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Systemic therapies for prostate cancer are likely to improve, and as they do, they will have enormous impact on the treatment of high-risk and locally advanced cancers. Further technical improvements in radiotherapy and alternative local modalities, such as cryoablation, are also likely, and will bring even more options for local control. It is certain these guidelines will continue to evolve.

Cryosurgery for the treatment of prostatic disease, a technique that originated in the mid-1960s and was almost abandoned in the mid-1970s, has re-emerged in the 1990s for the treatment of cancer of the prostate. This renewed interest is due to several factors, including the development of intraoperative ultrasound, the refinement of percutaneous access techniques, and improvements in cryosurgical apparatus. The modern technique features the transperineal percutaneous placement of several (generally five or six) metal probes, each 3 mm in diameter, in the prostate under ultrasound guidance. After insertion, the probes are cooled in a manner that produces complete freezing of the prostate and, if required, extraprostatic extensions of disease. The freezing process is monitored by ultrasound, which provides an image of the boundary of freezing as it advances through the prostate and thereby provides control of the extent of freezing. This review describes the historical background of prostatic cryosurgery and the current status of this new procedure, including the important issues of case selection, technique, and results. The recent nature of this experience precludes judgment of long-term merit, but the favorable short-term results of cryosurgical ablation of the prostate encourage further selective use of this technique in the treatment of prostate cancer. Definition of appropriate patient selection and optimal technique are needed to improve treatment by cryosurgery.

Subtle cytologic and histologic nuances have a major impact on diagnosis and, consequently, on therapy for superficial bladder cancer. Therefore, the urologist and the pathologist must carefully assess all clinical findings before a course of treatment can be determined. The urologist must advise the pathologist of all the circumstances surrounding a biopsy--whether its purpose is for preliminary clinical impression or diagnosis, the patient's recent treatment history, the availability of previous biopsy specimens for comparison, a thorough history of treatments that may induce characteristic cytologic changes that might lead to misdiagnosis, and alternate diagnostic possibilities drawn from initial pathology and treatment history. Armed with this information, the task of the pathologist is to provide as much data as possible regarding tumor histopathology from the biopsy specimens. Thus, establishment of a close working relationship between the urologist and the pathologist is an important tool for (1) initially characterizing superficial bladder cancer, which is essential in determining an appropriate course of treatment, and (2) accurately evaluating follow-up biopsies to determine the effectiveness of that treatment.

The decision to treat superficial bladder cancer with intravesical therapy should be predicated primarily on disease stage and grade as well as the patient's clinical history. Once the decision to proceed with intravesical therapy has been made, the clinician must select the appropriate agent. Several agents are available and the choice of which agent to use should be based on careful consideration of the potential benefit of a given drug versus its inherent risk of complications. The first drug to be administered intravesically, thiotepa is an alkylating agent used as first-line treatment for low-grade lesions; it has limited use against higher-grade tumors or carcinoma in situ. In addition, the low molecular weight of thiotepa results in significant systemic absorption, which often results in myelosuppression. Mitomycin, also an alkylating agent, has shown significant activity as both first-line therapy and in patients with recurrent disease. Unlike thiotepa, mitomycin has a relatively high molecular weight, and the incidence of significant bladder absorption and systemic side effects is low. Doxorubicin, which also possesses a high molecular weight, is used intravesically against superficial bladder cancer more frequently in Europe and Japan than in the United States. Immunotherapy with bacille Calmette-Guérin is the treatment of choice for carcinoma in situ and high-grade T1 lesions. It is associated with the highest incidence of both minor and major adverse reactions, however, and its use should be tempered by its potential toxicity.

Primary renal sarcoma represents approximately 1 per cent of all primary tumors of the kidney. The purpose of this study is to review the experience at Roswell Park Cancer Institute with the treatment of primary renal sarcoma. Four patients with a diagnosis of primary renal sarcoma admitted from 1976 to 1983 form the basis of this review. All patients underwent radical nephrectomy. The tumor was localized in two patients, and locally invasive in two patients. All patients had recurrence of metastatic disease. Patients with localized disease recurred at 19.0 and 25.0 months respectively. Patients with invasive disease recurred at 4.0 and 5.0 months respectively. Patients presenting with localized disease survived a mean of 34.0 months. Patients presenting with invasive disease died at 6.0 and 10.0 months from time of diagnosis. Primary renal sarcoma is a rare entity. Only patients presenting with localized disease have a reasonable chance for prolonged survival.

