the relationship between microvascular invasion and seminal vesicle invasion in prostatic adenocarcinoma. Radical prostatectomies with seminal vesicle involvement were examined histologically and immunohistochemically with antibodies directed against S-100 protein and factor VIII. Microvascular invasion of the seminal vesicles showed a positive correlation with microvascular and capsular invasion of the prostate (P = 0.006 and 0.048, respectively) and lymph node metastases. Tumor progression was found in 8 of 14 (57%) patients with microvascular invasion of the seminal vesicles, compared with 3 of 22 (14%) without microvascular invasion (P = 0.001). Microvascular invasion of the seminal vesicles is predictive of tumor progression and lymph node metastases in prostatic adenocarcinoma.

Polymerase chain reaction (PCR) was used to analyze a rarely deleted region of mitochondrial DNA (mtDNA) from 39 human renal cell carcinomas (RCC) and matched normal kidney tissue removed during radical nephrectomy. One tumor specimen (E.R.) had a unique PCR product approximately 250 base pairs (bp) smaller than the PCR product found in the normal E.R. kidney. Sequence analysis of the tumor-specific PCR fragment revealed a 264 bp deletion in the first subunit (NDI) of NADH:ubiquinone oxidoreductase (complex I) of the electron transport chain. Southern analysis of the RCCs demonstrated that approximately 50% of the mtDNA molecules in the primary RCC contained a unique 3.2 kb EcoRV restriction fragment found only in E.R. tumor mtDNA. Northern analysis demonstrated preferential transcription of the truncated NDI mRNA. None of the five metastases or any normal tissue from E.R. contained levels of the NDI deletion detectable by PCR. This is the first reported case of an intragenic NDI mtDNA deletion.

Recently mouse models have shown that expression of costimulatory molecules such as B7-1 on tumor cells can induce tumor-specific immunity, suggesting that tumor cells modified to express costimulatory molecules can be a potential tumor vaccine. To investigate the importance of B7-1 co-stimulation in induction of autologous tumor immunity in humans, we established a renal carcinoma cell line, RCC-1, from a tumor resection and studied the patient's antitumor immune responses in vitro. The RCC-1 cell line constitutively expressed major histocompatibility complex (MHC) class I, intercellular adhesion molecule (ICAM)-1, and leukocyte function-associated antigen (LFA)-3 molecules, and MHC class II molecules were induced by interferon-gamma (IFN-gamma) treatment in vitro. However, neither RCC-1- nor IFN-gamma-treated RCC-1 cells expressed B7-1, and both failed to induce T-cell proliferative responses in mixed lymphocyte and tumor cell reaction (MLTR) assays, suggesting that the costimulatory signals provided by cell adhesion molecules such as ICAM-1 and LFA-3 were not sufficient to elicit an antitumor immune response. However, on transfection of the human B7-1 into RCC-1, these cells were able to induce a significant T-cell proliferation in MLTR assays. This T-cell response could be blocked by anti-B7 mAb treatment of the tumor cells. RCC-1B7 cells also induced the generation of tumor-specific cytolytic T lymphocytes to the parent RCC-1 cells in vitro, with little nonspecific cytolysis of an unrelated RCC line, A498, or autologous phytohemagglutinin (PHA) blasts. This specific cytotoxicity could be abrogated by anti-CD8 mAb and complement treatment. In summary, our study indicates that B7-1-CD28 interaction plays a critical role in induction of autologous tumor-specific cytotoxic T lymphocytes (CTLs) in humans, suggesting that the costimulatory molecule transfected tumor cells could be useful in expanding tumor-specific autologous CTL in vitro for adoptive tumor immunotherapy.

