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A modified open renal biopsy technique was performed under local anesthesia on 129 patients over a 10-year period. This technique yielded sufficient tissue to establish a diagnosis for every patient. The mean number of glomeruli obtained was 54 +/- 3; the mean duration of the operation was 71 +/- 2 min. No deaths resulted and only one major complication developed following this procedure which required additional surgery. Two patients required blood transfusions following surgery and both had a bleeding abnormality. These results demonstrate that the modified open renal biopsy technique is a safe and reliable procedure that should be performed whenever the percutaneous route is either unsuccessful or contraindicated.

Growth factor activity was partially purified from human renal tumors and a human bladder cancer cell line by heparin-Sepharose chromatography. This activity stimulated bovine capillary endothelial cell proliferation and DNA synthesis in BALB/c 3T3 cells. Partially purified growth factor preparations from these tumors contained a protein with an approximate molecular weight of 17,000 which was recognized by a polyclonal antiserum raised against a peptide fragment of basic fibroblast growth factor (FGF). This growth factor activity appears to be related to basic fibroblast growth factor. Measurement of FGF-like activity in 50 urine samples from 32 adult males showed that 55% (6 of 11) of the urine samples from patients with bladder cancer and 100% (7 of 7) of the urine samples from patients with kidney cancer contained activity equivalent to more than 20 ng of basic FGF/h of urine production. In contrast, only 6% (2 of 32) of the urine samples from controls, patients with a benign disease, or patients with a history of bladder or kidney cancer contained this level of growth factor activity. These results suggest that patients with bladder or kidney cancer release an FGF-like factor into urine which may be used as a marker for these tumors.

The identification of the decapeptide luteinizing hormone-releasing hormone (LHRH) has led to the development of LHRH agonists, which are a new class of drugs for the treatment of advanced prostate cancer. These peptides have a modified amino acid structure that makes them more potent than LHRH. Prolonged administration of LHRH agonists results in down-regulation of the LHRH receptors in the pituitary and decreased secretion of luteinizing hormone. The result is decreased production of testosterone by Leydig cells, which is the basis for the use of LHRH agonists to treat prostate cancer. The effectiveness of LHRH agonists has been demonstrated in the United States in several randomized, controlled clinical trials. Daily administration of leuprolide produced equivalent results compared with diethylstilbestrol (DES). More recently, in two separate, randomized studies, the long-acting LHRH agonist Zoladex (ICI Pharma, Wilmington, Delaware) produced the same objective response rate as DES or bilateral orchiectomy. The equivalent response rates obtained with LHRH agonists indicate that these drugs can now be considered a reasonable treatment option for patients with metastatic prostatic cancer.

Dialyzed, concentrated urine from 21 patients with a history of bladder cancer or a gross bladder tumor was tested for cell motility activity using BALB/c/3T3 cells. Thirteen urine samples from patients with a gross bladder tumor produced a greater increase in cell migration than 8 urine samples from patients with a history of bladder cancer [167% +/- 14 (S.E.), 64% +/- 19, respectively; p less than 0.001]. Protease treatment of urine from a patient with bladder cancer caused a 95% loss of activity, while heating to 100 degrees for 2 min caused an 86% loss of activity. High-performance liquid chromatography of urine from a patient with bladder cancer revealed that the greatest activity was present in fractions with a molecular weight between 18,000 and 30,000. These results suggest that motility-stimulating factor may be a useful marker for detecting carcinoma of the bladder.

Carcinoma of the prostate is the second most common cause of cancer-related deaths in American men. This is due, in part, to the low percentage of cases that are diagnosed when the tumor is still curable. To improve early detection, routine screening has been performed using one or a combination of tests that included open prostate biopsy, serum acid phosphatase, the digital rectal exam, and transrectal sonography. These studies have been critically reviewed and the problems associated with prostate cancer screening have been discussed. No study has proven that routine screening reduces the mortality from prostate cancer. Furthermore, the positive predictive value and the sensitivity of each of these tests are too low for any of them to be useful for screening at the present time. To determine the value of screening, new studies are needed which should include a control group and an assessment of the disadvantages of screening as well as the potential benefits. Based on published reports, however, routine screening for prostate cancer using any test should be considered investigational at the present time.

Heparin affinity chromatography has been used to partially purify angiogenic factors from normal and neoplastic tissue. The same technique was used to partially purify angiogenic-like factors from two mouse bladder tumors and urine from mice with bladder cancer. Both MBT-2 and MB49 tumors contained heparin-binding 3T3 cell growth factor activity that was eluted by 1.2 to 1.4 M salt. The growth factor isolated from MBT-2 tumor was mitogenic for capillary endothelial cells. Analysis of the 1.2 M heparin eluate by high-pressure liquid chromatography showed that it consisted of two 3T3 cell growth factors with molecular weights of 16,000 and 26,000. The growth factor activity isolated from MB49 tumors had an affinity for Bio-rex 70 which was similar to other cationic heparin binding growth factors. Analysis of urine pooled from tumor-bearing mice by heparin-Sepharose chromatography demonstrated 3T3 cell growth factor activity in fractions eluted with 1 to 1.4 and 2.5 M dsalt, whereas no significant growth factor activity was detected in pooled urine from control mice. The growth factor activity found in mouse bladder tumors differed from epidermal growth factor, transforming growth factor-alpha, and platelet-derived growth factor in terms of affinity for heparin-Sepharose and molecular weight. The observation that urine from tumor-bearing mice contains increased concentrations of this growth factor compared to normal urine suggests that a similar relationship may exist for human urine.

