Surgical management of rectal cancer.
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Colorectal Surgery↗
Biomedical subjects
J M Northover
Publications and source records attributed to J M Northover.
Changes in E-cadherin immunoreactivity in the adenoma-carcinoma sequence of the large bowel.
We have used an avidin-biotin immunoperoxidase technique to localise epithelial cadherin (E-cadherin), a calcium-dependent cell-cell adhesion molecule, in 107 paraffin-embedded sections from 93 patients consisting of 24 with colorectal adenoma, 55 with rectal carcinoma and 14 with liver metastases. The corresponding primary colorectal tumours were also studied in these cases. E-cadherin was expressed by normal colorectal epithelial cells with typical membranous staining at the intercellular junctions. Loss of normal membranous E-cadherin expression and presence of cytoplasmic staining were found frequently in adenomas larger than 1 cm (P < 0.01), with high grade dysplasia and villous histology (P < 0.01). In primary rectal cancers, loss of membranous expression correlated with high tumour grade. No correlation was seen with Dukes and Jass stage, local extramural spread and 5-year recurrence rate. Complete loss of membranous E-cadherin immunoreactivity was seen in 7/14 (50%) liver metastases in which 6/7 (86%) showed intense membranous E-cadherin immunoreactivity in the corresponding primary tumour. Our data indicate that changes in E-cadherin immunoreactivity and cellular localisation correlate with size, severe dysplasia in adenomas and tumour grade in carcinomas. However, there seems to be no correlation between loss of membranous E-cadherin immunoreactivity and the invasive and metastatic potential of the carcinomas.
Adenoma↗
Keratin expression in the normal anal canal.
The pattern of epithelial keratin expression in the normal anal canal has not been extensively defined and is a necessary prerequisite to the interpretation of alterations in these intermediate filaments in pathological anal epithelial lesions. Thirty-five frozen tissue specimens of resected haemorrhoids were investigated immunohistologically for expression of 14 individual keratins (K) using a panel of 17 monoclonal antibodies. Perianal skin showed basal expression of keratinocyte Ks 5, 14 and 17, and suprabasal expression of keratinocyte Ks 14, 10, 1 and 16. Anal squamous epithelium showed persistent basal K5 and 17, basal and suprabasal K4, 13 and 16 positivity, with sporadic expression of K1 and 10. The expression of simple epithelial keratins in squamous epithelium adjacent to the anal transitional zone varied with basal expression of K7, K8, K18 and K19 and sporadic suprabasal expression of K7 and K19. The anal transitional zone (ATZ) expressed K19, as found in transitional epithelia elsewhere. The full thickness of epithelium was positive for the simple epithelial Ks 7, 8 18 and 19. Marked heterogeneity of keratinocyte keratin expression was seen. Basal layers expressed Ks 4, 13, 14 and 17 and variably K16, while suprabasal layers expressed Ks 4 and 13, 14 and 17 and variably K16, while suprabasal layers expressed Ks 4 and 13 and variably K14, 16 and 17. This anomalous expression of keratinocyte K4 and 13 has also been documented in transitional epithelium of the bladder. The anal glands and ducts showed a keratin distribution similar to the transition zone.(ABSTRACT TRUNCATED AT 250 WORDS)
Anal Canal↗
Variables associated with the risk of colorectal adenomas in asymptomatic patients with a family history of colorectal cancer.
