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Management of infected retroperitoneal hematomas can be technically challenging in patients who cannot undergo open surgical debridement. We report an innovative, minimally invasive treatment method that combines percutaneous catheter drainage with urokinase irrigation. CASE REPORT A 56-year-old man with multiple medical problems, including end stage renal disease, was hospitalized for treatment of a lefi renal abscess. Urine cultures revealed Proteus and Pseudomonas. Left nephrectomy was performed through a flank incision. Two weeks postoperatively fever, chills and left lower quadrant pain developed. Abdominal computerized tomography (CT) revealed a large left retroperitoneal hematoma. Blood cultures and needle aspiration of the left retroperitoneal space yielded coagulase-negative Staphylococcus. Intravenous antibiotic therapy was instituted and a percutaneous drainage tube was placed with periodic saline irrigation. Despite 10 days of irrigation and antibiotic therapy sepsis progressed and the overall condition of the patient deteriorated. Abdominal CT and a retrograde sinogram demonstrated that the solid component of the infected hematoma had failed to resolve (fig. 1). Because of tenuous clinical status, the patient was not considered a candidate for open surgical dcibridement. Therefore, 250,000 units of urokinase were infused through the drainage tube and allowed to dwell for 2 hours. The tube was then unclamped and vigorous

A prospective trial from July 1976 to September 1980 by the National Prostatic Cancer Project randomized newly diagnosed metastatic prostate cancer patients to DES 1 mg orally three times daily or orchiectomy; or DES, 1 mg, three times daily, plus cyclophosphamide at 1 mg/m2 iv every three weeks, or cyclophosphamide 1 g/m2 iv every three weeks plus estramustine phosphate (Estracyt) at 600 mg/m2 orally daily in three divided doses. There were 246 patients evaluated for response of 301 entered. These consisted of 83 on the DES/orchiectomy arm, 77 on DES plus cyclophosphamide, and 86 on Estracyt plus cyclophosphamide. Objective response rates, initially evaluated at 12 weeks, were similar among the treatments. However, chemotherapy as used in this study early in the diagnosis of metastatic disease appears to exhibit an improved effect on overall survival compared to hormone therapy alone. Analysis within groups having pain versus no pain at entry revealed a marked advantage after 80 weeks for chemotherapy when pain was initially present and a slight advantage during treatment (throughout follow-up) when the pain was absent. Median survival times were 92, 91, and 94 weeks, respectively, for the three treatments. The progression-free interval for responders showed no difference between initial treatments, although nearly one half of the patients are still in remission; hence, further follow-up will be essential. Side effects were not excessive for the chemotherapy treatment arms and patient compliance was good. This national multicenter trial provides the basis for further testing of chemotherapy agents at an earlier phase for patients with newly diagnosed metastatic prostate cancer.

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

Carcinoma of the penis is rare in this country. A total of 219 patients diagnosed to have carcinoma of the penis were analyzed retrospectively. The primary penile lesion was treated by partial amputation in 160 patients. Forty-two patients had inguinal node dissection. Forty-six patients received radiation therapy to the inguinal region. Sixty-five per cent of the patients with no palpable nodes at initial diagnosis survived for six or more years. Twenty-eight per cent of the patients with palpable nodes survived for three to five years, and 15% for six or more years. Ten per cent of the patients died of a second primary tumor.

Two hundred fifty patients with bladder tumor were evaluated over a three-year period. Cystoscopy, cytology, and random bladder and tumor biopsy were part of the workup. The follow-up of these patients resulted in a total of 509 cystoscopies, 772 specimens of bladder washings and urinary cytologies, and 503 tumor or selected mucosal biopsies. The value of cytologic study of bladder washings and cystoscopic urine samples as well as the importance of selected site mucosal biopsies in detecting "field changes" in the bladder epithelium associated with bladder tumors are discussed.

Superficial transitional cell carcinoma of the bladder (TCCaB) has a high incidence of recurrence. Intravesical thiotepa is the drug used most often for treatment. Intravesical mitomycin-C also has shown promise. Cisplatin has proven activity in patients with metastatic TCCaB and in experimental bladder cancer models. Patients who have no response to one intravesical agent such as thiotepa may respond to other agent(s) such as mitomycin-C or cisplatin. In this report we have evaluated 10 patients with superficial recurrent TCCaB who showed no response to intravesical thiotepa and were subsequently treated with mitomycin-C or cisplatin. Six patients were treated with cisplatin and 4 with mitomycin-C. The 4 treated with mitomycin-C had complete response or partial response within three months. Of the 6 treated with cisplatin, 4 had complete response within three months, and 2 had no response.

