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I C Talbot

Publications and source records attributed to I C Talbot.

At least 91 records · Page 5Linked to original sources
PubMed1995

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↗
PubMed1995

Immunohistochemical study of the colonic muscle and innervation in idiopathic chronic constipation.

PURPOSE: This study was designed to investigate neural and muscular features of the colonic wall in patients with severe idiopathic constipation. METHODS: By using quantitative immunohistochemistry, resected specimens from 14 patients with idiopathic chronic constipation and 17 nonobstructed cancer controls were studied. RESULTS: Routine histology revealed no significant histologic abnormality throughout the colon apart from four cases of melanosis coli. Ratio of the thickness of circular to longitudinal muscle was significantly lower in the left colon in constipated subjects. The myenteric plexus appeared morphologically normal in all subjects. S-100 protein, which stains neuronal supporting tissues, demonstrated an increase in the proportion of neural tissue in the myenteric plexus. There was an increased number of PGP-9.5 immunoreactive nerve fibers in the muscularis propria in constipated patients, and this was significantly higher in the ascending and descending colon. CONCLUSION: Intractably constipated patients have alterations in the neural composition of the colonic myenteric plexus and innervation of the circular muscle.

Adolescent↗
PubMed1995

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↗
PubMed1995

Detection of c-Ki-ras mutations in faecal samples from sporadic colorectal cancer patients.

Colonic exfoliated epithelial cells in faecal material provide a source of human DNA which has been analysed for the presence of the tumour marker ras, in order to detect early tumour cells. The stool samples were subjected to a preliminary sample preparation step followed by centrifugation. DNA was extracted from both the centrifugation pellet and supernatant fractions, as well as from endoscopy washings, using a conventional phenol chloroform extraction method and was then purified on glass milk or spin columns. The purified DNA was amplified using mitochondrial primers and analysed for ras mutations using a non-radioactive, allele specific mismatch method. Corresponding tumour DNA was analysed for mutations using the same method. The results show that approximately 50% of the faecal samples analysed exhibited the presence of ras mutations which were also observed in the corresponding tumours. A double mutation was detected in one supernatant. Our findings represent an important stage in the development of a diagnostic test for the early detection of colorectal cancer.

Adult↗
PubMed1995

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↗
PubMed1995

Effect of longterm misoprostol coadministration with non-steroidal anti-inflammatory drugs: a histological study.

Prostaglandins are widely used in the prevention and healing of non-steroidal anti-inflammatory drug (NSAID) induced gastric and duodenal ulcers, but their longterm effect on the human gastric mucosa is unknown. This study assessed the effect of coadministration of prostaglandins with NSAIDs on the histology of the gastroduodenal mucosa. Histological appearances (using the Sydney system) of gastric biopsy specimens from 180 patients receiving longterm NSAID treatment of whom 90 had been receiving misoprostol (400-800 micrograms/day) for one to two years were studied. Both groups of patients were comparable with regard to clinical and demographic details. There was no significant difference (p > 0.1) in the prevalence of chronic gastritis (total, corpus or antrum only) between patients receiving (36 of 90 (40%)) or not receiving misoprostol (35 of 90 (39%)). Chronic gastritis was equally associated with the presence of Helicobacter pylori, 86% and 73% (p > 0.1), respectively, in the two groups. Significantly fewer patients receiving misoprostol had reactive gastritis than those receiving only NSAIDs (8 (9%) versus 27 (30%), p < 0.01). Reactive gastritis was not associated with H pylori. Thirty nine (43%) of the misoprostol treated patients had normal histology compared with 16 (18%) receiving only NSAIDs (p < 0.01). These results show two different patterns of gastric damage in patients receiving NSAIDs, namely chronic and reactive gastritis. Misoprostol treatment was associated with a significantly reduced prevalence of reactive gastritis and it is suggested that this, along with its antisecretory action, may explain the reduced prevalence of gastroduodenal lesions when coadministered with NSAIDs.