Objectives: Prostate-specific antigen (PSA) has become the most useful serum tumor marker in the diagnosis and screening of prostate adenocarcinoma. The currently cited reference range of normal (0 to 4.0 ng/mL monoclonal) lacks both the sensitivity and specificity to be universally accepted as a screening test, and alternatives to serum PSA have been proposed, such as PSA density, PSA velocity, and age-adjusted PSA. Age-adjusted PSA takes into account the facts that as men grow older the prostate enlarges and that screening should have maximum sensitivity in younger men and maximum specificity in older men., Methods: A population of 4,710 men with no known history of prostate adenocarcinoma underwent 5,629 examinations by transrectal ultrasound of the prostate (TRUS) from 1987 to 1994. This population consists of Mobile Urology Group, Mobile, Alabama, and Emory University, Atlanta, Georgia, patient databases. We have examined our data to determine the sensitivity, specificity, and positive predictive values for normal range PSA (0 to 4 ng/mL) versus age-specific PSA values., Results: A total of 2040 patients had an abnormal digital rectal examination (DRE) and 3581 procedures were performed for an elevated PSA and a normal DRE. Biopsies were performed in 2,657 patients with 945 (35.6%) positive for cancer. Criteria for biopsy included elevated PSA (more than 4 mg/mL), PSA density more than 0.15 abnormal DRE, or suspicious TRUS. Patients were grouped according to decade: group 1 (ages 40 to 49 years, n = 183), group 2 (ages 50 to 59 years, n = 1018), group 3 (ages 60 to 69 years, n = 2358), and group 4 (ages 70 to 79 years, n = 1687)., Conclusions: Use of the age-specific range for PSA increases the sensitivity in younger men more likely to benefit from treatment, and decreases the biopsy rate in older patients who may not be candidates for aggressive treatment. Age-adjusted PSA is the most valuable for patients over the age of 70 years of whom 22% would be spared TRUS with biopsy.

Conservative renal surgery is a viable alternative for patients in whom preservation of renal function is important. The long-term survival is similar to that of radical nephrectomy, especially in low-grade malignancies. The technique is unproven in patients with a normally functioning contralateral renal unit, although it may be an option in small, peripheral, low-grade lesions.

Objectives: To examine the effects of intravesical suramin on N-methyl-N-nitrosurea (MNU)-induced bladder tumors in Fischer 344 rats., Methods: Multiple cohorts of female rats received four biweekly intravesical instillations of MNU. A control group received no other treatment, the experimental group received 25 mg/kg intravesical suramin twice a week beginning at week 6., Results: After 18 weeks from the first instillation of MNU, 60% to 65% of control animals developed papillary transitional cell carcinoma, compared with only 0% to 10% of the suramin-treated animals (P = 0.01 to P = 0.0007). There was no local or systemic toxicity observed., Conclusions: Intravesical suramin is an effective chemopreventative therapy for transitional cell carcinoma in vivo with minimal toxicity.

Objectives: The goal of this research was to assess whether methoxypsoralen compounds in combination with ultraviolet light were effective in preventing cellular proliferation in an in vitro model of human transitional cell carcinoma., Methods: Three methoxypsoralen compounds, 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP), and 4'-aminomethyl 4,5'-8'-trimethylpsoralen (AMT), were added in vitro to T-24 transitional cell carcinoma cells. Psoralens directly bind to DNA, cross-linking the strands when exposed to ultraviolet light and thereby prevent cellular division., Results: In vitro activity was demonstrated utilizing AMT and ultraviolet radiation at 320 to 340 nm, preventing cellular proliferation in T-24 transitional cell carcinoma., Conclusions: Methoxypsoralen compounds in combination with ultraviolet light are effective in preventing proliferation of bladder carcinoma cells in vitro. This therapy may prove to be effective in clinical early stage transitional cell carcinoma and warrants further assessment.

Objective: This study evaluates the accuracy of comparing serum prostate-specific (PSA) levels in the range between 4.1 ng/mL and 10.0 ng/mL (monoclonal) to the volume of the transition zone (TZ) of the prostate and total gland volume as a predictor of a positive biopsy., Methods: Using sonographic voluming of the entire prostate and of the TZ, prostate-specific antigen density (PSAD) and prostate-specific antigen density of the TZ (PSAT) were calculated in 21 biopsy-positive patients and 38 biopsy-negative patients. Biopsy was directed at sonographically suspicious areas and did not include sextant biopsies., Results: A statistically significant association was determined between a positive biopsy and gland volume, TZ volume, and PSAT. The association of a positive biopsy with PSA and PSAD was not statistically significant., Conclusions: PSAT is more accurate in predicting a positive biopsy than is PSAD for PSA levels between 4.1 ng/mL and 10.0 ng/mL.

