Z. Wajsman

Measurements of Prolactin and Androgens in Patients with Prostatic Diseases

Testosterone (T), dihydrostestosterone (DHT) and prolactin (HPr) levels were determined in normal males and females, in patients with benign prostatic hypertrophy (BPH) and in clinically stable patients with prostatic carcinoma (CAP), intact and orchiectomized. CAP patients were either untreated or on different modalities of therapy. The HPr levels were higher in prostatic cancer patients, in BPH patients, and in subjects on estrogen therapy. No significant differences were found between controls or patients treated with 5-Fu plus cytoxan. The T and DHT levels were decreased in all noncontrol subjects. The levels of DHT in intact, untreated CAP patients or those receiving 5-FU plus cytoxan were significantly higher than in BPH patients. Based on these observations, it appears that HPr could be involved with T and DHT in a feedback control role, especially in BPH. The alterations in these hormone levels in CAP treated or untreated patients are in marked contrast and must be evaluated further.

Current Status of Classification and Staging of Prostate Cancer

The international TNM classification system for prostatic cancer has been recently revised and is most helpful for comparisons between various groups of patients. Today in the United States, the evaluation of certain factors related to clinical and pathologic staging are being further altered. These include primary grade of tumor and the extent and techniques of tumor staging. New tests for acid phosphatase and alkaline phosphatase isozymes are being concurrently evaluated. Advances in the past six years have contributed to further redefinition and subgrouping of previous conventional staging or prognostic assessment of prostatic cancer. Localized (Stage B, C), occult (Stage A), or generalized (Stage D) tumors are being subdivided. Although grade of the primary tumor has been thought to be important only recently has a consensus been achieved by the National Prostatic Cancer Project for a system of assessment that uses cellular patterns and nuclear changes. Aspiration cytology may be a useful adjuvant. The role and type of pelvic lymph node assessment, whether operative, radiographic, or by thin needle percutaneous aspiration, is undergoing additional study.

The clinical value of lymphangiography: are the nodes surrounding the obturator nerve visualized?

Twenty-five patients subjected to pelvic node dissection for urologic malignancies underwent bilateral pedal lymphangiography preoperatively. Postoperatively, 50 samples of the nodes selectively removed from the regions surrounding the obturator nerve were radiographed. All 50 samples revealed the presence of radiopaque dye. The lymph nodes surrounding the obturator nerve represent the first point of lymphatic metastases in carcinoma of the prostate and the bladder. Their visualization by lymphangiography emphasizes the importance of such a diagnostic study for the correct clinical staging of these diseases. The lymphatic anatomy of the pelvis is reviewed and compared to the radiological findings in lymphangiography.

Effects of Diethylstilbestrol and Estramustine Phosphate on Serum Sex Hormone Binding Globulin and Testosterone Levels in Prostate Cancer Patients

Serum testosterone-estradiol binding globulin and total testosterone were measured in 2 groups of male controls (less than 50 and more than 65 years old) and in 7 groups of prostatic cancer patients treated with various endocrine manipulation procedures, including orchiectomy, and estramustine phosphate and diethylstibestrol therapy. There were 133 individuals studied. Total serum testosterone levels were significantly higher in the younger versus the older control group and testosterone-estradiol binding globulin levels were significantly higher in the older men. Whereas orchiectomy reduced serum testosterone to low concentrations (72 plus or minus 11 ng. per 100 ml.) testosterone-estradiol binding globulin levels were not altered. In contrast, estramustine phosphate and diethylstilbestrol therapy, when administered to intact or castrated patients, resulted in depressed testosterone and markedly elevated testosterone-estradiol binding globulin serum levels, particularly in those patients receiving estramustine phosphate (less than 35 ng. per 100 ml. and more than 6 micrograms per 100 ml., respectively). These studies led to the conclusion that diethylstilbestrol or estramustine phosphate therapy is significantly more effective than orchiectomy in eliciting a concomitant elevation of testosterone-estradiol binding globulin and a depression of total testosterone. Even though free serum testosterone was not measured in the present study the law of mass action would indicate that in those patients with high testosterone-estradiol binding globulin (more than 5 microgram. per 100 ml.) and low total testosterone levels (less than 80 ng. per 100 ml.) the availability of biologically active (unbound steroid) testosterone would be negligible.

Chemotherapy of Advanced Renal Cell Carcinoma with Vinblastine and CCNU

Forty-four patients with advanced renal cell carcinoma (stage IV) were divided into 3 groups. The 23 patients in group 1 received CCNU alone,the 6 patients in group 2 received CCNU and vinblastine and the 15 patients in group 3 received methyl CCNU and vinblastine. The over-all response, subjective and objective, was 30% in group 1, 60% in group 2 and 54% in group 3. These results are compared to other existing modalities of treatment and appear to be superior.