The results of screening individuals referred to the Family Cancer Clinic at St Mark's Hospital from 1986 are presented. Colonoscopy was performed in 644 asymptomatic individuals (from 436 families) with a family history of colorectal cancer. Sixty nine (15.8%) of the families fulfilled the Amsterdam criteria for the hereditary non-polyposis colorectal cancer syndromes (HNPCC). Seven cases of colorectal cancer were diagnosed at an average age of 49 years; six at Dukes's stage A and one at stage C, four in subjects from Amsterdam criteria families. One hundred and forty four (22.4%) subjects had one or more adenomas. The prevalence of adenomas in the subjects from Amsterdam criteria families was 34 of 127 (26.8%) compared with 110 of 517 (21.3%) in those from other families; the age and sex adjusted odds ratio (OR) was 1.76 (p = 0.02). Factors influencing the prevalence of adenomas in screened individuals were evaluated. Multivariate analysis showed that independent variables significantly related to the risk of adenomas were: age (p < 0.0001), sex (p = 0.0002), and the number of generations (> or = 2 v 1) of relatives affected by either colorectal cancer or adenomas (p = 0.0006). The latter variable was more highly predictive of the probability of finding an adenoma at colonoscopy than a family history of two generations with cancer only (p = 0.056). The OR of having colorectal adenomas increased with age, by about twofold for each decade, and was twice as high in men than women, and in subjects with two or more generations relative to those with one generation affected by colorectal cancer or adenomas. Six of seven patients with cancer and 46 of 144 (31.9%) with adenomas had lesions proximal to the splenic flexure only. The proportion of individuals with proximal adenomas only was 47.1% in Amsterdam criteria families and 27.3% in the others (p=0.03). These findings support the view that colonoscopy rather than sigmoidoscopy is the method of choice for screening high risk groups.
Adenoma↗
Suggested screening guidelines for familial colorectal cancer.
Guidelines for screening for colorectal cancer in subjects with a positive family history of the disease, without the use of DNA based screening, are outlined. These suggestions are derived from (a) the experience of screening 644 subjects at an estimated lifetime risk of dying from colorectal cancer of 10% or more, in the St Mark's Family Cancer Clinic, over six years, and (b) a review of published studies, particularly incorporating the experience of the International Collaboration Group on Hereditary Non-polyposis Colorectal Cancer (HNPCC). Selection of subjects for surveillance depends upon the empirical evaluation of their risk of colorectal cancer, based upon family history details, with the exclusion of a diagnosis of familial adenomatous polyposis in the family. When DNA predictive tests for genes predisposing to HNPCC are available, surveillance can be directed at subjects with a germline mutation known to confer an increased genetic risk of colorectal cancer and discontinued in those at lower (or average) risk. In many subjects, however, DNA testing may still not be possible because of the failure to identify a predisposing mutation in an affected subject in their family. Any surveillance protocol can only be evaluated by long term follow up of those subjects in multiple centres.
Colonoscopy↗
Detection of free malignant cells in the peritoneal cavity before and after resection of colorectal cancer.
PURPOSE: This study was designed to select the best monoclonal antibody to stain malignant cells in peritoneal wash fluid, and to investigate the incidence of free malignant cells in preresection and postresection colorectal cancer peritoneal washings using a combination of conventional cytology and immunocytochemistry. METHODS: Peritoneal washings were taken from 35 consecutive patients undergoing colorectal cancer resection. RESULTS: Malignant cells were isolated on a density gradient and identified by conventional cytology and an indirect immunoperoxidase stain. Malignant cells were identified in peritoneal washings from 15 patients (preresection only n = 3, postresection only n = 4, both n = 8). The origin of free malignant peritoneal cells in 11 preresection-positive washings must be the serosa. The origin of these cells in the four postresection-positive patients is uncertain: serosal and luminal spillage were considered unlikely and no circulating cells were found in the mesenteric vessels near the tumor. CONCLUSION: Tumor cells may have leaked out from lymphatics cut during the dissection.
Aged↗
The Nm23 gene and colorectal cancer.
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Chromosome Deletion↗
Interobserver variation in the reporting of the histopathological grading of anal intraepithelial neoplasia.
AIM: To assess the consistency in the histological reporting of anal intraepithelial neoplasia (AIN) among experienced histopathologists. METHOD: One hundred anal biopsy specimens were retrieved from archival material at St Mark's Hospital, London and graded by five histopathologists according to criteria outlined by Fenger (six point scale, ranging from normal to invasive carcinoma). RESULTS: There was only moderate agreement among the pathologists, with unweighted k scores ranging from 0.09 to 0.48, and weighted k scores of 0.17 to 0.60. CONCLUSIONS: There is considerable interobserver variation in the reporting of AIN. A simplified system of grading may help to abolish this.