Two monoclonal antibodies, TuMark-BTA and MGH-1, were evaluated in patients with benign pathology, history of transitional cell carcinoma with no active disease and active transitional cell carcinoma. Both antibodies were accurate in predicting carcinoma in approximately two-thirds of patients. TuMark showed a 74% sensitivity and 50% specificity, while MGH-1 was more sensitive (86%) and less specific (38%). Positive predictive values for TuMark and MGH-1 were 79% and 78%, respectively.

Current staging of early prostate cancer separates patients into two groups: those with palpable and non-palpable tumors. Such staging relies on digital rectal examination in making this separation, despite the low sensitivity, low specificity, and low positive predictive value of this method. As an alternative, tumor volume may be useful for staging because of its powerful prognostic ability and its potential to be assessed clinically due to recent advances in imaging techniques such as transrectal ultrasound. In this study, we evaluate the utility of tumor volume in predicting progression of early prostate cancer based on the composite published evidence from nine pathologic studies of serially-sectioned prostates. Logistic regression revealed that tumor volume was a good positive predictor of all measures of tumor progression. There was a 10 percent probability of capsular invasion in tumors measuring about 0.5 cm3; 10 percent probability of seminal vesicle invasion in tumors measuring about 4.0 cm3; and 10 percent probability of metastases in tumors measuring about 5.0 cm3. These composite results suggest that tumor volume is a significant predictor of cancer progression. A volume-based prognostic index is proposed as an adjunct to staging for early prostate cancer.

Immunobiology techniques that once were the domain of research are increasingly being applied in the clinic. Transitional epithelium of the bladder undergoes some recognized immunologic changes as it becomes malignant, and their detection may have prognostic value. Examples of such changes are deletion of the ABO(H) blood group antigens, inappropriate expression of Lewis antigens, loss of beta-2 microglobulin and the MHC class 1 heavy chain, and alterations in the production of cellular adhesion molecules and integrins. Other possibly useful markers are ras oncogene products, Thomsen-Friedenreich antigen, epidermal growth factor receptor, and perhaps antigens unique to transitional-cell carcinoma.

Staging of prostatic adenocarcinoma is a systematic classification of the extent of disease based on clinical and pathologic criteria. This classification determines treatment and reflects ultimate expected clinical outcome. The technologic changes in diagnostic modalities need to be incorporated into the staging classification and a better assessment of biologic hazard of each individual tumor needs to be developed to further refine current treatment of prostate cancer.

Renal cell carcinoma extends into the lumen of the inferior vena cava in approximately 4% of patients at the time of diagnosis. Surgical removal of the intracaval tumor thrombus with radical nephrectomy is the preferred treatment for this malignancy. From January 1977 to June 1990, 31 such patients were examined for combined problems of renal carcinoma and intracaval tumor extension. Twenty-six of these patients underwent radical nephrectomy and vena caval thrombectomy. Ten patients had tumor thrombus confined to the infrahepatic vena cava, 11 had retrohepatic caval involvement, and 5 had extension to the level of the diaphragm or into the right atrium. Surgical approach was dictated by the level of caval involvement. Control of the suprahepatic vena cava plus temporary occlusion of hepatic arterial and portal venous inflow were necessary in some cases; cardiopulmonary bypass was required for transatrial removal of more extensive tumors. Five of the 26 patients had evidence before operation of distant metastatic disease; none of these survived beyond 12 months. The 5-year actuarial survival rate of the 21 patients without known preoperative metastatic disease was 57%. Complete surgical excision of all gross tumor appears to be critical for long-term survival in these patients.

