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Biomedical subjects

D Alderson

Publications and source records attributed to D Alderson.

At least 19 recordsLinked to original sources
PubMed1998

Loss of heterozygosity at microsatellite marker sites for tumour suppressor genes in oesophageal adenocarcinoma.

AIMS: Loss of cell cycle control is an important step in the development of human tumours. A number of tumour suppressor genes are involved in cell cycle control, including p16, p53 and Rb. The aim of this study was to seek evidence of deletions of these genes in oesophageal adenocarcinoma. METHODS: Paired (tumour and normal squamous epithelium) frozen tissue samples from 12 patients were analysed by polymerase chain reaction (PCR) for loss of heterozygosity (LoH) at five microsatellite marker sites (two each for p16 and Rb, one for p53). Aneuploid tumour cell populations were sorted by flow cytometry prior to PCR, to eliminate stromal cell contamination. RESULTS: Of the 12 tumours, 11 (92%) had LoH at one or more loci. LoH at the p53 locus occurred in nine of 12 tumours, at one or both p16 loci in seven of 11 tumours, and at one or both Rb loci in eight of 12 tumours. Five tumours had LoH at two tumour suppressor gene loci, and a further four tumours had LoH at loci for all three genes. CONCLUSIONS: Allelic deletions of p53, p16 and Rb are common in oesophageal adenocarcinoma, and may be important in the development of this disease.

Adenocarcinoma↗
PubMed1998

Nothing new under the sun: the management of epistaxis.

The management of epistaxis is reviewed from ancient times onwards. Many curious methods have been employed and indeed epistaxis has been encouraged at times. Although current management is based on sound principles folklore remedies still predominate amongst some of our patients. The basis of contemporary treatments was known and practised by our ancient forbears.

Epistaxis↗
PubMed1998

Oesophageal cancer staging using endoscopic ultrasonography.

BACKGROUND: Despite encouraging results from Europe and the USA, endoscopic ultrasonography has yet to become established in the UK for imaging gastrointestinal lesions. The aim of this prospective study was to investigate the accuracy of endoscopic ultrasonography for local tumour (T) and lymph node (N) staging of oesophageal cancer. METHODS: Endoscopic ultrasonography was performed in 50 consecutive patients with operable oesophageal cancer. Its accuracy for locoregional tumour staging was assessed and a detailed analysis of the distribution of ultrasonographically detected lymph nodes performed. RESULTS: Endoscopic ultrasonography was highly accurate for both local tumour (92 per cent correct T stage prediction) and lymph node (86 per cent correct N stage prediction) staging compared with final histology. The procedure was also superior to open surgical staging performed by the surgeon; it had a tendency to overestimate malignant involvement of individual lymph nodes and had only limited ability to identify small benign lymph nodes, particularly in the abdomen. CONCLUSION: Endoscopic ultrasonography was reliable for both local tumour and lymph node staging of oesophageal cancer.

Adenocarcinoma↗
PubMed1998

Diet, reflux and the development of squamous cell carcinoma of the oesophagus in Africa.

BACKGROUND: Squamous cancer of the oesophagus has reached epidemic proportions in Africa in the past few decades. There are many known associations but as yet no well established theory of causation. METHODS: Relevant literature was found by manual review of appropriate journals and literature, Medline searches and cross-referencing. Published theories of causation of endemic cancer of the oesophagus were assessed in the light of available evidence. A hypothesis based on that evidence was formulated. RESULTS AND CONCLUSION: A predominantly maize-based diet is high in linoleic acid, a precursor for gastric prostaglandin synthesis. In combination with low intake of other fatty acids and riboflavin, high levels of prostaglandin E2 are produced in gastric mucosa, leading to reduced gastric acid secretion, relaxation of the pylorus and a reduction in lower oesophageal sphincter pressure. These events result in combined reflux of duodenal and gastric juices low in acidity into the oesophagus. Resulting dysplasia strongly predisposes to local squamous carcinogenesis. This is now a fertile area for research, which may open the way for preventive action.

Africa↗
PubMed1998

Influence of luminal obstruction on oesophageal cancer staging using endoscopic ultrasonography.