Angiogenic activity has been assessed in biopsy specimens from 49 patients with transitional cell carcinoma, benign prostatic hypertrophy and vesicoureteral reflux. Over 95% of the specimens containing malignant and premalignant transitional epithelium stimulated capillary proliferation on rabbit iris. In contrast, less than 10% of normal tissues had this effect. Sixty-one per cent of specimens with inflammatory round cells were angiogenic but this was reduced to 10% by preincubation with rabbit antihuman lymphocyte serum. Cystitis cystica also induced capillary proliferation even if incubated with the antilymphocyte serum. Angiogenic capacity may be an early marker of preneoplastic and neoplastic lesions of the human bladder.

A new technique is described for long term placement of an indwelling catheter into the mouse bladder. This technique allows the animal to void normally while receiving an intravesical infusion for several weeks. The presence of the catheter still enables MBT-2 tumor cells to implant into the bladder wall. This model will be useful for investigating the effect of various anticancer agents administered intravesically over prolonged periods of time.

We reviewed our experience with transrectal aspiration biopsy during an 18-month period. This procedure was the sole technique used in 75 men and prostatic cancer was diagnosed in 19. Two of these patients were not treated because a core biopsy performed at another hospital was negative for carcinoma. Aspiration and transperineal core biopsies were performed in 62 other cases. The sensitivity of aspiration to diagnose prostatic cancer was 98 per cent (45 of 46 biopsies) compared to only 81 per cent (37 of 46) for the core biopsy method. No patient suffered a complication following the aspiration biopsy. These data further support the value of transrectal aspiration biopsy as a sensitive, easy to perform method for sampling an abnormal prostate. More widespread use of this technique in the United States should be encouraged.

Transrectal aspiration and transperineal core biopsies were performed on 38 patients with suspicious prostatic examinations. The false negative rate was 14 per cent by the core method but no cancer was missed by the aspiration technique. There was insufficient material for diagnosis in 14 per cent of the biopsies obtained by the core technique but in only 3 per cent with the aspiration biopsy method. Malignant cells were confirmed by cytology in 1 patient who had had 2 normal core biopsies. The cytological grade was only moderately consistent with the Gleason sum. No complications developed after either procedure. Transrectal aspiration biopsy offers several advantages over conventional biopsy methods and should be used regularly to diagnose abnormalities of the prostate.

The ability to detect prostatic cancer by transrectal ultrasonography was evaluated in a prospective blind study of 216 men. The sensitivity of transrectal ultrasonography was 86 per cent but the specificity was only 41 per cent. Tumors less than 1 cm. in diameter were most difficult to detect by transrectal ultrasonography. The positive and negative predictive values of transrectal ultrasonography were 36 and 89 per cent, respectively. Abnormal scans that strongly suggested carcinoma were present in 10 per cent of the men who had a normal digital examination but no biopsy was performed. Transrectal ultrasound is a sensitive method to detect all but small prostatic tumors and it can detect tumors that are not evident by digital examination. To date, however, transrectal ultrasonography may be difficult to use for routine screening in the United States because of the low positive predictive value. Nevertheless, further investigation of this technique is warranted to define its role in improving the diagnosis of prostatic cancer.

Neoplastic and non-neoplastic mammalian urothelium was tested for angiogenesis activity in the rabbit iris assay. Tiny fragments of tissue were placed on a rabbit's iris and observed through a slit lamp stereoscope for as long as 4 days after implantation. Angiogenesis activity was demonstrated either by the appearance of new capillary growth or, following an injection of fluorescein, by a green fluorescence around an implant. Capillary proliferation was stimulated by 99 per cent of the specimens containing malignant urothelium, while only 9 per cent of normal urothelial specimens had this effect (p less than .001). Cells grown in vitro were similarly tested for angiogenesis by implanting 1 mm. fragments of collagen coated either with malignant or normal cells. A total of 92 per cent of the specimens covered with neoplastic cells induced angiogenesis, while only 15 per cent of the implants covered by normal cells caused this response (p less than .001). Benign reversible hyperplasia was induced in a rabbit bladder by systemic administration of cyclophosphamide, and an angiogenic response could not be detected in a small number of specimens. The results suggest that angiogenesis activity may be a reliable method for distinguishing between benign and malignant bladder tissue.

Prostate cancer is of increasing concern because its mortality has not decreased significantly in the last 30 years. It is suggested that a reduction in death rate may be possible as a result of early detection of the disease, but several factors indicate that presently, routine screening cannot be justified.

