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N A Shepherd

Publications and source records attributed to N A Shepherd.

At least 55 records · Page 3Linked to original sources
PubMed1995

Proliferative compartment deregulation in the non-neoplastic colonic epithelium of familial adenomatous polyposis.

Previous work has shown abnormalities in the proliferative activity of the colorectal mucosa in familial adenomatous polyposis (FAP). Some doubts remain about the validity of these findings because of difficulties in excluding adenomatous crypts, particularly in methods using tritiated thymidine, bromodeoxyuridine, and ornithine decarboxylase. The proliferative activity of the epithelium in colonic resections from 20 FAP patients was compared with that of age, sex, and site matched controls using a new monoclonal antibody MIB1 to assay the expression of Ki-67 antigen in routinely processed tissue. The labelling indices were very similar in the polyposis and control cases (25.5 (1.4)% and 26.7 (1.7)% respectively) but analysis of the distribution of labelled cells showed a significant shift of the proliferative compartment towards the luminal surface in the FAP group. Specifically, the labelling index was lower in the basal fifth of the polyposis crypts and higher in the two fifths at the luminal surface. These results show that analysis of proliferative activity in FAP is now achievable in routine histological material and indicate deregulation of proliferative control in the FAP colonic crypt. This may form a useful diagnostic adjunct to standard clinical and molecular genetic techniques, particularly in view of the current interest in dietary and pharmacological intervention in sporadic colorectal carcinoma.

Adenomatous Polyposis Coli↗
PubMed1995

c-erbB-2 overexpression in the dysplasia/carcinoma sequence of Barrett's oesophagus.

AIMS--To investigate overexpression of the oncoprotein c-erbB-2 in the dysplasia/carcinoma sequence of Barrett's columnar-lined oesophagus (CLO). METHODS--Immunohistochemical staining was performed using the monoclonal antibody NCL-CB-11 on formalin fixed tissue from 31 cases of Barrett's carcinoma, 20 cases of cancer associated dysplastic CLO, seven cases of dysplastic CLO without cancer, and 20 cases of non-dysplastic CLO. Membranous staining was regarded as positive for c-erbB-2 overexpression; cytoplasmic staining was recorded separately as its significance is uncertain. RESULTS--Membranous c-erbB-2 overexpression was observed in eight of 31 (26%) carcinomas and in none of the cases of dysplastic CLO. Variable cytoplasmic staining was seen in four of 31 (13%) tumours and seven of 27 (26%) cases of dysplastic CLO. No staining was observed in non-dysplastic CLO. CONCLUSIONS--C-erbB-2 overexpression is a relatively late event in the development of some Barrett's carcinomas and is unlikely to be involved in the early stages of neoplastic transformation of CLO.

Adenocarcinoma↗
PubMed1995

Influence of local peritoneal involvement on pelvic recurrence and prognosis in rectal cancer.

AIMS: To evaluate the influence of involvement of the peritoneal surface by carcinoma of the rectum on local recurrence and prognosis. METHODS: Prospective analysis of pathological prognostic factors in 209 resections for rectal carcinoma between 1988 and 1993 with meticulous pathological technique particularly to assess the relation of tumour to the peritoneal surface. Comprehensive clinical follow up with cause of death established from all available sources of information (hospital and general practitioner data) with necropsies where necessary. Local recurrence was determined by accepted clinical, radiological and pathological criteria. RESULTS: Local peritoneal involvement was detected in 25.8% (54/209) of cases. It was more common in women and was associated with tumour differentiation, size and site, and lymph node involvement. Local peritoneal involvement showed considerable prognostic disadvantage in all cases and in curative cases alone. Multivariate analysis demonstrated independent prognostic disadvantage for all cases although this was lost in the curative group. With a 30 month median follow up time, comprehensive clinical surveillance detected 25 (12.0%) local recurrences. Thirteen (52%) palliative cases had shown spread to involve the mesorectal (deep, circumferential) resection margin. Of the 12 curative cases, six were upper rectal cancers with local peritoneal involvement suggesting that tumour seeding into the pelvic peritoneal cavity was the cause of local recurrence. Local recurrence of the six other rectal tumours was probably because of intraluminal seeding in two, involvement of the distal margin in one, extensive extramural venous involvement in two, and tumour spread to the bladder in one. CONCLUSIONS: Comprehensive pathological analysis of a resection specimen can identify cases with a high probability of local recurrence which may benefit from early adjuvant therapy. Involvement of the peritoneal surface is a common event in rectal cancer, has adverse prognostic influence and may be an important factor in local recurrence of upper rectal carcinoma.

Adult↗
PubMed1994

Mohs surgery.