The in vitro cytotoxic activity of splenocytes from C3H/He mice implanted subcutaneously with 10(6) syngeneic MBT-2 tumor cells on day 0 was significantly enhanced after cyclophosphamide (100 mg./kg., intraperitoneally) given 2 days before tumor resection on day 17, with or without active specific immunization with BCG plus autologous irradiated tumor cells (vaccine) 1 week after tumor resection. Furthermore, a significantly lower tumor incidence was seen in mice challenged with 10(5), but not 10(6), tumor cells per mouse 24 hours after tumor resection on day 17 and treated with cyclophosphamide on day 15 and postoperatively with vaccine than was found in nontreated tumor resected mice. Phenotypic analysis of cells from spleen showed that cyclophosphamide pretreatment and postoperative vaccine, either singly or in combination, induced a significant increase of both CD44+ memory T cells and CD11b+ myeloid/macrophage cells. Thus, in addition to a specific antitumor immune response, a nonspecific cytolytic mechanism may also play a role in the observed antitumor effect.

Problem: Fifty-three patients (30 men, 23 women) with histologically proven adrenal carcinoma were reviewed. Nineteen (36%) had endocrine manifestations from functioning tumors. Arteriography was positive in 95% (19/20), CT scan in 94% (17/18), and ultrasound in 92% (12/13). Seventy-six percent of the patients, at the time of diagnosis, were stage III and IV. Most common metastatic sites were the liver, lymph nodes, bone, and lungs. Local recurrence developed in 39% of cases (15/38)., Method: Forty-one patients underwent an operation. Complete surgical removal of all gross tumor was achieved in 24 patients., Result: The overall median survival time was 8 months, and the estimated 5-year survival rate 19%. There were significant differences in survival between the various stages (P = 0.01) and between the group of patients who underwent complete excision of the tumor and those with incomplete resection (P = 0.002)., Conclusions: Complete surgical excision offers the best prospect for long-term survival in localized adrenal carcinoma.

The aim of the present study was to ascertain whether fluorescence in situ hybridization (FISH) of urine could be a useful approach in bladder cancer. Herein, we present the cytogenetic and FISH findings in patients with and without bladder cancer. The samples examined with FISH consisted of urine, bladder washings, and tumor tissue, when available. The results obtained show that the FISH technique, particularly when used on urine, is a very useful tool in the diagnosis, early detection, and management of bladder cancer.

Clinical and pathologic data of 36 patients with transitional cell carcinoma of the bladder were investigated to determine the significance on patient survival of these factors: pathologic grade and stage; the immunohistochemistry of eight cell and tumor markers; nuclear DNA flow cytometric parameters; and patient smoking status. The bivariate and multivariate statistical analysis significantly correlated patient survival rates with the immunohistochemical expression of blood group, isoantigens A (P less than 0.05), O(H) (P = 0.001), the oncogene-related protein ORP-p21 (P less than 0.05), the pathologic grade and stage (P = 0.002), and the tumor DNA ploidy (P less than 0.05). Smoking status correlated aneuploidy (P less than 0.05) and tumor expression of ORP-p21 (P less than 0.05) with the patient survival rate. Despite the relatively small number of patients in this study, the results suggest that the clinicopathologic variables are significant factors in survival of bladder cancer.