The response of patients with superficial transitional cell carcinoma of the bladder (STCB) to intravesical chemotherapy is variable; some patients enjoy a long period without recurrence, whereas others have recurrence of tumor within 2 years of removal of the primary lesion. Previously, others have demonstrated that the loss of normal cell surface antigens, such as ABO(H) blood group antigens or beta-2 microglobulin (B2M) has been correlated with more aggressive behavior by tumor. In this study, using immunohistochemical techniques, the authors evaluated the initial pretreatment biopsy specimen of bladder tumors for the presence of ABO(H) antigens and B2M. Data from this sample patient population, all with biopsy-proven STCB, indicate that expression of these two markers is predictive of a therapeutic response to prophylactic intravesical bacillus Calmette-Guerin (BCG) (Tice strain) after resection, and that expression of the two markers is of greater predictive value than expression of either antigen alone.

Ten patients were studied before and after autologous adrenal medullary transplantation to the central nervous system for Parkinson's disease to determine if the presence of new catecholamine-producing tissue near the hypothalamus would alter hypothalamic or pituitary function, mineralocorticoid levels, or catecholamine production. No clinically apparent ill effects occurred. Changes in endocrine function were largely short-term and transient: at 7-10 days after surgery, urinary catecholamine levels were significantly increased, PRL levels were significantly elevated despite markedly increased serum dopamine levels, and gonadal steroid levels (estradiol and testosterone) were significantly lower despite unchanged basal and stimulated levels of gonadotropins. Dehydroepiandrosterone sulfate was significantly reduced at 7-10 days after surgery and remained low at 3-6 months. Other changes at 3-6 months after surgery included increased stimulated corticotropin levels and reduced serum aldosterone response to upright posture. The changes at 7-10 days were probably due to stress or unilateral adrenalectomy or both; the changes at 3-6 months were likely due to unilateral adrenalectomy. We conclude that unilateral adrenalectomy and autologous adrenal medullary transplantation to the central nervous system does not produce clinically important changes in endocrine function; however, possible adverse consequences of long-term reduction of dehydroepiandrosterone sulfate levels cannot be excluded.

In patients with renal insufficiency, solitary kidney, or bilateral renal malignancies, conservative surgery for renal cell carcinoma has been suggested. The authors treated 17 such patients with either enucleation of tumor or partial nephrectomy. Overall survival from disease in this series was 58.8%. Seventy percent of patients undergoing enucleation and 42.9% undergoing partial nephrectomy survived with a mean follow-up period of 5 years. Survival or local recurrence rate after enucleative surgery is an effective treatment of renal carcinoma in selected patients, and despite concerns about tumor invasion of the pseudocapsule, the clinical data do not indicate any difference in survival. There was no significant difference between enucleation of tumor and partial nephrectomy regarding morbidity, mortality, or recurrence rate.

The use of aminoglycosides in urology is limited primarily either to preoperative prophylaxis or to acutely ill patients. Frequently in this latter group, there is little margin for error, and the appropriate drug(s) must be given at the outset. In addition to receiving antibiotics, patients in distress should be resuscitated with fluids, evaluated to determine the cause of their sepsis, and promptly and definitively treated. It is important early in the course of therapy to drain the site of obstruction or abscess, remove foreign bodies, or debride necrotic areas if medical measures are to be successful. The rationale for selection of an aminoglycoside and treatment in these patients is discussed, using six case studies as illustrations.

Fifty-eight percutaneous needle biopsies of adrenal masses were performed in 53 patients. The technique was initially successful in 44 (83%) of 53 patients. Five patients had second procedures because of initial failure or the possibility of sampling error. Fourteen biopsies were performed in nononcologic patients and 39 in patients with a known malignancy. None of the adrenal masses in nononcologic patients were malignant. Only 18 (46.1%) of the 39 masses in oncologic patients were metastases; the rest represented a variety of nonneoplastic conditions. Seven minor complications occurred in six patients. Two of these patients required transfusions for hypotension or decreases in hematocrit. No correlation was noted between needle size and complications. There were no pneumothoraces. The procedure is an accurate and safe alternative to surgical biopsy.