In this clinical trial of men with advanced prostatic cancer no longer responsive to hormone therapy 189 were randomized to receive estramustine phosphate, methotrexate or cis-platinum. Response evaluations were done in 158 cases. Objective response rates (complete, partial or stabilization of disease) were 34 per cent for estramustine phosphate, 36 per cent for cis-platinum and 41 per cent for methotrexate. Subjective parameters indicated a substantial advantage for pain improvement with methotrexate or cis-platinum over estramustine phosphate. Probabilities of continued response indicated some advantage for methotrexate and median response durations at this time were twice as long for methotrexate (32 weeks) as for cis-platinum (16 weeks), with estramustine phosphate intermediate (23 weeks). Survival rates for the original treatment randomization groups were not different at this time. Side effects of estramustine phosphate consisted primarily of nausea and vomiting and/or anorexia but to a lesser extent than with cis-platinum. These effects were somewhat less for methotrexate, for which the major side effects were stomatitis and leukopenia, as well as hepatic toxicity reflected by elevated serum glutamic oxaloacetic transaminase levels. Other side effects of cis-platinum were less than for methotrexate (no stomatitis), except for signs of renal toxicity (elevations in blood urea nitrogen and serum creatinine), which were greater. Methotrexate had a relatively high level of activity against metastatic, progressive, hormone nonresponsive prostatic cancer, with side effects that were substantial but manageable.

There were 121 men with hormonally refractory metastatic cancer of the prostate who were randomized to receive estramustine phosphate or vincristine, or the combination of these 2 agents. All patients had received prior radiation therapy (greater than 2,000 rad). There were 90 patients who could be compared for response. The objective response rates (partial regression or stabilization of disease) for the 3 treatment groups were 26 per cent for estramustine phosphate, 24 per cent for estramustine phosphate plus vincristine and 15 per cent for vincristine. Subjective parameters varied little among the 3 regimens. The median duration of response for those responding to estramustine phosphate was similar (20 weeks) to that for vincristine (22 weeks) and greater than that for the combination (13 weeks). The probability of survival did not differ significantly for patients randomized to each of the 3 regimens. The addition of vincristine to estramustine phosphate did not enhance the response rate achieved by estramustine phosphate alone and vincristine alone produced the lowest response rate. Estramustine phosphate continues to be the most active agent in previously irradiated patients with hormonally refractory metastatic cancer of the prostate.

The identification of bladder tumor characteristics which may affect tumor recurrence has been of interest to the clinician for a long time. Previous attempts to identify predictive factors of recurrence involved comparisons based on the twelve-month recurrence rate in a prospective clinical investigation of bladder tumor patients observed over a five-year period. A statistical regression model known as the proportional hazards model was employed to identify these factors using the disease free interval as the outcome variable. Prior bladder cancer history, age at admission, initial tumor stage, grade, number, size, shape, and site were examined. The results confirm that a patient's prior history of bladder cancer must be considered in evaluating his likelihood of tumor recurrence. The analysis then focuses on patients with no prior history for predictive factors of recurrence.

An analysis is presented on 45 patients undergoing pedal lymphangiography followed by retroperitoneal lymphadenectomy for non-seminomatous testicular carcinoma. Retroperitoneal node metastases were predicted correctly with the lymphangiogram in 10 of 20 patients (50 per cent). The over-all predictive accuracy was 62 per cent.

SUMMARY The future needs in this area appear to be continued systematic research. The most immediate research needs include the following: (1) the identification of new drug agents with activity in experimental systems and initiation of subsequent Phase I and II studies; (2) increased numbers of drug trials with established single agents to define more clearly those with activity; (3) continuing combination studies incorporating single agents with definite antitumor activity; (4) prospective randomized evaluations comparing combinations of the more active single agents to see whether the enhancement of antitumor effect is significant with multi-drug regimens; and (5) continued research into incorporation of systemic therapy into combined modality approaches to the primary therapy of bladder cancer in the context of randomized trials employing large numbers of patients. 12

The history and rationale for the use of cryosurgery are discussed, along with the association with stage and grade of the tumor. Also included are details of the surgical procedure used in the perineal approach, results of studies that address clinical benefit and the relatively few surgical complications, and, finally, patient survival. The section on immunotherapy describes its different categories (active nonspecific, active specific, and passive or adoptive immunotherapy) and details its clinical use in the treatment of prostatic cancer.