A model system for 3-dimensional "native-state" culture of tissues on collagen gels (Proc. Natl. Acad. Sci. USA 86:2013-2017; 1989) has been applied in this study to histologically normal human renal cortical tissue from 11 patients undergoing nephrectomy for renal cell carcinoma elsewhere in the kidney. Microbial contamination occurred in 12/90 cultures, the rest (78) were studied by visual inspection, histology, immunohistochemical analysis for pankeratin (epithelial cell origin), vimentin (mesenchymal cell origin), and p-glycoprotein (associated with proximal tubules), transmission electron microscopy (EM), incorporation of tritiated thymidine (3HTdR). In the first 10 days, explants showed 3HTdR-labeled cells in tubule structures. The surrounding gel was invaded by cells forming tubule structures, sometimes with basement membrane. Some of these cells showed labeling by 3HTdR and immunostaining positive for pankeratin and p-glycoprotein. EM showed well-polarized epithelial cells in tubule structures with tight junctions, interdigitating lateral processes, and microvilli characteristic of proximal and distal convoluted tubules. 3HTdR-labeled cells in tubule structures were observed even 2 mo. after Passage 1, 6 mo. after the initial explantation. Tubule growth was most active and fibroblast proliferation was negligible from 2 to 4 wk postexplantation. The proliferation of tubulelike cells and formation of tubulelike structures in this system represents an opportunity to study human renal cortical tissue in vitro, under conditions more closely resembling in vivo circumstances than are present in other in vitro systems suitable for long-term study. This model has potential use for in vitro toxicology studies and studies of renal physiology.

When present at diagnosis or when developing in the course of disease, the presence of bone metastases from prostate cancer is generally considered an indication to begin endocrine therapy, as this is clearly the most effective form of treatment for this problem. Endocrine therapy can stop progression of prostate cancer in 80-85% of cases. Endocrine therapy can relieve pain, prevent pathologic fractures, and prevent neurologic complications from bone metastases from prostate cancer. Rarely, bone scans may become normal after the start of endocrine therapy, but partial improvement or stabilization of bone scans are more commonly seen. While endocrine therapy has been the first line of treatment of metastatic prostate cancer for the past 50 years, the recent development of newer forms of endocrine therapy have increased the options in the past few years. In addition to orchiectomy and estrogens, newer alternatives include inhibitors of androgen synthesis, the class of agents termed "antiandrogens", and luteinizing hormone releasing-hormone (LHRH) analogues either alone or in combination. Orchiectomy causes a prompt fall in serum testosterone and is regarded by many as the "standard" form of endocrine therapy, but there is concern about the psychologic impact of surgery. Estrogens are being used less frequently today because of their real or potential side-effects, including cardiovascular and thromboembolic complications. The development of analogues of LHRH has resulted in another major choice for endocrine therapy, and one which is therapeutically equivalent to orchiectomy or estrogens. Since LHRH analogues may cause an early rise or "flare" in serum testosterone before it drops to castrate level, these agents should not be given alone to patients with severe pain or neurologic problems. The newly available antiandrogen flutamide can block the "flare", and may also improve survival when used with LHRH analogues or orchiectomy, especially when disease is less advanced. Not all studies of "combination therapy" support this conclusion. However, the use of flutamide is increasing significantly in the United States. Both the LHRH analogues and flutamide are fairly safe, but they are very expensive. Their use, in combination, is likely to become a progressively more common form of initial endocrine therapy in the future. The growing application of prostate specific antigen (PSA) as a tumor marker for prostate cancer has made the difficulty in interpreting changes in bone scans a much less critical problem in determining response to endocrine or other forms of therapy for advanced prostate cancer.

Although lymphocyst (retroperitoneal lymphocele) is not an uncommon complication after retroperitoneal surgery, with a reported incidence ranging from 0.6% to 48%, the occurrence of chylous ascites is a rare phenomenon. Most reports are anecdotal, and hospital records list the incidence of diagnosis as 0.001% of admissions. Diagnosis of chylous ascites is usually not difficult, inasmuch as aspiration and chemical analysis of the fluid yield the answer. Visualization of retroperitoneal fluid collection by computerized tomography or ultrasonography, however, does always raise the possibility of recurrence of tumor in cases where the primary operation was for cancer. Treatment of smaller lesions can be expectant. Respiratory exercises causing an increase in negative intrathoracic pressure may aid in the movement of fluid through the lymphatics. For larger collections, elemental diets and total parenteral nutrition are also often enough, but surgery is sometimes required. Simple insertion of a peritoneovenous shunt, as in this patient, can be as effective as major operations such as identification and ligation of the offending lymphatic or marsupialization of the cyst.