Anus Neoplasms↗
Prevention of colorectal cancer by once-only sigmoidoscopy.
There is no national screening programme for colorectal cancer in the UK despite the fact that the annual death toll from this disease exceeds that of breast and cervical cancer. Faecal occult blood testing (FOBT) is under evaluation for screening, but screening by sigmoidoscopy is not considered viable. This situation contrasts with the USA where both annual FOBT and screening by flexible sigmoidoscopy every 3 to 5 years are recommended from 50 years old. We seek to demonstrate that most of the benefit from the US screening policy would accrue from a single flexible sigmoidoscopy examination at age 55 to 60 years with appropriate colonoscopic surveillance for the 3% to 5% found to have high-risk adenomas (> or = 1 cm or villous histology). If applied nationally, this screening regimen could prevent about 5500 colorectal cancer cases and 3500 deaths in the UK each year, thus saving 40,000 years of life. We estimate that there would be little net cost to the National Health Service because savings obtained from treating fewer patients would largely offset the cost of screening. We recommend that a randomised trial to evaluate screening by single flexible sigmoidoscopy should start without delay. Such a trial would involve about 120,000 participants, and 15 years of follow-up would be required to obtain a clear answer on mortality, although information on incidence reduction would be available sooner.
Adult↗
Gene transfer therapy in cancer.
Gene transfer techniques have now achieved clinical realization in the wake of recent advances in recombinant DNA technology, together with increased understanding of the molecular biology and immunology of cancer. These novel treatments, and their applications and limitations merit intensive study.
Animals↗
Detection and enumeration of circulating tumour cells in colorectal cancer.
Immunocytochemistry was used in parallel with conventional cytology to detect circulating malignant epithelial cells in 42 patients undergoing resection for colorectal cancer. Preoperative peripheral and peroperative mesenteric venous blood samples were taken. Tumour cells were isolated on a density gradient and cytospins prepared. Slides were stained by conventional cytology (May-Grünwald-Giemsa) and by an indirect immunoperoxidase technique with the anticytokeratin antibody KG8.13. Using conventional cytology, definite morphological evidence of malignancy was observed in three patients and suspicious features in a further seven. Immunocytochemistry confirmed these findings in all three of the malignant but in only one of the suspicious cases. Counts of immunostained cytospins showed the concentration of tumour cells in blood samples from these four patients to be in the range 0-954 cells/ml. This study supports the use of immunological markers to detect and enumerate malignant cells. This method provides a powerful tool to investigate one aspect of the metastatic process.
Adult↗
Radioimmunoscintigraphy with technetium-99m labelled monoclonal antibody, 1A3, in colorectal cancer.
This study of radioimmunoscintigraphy (RIS) was primarily undertaken to determine how the imaging results related to surgical findings. Technetium-99m radiolabelled 1A3, a monoclonal antibody against a columnar cell surface antigen, was used. No adverse effects or thyroid uptake was observed in 127 studies. The 85 primary colorectal cancers were all image positive. In the assessment of recurrent tumour in the abdomen or pelvis, the accuracy was 33/35 (94%), including true-positive findings in some whose serum carcinoembryonic antigen was normal. There was a positive predictive value for abdominal or pelvic recurrence of 92% and a negative predictive value of 100%, at a prevalence of 66%. In those patients whose liver was able to be evaluated, the accuracy was 72/79 (91%). There was a positive predictive value for liver metastases of 88% and a negative predictive value of 93%, at a prevalence of 32%. The simple procedure for labelling antibody with 99mTc and its ready availability allow a completed report to be given within 24 h of the request.
Adult↗
E-cadherin expression in colorectal cancer. An immunocytochemical and in situ hybridization study.