Adult↗
PubMed1995

Flow cytometric analysis of DNA synthetic phase fraction of the normal appearing colonic mucosa in patients with colorectal neoplasms.

DNA synthetic (S) phase fractions of normal appearing colonic mucosa in Japanese and British patients with colorectal neoplasms were compared with those in patients without colonic neoplasms. Normal crypts were isolated from fresh surgical specimens of the large intestine by the use of EDTA. After fixation with 70% ethanol, isolated crypts were digested with pepsin into single nuclei suspensions. These were stained with propidium iodide and examined by flow cytometry. S phase fraction was calculated from the flow cytometry DNA histogram using Baisch's method. S phase fractions of normal appearing crypts in Japanese and British patients with colorectal tumours were not significantly different and analysed together. S phase fraction of normal appearing colonic crypts in 14 patients with familial adenomatous polyposis (FAP) was 10.23 (2.59%) (mean SD)) ranging from 5.8 to 18.8. S phase fraction of background normal mucosal in patients with large adenomas (over 2 cm) and adenocarcinomas were 9.74 (3.76%) (range, 2.7-16.1) and 8.93 (3.54%) (range, 2.9-18.9) respectively. In normal mucosa of patients without any colorectal neoplasms, S phase fraction was 8.99 (3.94)% (range, 3.9-17.7). There was no statistically significant difference in S phase fractions of normal mucosa in the four groups. Our results show that an increase in proliferative activity of background colonic crypts is not necessary for tumour development.

Adenocarcinoma↗
PubMed1995

p53 expression in ulcerative colitis: a longitudinal study.

p53 Mutation is a late event in the development of sporadic colorectal carcinoma (CRC). The timing of p53 mutations in the development of ulcerative colitis associated colorectal carcinoma (UCACRC) is, however, less certain and some reports suggest that it may be a relatively early event. This study sought to establish the timing of p53 mutations in neoplasia arising in ulcerative colitis. Blocks of 10 resected colorectal specimens from patients who had had a biopsy positive for dysplasia at least one year prior to resection were retrieved from the archives of St Mark's Hospital. Immunochemistry using the monoclonal antibody DO-7, specific for both mutant and wild type p53, was performed on sections from both the resection specimens and dysplastic biopsy specimens. Seven of the 10 resection specimens were positive for p53. Two of these seven specimens showed p53 overexpression in specimens taken two years before the development of carcinoma or high grade dysplasia. Five of the seven specimens were negative for p53 overexpression between one and four years prior to resection. These results suggest that p53 overexpression is usually a late event in the development of UCACRCs.

Colitis, Ulcerative↗
PubMed1994

Anal endosonography for identifying external sphincter defects confirmed histologically.

Defects of the external anal sphincter have traditionally been diagnosed by palpation, anal manometry and electromyography (EMG), but anal endosonography enables clear imaging of both the internal and external sphincter muscles. A study was performed to validate the interpretation of ultrasonographic images of external sphincter defects using histology as a 'gold standard'. In addition the accuracy of clinical examination, manometry, EMG mapping and anal endosonography in the diagnosis of sphincter defects were compared prospectively. Twelve consecutive patients with faecal incontinence (11 women, one man; mean age 46 (range 30-64) years) who required sphincter repair underwent clinical assessment, anal manometry, concentric-needle EMG mapping and anal endosonography before surgery. The endosonographer was unaware of the history or results of physiological tests and the surgeon performing the repair was blind to the ultrasonographic findings. At operation most or all of the suspected defect was excised and examined histologically. The pathologist was unaware of the endosonographic or operative findings at the time of reporting. Combined operative and histological examination identified an external sphincter defect in nine of the 12 patients. Anal endosonography correctly identified all nine defects and the three normal sphincters. The accuracy of clinical examination was 50 per cent and that of both EMG and anal manometry 75 per cent. In addition, anal endosonography identified a defect of the internal anal sphincter in eight patients. External sphincter defects identified by endosonography have not been previously verified histologically. Precise sphincter assessment is mandatory for the correct management of faecal incontinence. Anal endosonography is more accurate than clinical and conventional physiological methods and also provides information on the internal sphincter.