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Humans↗
PubMed1994

Adenocarcinoma arising in Barrett's oesophagus: evidence for the participation of p53 dysfunction in the dysplasia/carcinoma sequence.

Adenocarcinoma arising in Barrett's oesophagus is often preceded by mucosal dysplasia, but little is currently known about the aetiology or natural history of this dysplasia/carcinoma sequence. To investigate the participation of the tumour suppressor gene p53 in this sequence, an immunohistochemical analysis of p53 protein overexpression, which is known to closely correlate with point mutation of the p53 gene, was conducted in 30 patients with Barrett's adenocarcinoma. Adjacent Barrett's mucosa was dysplastic in 21 (70%) patients. Sixteen (53%) tumours overexpressed p53, 10 of which had adjacent dysplastic Barrett's mucosa. In all 10 patients, this dysplastic mucosa also overexpressed p53, predominantly in areas of high grade compared with low grade dysplasia. In contrast, none of the dysplastic mucosa adjacent to 11 tumours lacking p53 overexpression showed detectable values of p53. These results suggest that p53 dysfunction may participate in the progression from dysplasia to carcinoma in some patients with Barrett's oesophagus.

Adenocarcinoma↗
PubMed1994

Histological assessment of the Sydney classification of endoscopic gastritis.

To determine the significance of the endoscopic classification of gastritis proposed by a working party at the World Congress of Gastroenterology in Sydney 1990, 167 patients undergoing upper alimentary endoscopy were prospectively assessed by comprehensive endoscopic and histological methods. Ninety eight patients had endoscopic mucosal changes of gastritis according to the Sydney classification. Twenty six (27%) of these had histologically normal biopsy specimens. This was not statistically significantly different to the 26 (38%) of 69 with normal endoscopies whose biopsy specimens were histologically normal (chi 2 = 1.857, p > 0.1). Forty three (62.5%) patients with normal endoscopies had histological gastritis. No histological counterpart was found for the macroscopic appearances of the gastric mucosa said to show inflammation proposed by the Sydney classification of gastritis. These findings confirm the inappropriateness of an endoscopic diagnosis of gastritis and it is suggested such a term should be reserved for the histological findings.

Acute Disease↗
PubMed1993

Primary lymphoma of the small intestine. A clinicopathological study of 119 cases.

Small bowel lymphomas account for 20 to 40% of primary gut lymphomas in Western populations and are among the most common malignant tumours of the small bowel. We studied 119 cases of primary small bowel lymphoma presenting over 4 decades. Two thirds of the patients were men with a peak age incidence in the 7th decade. Common presenting features included abdominal pain, weight loss, small bowel obstruction, and acute abdomen. Tumours were classified using the Kiel European Association for Haematopathology Geneva Workshop scheme and phenotyped on paraffin sections; 66% were B cells, and 34% were T cell. In all cases, the antibodies L26 and polyclonal CD3 reliably distinguished between B- and T-cell tumours. Of the B-cell lymphomas, 62% were diffuse high grade, 20% were low-grade lymphomas of mucosa-associated lymphoid tissue, 11% had both low- and high-grade components, and 7% were other low-grade types. Of the T-cell lymphomas, 83% were high grade, and 49% were enteropathy associated. Most T-cell lymphomas were ulcerated plaques or strictures in the proximal small bowel; B-cell lymphomas tended to be annular or polypoid masses in the distal and terminal ileum. Survival data showed that low-grade B-cell lymphomas had the best outcome and T-cell lymphomas the worst. Adverse prognostic features included perforation, high-grade histology, multiple tumours and advanced stage.

Adolescent↗
PubMed1993

Regression of columnar lined (Barrett's) oesophagus with continuous omeprazole therapy.

Twenty-three adult patients with a columnar lined (Barrett's) oesophagus are being treated with long-term omeprazole, 40 mg daily. Twelve had never undergone anti-reflux surgery (Group 1), the other eleven having previously had insertion of an Angelchik anti-reflux prosthesis (Group 2). Endoscopy was carried out six months before, immediately before and six months, one year and two years into treatment. Multiple and standardized biopsies were taken at each endoscopy. Results from the two groups were similar. During the 6-month run-in period there was a statistically non-significant increase in the linear extent of the columnar mucosa, but this showed a progressive, statistically significant decrease during the two years of treatment. Other evidence for regression of the Barrett's mucosa includes the emergence of large numbers of macroscopic squamous islands within the abnormal mucosa, an increase in the number of microscopic squamous islands, and microscopic squamous encroachment of the abnormal mucosa at the squamo-columnar junction. Histological assessment showed a reduction in the proportion of sulphomucin-rich intestinal metaplasia, but this only achieved statistical significance in Group 1. The results substantiate the importance of acid in the pathogenesis of Barrett's oesophagus. Omeprazole may have a therapeutic role in bringing about regression of the metaplastic epithelium.