Expression of the epithelial-specific adhesion molecule E-cadherin has been assessed in paraffin-embedded tissue from a series of 72 colorectal carcinomas. Using immunocytochemistry and in situ hybridization it was found that E-cadherin expression was related inversely to tumor differentiation. Out of 44 well- and moderately differentiated tumors, 36 expressed good positivity, whereas 24 of 28 poorly differentiated tumors were E-cadherin-negative. Classification by Dukes stage revealed a highly significant difference (P << 0.001) between A and B (32 positive, four negative) and C1 and C2 (seven positive, 29 negative) stages in terms of immunoreactivity. Of the 32 lymph node metastases studied, 20 were negative for E-cadherin expression, as were seven of eight liver metastases. These results indicate that the down-regulation of E-cadherin levels in vivo is associated with the dedifferentiation, progression, and metastasis of colorectal cancer.
Adenocarcinoma↗
Anal human papillomavirus infection in heterosexuals with genital warts: prevalence and relation with sexual behaviour.
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Adult↗
Restriction enzyme analysis of mitochondrial DNA in colorectal tumours.
Total cellular DNA samples were isolated from 15 colorectal adenocarcinomas, 8 colon adenomas and their adjacent histologically normal colon mucosa. These DNA samples were digested separately with 13 different restriction endonucleases and analysed by Southern blot hybridization using a purified 32P-labelled human mtDNA probe. The fragment patterns from tumour mtDNA were compared to those from corresponding normal mtDNA. No evidence for large deletions, insertions, rearrangements or single base mutations in the detectable regions was detected. This suggests that other mechanisms may be responsible for the changes of colorectal tumour mitochondria.
Adenocarcinoma↗
Outcome of stapled revision of retracted ileostomy.
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Adult↗
Hereditary internal anal sphincter myopathy causing proctalgia fugax and constipation. A newly identified condition.
A newly identified myopathy of the internal anal sphincter is described. In the affected family, at least one member from each of five generations had severe proctalgia fugax; onset was usually in the third to fifth decades of life. Three members of the family have been studied in detail. Each had severe pain intermittently during the day and hourly during the night. Constipation was an associated symptom, in particular difficulty with rectal evacuation. Clinically the internal anal sphincter was thickened and of decreased compliance. The maximum anal canal pressure was usually increased with marked ultraslow wave activity. Anal endosonography confirmed a grossly thickened internal anal sphincter. Two patients were treated by internal anal sphincter strip myectomy; one showed marked improvement and one was relieved of the constipation but had only slight improvement of the pain. The hypertrophied muscle in two of the patients showed unique myopathic changes, consisting of vacuolar changes with periodic acid-Schiff-positive polyglycosan bodies in the smooth muscle fibers and increased endomysial fibrosis. In vitro organ-bath studies showed insensitivity of the muscle to noradrenaline, isoprenaline, carbachol, dimethylpiperazinium, and electrical-field stimulation. Immunohistochemical studies for substance P, calcitonin gene-related peptide, galanin, neuropeptide Y, and vasoactive intestinal peptide showed staining in a similar distribution to that in control tissue. A specific autosomal-dominant inherited myopathy of the internal anal sphincter that causes anal pain and constipation has been identified and characterized.
Adult↗
Human papillomavirus type 16 DNA in anal cancers from six different countries.
An association between anal squamous cell carcinoma and human papillomavirus (HPV) type 16 DNA has been documented in the UK. If HPV type 16 is an important aetiological factor in the development of this tumour it would be expected to occur in anal cancer tissues from other parts of the world. In this study a series of 173 anal squamous cell carcinoma tissue samples from five centres around the world have been examined by DNA hybridisation for HPV type 16 DNA sequences. HPV type 16 DNA was found in 50 of 173 (29%) of these. The prevalence of HPV associated anal squamous cell carcinoma was significantly lower in tissue from India and South Africa than in the Swiss, Polish, or Brazilian samples. HPV associated anal squamous cell carcinoma does occur in other countries and further investigations of the prevalence of these tumours in association with other HPV types are required.
Anus Neoplasms↗