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Biomedical subjects

C G Marks

Publications and source records attributed to C G Marks.

At least 37 records · Page 2Linked to original sources

Relation between stage, grade, proliferation, and expression of p53 and CD44 in adenomas and carcinomas of the colorectum.

AIMS: To investigate the changes in and relations among p53, CD44 and MIB-1 expression in adenocarcinomas of the colorectum and to determine whether these changes are progressive across the adenoma-carcinoma sequence. METHODS: Expression of p53 protein, CD44 adhesion molecule and MIB-1 proliferation antigen was detected using immunohistochemistry in 68 colorectal carcinomas and 32 colorectal adenoma. The staining characteristics were compared with degree of dysplasia in adenomas, and differentiation and Dukes' stage in carcinomas. Results were analysed and assessed using Spearman's rank correlation and independent t tests. RESULTS: p53 staining was present in som adenomas and correlated with the degree of dysplasia. There was significantly more staining in carcinomas than adenomas and significant correlation between staining and Dukes' stage. CD44 staining was maximal in adenomas, diminished in carcinomas and was minimal in metastasising carcinomas. There was inverse correlation between p53 and CD44 expression across the adenoma-carcinoma-metastasising carcinoma sequence. MIB-1 expression was highest in carcinomas but did not correlate with either p53 or CD44 expression. CONCLUSIONS: There are progressive changes in p53, CD44 and MIB-1 expression in adenomas and carcinomas. A combination of these tests may prove useful in assessing which patients with adenomas are at greatest risk of progressing to carcinoma.

Adenocarcinoma↗

Population screening for colorectal cancer: comparison between guaiac and immunological faecal occult blood tests.

There is concern about the low sensitivity of the guaiac-based Haemoccult test in mass population faecal occult blood (FOB) screening for the early detection of colorectal carcinoma. Hemeselect, an immunological FOB test, has been shown to be more sensitive for symptomatic colorectal cancer and may prove to be a more reliable screening method. In Brighton and Guildford, 4018 asymptomatic subjects aged 50-75 years were offered screening with Haemoccult and Hemeselect. A total of 1489 (37.7 per cent) completed both tests, of which 17 (1.1 per cent) were positive for Haemoccult and 145 (9.7 per cent) positive for Hemeselect (a total of 148 subjects had positive tests). Seven subjects (4.7 per cent) refused to be investigated. Colonic investigation in the remainder revealed nine cancers and 49 patients with 67 adenomas (32 tumours 1 cm or more in size). All cancers (Dukes A, six; B, one; C, two) were detected by Hemeselect (positive predictive value 6.2 per cent) but only one patient was Haemoccult positive (positive predictive value 5.9 per cent). Hemeselect detected 65 adenomas (31 of 1 cm or more) in 48 patients (positive predictive value 33.1 per cent) compared with 11 adenomas (seven of 1 cm or more) in eight patients who were positive for Haemoccult (positive predictive value 47.1 per cent). The test specificity for neoplasia was respectively 94.9 and 99.6 per cent. The Hemeselect positive rate is high but its substantial positive predictive value for cancer warrants continuing evaluation.

Aged↗

Effect on lymph node status of triple levelling and immunohistochemistry with CAM 5.2 on node negative colorectal carcinomas.

Several papers have recently assessed whether immunohistochemistry increases the accuracy of staging in node negative colorectal carcinomas, by showing micrometastases. The results have been contradictory. In this paper 542 nodes which were negative for tumour on routine sectioning, were stained with CAM 5.2. In addition, the tissue was levelled three times, this technique being more economical, to see if either or both techniques increased the pick up of micrometastases. Six nodes showed positive staining of occasional cells in the subcapsular and paracortical sinuses, but these were cytologically benign on review and were not thought to represent metastatic tumour. Triple levelling did not show any additional micrometastases.

Colorectal Neoplasms↗

Faecal occult blood screening for colorectal neoplasia in a targeted high-risk population.

A general practice-based programme was initiated in 1987 to identify individuals at high risk of developing large bowel cancer and offer them screening of faecal occult blood. In all, 5298 people from 21 general practices in the Guildford area were offered 7510 screening tests. In total, 5934 tests were completed (compliance rate 79.0 per cent) with 287 positive results (4.8 per cent). Of the patients with positive results, 44 had cancer and 38 polyps. The sensitivity of the test for cancer was 63 per cent, the specificity 96 per cent and the positive predictive value for all neoplasia 29 per cent. The detection rate of 44 cancers per 5934 people screened compares favourably with data from the Nottingham-based screening of an unselected population (0.74 versus 0.23 per cent).

Adult↗

Lymph node metastases in early rectal cancer.

Local excision of early rectal tumours is an attractive proposition, avoiding the morbidity and mortality of major resection and possible permanent stoma. This study was designed to investigate the incidence of lymph node metastases associated with tumours that are locally confined to the bowel wall. A total of 454 rectal excision specimens were reviewed. Twenty-two (20 per cent) of 109 patients with tumours locally confined to the bowel wall had metastases in local lymph nodes, although 14 of these had only one or two involved nodes. Three of 27 patients with tumours that did not penetrate through the submucosa had lymph node metastases. Less well differentiated tumours were more likely to have metastasized but there was no significant difference in the height or size of tumours or in the depth of invasion between patients with or without lymph node metastases.

Humans↗

Primary malignant melanoma of the rectum.

