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Biomedical subjects

J M Northover

Publications and source records attributed to J M Northover.

At least 73 records · Page 4Linked to original sources

Anal cancer and human papillomaviruses.

Epidemiologic and clinical evidence has suggested a possible association between anal cancer and human papillomavirus (HPV) types that are known to be associated with cervical and other genital cancers. Using Southern blot and dot blot analysis, the authors examined 45 primary anal malignancies for HPV DNA types 6, 11, 16, and 18. HVP 16, DNA was detected in 23 of 41 (56 percent) anal squamous-cell carcinomas (SCC) and in the lymph-node metastases of two of these tumors. In addition, HPV 18 DNA was detected in 2/41 (5 percent) anal SCCs. Anal SCC contained no detectable HPV 6 or 11 DNA. The remaining four primary anal malignancies were not squamous carcinomas and did not contain any detectable HPV DNA. Nonmalignant anal epithelium and malignant rectal mucosa obtained from surgical patients undergoing hemorrhoidectomy and abdominoperineal excision of the rectum did not contain any detectable HPV DNA. HPV 16 DNA in anal cancer was predominantly integrated into the host cell DNA. In situ hybridization was used to demonstrate that HPV 16 DNA in anal SCC tissues is confined to the nuclei of carcinoma cells. The results of this investigation closely parallel similar studies of cervical cancer and lend support to the concept of the involvement of HPV 16 and 18 in the development of anal and genital squamous-cell carcinoma.

Adenocarcinoma↗

Familial colorectal cancer and familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) affects around 1 in 10,000 individuals; the gene for this condition was recently shown to be located on chromosome 5, and it is only a matter of time before its precise location and function are determined, making prephenotypic, and even prenatal, diagnosis more generally available and reliable. In the mean time, care of FAP families will continue to depend on careful registration of family information, prophylactic bowel surgery and surveillance for other potentially serious manifestations of the disease. Upper gastrointestinal malignancies and desmoid tumours have overtaken colorectal cancer as the leading causes of death in some centres. Other dominantly-inherited colorectal cancer syndromes produce less striking phenotypes, but affect far more individuals than FAP. It appears that there are two patterns of hereditary non-polyposis colorectal cancer (HNPCC) syndromes, one involving cases of bowel cancer alone, the other associated with breast and gynaecological cancers; these may prove to be variable expressions of a common gene abnormality. More effort is required by clinicians managing cases of colorectal cancer to identify affected families in order to offer surveillance and appropriate treatment in the hope that such measures may prevent cancer in family members.

Adenomatous Polyposis Coli↗

Bone metastases in carcinoma of the rectum: a clinical and pathological review.

Bone metastases were confirmed in 48 patients after treatment of rectal cancer and occurred predominantly in the lumbar spine and pelvis. Most of the deposits were lytic and coexisted with widespread metastatic disease. Correspondingly, the median survival from diagnosis was only 4 months. The new prognostic classification for rectal cancer was applied to the original tumour specimens and categorized 23 of these tumours into group IV which confidently predicts a poor outcome compared with only eight by the method of Dukes.

Adult↗

Androgen receptors in colorectal adenomas.

To evaluate the potential effect of androgens on the development and growth of human colorectal adenomas, the prevalence and concentration of cytosolic androgen receptors (AR) were analysed in 26 adenomas and 19 samples of normal colonic mucosa by a hybrid ligand receptor-binding assay. AR were detected in 7 of the adenomas (26.9%), and in 6 of the normal mucosa samples (31.6%). In the adenomas, AR levels demonstrated were low, ranging from 6 to 31 fmol/mg cytosol protein, and dissociation constants (Kds) ranged from 0.17-2.7 X 10(-9) M. Of 13 adenomas excised from men, 6 (46%) had positive receptor activity, whereas only 1 of 13 (7.7%) from women was positive (P = 0.03, Fisher's exact test). There was no correlation between AR titre and patient age, or between adenoma size and histological type or degree of dysplasia. In normal mucosa, AR levels ranged from 7 to 33 fmol/mg and Kds ranges from 0.24-3.1 X 10(-9) M. There was no significant difference between either AR prevalence or levels in the adenomas and normal mucosa. The sex difference was exclusive to the adenoma. Endogenous androgen may play a role in adenoma development early in the promotional process.

Adenoma↗

Anovaginal and rectovaginal fistulas in Crohn's disease.