BACKGROUND: Endoscopic ultrasonography is technically limited in patients with obstructing oesophageal cancers if the endoscope cannot pass beyond the lesion. This problem may be overcome by preliminary endoscopic tumour dilatation, or by the use of narrower calibre 'blind' endoscopic ultrasonographic telescopes or fine-bore endoscopic ultrasonographic miniprobes. These alternatives are either potentially hazardous or time consuming and expensive. The aim of this prospective study was to determine the effect of oesophageal obstruction on the locoregional staging accuracy of endoscopic ultrasonography for oesophageal cancer. METHODS: Some 50 patients with oesophageal cancer underwent staging with endoscopic ultrasonography before oesophagectomy and the T and N stage determined by endoscopic ultrasonography was compared with final histology. In 11 cases of luminal obstruction no attempt was made to overcome the blockage and a limited mediastinal scan alone was performed. RESULTS: Malignant obstruction of the oesophagus did not greatly reduce the staging accuracy of endoscopic ultrasonography. It correctly assessed local infiltration in all patients with obstruction, and correctly predicted nodal stage in nine of 11 patients. CONCLUSION: Tumours large enough to cause luminal obstruction are nearly all full thickness (T3), and frequently have mediastinal lymph node metastases (N1) at the time of examination. This can usually be detected from limited endoscopic ultrasonography within the mediastinum.

Diagnostic Errors↗
PubMed1998

Primary yolk sac tumour of the liver in adulthood.

Primary yolk sac tumour of the liver is exceedingly rare. A 28 year old woman presented with a cystic liver mass and a markedly raised serum alpha-fetoprotein concentration. She underwent a partial hepatectomy for a suspected hepatocellular carcinoma but histological examination of the tumour revealed the classical morphological and immunohistochemical features of a yolk sac tumour. There was no evidence of an extrahepatic primary source. Review of this case, together with the six previously reported adult cases of primary yolk sac tumours of the liver, revealed several features of the tumour that may aid differentiation from hepatocellular carcinoma, with potential therapeutic implications.

Adult↗
PubMed1997

Investigation of oesophageal adenocarcinoma for viral genomic sequences.

Overexpression of the tumour suppressor gene product p53 is common in oesophageal adenocarcinoma. This may be due to gene mutation, but overexpression can also result from complexing between viral proteins and p53; a number of viruses are causally linked with malignancy. This study therefore investigated the prevalence in oesophageal adenocarcinoma of viruses whose gene products are capable of interacting with p53. Seventeen tumours and 17 normal oesophagi were screened for specific DNA sequences from human papilloma virus (HPV), Adenovirus type 12, Epstein-Barr Virus (EBV), and cytomegalovirus (CMV). Frozen sections were analysed by polymerase chain reaction, and results were confirmed by Southern blot hybridization. Overexpression of p53 was studied immunohistochemically. Overexpression of p53 was identified in 11 of 17 tumours. No viral sequences were detected for HPV, CMV, or Adenovirus in any tumour. EBV sequences were found in eight of 17 tumours, and eight of 17 negative controls. There is therefore no evidence of HPV 16, 18 and 33, Adenovirus 12 or CMV infection in oesophageal adenocarcinoma. EBV infection in the oesophagus is of doubtful significance, in view of the high incidence in the control population. Overexpression of p53 cannot be explained by complexing with common viral proteins, and must be related to other intracellular mechanisms.

Adenocarcinoma↗
PubMed1997

Immunohistochemical detection of p53 and c-erbB-2 in oesophageal carcinoma; no correlation with prognosis.

TNM staging of oesophageal cancer provides significant prognostic information but its clinical impact is limited as many patients present with advanced disease (i.e. T3N1). Additional prognostic markers may help separate those with 'good' and 'bad' prognosis tumours and so help with decisions such as selection for adjuvant therapy. p53 and c-erbB-2 overexpression may correlate with poor prognosis in oesophageal cancer, but this is uncertain. This study aimed to investigate the value of these biomarkers as prognostic indicators in resected oesophageal cancer. Two hundred and five oesophageal tumours (127 adenocarcinoma, 78 squamous) resected by a single surgeon between June 1979 and January 1991 were investigated for p53 and c-erbB-2 overexpression using DO-7 and CB-11 immunohistochemistry. Patient survival was analysed by Kaplan-Meir life tables. Median survival was 61 weeks (range: 5-747) and survival diminished significantly with increasing UICC stage (P < 0.0001). Sixty-eight per cent of squamous tumours and 66% of adenocarcinomas overexpressed p53 but there was no statistically significant correlation with prognosis. Twenty-six per cent of squamous tumours and 23% of adenocarcinomas overexpressed c-erbB-2, but again this did not correlate with survival. p53 and c-erbB-2 are commonly overexpressed in oesophageal cancer but do not appear to be related to prognosis in this large series of resected oesophageal cancers and other candidate biomarkers must be sought.

Adenocarcinoma↗
PubMed1997

Human papillomavirus and oesophageal squamous cell carcinoma in the UK.

