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Biomedical subjects

N A Shepherd

Publications and source records attributed to N A Shepherd.

At least 91 records · Page 5Linked to original sources
PubMed1989

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↗
PubMed1989

Observer study of the grading of dysplasia in ulcerative colitis: comparison with clinical outcome.

Patients with extensive ulcerative colitis are entered into surveillance programs that aim to detect premalignant changes. Biopsy specimens have been collected in the St Mark's Hospital (London) surveillance program over a 22-year-period. Specimens from patients reported as having dysplasia were reexamined. A total of 207 biopsy specimens from 86 patients were graded by five experienced pathologists according to the severity of the dysplasia. The overall agreement between the pathologists grading the specimens was poor; each pair agreed on between 42% and 65% of the slides. The best agreement was for slides that were said to show no dysplasia. Comparison with clinical outcome indicated that the pathologists most likely to diagnose dysplasia in patients with carcinoma were also likely to diagnose dysplasia in patients who did not go on to develop carcinoma. Calculating an average grade of dysplasia did not significantly improve diagnostic accuracy. Despite the findings of this interobserver study, dysplasia has been a successful marker in clinical practice. Pathologists should ensure that they have access to previous slides from the same patient and adequate clinical information before reporting biopsies as positive for dysplasia. An additional biopsy should usually be undertaken before surgery is considered.

Biopsy↗
PubMed1989

Primary malignant lymphoma of the large intestine complicating chronic inflammatory bowel disease.

Ten cases of malignant lymphoma of the colon and rectum complicating chronic inflammatory bowel disease are presented. Seven patients had chronic ulcerative colitis with a history varying from 6 to 20 years. There was extensive colitis in six of these patients and left-sided colitis in one. All seven lymphomas showed the pathological and immunohistological features of primary B-cell tumours of the gastrointestinal tract with a predominance of high-grade tumours. Three patients had Crohn's disease of the large intestine complicated by malignant lymphoma of the sigmoid colon or rectum. The history of Crohn's disease varied from 30 months to 20 years and in each case there was fissuring and fistulae. There was extensive anal involvement in two cases. Histologically the three lymphomas were heterogeneous: one was of 'granulomatous' T-cell type and the other two were markedly polymorphic and of equivocal phenotype. They were also characterized by numerous multinucleate tumour giant cells. Primary colorectal malignant lymphoma should be regarded as a rare, but significant, complication of ulcerative colitis. Immunosuppression may be an additional factor in the genesis of intestinal lymphoma in Crohn's disease. The prognosis appears to be dependent on factors already known to be of prognostic significance in primary gut lymphomas: a predominance of high-grade tumours suggests that the outlook is generally worse than that for idiopathic primary large intestinal lymphoma.

Adult↗
PubMed1989

Prognostic factors in colonic cancer.

Prognostic variables in 251 'curative' specimens of colonic cancer were studied. Subjective variables--tumour type, grade of differentiation, character of invasive margin and lymphocytic infiltration--were associated with fair to excellent levels of inter-observer agreement. Variables found to be of prognostic significance by univariate analysis were subjected to Cox regression analysis. This was undertaken for all three observers and for a consensus grading. No case in which direct spread in continuity was limited to the bowel wall was associated with a cancer-related death; 63 such specimens were removed as a group with an excellent prognosis and did not require further stratification. In the remaining 188 cases, all showing extramural spread, only lymph node invasion, character of invasive margin and tumour type were independent prognostic variables. The model differs from that developed previously for rectal cancer and is superior to the Dukes classification.

Carcinoma↗
PubMed1989

Familial visceral myopathy: a family with at least six involved members.

A family with at least six members affected by hollow organ visceral myopathy is described. Patients in the first or second decades of life developed symptoms which included weight loss, nausea and vomiting, abdominal pain and distension, constipation and diarrhoea, and urinary symptoms. The radiological features of the disease consisted of oesophageal aperistalsis, megaduodenum, and variable dilatation of the small and large bowel. Four patients had urinary tract involvement with dilatation of the ureters and/or incomplete bladder emptying. Two patients were severely affected and needed home parenteral nutrition and surgical treatment; others were symptomatic but remained well. The characteristic pathological abnormality was vacuolar degeneration predominantly affecting the longitudinal muscle. The disease in this family appears to be transmitted by autosomal dominant mode of inheritance.

Adolescent↗
PubMed1988

Ki-67 derived proliferative activity in colorectal adenocarcinoma with prognostic correlations.