The tumors in 249 patients presenting initially with stages Ta and T1 bladder cancer were analyzed for tumor progression and recurrence. Only transurethral resection and/or fulguration was used before the first recurrence. Patients who received intravesical chemotherapy after the first tumor recurrence were excluded from an analysis of progression. Progression according to stages Ta and T1, and grades I, II and III was 4, 30, 2, 11 and 45 per cent, respectively. All differences were statistically significant. Progression also correlated with nontumor dysplasia and size. High tumor grade, lamina propria invasion, atypia elsewhere in the bladder, positive urinary cytology, tumor multiplicity and large tumors were associated with shorter intervals free of disease.

Results of the first nationally randomized trial of the National Prostatic Cancer Project revealed a demonstrable advantage for chemotherapy in the management of advanced disease (Stage D in relapse from endocrine therapy). Both cyclophosphamide and 5-Fluorouracil showed improved activity over standard therapy. A second trial for patients previously irradiated, with less tolerance to myelosuppressive agents, revealed an advantage for estramustine phosphate and streptozotocin over standard therapy. Subsequently completed trials have revealed activity for prednimustine and imidazole carboxamide (DTIC). Trials currently underway for newly-diagnosed Stage D and for Stage D disease clinically stable to diethylstilbestrol (DES) show promising activity for DES combined with cyclophosphamide. Current trials with single agents in advanced disease are comparing methyl-CCNU and hydroxyurea with cyclophosphamide; another is evaluating estramustine phosphate and vincristine alone and in combination. The use of chemotherapy in earlier staged patients as adjuvants to definitive surgery or irradiation is underway in two clinical trials, where the effect of cyclophosphamide and estramustine phosphate as long-term therapies is compared with no additional treatment.

The survival rate has been improved for rhabdomyosarcoma of all sites in children by combining surgery, radiation and chemotherapy. However, very few children are alive today who have had sarcoma of the prostate. The prognosis appears to be better for sarcoma of the bladder than for sarcoma of the prostate. In our series all the children with prostatic sarcoma died within 7 months. 2 children with sarcoma of the bladder are cured.

Summary— Eighty-nine patients were treated for impotence with penile prostheses. The Small-Carrion prosthesis was used in 56 patients, the inflatable prosthesis in 27 and Pearman's prosthesis in 6 patients. The overall functional results with the Small-Carrion and inflatable prostheses were comparable.

From 1969 through 1976 we performed cryosurgery in 229 cases of prostatic cancer. This article presents survival in cryosurgery and other treatment groups. In every stage, despite a preponderance of large primary tumors and poor-risk patients, cryosurgery matched total prostatectomy and compared favorably to other modalities, including radiation therapy, at our center and elsewhere. According to previous authors, and in view of the present data, eradication of the local lesion is associated with better survival even in advanced cases. Cryosurgery provides a safe, effective method.

Sertoli cell tumor of the testis is rare. Of those reported only 10 per cent are malignant. An additional malignant Sertoli cell tumor is reported with a discussion of the pathological aspects and a review of the literature.

In this third cooperative chemotherapy trial of the National Prostatic Cancer Project 165 patients with histologically confirmed, relapsing clinical stage D prostatic cancer were randomized to receive either imidazole-carboxamide, procarbazine or cyclophosphamide. All patients had received and failed previous hormonal therapy. Patients whose disease progressed after 12 weeks on initial therapy were crossed over or randomized to receive an alternate drug. There were 129 patients available for comparison of treatments. The objective response rates (partial regression plus stable disease) were 26% for cyclophosphamide, 27% for imidazole-carboxamide and 14% for procarbazine. Subjective responses were noted in pain relief, improvement in performance status and weight gain. Procarbazine was associated with excessive toxicity, resulting in many patients (28%) discontinuing therapy within the first 3 weeks and closure of this particular arm of the study. The regimen of initial imidazole-carboxamide therapy with a later cross-over to cyclophosphamide when the disease continues to progress is associated with the longest increase in survival. Imidazole-carboxamide and cyclophosphamide appear to be active agents in advanced prostatic cancer and are worthy of continued use in this disease.