Human papillomavirus (HPV) has previously been identified in up to 67% of squamous cell carcinomas of the oesophagus. In particular, HPV types of 16 and 18 are believed to play an important role in neoplastic transformation, by means of their oncoproteins E6 and E7. Most of these studies, however, pertain to areas of high incidence of squamous cell carcinoma of the oesophagus (the Far East and South Africa). It is not known if HPV plays any role in the development of oesophageal squamous cell carcinoma in the UK, where the tumour is relatively uncommon. The polymerase chain reaction was used to examine frozen tissue from 22 oesophageal squamous cell carcinomas for the presence of specific DNA sequences from oncogenic strains of HPV. PCR products were further analysed by Southern blot hybridization. No HPV sequences were detected in any tumours. These results suggest that these types of HPV are not associated with oesophageal squamous cell carcinoma in this country. It is unlikely, therefore, that HPV plays a significant role in the pathogenesis of squamous cell carcinoma of the oesophagus in the UK.

Adult↗
PubMed1997

Brush cytology in the diagnosis of neoplasia in Barrett's esophagus.

Esophageal cytology may improve sensitivity for the detection of malignancy but can be difficult to interpret in the presence of inflammation. To assess the value of cytology in assessing patients with Barrett's esophagus a retrospective review was performed. One hundred and sixty two patients (87 esophageal/gastroesophageal junction adenocarcinoma, 65 non-dysplastic Barrett's esophagus and 10 dysplastic Barrett's esophagus) had biopsies and brushings taken for histological and cytological assessment. Eighty two of 92 patients with carcinoma or high-grade dysplasia had true positive malignant cytology. Seven of 65 patients with non-dysplastic but inflamed Barrett's esophagus had false positive malignant cytology. One of these patients had an esophagectomy on the basis of cytology but no tumor was found in the resection specimen. This translates into an 89% sensitivity and specificity of cytology for the detection of esophageal columnar neoplasia. Cytology from Barrett's esophagus can be misleading in the presence of severe inflammation. Cells from a benign Barrett's ulcer may appear frankly malignant when examined in isolation. Esophagectomy should not be performed on the basis of cytological evidence alone.

Adenocarcinoma↗
PubMed1997

Review: chemotherapy, irradiation and their roles in the management of oesophageal cancer.

The role of multimodality therapy in the treatment of oesophageal cancer has been extensively investigated in many longitudinal studies and randomized trials. Despite some promising results, no clear beneficial evidence has consistently been produced. At present it cannot be routinely recommended outside the context of controlled clinical trials.

Combined Modality Therapy↗
PubMed1997

Diffuse oesophageal spasm: diagnosis by ambulatory 24 hour manometry.

BACKGROUND: Diffuse oesophageal spasm (DOS) is a potential cause of intermittent chest pain and/or dysphagia. In the past, the diagnosis of DOS has relied on criteria obtained from standard oesophageal manometry (more than one simultaneous contraction in a series of 10 wet swallows with the rest being peristaltic). As symptoms are intermittent, however, 24 hour manometry may well be more suited to its investigation. AIMS: To determine the ability of 24 hour manometry to detect the symptomatic contractions of DOS and to compare standard, laboratory based manometry with 24 hour manometry in its diagnosis. PATIENTS: Three hundred and ninety consecutive patients referred with suspected oesophageal disorders. METHODS: Standard laboratory based manometry and 24 hour outpatient manometry. RESULTS: Sixteen patients were classified by 24 hour manometry as having DOS on the basis of painful contractions (spasms) of excessive duration and increased amplitude. Laboratory based manometry failed to detect the majority of these patients with DOS (14/16), and 53/55 were incorrectly labelled as having DOS on the basis of asymptomatic manometric findings. CONCLUSION: The detection of symptomatic DOS requires 24 hour manometry.

Adult↗
PubMed1997

Prospective comparison of endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography in the detection of bile duct stones.

BACKGROUND: Conventional ultrasonography is used widely in the investigation of gallstone disease but is limited in the detection of bile duct stones due to poor visualization of the distal bile duct. Endoscopic retrograde cholangiopancreatography (ERCP) is currently the investigation of choice for suspected choledocholithiasis, but is not without morbidity. Endoscopic ultrasonography clearly visualizes the entire extrahepatic biliary tree and avoids the need for ERCP in many patients. METHODS: Some 50 patients with suspected duct stones underwent endoscopic ultrasonography followed by ERCP. All cholangiograms were performed or interpreted by a second doctor blinded to the results of endoscopic ultrasonography. RESULTS: Both tests were successful in 46 patients; both tests failed in two patients and ERCP alone failed in a further two. Duct stones were confirmed in 24 patients. Sensitivity (95 per cent confidence interval (c.i.)) of ERCP and endoscopic ultrasonography in identifying these stones was 79 (58-93) per cent and 88 (68-97) per cent respectively; specificity (95 per cent c.i.) was 92 (75-99) per cent and 96 (80-100) per cent. CONCLUSION: Endoscopic ultrasonography accurately identifies bile duct stones. It is recommended in all patients with a risk of duct stones but especially in those with a history of ERCP-induced pancreatitis, when other pathology is suspected, when ERCP has failed, when bile duct abnormalities are suspected during pregnancy and in patients with acute pancreatitis.

