Detection of cancer in patients by reduced lymphocytic cortisol metabolism-enhancing effect.

A double-blind study was done on the plasma from 59 hospitalized patients to determine whether a diminished lymphocytic cortisol metabolism-enhancing effect among cancer patients could be used to distinguish them from persons with noncancerous diseases. Known concentrations of human lymphocytes from healthy donors were incubated with cortisol in media containing 50% phosphate-buffered saline (PBS) and 50% of one of the following additives: 1) homologous plasma (HP), 2) plasma from the patient being tested, or 3) additional PBS. Plasma in which the metabolism-enhancing effect was less than 70% of that obtained with HP was considered to be that of a cancer patient. Among the 19 patients known to have cancer, there were only two false-negative results, whereas among the 40 patients diagnosed as having noncancerous diseases, there were six false-positive results. Thus the test findings and the pathologic diagnosis were obviously correlated in approximately 90% of the patients.

Ascites in patients undergoing maintenance hemodialysis. Report of six cases and physiopathologic approach.

Six patients with chronic uremia in whom ascites developed during maintenance hemodialysis are described. Their clinical and biochemical findings are reviewed and compared with data of 10 hemodialyzed patients without ascites. Liver cirrhosis was the origin of ascites in only one case. Hypoalbuminemia, liver cirrhosis, congestive heart failure, peritonitis, peritoneal tuberculosis and carcinomatosis were uniformly absent in the other patients. Long-term and marked overhydration seems to be at the origin of ascites. Lack of peripheral edema, probably due to ascites compartmentalization, was a constant finding in every noncirrhotic patient with ascites. When long-term overhydration was stopped after successful kidney transplantation or by means of diminished water and salt ingestion, reversal of the syndrome was attained. Nevertheless, ascites because of liver cirrhosis was not influenced by means of kidney transplantation. In three patients with ascites who did not receive a transplant, a significant reduction in water and salt ingestion was reached after intensive psychotherapy which led to reversal of the ascitic syndrome. In one anephric patient ascites did not develop despite water overloading. Survival has not been influenced by the formation of ascites. Further research is needed to determine the mechanism of sodium transfer across the peritoneal membrane. Influence of humoral factors can be considered, if an active transport mechanism could be demonstrated.

In vitro induction of T suppressor lymphocytes in recipients of renal allografts by THF, a thymic hormone.

Lymphocyte subpopulations were determined in 13 patients, recipients of kidney allografts, 7 of them during an acute rejection episode (ARE). Monitoring of the T lymphocyte suppressor or T helper cells was performed by aid of the theophylline sensitivity test and the local xenogeneic graft-versus-host reaction (GVHR). An absence or a striking decrease of theophylline-sensitive T suppressor cells was found in all patients during ARE. Incubation of the lymphocytes of these patients with a thymic hormone, THF, raised the number of TS lymphocytes from nil or from a very low level to normal or above. The therapeutic use of THF in selected renal allograft recipients is proposed.

Hydrocortisone and inhibitors of prostaglandin synthesis. Potentiation of allograft survival in mice.

We studied the effects on survival of allogeneic skin grafts after treatment with hydrocortisone and/or inhibitors of prostaglandin synthesis: indomethacin and flufenamate. We found a marked synergistic effect of combined treatment with hydrocortisone and indomethacin or flufenamate. Neither hydrocortisone nor indomethacin or flufenamate, when given alone in relatively small doses, caused delayed graft rejection. However, when small doses of hydrocortisone were used in combination with flufenamate or indomethacin, the median survival time (MST) of allogeneic grafts was prolonged from 11.4 days to 20.9 and 23.8 days, respectively. Moreover, the increase in graft survival was comparable to that obtained by treatment with relatively high doses of azathioprine alone or combined with hydrocortisone. The finding of synergism between low doses of prostaglandin synthesis inhibitors and glucocorticoids in delaying graft rejection suggests that such treatment might provide a relatively safer means of achieving clinical immunosuppression than the high doses of steroids and azathioprine currently in use.

Specific attachment of T-lymphocytes from cancer patients to tumor cells.