Adult↗
PubMed1993

Distribution of mucosal pathology and an assessment of colonic phenotypic change in the pelvic ileal reservoir.

The mucosa of the pelvic ileal reservoir undergoes adaptive changes--inflammatory, architectural, and metaplastic--on exposure to the faecal stream. Twenty three quadruple loop ileal pouches constructed for ulcerative colitis (20 patients) and familial adenomatous polyposis (FAP) (three patients) were studied. No patient fulfilled clinical, endoscopic, or histopathological criteria for pouchitis. Standard duplicate biopsy specimens were taken from the proximal limb, the anterior wall, the posterior wall, and the body of the reservoir. An established scoring system was used and showed a highly significant increase in inflammatory scores in posterior wall biopsy specimens compared with those from the anterior wall. These results suggest that the adaptive changes are the direct result of contact with static faecal contents. One patient only showed significant inflammation in the proximal limb. There was no evidence of mucosal prolapse in any anterior wall biopsy specimen. Patients with colitis showed substantially more inflammatory and architectural changes than those with FAP. Ninety six per cent of pouches showed some colonic phenotypic expression as defined by mucin histochemical and PR 3A5 immunohistochemical studies. Our results suggest, however, that there may not be complete colonic metaplasia and that the mucin changes and other phenotypic alterations may represent a non-specific response to pouch inflammation and not a prerequisite for the development of pouchitis. The focal nature of the inflammatory and architectural changes, which may be the result of direct contact with static faecal residue, are clearly shown. A single random biopsy specimen of pouch mucosa is of limited value in assessing pathological changes and screening for potential neoplastic change within the reservoir.

Adenomatous Polyposis Coli↗
PubMed1993

Pathology of the defunctioned rectum in ulcerative colitis.

Faecal stream diversion may induce inflammatory changes in the defunctioned segment of the large intestine. These changes are predominantly mucosal, although confusing histological features including granulomas may be present. The pathology of 15 defunctioned rectal stumps has been studied. All patients had previously undergone urgent total colectomy for ulcerative colitis and rectal stumps had been left in situ while they awaited pelvic ileal reservoir construction. All rectal stumps showed predominantly mucosal disease but there were additional features such as florid lymphoid follicular hyperplasia (12 cases), transmural inflammation (nine cases), granulomas (four cases), fissures (eight cases), and changes akin to ischaemia or to pseudomembraneous colitis (four cases). These changes may result from a combination of defunctioning and of active ulcerative proctitis. Some induce a histological appearance that may mimic Crohn's disease. Nevertheless review of all 15 colectomy specimens showed unequivocal ulcerative colitis and none of the patients has subsequently shown any clinical, radiological, or pathological evidence to support a diagnosis of Crohn's disease. Histology of the rectal stump in ulcerative colitis may lead to an erroneous diagnosis of Crohn's disease and the patient may subsequently be denied the advantage of a pelvic ileal reservoir.

Adult↗
PubMed1993

Inverted hyperplastic polyposis of the colon.

AIMS: To describe and evaluate two apparently unique cases of inverted hyperplastic (metaplastic) polyposis of the colon. METHODS: The cases were analysed by standard histopathological, histochemical, and immunohistochemical techniques and the findings compared with those of regular hyperplastic polyps of the colorectum. RESULTS: Both patients were middle-aged men with concurrent adenocarcinoma of the proximal large intestine. The inverted polyps numbered 18 and 12, measured between 0.4 and 2.5 cm in diameter, and all were present in the proximal ascending colon. The polyps had characteristic macroscopic features: they were positioned on the apex of mucosal folds and demonstrated surface pitting and mucus hypersecretion. Histologically, inversion and misplacement of hyperplastic epithelium was related to lymphoglandular complexes. The polyps showed all the histochemical and immunohistochemical features of regular hyperplastic polyps. CONCLUSIONS: Inverted hyperplastic polyps are an unusual but distinctive polyp of the proximal colon, may be multiple, and share the phenotypic changes of regular hyperplastic polyps. The pathogenesis of epithelial inversion probably relates to misplacement of epithelium through anatomical defects in the muscularis mucosae due to mechanical forces. The polyps may mimic both adenomas and carcinomas. The neoplastic potential of inverted hyperplastic polyposis is likely to be very low: one polyp only showed adenomatous change.

Adenocarcinoma↗
PubMed1992

Fat-wrapping in Crohn's disease: pathological basis and relevance to surgical practice.