Adolescent↗
PubMed1996

Plasminogen activators in oesophageal carcinoma.

The expression of components of the plasminogen activator system was investigated in patients with oesophageal carcinoma. Tumour and normal mucosa were obtained from resected oesophageal carcinomas and antigens were measured by enzyme-linked immunosorbent assay. Median levels of urokinase plasminogen activator (uPA) and the uPA receptor were higher in carcinoma than in matched normal mucosa (squamous cell carcinoma: uPA 4.05 versus 0.66 ng antigen per mg protein, uPA receptor 1.95 versus 0.50 ng/mg, n = 10, P < 0.05; adenocarcinoma: uPA 2.16 versus 0.61 ng/mg, uPA receptor 2.01 versus 0.49 ng/mg, n = 8, P < 0.05). Tissue plasminogen activator (tPA) level was lower than control values in squamous cell carcinoma but not in adenocarcinoma (1.97 versus 4.70 ng/mg, P < 0.05). There was no difference in plasminogen activator inhibitor (PAI) 1 level between carcinoma and normal mucosa. The PAI-2 level was lower than that in normals in adenocarcinoma only (6.0 versus 64.77 ng/mg, P < 0.05). These data support the hypothesis that membrane-bound uPA has a role in the breakdown of extracellular matrix in invasive oesophageal carcinoma.

Adenocarcinoma↗
PubMed1996

Development of an EORTC questionnaire module to be used in quality of life assessment for patients with oesophageal cancer. The EORTC Quality of Life Study Group.

Quality of life (QOL) assessments in patients with oesophageal cancer should provide clinically meaningful data that can assist management decision making. This study describes the development of a specific module for oesophageal cancer to use with the European Organisation into Research and Treatment of Cancer (EORTC) QOL questionnaire, the EORTC QLQ-C30. Relevant QOL issues were generated from a literature search and interviews with patients and oesophageal cancer specialists. Issues were formulated into items compatible with those of the EORTC QLQ-C30. The provisional module was pretested in patients from the United Kingdom, Spain and Sweden. The resulting module, the QLQ-OES 24, includes 24 items conceptualised as containing six scales and five single items. The addition of an oesophageal cancer-specific module to the core questionnaire should improve the sensitivity and specificity of the core instrument to allow detection of even small benefits accrued from new treatment modalities.

Aged↗
PubMed1995

Oesophageal acid clearance in patients with severe reflux oesophagitis.

Previous studies examining oesophageal acid clearance have employed a variety of techniques to induce or simulate acid reflux. Clearance abnormalities have been deduced from abnormal standard motility studies, barium radiology or from 24-h pH recordings. In this study a 24-h pH and oesophageal motility recording system was used to study naturally occurring acid reflux episodes in control subjects and in two groups of patients with severe acid reflux disease (erosive oesophagitis and oesophageal stricture). Acid clearance was compared between the subject groups. Patients with oesophageal stricture were found to have poor oesophageal peristaltic ability and particularly poor oesophageal acid clearance. Those with erosive oesophagitis had normal peristaltic swallowing but abnormal acid clearance. This study has characterized, for the first time, the abnormalities in acid clearance during naturally occurring acid reflux episodes in patients with severe reflux disease. A more complete understanding of these clearance abnormalities could influence future medical and surgical strategies in the management of severe gastro-oesophageal reflux disease.

Adult↗
PubMed1995

Observer variation in assessment of quality of life in patients with oesophageal cancer.

Quality of life (QOL) assessment may improve the evaluation of treatment for oesophageal cancer but patient compliance using self completion questionnaires is often poor. The use of a proxy to estimate QOL might improve data collection from patients who are either unable or unwilling to complete the questionnaire. This study examined whether a doctor or patients' carers could accurately assess QOL using the QLQ-C30 questionnaire developed by the European Organisation for Research and Treatment of Cancer Study Group on Quality of Life. One doctor, 52 patients and 39 carers completed the instrument independently. Proxy and patient ratings were analysed for agreement using weighted kappa scores. Agreement was poor or moderate in most QOL scales and items (kappa < or = 60). This study demonstrates that a carer or doctor is not sufficiently accurate to postulate the patient's responses to the questionnaire. Quality of life data, therefore, should come from the patients themselves.

Adult↗