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A D Spigelman

Publications and source records attributed to A D Spigelman.

At least 37 records · Page 2Linked to original sources
PubMed2001

Familial adenomatous polyposis: more evidence for disease diversity and genetic heterogeneity.

Familial adenomatous polyposis (FAP) is characterised by the presence of profuse colonic carpeting of adenomas throughout the entire colon and rectum. The genetic basis of FAP has been shown to be primarily associated with germline mutations in the APC gene. Notwithstanding, several reports have been published indicating that there is genetic heterogeneity in FAP and that the most likely explanation is the existence of another gene. In this report we further delineate the genotype/phenotype correlation in families that harbour germline mutations in the APC gene and identify some previously unreported changes in the APC gene which predispose to an attenuated disease phenotype. From 53 index patients diagnosed with either FAP or attenuated FAP, 27 harboured changes in the APC gene. The remaining 26 patients were further subgrouped according to their colonic phenotype. There were nine patients with a mixed hyperplastic/adenomatous colonic phenotype and there were 17 patients with an adenomatous colonic phenotype. Evaluation of the disease characteristics of these patients and their families is presented which may aid in the identification of new genes associated with colonic polyposis.

Adenomatous Polyposis Coli↗
PubMed2000

Hereditary nonpolyposis colorectal cancer in 95 families: differences and similarities between mutation-positive and mutation-negative kindreds.

Hereditary nonpolyposis colorectal cancer (HNPCC) describes the condition of a disparate group of families that have in common a predisposition to colorectal cancer in the absence of a premalignant phenotype. The genetic basis of this disease has been linked to mutations in genes associated with DNA mismatch repair. A large proportion of families harbor changes in one of two genes, hMSH2 and hMLH1. Approximately 35% of families in which the diagnosis is based on the Amsterdam criteria do not appear to harbor mutations in DNA-mismatch-repair genes. In this report we present data from a large series of families with HNPCC and indicate that there are subtle differences between families that harbor germline changes in hMSH2 and families that harbor hMLH1 mutations. Furthermore, there are differences between the mutation-positive group (hMSH2 and hMLH1 combined) of families and the mutation-negative group of families. The major findings identified in this study focus primarily on the extracolonic disease profile observed between the mutation-positive families and the mutation-negative families. Breast cancer was not significantly overrepresented in the hMSH2 mutation-positive group but was overrepresented in the hMLH1 mutation-positive group and in the mutation-negative group. Prostate cancer was not overrepresented in the mutation-positive groups but was overrepresented in the mutation-negative group. In age at diagnosis of colorectal cancer, there was no difference between the hMSH2 mutation-positive group and the hMLH1 mutation-positive group, but there was a significant difference between these two groups and the mutation-negative group.

Adolescent↗
PubMed2000

Development of duodenal cancer in a patient with familial adenomatous polyposis.

A Japanese woman with familial adenomatous polyposis in whom a duodenal ampullary adenoma underwent malignant change during a 10-year follow-up period is reported. After restorative proctocolectomy in 1989, and extensive small bowel resection for desmoid disease in 1991, regular surveillance duodenoscopies, including three to nine biopsies (mean, 4.8) were performed annually or biannually. Until 1995, the endoscopic findings of duodenal polyposis (including an ampullary polyp) did not progress and the histopathology did not worsen. In 1996, there was an increase in the number and size of the duodenal polyps, and the ampulla of Vater looked enlarged. Open surgery was discussed but not proceeded with because of the risk for short bowel syndrome. In January 1998, she was admitted with a diagnosis of acute pancreatitis. Duodenoscopy and radiological examination revealed that an advanced ampullary cancer had developed, and histopathology revealed a well-differentiated adenocarcinoma. Multiple hepatic metastases and ascites led to her death, in June, 1998. This in-vivo demonstration of the adenoma-carcinoma sequence highlights current limitations in the surveillance and treatment of duodenal lesions.

Adenomatous Polyposis Coli↗
PubMed2000

Gastroduodenal lesions in familial adenomatous polyposis.

Prophylactic colectomy is generally recommended for patients with familial adenomatous polyposis (FAP) who are inevitably affected with large bowel cancer. After prophylactic colectomy has been performed, gastrointestinal malignancy is the leading cause of death. Duodenal adenomas are found in patients with FAP and the adenoma-carcinoma sequence exists in the FAP duodenum, suggesting that treatment of duodenal polyps might be beneficial. Several methods of treatment for duodenal lesions in patients with FAP have been reported, but the current treatment options are not ideal. The nonsteroid anti-inflammatory drugs, sulindac and aspirin, are used for chemoprevention, while recently developed cyclooxygenase-2 inhibitors may be of some use in the future. Endoscopic polypectomy has been attempted for duodenal polyps and open surgical polypectomy has proven to be effective for selected patients. Photodynamic therapy and Argon plasma coagulation may be suitable to treat carpeted polyposis. New methods of duodenal resection, such as pancreas-preserving duodenectomy and pylorus-preserving pancreaticoduodenectomy, might be considered for severe duodenal polyposis; however, because prophylactic duodenal surgery has been considered too aggressive, surveillance duodenoscopy is usually performed to detect duodenal cancer at an early stage.

Adenoma↗
PubMed2000

A survey of surgical audit in Australia: whither clinical governance?