The present study describes a new approach for detecting the immune reaction of peripheral blood lymphocytes of cancer patients against tumor antigens. T-lymphocytes from patients with carcinoma of the urinary bladder were found to attach specifically to monolayers of cells of urinary bladder carcinoma line (T24). The attached T-cells were identified by their capacity to form E-rosettes with sheep red blood cells. The number of rosette forming--target attached lymphocytes (RF--TAL) was 6 times higher in bladder carcinoma patients than in healthy controls or in patients bearing other types of cancer.

A mouse ear reaction for assessment of human lymphocyte immunocompetence.

A mouse ear reaction for testing cell mediated immunity of human lymphocytes using the local graft-versus-host reaction assay is described. Five million human mononuclears were locally injected into the ears of immune suppressed NZW mice. The reaction mounted was quantitated by determining the 125I-Iodo-Deoxyuridine (125I-UdR) incorporation in both ears. The ratio of 125I-UdR incorporation, of the injected to that of the non-injected ear (GVHR index), 7 days after lymphocyte injection, served as an accurate measure for the extent of the reaction. Only normal human mononuclears and purified, separated normal human T lymphocytes mounted a local graft-versus-host reaction. Whereas normal human B lymphocytes, chronic lymphatic leukemia B lymphocytes, mononuclears from patients with transitional cell carcinoma of the bladder, irradiated normal human mononuclears, mouse syngeneic mononuclears, or human erythrocytes gave no positive reaction. These experiments demonstrate that this assay can be used to quantitate an in-vivo specific graft-versus-host reaction.

Occult progressive renal damage in the elderly male due to benign prostatic hypertrophy.

A review of the case histories of 345 patients who underwent protatectomy showed that 1.7 percent (6 patients) had "occult and progessive renal damage" secondary to prostatic hypertrophy. All these men were over the age of 60 and the disturbances in micturition were so mild that the patients were unaware of, or chose to ignore them. The presenting symptoms were nonspecific and included generalized weakness, anorexia, nausea, constipation, and weight loss. Investigation revealed impaired renal function of varying degrees. Prostatectomy was associated with a dramatic improvement in all 6 patients. Physicians should be aware of the clinical entity of occult and progressive renal damage secondary to obstruction of the bladder outlet, especially in the elderly male. Uremia can develop with minimal urinary symptoms. Elderly men often suppress or deny their symptoms because of the fear of operation.

Immunocytochemistry of epithelial markers in citral-induced prostate hyperplasia in rats.

Immunocytochemical characterization of several epithelial markers using the PAP technique was analyzed during different stages of induced prostatic hyperplasia in rats. Intact adolescent rats (42 days old) were treated with citral (3,7 dimethyl-2,6 octadienal) for 10, 30 and 100 days and their ventral prostate compared to untreated, matched-age animals. Among the epithelial markers studied the prostatic specific acid phosphatase was present in hyperplastic prostates of rats. The immunoreaction showed a fair correlation with the severity of lesion and duration of treatment. The prostatic specific antigen showed equally immunoreactive in both control and treated rats. The hyperplastic and normal rat prostates did not show immunoreactivity towards the other epithelial cell markers such as epithelial membrane antigen, carcinoembrionic antingen and alpha-fetoprotein antisera. It is concluded that prostatic specific acid phosphatase, and to a lesser extent prostatic specific antigen, might represent valuable markers for comparative studies of prostatic hyperplasia in rodents.

Is open prostatectomy really obsolete?

A total of 1,066 prostatectomies treated by us from 1985 to 1989 were reviewed. The necessary comprehensive data were available on 710 cases. Open (Millin's retropubic) prostatectomy (RPP) was the procedure of choice for large glands and transurethral resection (TURP) for smaller glands: 408 had had RPP and 262 TURP; 14.5 percent of the TURP group eventually needed a second procedure during a one to six-year follow-up compared with only 2.6 percent of the RPP group. Forty other patients who had been operated on elsewhere were referred to us for a second, repeat procedure; 30 also previously had had a TURP. Total hospitalization, operating time, and complications were better in the long run in the RPP group compared with the TURP group. It is believed that open prostatectomy still has a respectable place in urology and therefore, should be considered and also taught to residents for use in dealing with large glands.

Local hyperthermia for prostate cancer.