Cryostat sections from samples of 108 colorectal carcinomas were stained with the murine monoclonal antibody Ki-67, which is expressed in proliferating cells. Ki-67 immunoreactivity was assessed independently by two pathologists using a semi-quantitative method. There was excellent correlation between the two observers. Ten cases were assessed quantitatively by counting at least 2000 cells and there was a very good correlation between this method and the semi-quantitative method. The carcinomas showed a wide range of Ki-67 labelling, reflecting a variation in proliferative activity. The tumour labelling index ranged from 1 to 80 per cent positivity: there was also heterogeneity of labelling within many of the tumours. There was no correlation between Ki-67 derived proliferative score and known prognostic parameters, including Dukes stage, New Prognostic Classification grade, lymph node status, tumour differentiation, venous spread, invasive margin, lymphocytic infiltrate, and curative versus palliative surgery. Nevertheless, it is concluded that Ki-67 immunohistochemistry provides a reliable and reproducible method of assessment of proliferative activity in colorectal cancer. Ki-67 immunohistochemistry may have a clinical application in the selection of patients with colorectal cancers who might benefit from radiotherapy and/or chemotherapy, particularly those with unresectable or locally recurrent tumours.

Adenocarcinoma↗
PubMed1988

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↗
PubMed1988

Primary malignant lymphoma of the colon and rectum. A histopathological and immunohistochemical analysis of 45 cases with clinicopathological correlations.

Primary colorectal lymphoma accounts for only about 0.2% of large intestinal malignancies. Management difficulties are compounded by a lack of consistent pathological reporting and by the use of numerous different classifications. Forty-five cases of primary colorectal lymphoma are included in this study. The presenting features are indistinguishable from those of colorectal cancer. Seven patients had a history of chronic ulcerative colitis but no other predisposing factors were identified. Immunohistochemical studies showed that all tumours were of B-cell phenotype. Most tumours were difficult to characterize using standard pathological classifications such as Kiel, except for the 11 cases of malignant (multiple) lymphomatous polyposis, which were morphologically diffuse centrocytic lymphomas. Twenty-nine lymphomas showed the morphological and immunohistochemical features associated with tumours arising in mucosa-associated lymphoid tissue. These tumours showed variable but often marked polymorphism and we have used the term polymorphic B-cell lymphoma to describe them. Consistency was achieved between three observers as to whether these tumours were low or high grade, and grade was found to be prognostically important. A modified Dukes staging system was adopted and there was a trend for early stage to give prognostic advantage. This study supports the view that surgery should be the primary treatment for localized lymphoma of the gastrointestinal tract with radiotherapy and/or chemotherapy for advanced cases and for malignant lymphomatous polyposis.

Colonic Neoplasms↗
PubMed1988

Brush cytology of the colon and rectum in ulcerative colitis: an aid to cancer diagnosis.

In a prospective study of 100 patients with ulcerative colitis, 82 of whom had extensive colitis, carcinoma and dysplasia were distinguished cytologically from reactive hyperplasia. Six patients had carcinoma complicating colitis and satisfactory samples were obtained from five; the cytological appearances were interpreted as carcinoma in three and as dysplasia in two. Seventy eight patients had not developed carcinoma or dysplasia; the cytological appearances were interpreted as negative for dysplasia in 75 and indefinite for dysplasia in three. In patients who had developed dysplasia the changes seemed to be more widespread on cytological rather than on histological examination. Brush cytology may complement histological assessment in patients with ulcerative colitis who have developed strictures or in whom there is a high suspicion of neoplastic change.

Adenoma↗
PubMed1987

Exogenous pigment in Peyer's patches.

Dark brown granular pigment was found consistently in macrophages in the deep aspect of adult Peyer's patches. Tissue sections from intestinal resections of 35 patients with a variety of pathologic diagnoses and of seven postmortem cases with no evidence of gastrointestinal disease were examined for the presence of this pigment. It was found in all patients over the age of 6 years (34 cases) but was not found in any children below that age (eight cases). Scanning electron microscopy with secondary and backscattered electron imaging and x-ray energy spectroscopy were performed on routine histologic sections. The pigmented macrophages contained aluminum and silicon, diffusely present throughout the cytoplasm, and numerous discrete foci of titanium. Pigment containing these same elements has also been found around dilated submucosal lymphatics, in mesenteric lymph nodes, and in some transmural inflammatory aggregates of Crohn's disease. The pigment probably is derived from the diet and actively taken up by Peyer's patches, which are able to incorporate inert particulate matter.