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

A study of urinary cytology and selected mucosal biopsies in conjunction with cystoscopy provided additional information of value in the management of 318 patients with bladder cancer. These procedures were especially helpful in patients with no visible lesions on follow-up cystoscopies in assessing the bladder epithelium, the behaviour of which may be unpredictable in that no further tumours may occur, or they may arise at irregular intervals.

Through the routine use of cultures from saline slush transport solution and the initial and final organ perfusates, 14 of 81 cadaver allografts (17.3%) were found to have been contaminated before transplantation. Gram negative organisms, cultured from 5 of the 14 contaminated allografts, resulted in the recipient's death on the first encounter with this problem and the loss of two other allografts. Early antibiotic therapy begun even without evidence of overt infection appeared to prevent any further deaths or graft loss in those whose allografts were contaminated and yielded an overall survival comparable to that of uncontaminated allografts. Without such an approach to the study of perfused cadaver allografts and the management of them when found to be contaminated, this type of infection may go undetected and contribute to allograft and patient loss.

Serum alpha-fetoprotein and beta-human chorionic gonadotrophin levels were estimated in 115 patients. Sixty-nine patients had non-seminomatous germ cell tumours and 34 patients had seminomas. Twenty-six patients showed elevated serum makers.

Perineal cryosurgical destruction of the prostate has been practiced at the University of Iowa since 1969 for a select group of patients with primary adenocarcinoma of the prostate. We have reviewed this technique in the past and analyzed it with respect to both patient survival and elimination of the local lesion. In this report we have evaluated 14 patients who received combination cryosurgery and external radiation therapy for prostatic adenocarcinoma. Several clinical parameters were examined with emphasis placed on control of the local lesion and obviating the need for urinary diversion or transurethral resections to relieve obstructive symptoms.

We evaluated the survival rate and time to recurrence for 114 patients in whom an initial histological diagnosis of stage B1 or B2 bladder tumor was made between 1974 and 1983. The 5-year survival rates for stages B1 and B2 disease, respectively, were 63 and 38 per cent in 43 patients treated by transurethral resection alone, 48 and 54 per cent in 40 treated by preoperative radiation and radical cystectomy, 33 and 25 per cent in 15 treated by radical cystectomy alone, and 53 and 11 per cent in 16 treated by definitive radiation therapy alone. Similar results were found among the groups with regard to time to development of metastases. The distribution of stage, grade and number of tumors was not significantly different among the treatment groups. Patients in the transurethral resection group were older, and had smaller tumors and more medical problems. Comparing transurethral resection of muscle invasive bladder tumors to standard radical surgery with or without radiotherapy yielded comparable long-term survival and time to distant recurrence.

Periodate-oxidized ADP (oADP) and periodate-oxidized ATP (oATP) stimulate the permeability transition in energized rat liver mitochondria measured as the Ca2+-efflux induced by Ca2+ and Pi. In the presence of Mg2+ and Pi, mitochondria lose intramitochondrial adenine nucleotides at a slow rate. oATP induces a strong decrease of the matrix adenine nucleotides which is inhibited by carboxyatractyloside. Under these conditions, Mg2+ prevents the opening of the permeability transition pore. EGTA prevents the Pi-induced slow efflux of adenine nucleotides, but is without effect on the oATP-induced strong decrease of adenine nucleotides. This oATP-induced strong adenine nucleotide efflux is inhibited by ADP. oATP reduces the increase of matrix adenine nucleotides occurring when the mitochondria are incubated with Mg2+ and ATP. This effect of oATP is also prevented by carboxyatractyloside. oATP is not taken up by the mitochondria. It is suggested that oATP induces a strong efflux of matrix adenine nucleotides by the interaction with the ADP/ATP carrier from the cytosolic side. The induction of the mitochondrial permeability transition by oADP and oATP is attributed to two mechanisms—a strong decrease in the intramitochondrial adenine nucleotide content, especially that of ADP, and a stabilization of the c-conformation of the ADP/ATP carrier.

Pelvic lymphadenectomy was performed in 187 patients as a staging procedure for carcinoma of the prostate. Clinical impression of lymph nodes during dissection appears to be inaccurate in a large number of patients. We therefore believe that if radical surgery is planned for clinically localized tumor, the histologic status of the removed nodes should be confirmed before surgical extirpation of the tumor.