The T cell hybridoma FS7-20, produced by the fusion of normal B10.BR T cells to the AKR thymoma BW5147, was found when stimulated with concanavalin A (Con A) to produce the lymphokines: interleukin 2 (IL 2), interferon-gamma (IFN gamma), macrophage-activating factor (MAF), Ia induction factor IaIF), and the B cell helper factor interleukin X (IL X). The clones and subclones of FS7-20 varied dramatically in their ability to produce these lymphokines, presumably because of karyotypic variations. The ability to produce IL 2 segregated independently from the ability to produce the four other lymphokine activities; however, production of the latter activities showed a strong correlation. This coordinate production of IFN gamma, MAF, IaIF, and IL X was also observed with a cloned normal cytotoxic T cell line, cr15. These results suggest either that IFN gamma, MAF, IaIF, and IL X are all manifestations of a single molecular species or that, although these activities are different structurally, their production is controlled by a common genetic mechanism. In support of the first possibility, the IFN gamma, MAF, IaIF, and IL X activity produced by FS7-20 were all found to be equally sensitive to inactivation at pH 2. These results illustrate the usefulness of using T cell hybridomas for the study of lymphokines.

Patients with incontinence after prostatectomy were examined for long-term results following implantation of a Kaufman prosthesis. These appears to be a dichotomy between patients who underwent implantations of the device after radical procedures versus those who had been operated upon for benign disease. Patients undergoing implantation of the prosthesis after an operation for malignant disease experienced a higher rate of complications and a lower over-all continence rate. Also, patients who underwent implantation of the Kaufman prosthesis in conjunction with the Small-Carrion prosthesis showed a 100 per cent failure rate. It appears from the data that the Kaufman prosthesis is not the long sought panacea.

Cystitis cystica was studied with the aid of electron and immunofluorescence microscopy. By electron microscopy, the epithelium demonstrated morphologic features suggestive of an active metabolism. Secretory-type granules were seen in the cytoplasm just beneath the luminal membrane of surface columnar cells. Microvilli of the plasma membrane also were seen at the luminal surface. Rough endoplasmic reticulum and Golgi apparatuses were present. The cells were rich in mitochondria. By immunofluorescence microscopy, IgA, secretory piece and IgM were localized in the epithelial cells, especially at the luminal surfaces. IgG was occasionally found. These findings contrast markedly with the transitional cells and their relatively scanty content of secretory-type organelles. In addition, they may explain the large amounts of IgA in the urine of patients with cystitis cystica.

Numerous neoplasms, including colonic, lung, stomach, and prostate, have been found to have increased concentrations of lipid-associated sialic acid (LASA). CA 19-9 is a carbohydrate antigen found on the membrane surface of pancreatic, gastric, and colonic cancers. A prospective study involving 25 patients (15 males, 10 females) with renal cell carcinoma (RCC) was undertaken to examine the clinical value of these two markers. Patients' ages ranged from twenty-five to seventy-seven years (mean 56 years). The group consisted of 9 Stage I, 1 Stage II, 5 Stage III, and 10 Stage IV patients. Twenty three of the 25 had known disease present when tested. Eleven patients with no known tumor were used as an age-matched control group. Sixteen of the 23 patients with known disease (70%) had elevated LASA values. Nine of the 11 control patients (82%) had normal LASA values. Three of 7 patients with values obtained pre- and post-nephrectomy showed levels returned to normal after nephrectomy; 3 had persistent LASA elevation and were found to have either metastatic or recurrent disease, and 1 had a persistent elevation of his LASA value without known metastatic or recurrent disease. When the 23 patients with known disease were compared according to stage, 62 percent of Stages I and II, 80 percent of Stage III, and 70 percent of Stage IV had elevated LASA values. There was no statistically significant difference between LASA values and tumor stage. CA 19-9 values obtained in 15 of 25 patients with RCC were within normal range.