While hormonal therapy has been the usual and appropriate treatment of advanced or metastatic prostatic cancer for the past 50 years, the recent development of new therapeutic agents as medical alternatives to orchidectomy has drastically altered the options and perspectives in the treatment of this disease. Estrogens had been the only commonly used drug therapy in the United States. Newer alternatives include androgen synthesis inhibitors, a class of agents termed antiandrogens, and gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH)] analogues, either alone or in combination. As the result of basic scientific studies and prospective clinical trials which have examined the issue of risk versus benefit, several trends have emerged. In the United States, orchidectomy is waning as the primary treatment option for metastatic prostatic cancer, while estrogen use has declined drastically; GnRH analogues are being prescribed more frequently. Furthermore, combination therapy with GnRH analogues (or orchidectomy, to a lesser extent) and the antiandrogen flutamide is gaining wider acceptance as a primary treatment option. The rationale, advantages, and real or potential disadvantages of these various treatment options are discussed.

Between 1980 and 1989, 186 patients with testicular tumors were seen at Roswell Park Memorial Institute. Of these, 66.6 percent (124/186) were diagnosed to have nonseminomatous germ cell tumors (NSGT) and 22 percent (41/186) were clinically determined to have Stage I disease. Patients with clinical Stage I NSGT either underwent observation or retroperitoneal lymph node dissection (RPLND). Recurrence in the observation group of patients was 23.5 percent (4/17) between four and eighteen months (mean 10 months) with the retroperitoneum being the most common site. All but 1 patient (80%) were salvaged with platinum-based combination chemotherapy. Of the 24 patients who had RPLND, 21 percent (5/24) had a false-negative metastatic evaluation. All the patients who had surgically documented metastatic disease were successfully treated with chemotherapy. The similar recurrence rates in the observation group and the false-negative RPLND group suggest that the failure rate in the observation group is a result of the inability to stage accurately patients with NSGT. RPLND continues to be the standard therapy in patients with clinical Stage I disease. Despite its high recurrence rate, observation should, however, be offered to well-motivated and selected patients since salvage platinum-based combination chemotherapy is very effective and the majority of patients in this group are spared a major operative procedure.

Several cytotoxic agents have been identified as effective in the treatment of superficial transitional cell carcinoma of the bladder, including doxorubicin, thiotepa and mitomycin-C. An in vitro study was conducted to assess the interactions of these three drugs against a well differentiated human bladder tumor cell line, RT-4, to identify and evaluate synergistic combinations among these agents. Cytotoxicity was evaluated by a colorimetric assay based on the capacity of viable cells to metabolize a tetrazolium dye, MTT, to produce a colored formazan product. The analyses of drug interactions were done by the isobolographic method (construction of isoeffect plots). The combination of doxorubicin and thiotepa was found to be the most synergistic, followed by the combination of doxorubicin and mitomycin-C. The combination of mitomycin C and thiotepa demonstrated an unpredictable effect. These findings suggest the combination of doxorubicin and thiotepa has potential advantage for chemotherapy of superficial bladder tumors.

Endometrioid carcinoma of the prostate is considered a variant of classical prostatic ductal carcinoma. Endometrioid carcinoma variant often has the unique clinical presentation of gross hematuria. The propensity of this tumor to spread within the urothelium makes local failure of curative therapy commonplace. We present 2 representative cases with a review of followup surveillance procedures and treatment options for the local recurrence once identified.

Transrectal ultrasound was performed in 20 patients with suspected local pelvic recurrence after a radical pelvic operation: 9 had undergone radical prostatectomy and 11 had undergone radical cystoprostatectomy. Transrectal sonography verified the presence of recurrence in 19 of 20 patients (95%) and this was confirmed by biopsy of the visualized lesions. Analysis of the sonographic echo patterns encountered revealed that in 14 of 19 recurrent neoplasms (71.5%) the echogenic pattern was hypoechoic. In the remaining 6 patients (31.5%) the echo pattern was isoechoic. No hyperechoic lesions were noted. Based upon our findings and because of the low costs compared to other diagnostic modalities transrectal ultrasound represents an ideal technique to compliment the digital rectal examination in evaluation of patients suspected of harboring a local pelvic recurrence after a radical pelvic operation.