Aluminum↗
PubMed1987

Epithelial misplacement in Peutz-Jeghers polyps. A diagnostic pitfall.

Early difficulties with the interpretation of the histopathology caused overdiagnosis of cancer in the Peutz-Jeghers syndrome; and there is still controversy about the magnitude of risk of gastrointestinal carcinoma. Most workers now believe that there is a small but definite increase in the incidence of gastrointestinal carcinoma in Peutz-Jeghers polyps and most of these cancers occur in the upper gastrointestinal tract. In a review of 491 Peutz-Jeghers polyps in the records of St. Mark's Hospital Pathology department, misplacement of epithelium was found in approximately 10% of small intestinal polyps and closely mimicked adenocarcinoma. This "pseudoinvasion" was not observed in polyps of the stomach or colon. The epithelial misplacement may involve all layers of the bowel wall; and the most helpful histological discriminators include a lack of cytological atypia, the presence of the normal epithelial cell subtypes and a brush border, hemosiderin deposition, and intramural mucinous cysts. Epithelial misplacement may account for the overdiagnosis of carcinoma arising in Peutz-Jeghers polyps as reported in the literature.

Adenoma↗
PubMed1987

Malignant lymphoma with eosinophilia of the gastrointestinal tract.

Lesions of the gastrointestinal tract with massive tissue eosinophilia may present a difficult diagnostic problem. In a series of 250 gastrointestinal lymphomas drawn from the files of St Bartholomew's and St Mark's Hospitals there were 28 cases of a lymphoma with distinctive histological features, characterized by a massive tissue eosinophilia. Two of these tumours were present in the stomach and 26 in the small intestine. Eight of the latter were associated with coeliac disease. On low power examination a zoning phenomenon was regularly seen and fissuring ulceration, with perforation and fistula formation, was a common finding. The tumour cells were large and pleomorphic with irregular nuclear morphology and prominent nucleoli. Eosinophils were the predominant inflammatory cell associated with the lymphoma but plasma cells, epithelioid histiocytes and small lymphocytes were also present. Vascular changes were prominent. Involved lymph nodes showed gross expansion of the paracortex by tumour. Immunohistochemical studies showed that this lymphoma was probably of T-cell origin.

Aged↗
PubMed1987

Soft tissue gliomatosis--heterotopic glial tissue in the subcutis: a case report.

A subcutaneous nodule composed of heterotopic glial tissue is reported. The lesion was present in the subcutaneous tissue of the chest wall in a 2-year-old female. Histologically it was composed of loosely textured fibrillary neuroglial tissue in a densely hyalinized collagenous stroma. Immunohistochemical staining for glial fibrillary acidic protein was positive. The possible origin of this soft tissue glial heterotopia is discussed and the subject of heterotopic glial tissue is reviewed.

Axilla↗
PubMed1987

Neuromuscular and vascular hamartoma of the small intestine: is it Crohn's disease?

Neuromuscular and vascular hamartoma has been described as a specific, if rare, stricturing condition of the small intestine. In this paper four cases with very similar macroscopic and histological features to those described as 'neuromuscular and vascular hamartoma' are presented. In three of the patients there was an earlier histologically proven diagnosis of Crohn's disease of the small intestine. We believe that 'neuromuscular and vascular hamartoma' is not a hamartomatous condition but may be seen as part of the histological spectrum of Crohn's disease, possibly in a chronic and 'burnt out' phase. Indeed the presence of these changes may provide additional evidence for the diagnosis of Crohn's disease.

Adult↗
PubMed1987

Granular cells as a marker of early amiodarone hepatotoxicity: a pathological and analytical study.

Two contrasting cases of amiodarone hepatotoxicity are described. In one, perivenular collections of swollen cells, probably macrophages, with granular cytoplasm in an otherwise nearly normal liver were observed. Transmission electron microscopy showed that the cytoplasmic granularity was due to lysosomal bodies of various sizes. X-ray energy and wavelength spectroscopic analysis showed a high iodine content in these lysosomal bodies, good presumptive evidence of the presence of amiodarone or one of its metabolites. In the second case there was a micronodular cirrhosis, and similar granular cells also containing iodine were seen in the fibrous connective tissue. These cases seem to represent the very early and late stages of amiodarone hepatotoxicity. In a patient taking this drug aggregates of swollen granular cells may be a sensitive and histopathologically useful marker of early amiodarone toxicity.

Amiodarone↗