Hyperthermia for treatment of cancer is known to be beneficial both in itself and in conjunction with other forms of treatment, particularly radiotherapy. We have developed a new machine for local hyperthermia (41-44 degrees C) to the prostate, by transmission of microwaves (915 MHz) via a rectal probe. Patients were treated on an outpatient basis and did not require any anesthesia or sedation. There were no complications. Good results, measured by local control, disappearance of malignancy, relief of obstructive symptoms and pain, have been obtained in a series of 44 cases. More studies with this promising new modality are in progress.

Spontaneous extravasation of urine in chronic ureteric obstruction.

Two cases of spontaneous extravasation of urine in chronic ureteric obstruction are presented. In 1 case the long-standing partial ureteric obstruction was caused by enlarged lymphomatous glands, and extravasation was followed by a perinephric abscess. In the second case, believed to be unique, there was a moderate chronic ureteric obstruction post irradiation, and extravasation was induced by a sudden rise in intra-abdominal pressure due to vomiting.

Early combined hormonal and chemotherapy for metastatic carcinoma of prostate.

Twenty-five patients with confirmed Stage D carcinoma of the prostate were treated by a combination of bilateral orchiectomy, estrogen, and chemotherapy soon after diagnosis was established. Patients were given diethylstilbestrol (DES) 3 mg. daily, and a weekly intravenous injection of 5-fluorouracil (5-FU) 10 mg./Kg. and cyclophosphamide 10 mg./Kg. They were followed up for between sixteen and forty-two months. The majority of patients reported a subjective improvement. Objectively, the primary tumor shrunk by more than 50 per cent in 84 per cent of the patients, while in 64 per cent there was improvement in the lesions shown on bone scan. The cumulative survival rate during three and one-half years was 76.5 per cent. These encouraging preliminary results appear to justify the early initiation of combined therapy in larger numbers of patients with Stage D prostatic carcinoma.

Diseases of prostate treated by local microwave hyperthermia.

A new method is described for the treatment of diseases of the prostate with local hyperthermia applied transrectally by microwaves. A series of 500 treatment sessions given to 74 patients with 14 controls, is reported. Thirty patients had advanced cancer of the prostate, 37 had benign hyperplasia and were unsuitable for surgery, and 21 had chronic prostatitis. Marked objective and subjective improvement was noted in the majority in twenty-four months of follow-up.

Nortriptyline hydrochloride in urology.

Forty female patients suffering for long periods from frequency, urgency, and dysuria without any definite organic cause received nortriptyline chloride for three weeks. In 75 percent there was either considerable improvement or total disappearance of urinary complaints. At the same time the in vitro effects of the drug were tested using the isometric muscle contraction technique. Nortriptyline was found to have anticholinergic properties. The importance of this effect in the clinical study and the possible mode of action of the drug are discussed.

Local hyperthermia to canine prostate. A pilot study.

Repeated treatments of localized deep microwave hyperthermia were given to a series of dogs by means of a 915 MHz, water-cooled skirt-type applicator. The applicator was inserted into the rectum and directed toward the prostate in order to heat it by means of the absorbed microwaves while keeping the rectal wall at a lower temperature by surface cooling of the applicator itself. Sessions were given for different lengths of time ranging between ninety minutes and five hours, during which the prostate temperature was kept at 42.5 degrees C (+/- 0.5 degrees C) or 44.5 degrees C (+/- 0.5 degrees C). Three-dimensional temperature distributions in the prostate were measured accurately and verified by a Luxtron Fluoroptic Unit. Temperatures were constantly monitored in the rectal wall and in the prostatic urethra. Thorough and systemic follow-up was done before, during, and after each treatment, and the observations are reported. Two interesting preliminary observations were made: (1) differential blood counts showed significantly monocytosis following the treatments and lasted for at least one week, and (2) values of creatinine phosphokinase (CPK) and serum glutamic oxaloacetic transaminase (SGOT) were found to rise irreversibly in those animals which were later found to have definite histopathologic evidence of localized necrotic damage.

Combined hormone-chemotherapy for metastatic prostatic carcinoma. Eleven-year follow-up.