A recently described collagen gel culture technique has been modified to evaluate the growth characteristics and chemosensitivity patterns of genitourinary neoplasms. Fresh human surgical explants incorporated radiolabeled DNA precursors [H3)thymidine or deoxyuridine) in 97% of 38 patient specimens (18/19 bladder, 3/3 prostate, 2/2 testis, 13/14 renal), after being maintained for three to 13 weeks/passage, with several specimens reaching their sixth passage (20 months). Control cellular DNA incorporation ranged from five to 90% (#cells labeled/#cells evaluated), with median labeling for bladder 30%, prostate 80%, testis 90%, and renal 80%. Original histopathologic classification was maintained in all cases. Tumor volume and glucose consumption were other measurable parameters. Seventy-three surgical specimen cultures were treated with chemotherapeutic agents after a minimum of four weeks in culture. Single agent exposures were 24 hours at 1X and 10X reported peak plasma concentrations. Combination agents were sequenced as in current clinical protocol for bladder tumors and fourteen day continuous fluorodeoxyuridine (FdURD) exposure for renal tumors. Sensitivity was found in 1/2 prostate and 1/10 renal tumors to Adriamycin, 8/15 bladder and 1/2 testis tumors to cisplatin, 11/28 renal tumors to FdURD and 6/16 bladder tumors to MVAC combination chemotherapy. This culture system offers the advantages of in vivo-like solid tumor growth, a high culture success rate, longevity in culture, maintenance of the primary histopathology and reproducible chemosensitivity response.

We reviewed 77 consecutive autopsies performed between 1965 and 1982 on patients who had been treated for germ cell tumors of the testis at our institute. Identifiable germ cell tumor was present at autopsy in 64 cases. On review, a single pattern was seen at autopsy in the majority of the cases (69.7 per cent) compared to the primary tumors, in which single patterns were seen in only 45 per cent. The occurrence of yolk sac tumor as the sole element in 6 of 29 autopsy specimens of nonseminomatous tumors after the introduction of the current standard 3-drug therapy and only once in 32 autopsies before 1976 appears significant. A possible explanation for this finding is that the yolk sac element was obscured by more aggressive and rapidly growing varieties of tumor in the earlier years but proved less responsive to chemotherapy.

A phase I trial of human recombinant tumor necrosis factor (rH-TNF) has been carried out in patients with advanced solid tumors. Sixty-six courses of the drug were given by 1 h IV infusion, daily for 5 days to 33 patients at doses of 5, 10, 20, 30, 45, 60, and 80 x 10(4) U/m2/day. All patients received isotonic saline (up to 21/day) and either indomethacin or ketoprofen. Acute toxicity resembled that seen with the phase I study of a single dose (5). Dose limiting toxicity was acute, rapidly reversible, hepatic dysfunction and hypotension. Hypertension during drug infusion and dyspnea were marked in some patients. There was one complete and one minor response, both in patients with renal cell carcinoma. The dose of 80 x 10(4) U/m2/day x 5 was poorly tolerated and the recommended starting dose for phase II studies is 60 x 10(4) U/m2/day x 5. Caution is recommended in treating patients with pre-existing hepatic function abnormalities, hypertension, hypotension or significant obstructive airway disease.

A total of 14 patients with nonseminomatous testicular tumors presenting with characteristics indicative of a poor prognosis were treated with cytoreductive chemotherapy, surgery and immediate reinduction chemotherapy. Of the 14 patients 12 presently are alive without evidence of disease (median followup 18 months). This new approach has improved significantly the outcome of these patients.

The records of 100 patients with localized prostatic cancer were examined retrospectively in an effort to determine the usefulness of routine 99mtechnetium bone scans following definitive therapy with 125iodine implantation or external beam irradiation. With a mean followup of 47 months per patient 19 per cent of these patients had positive scans and an additional 15 per cent had scans that were considered equivocal. Of the 100 patients none had a positive scan in the absence of either an elevated serum acid phosphatase or bone pain. In our series the low incidence of positive scans as the sole evidence of disease progression does not support its routine use after definitive therapy for localized carcinoma of the prostate.