The diagnosis of a primary rectal malignant melanoma has been the subject of considerable argument for many years, principally on the grounds that extension from a primary anal lesion was often impossible to exclude. This paper provides evidence that certain melanomas can be recognized as primary rectal tumours, not only from careful anatomical assessment of the site of the tumour, but also by showing that they arise on a background of benign melanocytic proliferation in the rectal mucosa. The clinical presentation of these lesions, their possible mechanism of origin and their treatment is discussed.

Aged↗

Extent of mesorectal spread and involvement of lateral resection margin as prognostic factors after surgery for rectal cancer.

The extent of tumour growth beyond the muscularis propria (mesorectal spread) was measured in specimens from 167 consecutive patients with rectal cancer. The 5-year survival was significantly greater in patients with slight mesorectal spread (4 mm or less) than in those with more extensive mesorectal spread (55% [95% confidence interval 42-66%] vs 25% [13-38%]). The prognostic value for survival of mesorectal spread was independent of the presence of lymphnode metastases. There were also significant differences in survival between patients with slight and extensive mesorectal spread among patients with Dukes' stage B tumours (66% [41-82%] vs 37% [14-60%]) and those with Dukes' stage C tumours (30% [12-52%] vs 18% [6-34%]). Thus mesorectal spread of rectal cancer is an important determinant of survival, and its accurate measurement may serve to subdivide Dukes' B and C cases. In this study tumour involvement of the lateral resection margin was not a useful predictor of local recurrence, but it did correlate with poor prognosis.

Actuarial Analysis↗

An evaluation of Fecatwin/Feca EIA; a faecal occult blood test for detecting colonic neoplasia.

A combination guaiac and immunological test Fecatwin/Feca EIA for the detection of faecal occult blood was used in the investigation of 535 symptomatic patients in order to assess the value of this combined test in the detection of colorectal neoplasia. The addition of the immunological part of the test led to an improvement in specificity for colorectal cancer from 80% to 91% and an increase in the positive predictive value of the test for colorectal cancer from 14% to 24%. However, there was a fall in sensitivity from 75% to 67%. There was no substantial advantage in the addition of the immunological part of the test to justify the extra laboratory workload incurred.

Colonic Neoplasms↗

The surgical treatment of intestinal obstruction due to left sided carcinoma of the colon.

Forty two consecutive patients who underwent surgery for an obstructing carcinoma of the left colon over a 5 year period were studied retrospectively. Twelve patients underwent an initial defunctioning procedure with no hospital deaths but with four deaths after a mean follow-up of 25 months. Of the 30 patients who had a primary tumour resection, 7 died during the first hospital admission and a further 4 during a mean follow-up period of 23.7 months. The hospital mortality following primary resection was related to the site and timing of the anastomosis. During the first hospital admission 3 of 5 patients died after colocolic anastomosis, 3 of 10 died following ileocolic anastomosis, but only 1 of 15 died in those who did not have a primary anastomosis performed. The mean hospital stay of patients undergoing a delayed resection was 41 (s.e. (mean) 2.8) days compared to 24 (s.e. (mean) 2.8) days in those undergoing a primary resection. Primary tumour resection with a delayed anastomosis is recommended on the basis of these findings.

Adult↗

Clearance technique for the detection of lymph nodes in colorectal cancer.

Lymph node metastases are an important determinant of prognosis following surgery for colorectal cancer. A xylene alcohol clearance technique has been employed in Guildford to facilitate the identification of lymph nodes in the mesorectum of rectal cancer specimens. The numbers of lymph nodes and lymph node metastases were compared with seven other centres and St. Mark's Hospital, where clearance techniques were not employed in patients undergoing a randomized trial of pre-operative radiotherapy for rectal cancer. The total number of lymph nodes identified per patient in the mesorectum of patients at Guildford (mean = 23.1 +/- 1.18) was significantly higher when compared with patients at St. Mark's Hospital alone (mean = 13.1 +/- 0.86) and the seven combined "non-cleared' centres (mean = 10.5 +/- 0.6) (P less than 0.001). The number of lymph node metastases per patient was significantly higher in the Guildford series (mean = 3.21 +/- 0.58) when compared with the seven combined centres (mean = 1.9 +/- 0.3) (P less than 0.05). The numbers of lymph node metastases found in the lowest part of the specimen close to the levator ani were significantly higher in the Guildford patients (mean = 1.2 +/- 0.4) compared with St. Mark's Hospital (mean = 0.13 +/- 0.1) and the seven combined 'non-cleared' centres (mean = 0.56 +/- 0.1). This clearance technique identified not only a greater number of lymph nodes but also more metastases within those nodes, particularly in the supralevator area of the mesorectum.

Colonic Neoplasms↗

The septic complications of sigmoid diverticular disease.

In 2 years 41 patients were treated surgically for septic complications of diverticular disease of the sigmoid colon. Nine patients had fistulae arising from sigmoid diverticular disease. Resection of the sigmoid was undertaken as the primary procedure in 8 patients with anastomosis in 5. Thirty-two patients had pericolic abscesses or peritonitis. The outcome (morbidity, length of stay) of the 21 patients who underwent primary resection was compared with that of the 11 patients treated by defunctioning colostomy alone. The better results in the larger group of 21 patients indicate that primary resection should be the treatment of choice for the septic complications of diverticular disease.

Abscess↗