Biomedical subjects
Publications and source records attributed to G D Chisholm.
Modifications to the TNM classification for bladder cancer, introduced in 1979, are described. The use of this classification was evaluated in 106 new patients. It proved to be satisfactory for in situ and papillary tumours but major problems occurred in attempting to separate superficially invasive from deeply invasive tumours. Several aspects of this classification require further consideration and modifications are proposed.
The criteria for the diagnosis of progression of prostatic cancer after primary treatment by androgen suppression (oestrogen escape) were studied in 30 patients. Objective criteria are essential for this diagnosis and in this study the bone scan was the most useful criterion. Twenty-one of these patients had a secondary orchiectomy: one patient showed a partial objective response and 3 had a subjective response. It is concluded that an orchiectomy following failed primary oestrogen therapy is an ineffective procedure and therefore unjustifiable and that alternative treatments must continue to be evaluated.
Three hundred consecutive male partners of infertile marriages had serum samples tested for sperm agglutinating and sperm immobilising antibodies, using a micro-technique: 30.3% were found to be positive. Out of a control group of 100 fertile men 10 had antibodies detected (10%) and these at low titre; this difference was significant. The results of these serum tests were found to correlate with the results of seminal plasma tests, the mixed antiglobulin reaction for IgG and sperm cervical mucus contact testing, although all of these tests were less discriminatory with regard to fertility. The serum micro-immobilisation test showed a statistical association with fertility when analysed in those couples where both husband's and wife's tests showed no other bar to fertility.
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Rectal invasion by carcinoma of the prostate occurs in a significant number of cases (approaching 10%). A case of a rectovesical fistula owing to direct extension of a prostatic carcinoma is reported. This complication of the disease has not been described previously.
Three thousand, six hundred and four patients with carcinoma of the prostate attending the Royal Marsden Hospital, St Peter's Hospitals and all non-teaching hospitals of the South Metropolitan regions were reviewed, in addition, data from 1869 cases of prostatic carcinoma registered in the 2 South Metropolitan regions with determinable social class were compared with data collected from both teaching and non-teaching hospitals. Carcinoma of the prostate showed an increased incidence with decreasing socio-economic class.
The results of multiple biopsies from apparently non-tumour bearing bladder mucosa were studied in 154 patients with bladder cancer; 33% of the biopsies from apparently normal mucosa showed histological abnormalities including 4.5% with carcinoma. When the mucosa appeared red but flat, 52% of the biopsies showed histological abnormalities including 14% with carcinoma. Biopsies from mucosa that had a granular or mossy appearance showed carcinoma in 42%. A more aggressive management policy was adopted in 12 patients (8%) as a direct result of the biopsy findings.
Techniques of prostatic lymphoscintigraphy using 99mTc phytate (TP) and 99mTc antimony sulphide colloid (ASC) have been evaluated in 30 patients. The most successful technique was a superficial perianal injection of ASC. In general, definition of the regional lymph nodes lacked the precision and clarity that would be required for the technique to be used in staging of prostatic or other pelvic tumours; further development of the technique is recommended.
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Male ventral and female prostates of Praomys (Mastomys) natalensis were examined with the electron microscope. The findings support and add to information obtained with the light microscope on tissues from normal, castrated and ovariectomised animals. Our results indicate that although the female prostate may be considered a homologue of the male ventral ventral prostate anatomically and histologically, there are differences in sub-cellular morphology and hormone dependence. Cells of the intact ventral prostate of the male are characterised by prominent dilated Golgi vesicles and electron-dense "mature secretory granules" seen in the apical region of the cell. In the cells of the female prostate these features are absent. These morphological differences reflect the influence of hormones upon the cells, as shown by the reduction of the dilated Golgi vesicles in the castrated male and conversely, their occasional presence in the cells of the oestrous female. Comparison of castrated and ovariectomised animals shows that the male ventral prostate is much more dependent on androgens than the female is on ovarian hormones. There are several modes of secretion in the male ventral and the female prostate. These are by acellular and cellular blebbing, by a variety of secretory vesicles into the acinar lumina, and by a system of "double walled" vesicles not previously described.
A steroid receptor protein was isolated from the cytoplasmic fraction of Mastomys prostate. Following in vivo and in vitro labelling of the tissue with tritiated testosterone or dihydrotestosterone, samples were analysed by gel exclusion chromatography or sucrose density gradient centrifugation. A steroid receptor complex was isolated on Sephadex G-200. Analysis of the steroids associated with this complex showed that the major part of the bound radioactivity was 5 alpha-dihydrotestosterone. The binding was inhibited by unlabelled testosterone and could not be demonstrated in the liver cytosol. Using sucrose density gradient centrifugation, the dihydrotestosterone receptor complex sedimented at 5.6 s together with heavier aggregates. In the presence of 0.4 M KCl a single complex was sedimented at 4.6 s. The results demonstrate a receptor protein in the cytosol of the Mastomys prostate which binds to dihydrotestosterone and is comparable to that of rat prostate.
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Bone scanning with 99mTc-Sn-HEDP, radiographic skeletal survey and determination of plasma acid and alkaline phosphatase values were carried out in a consecutive series of 90 untreated patients with carcinoma of the prostate. 99mTc-Sn-HEDP provided satisfactory bone imaging and was convenient in use. The addition of bone scanning to radiographic survey increases the detection rate of skeletal metatases by 16%. Radiography increases the accuracy of bone scanning by identifying false positive scans due to benign disease and false negative scans when there are diffuse symmetrical bony metastases. The plasma phosphatases alone are less accurate staging tests. The acid phosphatase data support the validity of scan positive--X-ray negative findings. Bone scan abnormalities due to secondary deposits usually precede elevation of plasma alkaline phosphatase.
Serial bone scans and radiographic surveys were performed in 167 patients with histologically proven carcinoma of the prostate: 435 scans and surveys were performed. Nineteen of 99 patients with negative findings on diagnosis have become positive on follow-up. Forty-nine patients had positive findings on presentation; 8 have regressed on follow-up and 26 have progressed; 15 have remained unchanged. This is a sensitive method of follow-up in patients with carcinoma of prostate. Changes occurred in bone scans and skeletal surveys before any alteration in serum acid or alkaline phosphatases, symptoms of metastases or change in prostatic size in the majority of cases. The documentation of progression from MO to M1 disease presents no problems. However, problems in quantitation may arise in patients presenting with M1 disease.
The suitability of an exchange assay with methyltrienolone (R1881) for the measurement of androgen receptors in human prostatic tumours has been investigated. Having established the specificity of this compound for androgen receptor assay, a pilot study was carried out to measure dihydrotestosterone (DHT) receptor in 27 cases of benign hypertrophy and 18 cases of malignant tumour of the prostate.