Chemotherapy of Advanced, Hormonally Resistant Prostatic Carcinoma

9 advanced prostate cancer patients were given a dose of 1-(2-chlorethyl-3[4-methyl cyclohexyl]-1-nitrosourea) (MeCCNU) 175 mg/m2 orally every 6 weeks. All of them had previously failed on hormonal therapy. 8 patients have progressed during the chemotherapy and only 1 was considered to be stable during a period of 18 weeks. Hematologic toxicity was seen in 3 patients. 21 patients with advanced prostatic carcinoma who failed hormonal therapy were treated with a combination of estracyt (600 mg/m2/day) plus MeCCNU (175 mg/m2/6 weeks) in oral doses. 1 patient had stable disease for about 30 weeks and another one had a subjective response for 12 weeks. 11 patients had hematologic toxicity and 5 of them required dose modification. 10 patients with stage D carcinoma of the prostate were given oral estracyt at a dose of 600 mg/m2/day plus cis-diamminedichloroplatinum (DDP) at an intravenous dose of 60 mg/m2 twice a week repeated every 3 weeks plus methotrexate (MTX) at an i.v. dose of 100 mg/m2 twice a week, repeated every 3 weeks. All of the patients had failed on prior therapy. 9 patients are evaluable, 4 patients had an objective response and 2 others had a subjective response. 2 patients had hematologic toxicity (life threatening) and 2 others had a decrease in creatinine clearance to 60 mg/min and required dose modification. The combination of estracyt + DDP + MTX or a modification seems to be promising.

A Study of the Effect of Papaverine in Neuroblastoma Using the Experimental C1300 Murine System

The effect of papaverine on transplantable C1300 murine neuroblastoma model was evaluated. Subcutaneous inoculation of A/J mice with 10(6) C1300 cells resulted in predictable tumor growth and animal death in 36 +/- 5 days. In 33% of control animals, lung and liver metastases were observed. Subcutaneous injections of papaverine prior to tumor inoculation and during the tumor growth failed to show any detectable effect on local growth of the tumor. Benign transformation of the primary tumor was not observed. However, papaverine injection 21 days after tumor inoculation was associated with only 9% incidence of metastatic development. Papaverine treatment, when started one day prior to tumor inoculation or 10 days after tumor implant, resulted in complete prevention of all detectable metastatic growth, while having no apparent effect on local tumor growth. Further study of papaverine effect in the neuroblastoma murine model is indicated.

Eight years of experience with preoperative angiographic and lymphographic staging of bladder cancer.

Our experience with the preoperative staging of bladder cancer by bilateral selective hypogastric arteriography has been accumulated since 1968. More than 150 patients have been studied by selective angiography before radical cystectomy. Our latest series of 52 patients (1972 to 1976) compares to our previous experience demonstrating angiographic staging accuracy to detect bladder invasion and occult metastases at a rate exceeding that of clinical staging alone. Arteriographic staging of D lesions, when supplemented with lymphography, approaches 100 per cent accuracy. Falsely negative lymphograms currently are extremely uncommon (1.9 per cent). In several illustrated instances angiographic staging was proved to be even more accurate than the pathologic staging of a limited cystectomy specimen. The over-all angiographic and lymphangiographic staging accuracy in our most recent series of cystectomy patients was 78.8 per cent. The techniques and reliability of the data are discussed in detail, including the factors that interfere with the exact arteriographic staging of bladder cancer. However, these factors are more troublesome in early stage lesions. These studies demonstrate the role and value as well as areas of limitation of preoperative arteriography and lymphography in the evaluation of invasive bladder cancer.

Shigella sonnei bacteremia Unusual antibody response from immunosuppressive therapy following renal transplantation

Abstract Shigella sonnei bacteremia developed in a patient who had undergone renal transplantation and immunosuppressive therapy; following treatment with chloramphenicol and lincomycin, the patient recovered from the infection. Possibly because of the concurrent immunosuppressive therapy, the patient had only a modest antibody response against the infecting microorganism but, unexpectedly, produced antibodies in high titer against a recently recognized antigen shared by enteric bacteria.

Sisomicin in urinary tract infection tolerance and wfficacy study

Twenty-one patients with gram-negative urinary tract infections were treated with sisomicin, a new aminoglycoside antibiotic. Bacteriologic cure was achieved in 62 per cent of patients, and improvement in another 33 per cent. Mild transient elevation of serum creatinine occurred in 3 patients. No other toxicity was observed. Further clinical trials with more frequent dose administration and in combination with other antibiotics is suggested.