Between 1957 and 1985, 886 women with Crohn's disease and an intact distal large bowel were seen at St. Mark's Hospital. Ninety of these patients developed a fistula between the vagina and anus or rectum at an average age of 34 years. The track of the fistula was clearly documented in 80 patients and was extrasphincteric or suprasphincteric in 36, transsphincteric in 42 (high 13, low 29), and superficial in two. Of the 90 patients, 12 (13 percent) were managed throughout without recourse to surgery. Twelve (13 percent) had the fistula laid open or drainage of an abscess as the only surgery. Twelve (13 percent) underwent repair of the fistula and, of these, eight remain symptomatically cured. One has had further symptoms but no surgery while three later underwent proctectomy for rectal disease. In eight patients the colon was removed and the rectum defunctioned and in 34 the rectum was excised as the initial surgery after development of the fistula. The remaining 12 (13 percent) underwent later proctectomy for rectal disease or failed conservative management of the fistula. Extensive colonic involvement, rectal disease, or associated anal lesions were the main reasons for rectal excision in 38 patients. In only ten was the rectovaginal fistula a prominent indication for proctectomy. As medical treatment, repair, or other local surgery were successful in one third of the patients, these options should always be considered in the first instance.

Adolescent↗

Dysplasia and deoxyribonucleic acid aneuploidy in the assessment of precancerous changes in chronic ulcerative colitis. Observer variation and correlations.

Cancer prevention in patients with long-standing ulcerative colitis depends on the detection of epithelial dysplasia in colorectal biopsy specimens. Deoxyribonucleic acid analysis by flow cytometry has also been used to examine biopsy specimens, and might be a more quantitative method of detecting precancerous change. Histology and flow cytometry were used to analyze 333 paraffin blocks from colectomy specimens of 58 patients with extensive ulcerative colitis; 22 of these patients had developed carcinoma. Interobserver agreement between three experienced pathologists grading the sections was good for high-grade dysplasia and no dysplasia, but poor for low-grade and indefinite dysplasia. Deoxyribonucleic acid aneuploidy was easier to recognize than dysplasia and, as with dysplasia, it was found to be associated with patients who had developed carcinomas. The presence of deoxyribonucleic acid aneuploidy correlated with the presence of dysplasia. We believe that dysplasia is a useful marker of premalignant change and that flow cytometry may be useful as a complement to histologic examination when dysplasia is suspected.

Adult↗

Results of curative surgery for colorectal cancer.

It is sometimes suggested that the results achieved by curative surgery for colorectal cancer have reached their peak. This is an over simplification. It may be, though this is not proven, that the principles of curative surgery have reached their limits, but the application of those principles is not uniform, leaving room for improvements in all the outcome parameters discussed. It may also yet be shown that the limits of 'conventional' radical surgery can be extended with advantage.

Colorectal Neoplasms↗

A new prognostic classification of rectal cancer.

Only 60% of patients having radical surgery for rectal cancer are cured of their disease. The ideal system of classification would identify just two categories--the cured and those who will die of their disease. Specimens from 379 patients who had undergone radical surgery for rectal cancer more than 20 years ago were re-examined in order to identify discrete pathological variables that independently influence long-term survival. The selected variables were given weighted scores and the score range was divided to provide four prognostic groups. The model was tested on a second data set comprising 331 patients and gave similar results. The new prognostic classification is simple to use and is superior to staging by the method of Dukes because it places twice as many patients into groups that provide a confident prediction of clinical outcome.

Adenocarcinoma↗

Activities of the Leeds Castle Polyposis Group.

In June 1985 an international meeting took place at Leeds Castle, England, to discuss some of the problems facing those caring for polyposis patients and conducting research in the field. From this grew the Leeds Castle Polyposis Group, comprising workers from 19 centers around the world; they agreed to cooperate initially in the collation of retrospective data with the hope that this would lead to prospective studies including comparative therapy trials. So far four retrospective pro formas have circulated. The data from these and plans for further projects will be discussed at the next meeting of the group in Washington in April 1987.

Adenomatous Polyposis Coli↗

Value of flow cytometric determination of ploidy as a guide to prognosis in operable rectal cancer: a multivariate analysis.

The DNA content of 203 cases of rectal cancer, with at least 15 years follow-up, was analysed by flow cytometry. One hundred and twenty-nine (64%) were DNA aneuploid and corrected survivals were significantly influenced by ploidy distribution (p less than 0.01). The DNA content and details of stage and grade were subjected to multivariate analysis using the Cox regression model. Ploidy was entered into models including Dukes' stage alone, tumour differentiation alone, Dukes' stage and differentiation in combination and a more comprehensive range of discrete stage- and grade-related parameters. All four models demonstrated its independent contribution to survival. However, its contribution was very small (5%, 18%, 5%, 4% respectively). These findings illustrate that results based on new technological developments should not be viewed in isolation, but their values must be assessed in combination with traditionally available data by means of multivariate analysis.

Adenocarcinoma↗