The connective tissue changes that accompany intestinal Crohn's disease have received little attention from pathologists. This is particularly so with fat hypertrophy, and yet surgeons have long recognized the phenomenon of fat-wrapping in the intestines and used it to delineate the extent of active disease. A consecutive, unselected series of 27 intestinal resections performed on 25 patients for histologically confirmed Crohn's disease was studied to correlate fat-wrapping with other clinicopathological features. Fat-wrapping was identified in 12 of 16 ileal resections and in seven of 11 large bowel resections. It correlated closely with transmural inflammation and there was a relationship between fat-wrapping and other connective tissue changes including fibrosis, muscularization and stricture formation. Morphometry demonstrated that there was true hypertrophy and that fat-wrapping does not relate solely to bowel wall shrinkage. There was correlation with ulceration but in 11 cases macroscopic ulceration extended beyond the fat-wrapping and in six to surgical resection margins. The pathological features of 225 small intestinal resections were reviewed and fat-wrapping was seen only in Crohn's disease. Fat-wrapping correlates best with transmural inflammation and represents part of the connective tissue changes that accompany intestinal Crohn's disease. Findings also suggest that fat-wrapping alone should not be used as an accurate marker of disease extent at the time of surgery.

Adipose Tissue↗
PubMed1992

The role of pathology in pelvic ileal reservoir surgery.

The increasing use and success of pelvic ileal reservoir surgery places an ever more demanding role onto the surgical pathologist. Close surgical and pathological cooperation is critical for preoperative patient selection, for intraoperative diagnostic confirmation and for postoperative follow up. The long term consequences of pouch construction are, as yet, unknown, but there is much evidence to substantiate the need for life-long surveillance by clinical, endoscopic and pathological means to maximise the benefits of the pelvic ileal reservoir to the patient. This paper reviews the pathological input into these aspects of pelvic ileal reservoir surgery together with a critical appraisal of the likely long term consequences of pelvic ileal reservoir construction.

Adenomatous Polyposis Coli↗
PubMed1992

Endoscopic crescentic fold disease of the sigmoid colon: the clinical and histopathological spectrum of a distinctive endoscopic appearance.

In this paper we describe an endoscopic appearance of the sigmoid colon characterised by mucosal swelling, erythema and haemorrhage strictly localised to the crescentic mucosal folds. In a 5-year period these changes were seen in 34 (1.42%) of 2380 colonoscopies and fibreoptic sigmoidoscopies. The majority of patients were middle-aged or elderly. Diverticular disease was present in most (82%) but the abnormalities were confined to the crescentic mucosal folds with sparing of the diverticular orifices. The majority of patients presented with a history of bleeding per anum. Histologically there was a spectrum of changes varying from minor vascular congestion to florid active inflammatory disease with crypt architectural abnormalities mimicking ulcerative colitis, but rectal biopsies were invariably normal. Three patients later progressed to typical distal ulcerative colitis and two other patients presenting to us with endoscopic crescentic fold disease had a previous histologically documented history of distal ulcerative colitis. In three patients the histological features were of mucosal prolapse. About half the patients required some form of therapy to control their symptoms. Steroids and/or sulphasalazine were of value although two patients subsequently underwent sigmoid resection, one to control bleeding and the second for a diverticulosis-associated stricture. Whilst endoscopic crescentic fold disease represents a specific endoscopic appearance the clinical and histological features indicate a wide spectrum of disease.

Adult↗
PubMed1992

An Eudragit-coated prednisolone preparation for ulcerative colitis: pharmacokinetics and preliminary therapeutic use.

Prednisolone metasulphabenzoate, a steroid with poor colonic absorption, was coated with the pH-dependent acrylic resin Eudragit S, as a means of delivering an orally administered preparation to the proximal colon. The therapeutic potential of delivering this steroid with potentially less systemic side-effects to the proximal colon was assessed in extensive ulcerative colitis. Plasma and urine prednisolone profiles in 6 healthy volunteers confirmed minimal absorption from Eudragit S-coated prednisolone metasulphabenzoate compared to prednisolone acetate: peak plasma prednisolone concentrations 29 +/- 21 ng/ml vs. 570 +/- 185 ng/ml (P less than 0.01), area under curve measurements 204 +/- 214 vs. 2724 +/- 1236 ng.h/ml (P less than 0.01). Prednisolone metasulphabenzoate coated with Eudragit S (30-60 mg daily) was then administered for 12 weeks to 12 patients with colonoscopically proven extensive ulcerative colitis in relapse. Symptoms, sigmoidoscopic appearances and rectal histological abnormalities all improved during therapy. Complete clinical remission occurred in 7 patients, a partial response in 2 patients and no response in 3 patients. Cortisol responses to tetracosactrin demonstrated no significant adrenal suppression following treatment. Eudragit S-coated prednisolone metasulphabenzoate may be a useful treatment for extensive ulcerative colitis, without risk of systemic steroid side-effects.

Acrylic Resins↗