Adult↗
PubMed1994

Non-polypoid adenoma of the large intestine.

In order to find non-polypoid (flat) adenomas in the large intestine, one hundred and twenty-six consecutively resected large bowels were stained with methylene blue or haematoxylin and examined using a stereoscopic microscope with special attention to pit pattern abnormalities. The primary diseases were classified into familial adenomatous polyposis (FAP) in 9 cases, multiple adenomas in 2 cases, colorectal cancers in 90 cases, Crohn's disease in 5 cases, ulcerative colitis in 2 cases, constipation in 9 cases, diverticular disease in 3 cases and others in 6 cases, respectively. Thirty-five flat adenomas were detected in 14 colons (14/126 = 11%). Twenty-one flat adenomas were found in 9 non-FAP cases (7 colons removed for cancer and 2 for multiple adenomas) and the remaining 14 flat adenomas were found in 5 FAP colons. No flat adenomas were found in any of the 25 colons removed for non-neoplastic disease. Nine flat adenomas (26%) had a depressed shape. The mean age of the non-FAP cases was 57 years and that of the FAP cases was 29 years (P < 0.005). The mean size of non-FAP flat adenomas was 6.1 mm and that of FAP flat adenomas was 3.1 mm (P < 0.005). Non-FAP flat adenomas were more frequently right-sided than those in FAP. Epithelial dysplasia was graded as mild in 31 (89%) and moderate in 4 (11%), respectively. Moderate dysplasia was found in non-FAP cases exclusively. These results suggest that flat adenomas may be heterogeneous. The significance of these lesions is discussed.

Adenoma↗
PubMed1994

Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis.

BACKGROUND/AIMS: Cancer surveillance in patients with ulcerative colitis is of unproven benefit. This study assesses the efficacy and analyzes factors limiting the success of a surveillance program during a 21-year period in 332 patients with ulcerative colitis to the hepatic flexure and disease duration exceeding 10 years. METHODS: Clinical assessment and sigmoidoscopy with biopsy was undertaken yearly. Colonoscopy and biopsy every 10 cm throughout the colon was performed every 2 years or more often if dysplasia was found. Only biopsy specimens reported as showing dysplasia were reviewed. RESULTS: Surveillance contributed to detection of 11 symptomless carcinomas (8 Dukes A, 1 Dukes B, and 2 Dukes C), but 6 symptomatic tumors (4 Dukes C and 2 disseminated) presented 10-43 months after a negative colonoscopy. Dysplasia without carcinoma was confirmed in 12 symptomless patients who underwent colectomy. The 5-year predictive value of low-grade dysplasia for either cancer or high-grade dysplasia was 54% using current criteria. CONCLUSIONS: Surveillance identified some patients at a curable stage of cancer or with dysplasia. Limiting factors were failure to include patients with presumed distal colitis, biennial colonoscopy, the number of biopsy specimens at each colonoscopy, and variation in histological identification and grading of dysplasia.

Adenomatous Polyps↗
PubMed1994

Anal carcinoma--a histological review.