The bioCarbon ureterostomy device is a stomal prosthesis for upper tract urinary diversion that has had preliminary successes in animal and human trials in Europe and Peru. Implantation of a pure carbon stomal prosthesis offers the potential advantages of high biocompatibility, lack of encrustation, and elimination of stomal stenosis which is frequently associated with cutaneous ureterostomy. Nine bioCarbon ureterostomy devices were implanted from August, 1984 through July, 1985. Although successful implantation was achieved in 2 patients, the complication rate was high. The bioCarbon ureterostomy device has potential as an alternative form of urinary diversion. However, significant problems need to be remedied before it can be recommended for routine clinical application.

The most important method for evaluating the pathogenesis of male infertility is open testicular biopsy. Herein we describe a method of aspiration biopsy of testis for histologic examination. Sexually mature dogs and rats treated with chemotherapeutic agents and ionizing radiation were followed with periodic testicular aspiration biopsy during and after treatment. The histologic findings from the aspiration biopsy compare with the results of routine histologic examinations in assessing spermatogenetic activity and delineating pathologic changes. The puncture in the experimental animals was performed under general anesthesia. In human patients testicular biopsy could be done under local anesthesia in an outpatient clinic. The procedure would be less painful, minimally invasive, and more cost-effective.

A limited clinical trial of Interferon-beta (Human Fibroblast Interferon) in the treatment of advanced, hormone-refractory prostate cancer was conducted by the National Prostate Cancer Project (NPCP Protocol 2100). Sixteen patients with metastatic prostate cancer who had failed prior hormone therapy were entered into the study. Treatment consisted of 6 X 10(6) units of Interferon-beta intravenously three times per week for 12 weeks. Chills and fever were seen in ten of the 16 patients (62.5%), and mild hematologic toxicity occurred in four patients. No complete or partial responses were observed. Three patients had stable disease by NPCP criteria for a mean duration of 6.3 months. Progression of disease was seen in 13 of the 16 patients, eight of whom progressed during therapy. The results of this study suggest that Interferon-beta has limited efficacy in the treatment of advanced, hormone-refractory prostate cancer.

The results of arterial embolization of symptomatic pelvic osseous metastases associated with extensive soft tissue tumors in 5 patients with renal cell carcinoma are presented. Of the 5 patients 4 experienced significant relief of pain and improved performance status, as well as objective evidence of bone recalcification or tumor reduction at an average followup of 10 months. One significant complication occurred in a patient with previous local irradiation. Possible advantages over conventional external beam radiation therapy of metastatic renal cell carcinoma and future applications of arterial embolization of bulky metastatic tumors are discussed briefly.

DNA histograms were measured by flow cytometry for 656 human solid tumors (365 primary and 291 metastatic). The proportion of aneuploid cells in cell suspensions obtained by mechanical disaggregation was significantly higher than those obtained after enzymatic disaggregation (collagenase + DNAse) of the same tumor. A strong correlation was observed between the values of DNA-indices measured after staining with propidium iodide and with 4',-6-diamidino-2-phenylindole (r = 0.97). Aneuploid cells were observed in 430 tumors (66%); 30 of these had two aneuploid stemlines, and two had three aneuploid stemlines. The overall frequency of aneuploidy was 61% among primary and 71% among metastatic tumors. The median value of the DNA index was 1.67 for 224 primary aneuploid tumors and 1.68 for 206 metastatic aneuploid tumors. For most diseases, the largest proportion of aneuploid primary and metastatic tumors had DNA-indices in the hypertriploid region. No major differences in frequency and degree of aneuploidy was observed between primary and metastatic tumors. For carcinomas of the bladder and prostate, frequency of aneuploidy was higher among poorly differentiated, than among moderately and well-differentiated tumors. For carcinomas of the breast and for sarcomas, tumors with DNA-indices of greater than 2.0 were observed mostly in the poorly differentiated group. For patients with carcinomas of the bladder and prostate most tumors at earlier stages of disease were diploid; whereas most tumors at later stages of disease were aneuploid. For patients with carcinomas of the ovary, colon, and kidney, no relationship between stage of disease and aneuploidy was evident.