In the past thirty years, the mortality rate from prostate cancer has not declined. This is due in part to the small number of tumors diagnosed while they are still curable by surgery or radiation. Recent studies have demonstrated that transrectal sonography can detect nonpalpable tumors, which are usually potentially curable. As a result, some physicians now recommend routine screening of all men over age fifty. The main goal of a cancer screening test is to help reduce mortality. To date, it has been shown that screening can increase early detection and survival, but there is no experimental evidence that screening reduces mortality. Therefore, screening for prostate cancer may not be worthwhile. The large number of prostate tumors found on autopsy series indicates that only a small fraction of patients with prostate cancer actually die of it. The risk of screening is that many insignificant tumors may be diagnosed and patients may be treated unnecessarily, resulting in significant morbidity, mortality, and expense. For now, it may be appropriate to let patients choose whether or not to have the test performed, after informing them screening can increase early detection, but could also result in overdiagnosis and treatment. However, screening should not be advocated across-the-board until a randomized, carefully controlled, large-scale clinical trial has shown that it saves lives.

Superficial transitional cell carcinoma (TCC) of the bladder and carcinoma in situ (CIS) have a high recurrence rate and a variable incidence of progressive disease. Conventional intravesical agents used to treat these carcinomas have achieved only a variable degree of success, and have adverse side effects. Recently, intravesical interferon has been explored as a treatment for TCC and CIS. In a randomized, controlled trial, patients with CIS exhibited a significantly higher rate of complete response (CR) to high-dose (100 x 10(6) IU) than to low-dose (10 x 10(6) IU) interferon (45% vs 6%, respectively, p less than 0.0001). To date, 9/19 patients in the high-dose CR group have maintained a CR for at least six months. Five patients receiving high-dose therapy and 5 receiving low-dose therapy subsequently underwent cystectomy, but median time to surgery was 33.5 weeks for the high-dose group vs eighteen weeks for the low-dose group. Intravesical interferon was generally well tolerated. These results suggest that randomized clinical trials are warranted to assess the efficacy of intravesical interferon, as compared to BCG, for the treatment of CIS.

We report on a patient who had a urothelial tumor with tri-differentiation into transitional squamous and adenocarcinoma after ingestion of 285 gm. cyclophosphamide during a 15-year-period. The possibility is again raised that the use of high doses of this drug over long periods may be associated with an increased incidence of carcinoma of the bladder. Frequent cystoscopic examinations may be warranted in patients who have received large cumulative amounts of the drug

An early detection study for prostate cancer was initiated to determine the effect of routine digital rectal examinations on the stage of prostate cancer at diagnosis. A prostate biopsy was recommended if induration, asymmetry or nodules were detected on the digital examination. During a 6-year period 4,160 examinations were performed on 2,131 men more than 45 years old. A prostate biopsy was performed on 144 men and 36 malignant tumors were detected, of which 68 per cent were clinically localized. Pelvic lymph node metastases were found in 6 per cent of the surgically staged cancer patients and in 10 per cent of the patients who had a high grade tumor. Surgical staging revealed that 50 per cent of the patients with clinical stage B disease were upstaged to stage C or D1 disease. These results suggest that mass screening programs using digital examination may not add sufficient benefit over conventional medical care to warrant the expense. Definitive proof that screening can lower the mortality rate from prostate cancer can be obtained only by a prospective randomized clinical trial.

We reviewed the English-language literature over a 16-year period (1960 through 1976) on the subject of prophylaxis with systemic antibiotics in surgery. Trials in genitourinary and cardiovascular surgery were not reviewed. Our definition of prophylaxis is antibiotic administration of the absence of infection or contamination. Of 131 articles reporting clinical trials using systemic antibiotics for prophylaxis, only 24 met the criterion on an appropriately designed study that generated evaluable data. In these, systemic antibiotics were shown to be of value in reducing wound infections after abdominal and vaginal hysterectomy, cesarean section, biliary surgery, total hip replacement, and microneurosurgical craniotomy. Antibiotic prophylaxis was of no value in laparotomy and groin hernia repair. Patients undergoing any of 21 different operations did not benefit from prophylactic antibiotic administration, though study groups were too small or infection rates too low to allow for firm conclusions. In certain patients at high risk of infection, systemic prophylaxis is warranted. Future clinical studies must be designed as randomized, blinded, prospective trials, with antibiotics administered by a parenteral route beginning preoperatively.

Transrectal aspiration biopsy is useful as an alternative method to examine the prostate. As a means to improve the sensitivity of this method we investigated the significance of cellular atypia. Transrectal aspiration biopsy revealed highly atypical cells in 30 of 225 patients and in 17 patients slightly atypical cells were found. Biopsy was repeated in 22 patients with highly atypical cells and cancer was confirmed in 17 (77 per cent). In the group with only slight atypia 2 of 6 patients had cancer upon repeat prostatic biopsy. When transrectal aspiration biopsy contains highly atypical cells biopsy should be repeated to avoid a false negative diagnosis. These results suggest that atypia is an abnormal finding that must be followed clearly to maintain a high sensitivity with this biopsy method.