Epidemiological evidence of an association between anal carcinoma and symptomatic HIV-related disease suggests that the number of cases of this disease may increase significantly over the next few years. The role of oncogenic HPV types in the pathogenesis of anal carcinoma is substantiated by both epidemiological evidence that tumours are associated with a past history of anal warts and by experimental evidence showing that over 85% of tumours contain HPV 16/18 DNA on PCR. The physical state of the virus in the tumour cell genome is currently under investigation, and cellular interactions between HPV, HIV and other sexually transmitted viruses require further research. Clinical studies have shown that patients with anal warts and those who are HIV positive also show an increased tendency to develop dysplasia within the anal epithelium. However, the malignant potential of dysplasia remains unclear and, it presents problems in management, particularly when multifocal and high grade. Problems in classification of anal carcinomas involve both the site of the tumours and the histological appearance. Despite the difficulties which exist in estimating the origin of a tumour from canal or margin, this information does appear to have clinical significance and should therefore continue to be assessed. Recent morphological and keratin studies have emphasized the heterogeneity of these tumours and have revealed a similar heterogeneous profile of keratin expression in the normal anal epithelium. These results support the body of opinion which suggests that, with the exception of small cell carcinoma and adenocarcinoma, anal carcinomas should be considered as squamous cell tumours which are able to display a range of further morphological characteristics within which ductal differentiation and mucin production appear to carry the worst prognosis. Although there is no universally accepted staging system for anal carcinoma, depth of invasion and extent of spread at the time of diagnosis are the most important clinical factors determining survival and response to therapy. Randomized clinical trials are now under way to compare the outcome of various combinations of radiotherapy and chemotherapy, which have replaced radical surgery as a first line treatment and resulted in a significant decrease in patient morbidity from this disease.

Anus Neoplasms↗
PubMed1994

Clinicopathological characteristics of colorectal carcinoma complicating ulcerative colitis.

This study examined three features associated with colorectal carcinoma complicating ulcerative colitis: (a) the distribution of 157 cancers in 120 patients with ulcerative colitis treated at St Mark's Hospital between 1947 and 1992; (b) the frequency at which dysplasia was found at a distance from the tumour in 50 total proctocolectomy specimens in which an average of 27 histology blocks were reviewed, and (c) the five year survival rate according to Dukes's stage and participation in a surveillance programme. Of 157 carcinomas, 88 (56%) occurred in the rectosigmoid, 19 (12%) in the descending colon or splenic flexure, and 50 (32%) in the proximal colon. Among the 120 patients, the rectum or sigmoid colon contained cancer in 81 (67.5%). Dysplasia was detected in 41 of 50 reviewed proctocolectomy specimens (82%). Dysplasia distant to a malignancy occurred in 37 (74%); two were classified indefinite, probably positive, 19 were low grade, and 16 were high grade; in 18 specimens there was an elevated dysplastic lesion. Survival was related to the Dukes's stage: about 90% of patients with Dukes's A or B cancer were alive at five years. The five year survival of 16 patients in whom cancer developed during surveillance was 87% compared with 55% of 104 patients who did not participate in surveillance (p = 0.024).

Adult↗
PubMed1994

Increased leukotriene B4 release from ileal pouch mucosa in ulcerative colitis compared with familial adenomatous polyposis.

Pouchitis may complicate the construction of an ileal pouch after colectomy for ulcerative colitis (UC) but not familial adenomatous polyposis (FAP). To examine whether differences in eicosanoid metabolism might explain why pouchitis is largely confined to UC patients, this study compared arachidonic acid stimulated release of immunoreactive leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) from macroscopically uninflamed pouch mucosal biopsy specimens incubated in vitro from patients with UC and FAP. The study also compared eicosanoid release from inflamed and uninflamed pouches in patients with UC. In uninflamed pouches, median LTB4 release was nearly twice as high in UC as in FAP (p = 0.001), but there was no significant difference in PGE2 production. In UC, stimulated eicosanoid release from uninflamed functioning pouch mucosa was not significantly different from that from either ileostomy or defunctioned pouch mucosa. LTB4 and PGE2 release were significantly greater from inflamed than uninflamed pouch mucosa in UC (p = 0.001 and 0.01, respectively). Leukotriene synthesis inhibition or receptor antagonism, or both merit therapeutic evaluation in pouchitis. Increased release of LTB4 from endoscopically normal pouch mucosa suggests increased 5-lipoxygenase activity in patients with UC and could contribute to their predisposition to pouchitis.

Adenomatous Polyposis Coli↗