A retrospective study of the incidence and clinical course of transitional cell carcinoma of the urethra is reported. Of 110 consecutive male patients who underwent cystectomy during a 9-year period, 9 had or developed a urethral tumour. Five patients undergoing radical cystectomy had known or suspected urethral involvement which was confirmed at urethrectomy. All 5 had deeply invasive (T3 or T4) transitional cell carcinomas of the bladder and subsequently died of metastatic disease. Four patients underwent urethrectomy because of signs or symptoms of urethral recurrence at an average interval of 2.5 years after cystectomy. There were two deaths in this group, neither of which appeared to be due to urethral recurrence. Six additional patients had undergone prophylactic urethrectomy because of prostatic urethral involvement or diffuse carcinoma in situ in the cystectomy specimen, and none had identifiable tumour in the anterior urethra. The residual urethra is a potential focus for recurrent tumour and this necessitates careful follow-up with serial cytology, but the low incidence of urethral recurrence (3.5% in this series) does not appear to warrant routine urethrectomy at the time of cystectomy.

We report a prospective study of 136 patients with biopsy proved bladder tumor who underwent 311 evaluations with cystoscopy, urinary cytology, bladder washing and, when indicated, bladder biopsies. Cytology results from bladder washings were superior to routine urinary cytology studies in detecting abnormal cells. Also, there was a significant increase in the number of positive cytology studies in bladder washings from patients with no evidence of tumor by cystoscopy but who had biopsy proved dysplasia. Multiple selective bladder biopsies showed a higher incidence of mucosal abnormalities if the primary tumor was of a higher grade.

We report 3 cases of ureteral obstruction following aortoiliac prosthetic graft surgery owing to secondary retroperitoneal fibrosis around anteriorly positioned ureters. The reversal of symptoms and radiographic demonstration of relief of obstruction after oral steroid therapy are discussed. The necessity of placing such grafts behind the ureters is reiterated and the routine performance of preoperative and postoperative excretory urography is suggested. A trial of steroid therapy following early detection of such obstruction in lieu of early surgical exploration is discussed.

Despite impressive advances in the therapy of testis tumors, many controversies remain regarding the optimal therapy for each stage of disease. Primary cytoreductive chemotherapy is the treatment of choice for all advanced germ cell tumors, whether nonseminomatous or seminomatous. The distinction between seminomas and other germ cell tumors may be more historic than real. A unified staging system is desperately needed so that results of treatment modalities may be more easily compared, and the need for further multiinstitutional, randomized treatment protocols is also evident. With present treatment options, about 90% of all patients with germ cell tumors should be cured of their diseases, and aggressive efforts at early recognition and the development of newer therapies for relapsing patients are indicated. While further consideration of the long-term consequences of the various treatment modalities is necessary, any resultant modifications in treatment strategy cannot be at the expense of present cure rates.

A comparison of the early morbidity of pelvic lymphadenectomy plus radical prostatectomy versus lymphadenectomy alone is reported. Fifty-one patients underwent the combined procedure; 26 had lymphadenectomy alone. Incidence of early complications was 35% in patients undergoing prostatectomy and node dissection and 27% in patients undergoing lymph node dissection only, a difference which is not statistically significant. Thrombophlebitis and pulmonary embolus occurred after the combined procedure. There was one postoperative death in the combined surgery group. The results of this study suggest that lymph node dissection may be performed at the time of radical prostatectomy rather than as a staging procedure, and emphasize the importance of pelvic lymph node dissection in the evaluation and treatment of clinically localized prostate cancer.

Cytogenetic analysis of a primary adrenocortical carcinoma revealed clonal rearrangements of several autosomes and sex chromosomes. In all metaphases the following marker chromosomes were present: 4p+,t(3;12)(p14;p13),14q+, t(15;20)(p11;q11), t(5;18) (p13.3;p11.2), psu dic(18)t(18.3)(p11.39;p12), and psu dic(20)t(20;9)(q11.2;p11). The results are discussed in relation to the cytogenetic findings in other solid tumors, especially of the kidney.