The transformation of a normal cell through dysplasia to the malignant state usually is associated with changes at the molecular level within the nucleus, cytoplasm and cell surface. These changes can be monitored by the loss of normal cell surface antigens, such as the blood group antigen ABO(H) and major histocompatibility complex antigens, which in the human correlate with the histocompatibility locus antigens. A group of patients with bladder biopsy and diagnosis ranging from normal through severe dysplasia to papillary transitional cell carcinoma, invasive transitional cell carcinoma and carcinoma in situ were evaluated for the presence or absence of beta-2-microglobulin. This 11,000 molecular weight protein was used as an indirect marker for the major histocompatibility complex antigens on the cell surface. With immunoperoxidase as a marker, the presence of beta-2-microglobulin was seen in all patients with normal epithelium as well as benign disease. However, with progression through dysplasia to carcinoma there was progressive deletion of the beta-2-microglobulin. Carcinoma in situ exhibited minimal expression of the beta-2-microglobulin. The use of beta-2-microglobulin as a marker for major histocompatibility complex antigens on the cell surface may prove to be useful for monitoring transitional cell carcinoma.

Homozygous nude (nu/nu) mice were inoculated ip with either highly malignant human bladder transitional cell carcinoma or human prostate adenocarcinoma. These animals were subsequently given injections of normal human T-lymphocytes to restore the known T-lymphocyte deficiency present in homozygous nude mice. Metastatic spread of the prostate and bladder carcinomas was evident in mice given human T-lymphocytes. Although tumor growth was observed at the sites of tumor inoculation, no tumor spread was observed in mice not receiving T-lymphocytes.

Metastatic renal cell carcinoma remains a frustrating disease to treat. Although there is significant evidence that this tumor is responsive to alterations in the immune system, a complete understanding of the antitumor immune response is still elusive. The early trials have been aimed primarily at nonspecific methods for stimulation of the immune system, with the equal possibility that aside from stimulation of the effector cells responsible for tumor containment, there may be stimulation of other mechanisms that will inhibit this response. The better responses in some cases appear to be in the treatments that produce the most toxicities, though even these treatments only have a 20% to 30% response in most trials. Although the prior trials of immunotherapy have yielded modest results, they have provided a better understanding of the immune system in the oncologic setting. Newer trials are now being directed at combinations of lymphokines, which is the beginning of the application of basic science in the clinical setting. With a better appreciation of the basic science behind the immune response, the current factors available will be put into better therapeutic perspective, and newer factors, including various growth factors, may play an important role in future therapy. Also, the addition of antisuppressor regimens to stimulation trials is a sign of recognition of the complexity of the immune response. Aside from suppressor cells, investigators are beginning to realize that there are circulating proteins probably generated either by the tumor or in response to the tumor that are immunosuppressive (eg, circulating IL-2 receptors). Inhibition of these proteins by pheresis or other methods may provide increased immunoreactivity to the tumors, as has already been shown in a small series. Monoclonal antibodies offer the promise of the most specificity; however, the technology is still far from making this therapy imminently available. Only through additional laboratory and clinical investigation, will significant advances be made.

Bilateral renal cell carcinoma, malignant tumors of a solitary kidney or renal carcinoma in the presence of a contralateral kidney with compromised function may be treated by simple enucleation of the tumor, usually pseudoencapsulated, permitting relatively avascular removal. We treated 5 such patients by surgical enucleation of renal cell carcinoma who have survived for intervals of 9 months to 5 years without evidence of recurrent local or metastic disease. The simplicity of the technique offers several advantages, primarily those of applicability to lesions of any portion of the kidney and the minimal disturbance of renal hemodynamics and renal function.

In an attempt to prevent ejaculatory dysfunction associated with retroperitoneal lymphadenectomy, the dissection has been modified to stay above the inferior mesenteric artery. Using this approach, there has been no adverse impact on survival (at least 18 months follow-up) in 18 patients with nonseminomatous germ cell tumors.