Thirty-six patients with histology-proved Stage D2 carcinoma of the prostate were treated with a combination of bilateral orchiectomy, diethylstilbestrol 3 mg/day, and chemotherapy (5-fluorouracil and cyclophosphamide) soon after diagnosis was established. The combined therapy was well tolerated by the patients, and complications were not severe and of a transient nature. The majority of patients showed a subjective and objective improvement: 75 per cent of patients had relief of bone pain, and 80 per cent reported relief in urinary symptoms. There was regression or stabilization of the primary tumor in 82.2 per cent. Disappearance or stabilization of osteoclastic lesions on bone scans was noted in 55.5 per cent of patients. The cumulative survival rate at eleven years is 55.5 per cent.

Fifteen years' experience of combined hormone/chemotherapy in metastatic prostate cancer.

Fifteen years ago we embarked on a treatment protocol for prostatic cancer patients with widespread disease (Stage D2) which included both hormonotherapy (i.e., orchiectomy and diethylstilbestrol [DES] 5 mg/day--later substituted with cyproterone acetate [CPA] 0.2 g/day) and chemotherapy (cyclophosphamide and 5-fluorouracil 10 mg/kg/week). The rationale for such an approach was the universally poor results obtained from the conventional approach which advocated consecutive single-treatment schedules once the previous therapy had ceased to be effective. As such a conventional approach probably allowed the selection of new resistant cell clones, we assumed that perhaps an aggressive combined systemic therapeutic approach from the start, would give such a group of patients--already with generalized disease--a better long-term result. In retrospect, after fifteen years, the chemotherapy on a series of 50 patients so treated has been well tolerated with only minimal, temporary side effects. This regimen was continued up to five years with a reduced maintenance dose. The hormonotherapy was also well tolerated, and was fully maintained. Only 28 percent died of their disease (16% within the first 2 years); 28 percent died of other causes; 40 percent are still alive (14% with clinical disease). In only 9 cases was the chemotherapy discontinued for various reasons. No control arm was originally designed in this protocol, but the long-term results suggest that our original concept was probably valid. Further studies, with the possible use also of newer chemotherapeutic agents, may well justify considering this combined therapeutic approach when dealing with this disease in its widespread form.

Widespread dissemination of gelfoam particles complicating occlusion of renal circulation.

Embolization of renal circulation by Gelfoam particles in a thirty-two-year-old man with renal carcinoma was followed by retrograde regurgitation of the injected particles upstream, with resultant occlusion of the celiac trunk and the superior mesenteric artery. This was followed by a stormy clinical course, which the patient survived. Several possible explanations are offered for the occurrence of this complication.

Malignant melanomas of female urethra.

Primary melanoma of the female urethra is extremely rare. Treatment by surgery, radiation, and chemotherapy has been uniformly ineffective. We herein report on 2 patients with primary malignant melanoma of the urethra treated with immunotherapy and chemotherapy. The first patient died four years after the initial diagnosis, and the second died after two years. Chemo-immunotherapy may be considered as an additional, palliative form of treatment in the management of primary melanoma of the female urethra, but cystourethrectomy should be the initial form of treatment.

Penile edema and meatal ulceration after intravesical instillation with bacillus Calmette-Guerin.

Bacillus Calmette-Guérin (BCG) bladder instillation is an accepted treatment modality in the management of superficial transitional cell carcinoma but is associated with frequent side effects. A report of intravesical BCG-induced penile edema and meatal ulceration that occurred in 2 patients is presented. During induction therapy, both patients complained of progressive penile edema. In 1 patient the edema appeared after the second instillation and in the other after the fourth instillation. Edema was associated with ensuing meatal ulceration and enlarged inguinal lymph nodes. BCG instillation was aborted, and oral antituberculous treatment was initiated. There was no report of external spillage during the administration of BCG or of genital or urethral trauma during catheterization. Patients were treated at different clinics but with BCG of the same strain and batch. Symptoms continued for 6 weeks until they abated. Both patients were managed with oral antituberculous drugs for a period of 3 months. Adverse effects of BCG intravesical administration affect several organs in the genitourinary system. The penis and urethra may also be involved, presenting as penile edema and meatal ulceration. Physicians who administer BCG must be familiar with the possible complications and their appropriate management.