A postal survey was undertaken to determine the extent of surgical audit in Australian public hospitals in the context of clinical governance. Participants were 88 surgical units from 74 Australian public hospitals in 1998 with more than 70 beds. The main outcome measures were performance of audit, methods used, frequency, documentation and perceived adequacy of resources and comparison of performance with Royal Australasian College of Surgeons requirements for re-certification. The main findings were that most units performed audit, but over two-thirds declared that they had insufficient resources to conduct audit according to College requirements, while a substantial proportion did not comply with other published guidelines for the conduct of audit meetings. The conclusion from this survey is that surgical audit will be unable to play its part in quality initiatives inherent in the clinical governance concept unless appropriately resourced.

Australia↗
PubMed1998

Malignant change in a duodenal adenoma in familial adenomatous polyposis: report of a case.

Patients with FAP (familial adenomatous polyposis) are known to be at high risk for duodenal cancer. Although the adenoma-carcinoma sequence is thought to exist in the duodenum, clinical observation of the development of duodenal adenoma to cancer has rarely been reported. We outline a 44-yr-old postcolectomy man with FAP who underwent regular gastroduodenoscopy annually or biannually and was found to be harboring duodenal ampullary cancer 5 yr after colectomy. Endoscopic and pathological examination of the ampullary lesion during these 5 yr revealed progression of pathology from adenoma to carcinoma. Pathology of the surgical specimen confirmed ampullary cancer. This in vivo demonstration of the adenoma-carcinoma sequence highlights the current limitations of duodenal surveillance in FAP.

Adenoma↗
PubMed1997

The use of 32P-postlabelling in studies of the nature and origin of DNA adducts formed by bile from patients with familial adenomatous polyposis and from normal patients.

32P-postlabelling is a highly sensitive technique for the detection of DNA adducts. It is unique in that it requires no prior knowledge of the nature of adducts or adduct-forming species under investigation. In the past, we have used this technique to investigate the role of bile in the production of foregut adenomas in patients with familial adenomatous polyposis (FAP). We have found that bile contains constituents that form DNA adducts directly, and after metabolic activation, and that the bile of FAP patients has an increased capacity for adduct formation with DNA in vitro, in human cell lines in culture, and in the gastrointestinal tract of rats given bile by gavage. The sensitivity of 32P-postlabelling is such that it is difficult to obtain sufficient quantities of DNA adducts for chemical analysis. The nature of the adducts produced by bile, or of the bile constituents that produce them is as yet undetermined. In the present studies, we have combined 32P-postlabelling with indirect methods to gain some insight into the nature of DNA adducts produced by bile and the properties of the reactive species that form them. Firstly, bile was incubated with synthetic monodeoxynucleotides or polydeoxynucleotides. Bile did not produce adducts when incubated with monodeoxynucleotides or single-stranded polydeoxynucleotides. However, it did produce adducts when incubated with double-stranded polydeoxynucleotides. The pattern of adduct formation suggested that human bile forms a mixture of adenine and guanine adducts. Secondly, bile was fractionated by extraction with blue cotton or with neutral, acid or alkaline organic solvent. Blue cotton, which efficiently and selectively absorbs mutagens having 3 or more fused aromatic rings, did not absorb biliary constituents that could form adducts with DNA in vitro or with DNA of MCL-5 cells, a metabolically competent human cell line. This suggests that biliary DNA adduct precursors are polar compounds that contain fewer than 3 aromatic rings or are non-aromatic. Acidic organic extracts of human bile produced much higher levels of DNA adducts in vitro or with DNA of MCL-5 cells than did neutral or alkaline organic extracts, suggesting that constituents of bile that form DNA adducts are acidic in nature.

Adenomatous Polyposis Coli↗
PubMed1997

Screening modalities in familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer.

The syndromes known as familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) represent paradigms of the arguments for and against screening surveillance. This article details the protean manifestations of these conditions. It is not a how-to-do-it article with a suitably selected tranche of endoscopic pictures, but rather, it is an attempt to see what should be done.

Adenomatous Polyposis Coli↗
PubMed1997

p53 and K-ras status in duodenal adenomas in familial adenomatous polyposis.

BACKGROUND: The genetic alterations in patients with familial adenomatous polyposis (FAP) and duodenal adenomas are poorly characterized when compared with data relating to colorectal tumorigenesis in the same patients. METHODS: Point mutation of the K-ras oncogene and point mutation and overexpression of the TP53 tumour suppressor gene were investigated in 32 duodenal polyps (seven without mucosal pathology, 23 with mildly dysplastic adenomas and two with moderately dysplastic adenomas) from 21 patients with FAP. RESULTS: K-ras mutation, TP53 mutation or positive p53 staining were not found in duodenal polyps without histological abnormality. Of 25 duodenal adenomas, K-ras mutation was found in three (two mildly dysplastic, one moderately dysplastic), 20 showed positive p53 immunostaining, and mutation of the TP53 gene was found in one moderately dysplastic adenoma. p53 protein overexpression in duodenal adenomas was significantly more frequent than mutation of either K-ras or TP53 (P < 0.01). CONCLUSION: p53 dysfunction is a hallmark of duodenal adenomas in patients with FAP. Overexpression may indicate DNA damage and thus an early step in tumorigenesis.

Adenoma↗