Flow cytometry (FCM) was used to study the DNA distribution of 99 tumor biopsy specimens and 41 bladder irrigation samples from patients with transitional cell carcinoma of the bladder. For tumor biopsy and cystectomy specimens, the frequency of aneuploidy increased with advancing tumor stage and grade. All T0 tumors were diploid. Twenty-seven percent of T1, 71.4% of T2, and 75% of T3 and T4 tumors were aneuploid. All Grade I tumors were diploid. Thirty percent of Grade II and 76.9% of Grade III tumors were aneuploid. The frequency of aneuploidy of tumors in the early stages (Ta, T1) is similar to the incidence of subsequent progression by these tumors described in the literature. For irrigation fluids, the relationship between grade and stage and the frequency of aneuploidy was similar to the relationship seen with tumor specimens. All four patients with only carcinoma in situ had aneuploid cells in their irrigations. The comparison of FCM data of bladder biopsy and bladder irrigation from the same cystoscopic evaluation suggests adequate representation of tumor cells in the irrigation fluids for almost all cases. The authors conclude that DNA ploidy analysis by FCM appears useful in a clinically important group of patients with aneuploid superficial tumors of moderate or high grade. Bladder irrigation analysis appears useful in the follow-up of patients with a history of carcinoma in situ and those with aneuploid tumors.

A retrospective study of all cases of seminoma treated at Roswell Park Memorial Institute from 1970 through 1979 was conducted. Fifty-six evaluable patients treated initially with radiation therapy were seen during this period, and the overall survival rate at an average follow-up period of 52 months was 82%. The survival rate in patients with bulky abdominal or supradiaphragmatic metastases was only 33% (4 of 12 patients). Treatment failures were analyzed to determine their apparent causes and the implication of such failures to the future management of seminoma. The use of combination chemotherapy as the initial treatment modality in advanced seminoma is discussed in light of these results.

To determine the effect on survival of excision of a solitary metastasis from renal cell carcinoma, the records of 29 patients seen at our institute within the last 15 years (1972 to 1986) who underwent such an operation were reviewed. Metastasis was present at diagnosis in 11 of the 29 patients, while 18 had metastasis 2 months to 11 years after nephrectomy, with an average interval free of disease of 38 months. There were 13 pulmonary metastases, 6 bone lesions and 10 other lesions. The estimated over-all survival rate for this group was 41 per cent at 2 years and 13 per cent at 5 years after excision of the metastasis. Only 2 of the 29 patients currently are alive with no evidence of disease 42 and 53 months since excision of the metastasis. Neither the presence nor absence of a metastasis at diagnosis nor the interval between nephrectomy and the development of a metastasis in patients without metastatic disease at diagnosis appeared to influence survival after excision of the metastasis. Unlike previous reports, these results suggest that the beneficial effects of excision of metastatic renal cell carcinoma are limited to improved short-term survival postoperatively and that surgical cure of patients with metastatic renal cell carcinoma is a relatively uncommon event.

From July, 1980, to June, 1983, 319 patients with newly diagnosed metastatic prostatic cancer were randomized to one of three treatment protocols: diethylstilbestrol (DES) or bilateral orchiectomy, cyclophosphamide plus 5-fluorouracil plus DES, and estramustine phosphate (Emcyt). Ninety-three per cent of 296 patients were eligible for evaluation. This report shows no difference in survival, disease-free progression time, or status regarding pain at entry. Other prognostic factors failed to reveal any difference within any of the treatment protocols.

In the RPMI mouse renal cell tumor, N1-acetylspermidine (N1AS) was found to be a constant and major component (18 to 25%) of the polyamine pool. Early i.m. growth induced urinary N1AS excretions up to tenfold normal, equivalent to a daily turnover of the entire tumor polyamine pool. N1AS excretion was correspondingly lower during more limited s.c. tumor growth. In nine other mouse tumors, N1AS pools were low or negligible, and correspondingly urinary N1AS or N8AS increased only in advanced growth, and less significantly. Urinary N1AS was elevated likewise in immature untumored mice. Thus, the enriched N1AS pool of the renal cell tumor was separately distinguishable as a direct source of elevation of urinary N1AS. N1AS was selectively abolished from the renal cell tumor by prolonged BCNU treatment, but was not rapidly depleted by the polyamine inhibitor DFMO. In cell culture, the RPMI renal cell tumor contained unusually high uninduced levels of sperm(id)ine N1-acetyltransferase, a potential source of N1AS. N1AS pools were also significantly elevated in human renal cell tumors.