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Biomedical subjects

D Alderson

Publications and source records attributed to D Alderson.

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

Tracheal paraganglioma: a diagnostic dilemma culminating in a complex airway management problem.

A 41-year-old man presented to his general practitioner (GP) with a wheeze and dyspnoea on exercise. Asthma was diagnosed and treatment with inhaled corticosteroid and a beta(2)-agonist commenced. Despite this, his condition deteriorated over three weeks culminating in stridor, requiring emergency admission to hospital. Nasendoscopy revealed a polypoidal lesion in the upper trachea, acting like a ball valve. A local anaesthetic tracheostomy, secured his airway. Subsequent direct laryngoscopy allowed avulsion of the lesion. Alternative methods of airway management are discussed. Histology revealed a paraganglioma. The aetiology of paragangliomas is described and a literature review of tracheal paraganglioma is presented. Post-operative recovery was unremarkable. However, tumour recurrence occurred at nine months. A subsequent revision tracheostomy and laser resection has ensured disease-free survival, one year later. We recommend that acute onset wheeze, refractive to appropriate therapy, should be referred for urgent examination of the upper aerodigestive tract.

Acute Disease↗
PubMed2001

Oesophageal surgery.

Explore the source record for details and available documents.

Esophageal Motility Disorders↗
PubMed2000

IGFBP-3 prolongs the p53 response and enhances apoptosis following UV irradiation.

Neoplastic transformation is characterised by an imbalance in favour of cell growth over programmed cell death (apoptosis). The tumour-suppressor gene p53, responsible for maintaining cell-cycle control, is mutated in the majority of human cancers. Loss of function of the target genes of p53 are therefore important in tumourigenesis. One such target gene is the insulin-like growth factor binding protein-3 (IGFBP-3), an extracellular protein responsible for the carriage of IGF-I but which can act independently of IGF-I, inhibiting cell growth and enhancing apoptosis. Using the KYSE 190 oesophageal carcinoma cell line, we have demonstrated that IGFBP-3 alone has no effect on cell growth or cell survival. However, it significantly enhanced apoptosis, with a 67% increase in the pre-G1 peak on flow cytometry following UV irradiation. The increase in p53 was enhanced and prolonged when cells are stressed in the presence of IGFBP-3. These data suggest an autocrine/paracrine feedback loop exists between IGFBP-3 and p53, which may provide the social control necessary to maintain normal tissue homeostasis.

Apoptosis↗
PubMed2000

A prospective longitudinal study examining the quality of life of patients with esophageal carcinoma.

BACKGROUND: Quality of life (QL) measurement provides detailed information about outcome from the patient's perspective. This study assessed the impact on short and long term QL of esophagectomy and palliative treatment in patients with esophageal carcinoma. METHODS: Consecutive patients undergoing potentially curative esophagectomy or purely palliative treatment completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the dysphagia scale from the EORTC QLQ-OES24 before treatment and at regular intervals until death or for 3 postoperative years. Median scores were calculated for patients surviving more than 2 years after surgery (n = 17), for patients surviving less than 2 years after esophagectomy (n = 38), and for patients undergoing palliative treatment (n = 37). RESULTS: Baseline functional and symptom QL scores were similar in both groups of patients undergoing esophagectomy, and these were better than scores from patients selected for palliative treatment. Six weeks after esophagectomy, patients reported worse functional, symptom, and global QL scores than before treatment. In patients who survived at least 2 years, QL scores returned to preoperative levels within 9 months, but patients who died within 2 years of surgery never regained their former QL. In both groups, dysphagia improved after surgery and the improvement was maintained until death or for the duration of the study. Patients undergoing palliative treatment reported gradual deterioration in most aspects of QL until death. CONCLUSIONS: Esophagectomy has a negative impact on QL; this effect is transient for patients who survive for 2 or more years. This finding should be considered when selecting patients for surgery.

Aged↗
PubMed2000

Quality of life in patients with oesophageal cancer.

There is a growing interest in assessing quality of life in patients with oesophageal cancer because it provides detailed information of the patients' perception of the benefits or harms of treatment. Yet few studies have prospectively measured quality of life using validated appropriate instruments. There are now several questionnaires for patients with cancer, although these are not sufficiently sensitive to small but clinically important changes in quality of life. It is therefore recommended that a disease-specific module is used in conjunction with generic measures. The European Organisation into Research and Treatment of Cancer (EORTC) QLQ-OES24 is currently completing an international validation study. It is used with the EORTC QLQ-C30 core instrument and is designed for patients undergoing potentially curative treatment or palliation of malignant dysphagia. Studies that have assessed quality of life after oesophagectomy have generally found that survivors do regain their former health. Little is known about the effect of neoadjuvant chemoradiation on patients' quality of life. Following endoscopic palliation of dysphagia, quality of life can be maintained and improvement of swallowing is seen. A validated appropriate assessment of quality of life should be included in future palliative trials and in studies of new treatments which may marginally influence survival but cause significant side effects.

Deglutition Disorders↗
PubMed2000

Prognostic value of quality of life scores in patients with oesophageal cancer

AIMS: Quality of life (QL) data are useful in evaluating treatment, in screening or psychosocial morbidity and there is accumulating evidence to show that they predict survival. This study investigated if baseline QL scores are prognostic for patients with oesophageal cancer. METHODS: Between 1993 and 1995, 89 consecutive new patients with oesophageal cancer completed baseline QL assessments with the EORTC QLQ-C30 questionnaire and the dysphagia scale from the oesophageal cancer module. Cox's proportional hazards models were used to assess the impact of QL variables on survival (82 patients have died). RESULTS: Univariate analyses revealed that better baseline physical and role function scores were significantly associated with increased survival (P </= 0.001) and worse fatigue, appetite loss and constipation scores were significantly associated with shorter survival (P < 0.01). Multivariate analysis, taking account of associations between the QL scores and adjusting for age, tumour node metastasis classification T, N and M stage, showed that only physical function at baseline remained significantly associated with survival (P = 0.002); adjusting for sex, histology and comorbid disease did not alter the findings. CONCLUSIONS: There is evidence to suggest that QL parameters may be important prognostic factors for patients with oesophageal cancer. Stronger evidence may be gained from a more highly powered study, and further understanding of the associations between QL variables and clinical data is needed.

Journal Article↗
PubMed2000

Investigating the proximal limit of lymphadenectomy in patients with adenocarcinoma of the oesophagus in the mid-thoracic region

AIMS: The benefit of extended lymphadenectomy in patients with squamous cell carcinoma of the oesophagus is established, but there is little evidence to support this in patients with adenocarcinoma. The aim of this study was to investigate the extent of lymphatic spread of oesophageal adenocarcinomas, and particularly the proximal spread in tumours located in the mid thorax. METHODS: Twenty-six consecutive patients with tumours arising between 29 and 35 cm from the incisor teeth underwent three-stage oesophagectomy with two-field lymphadenectomy, including nodes in the recurrent laryngeal chains. The proximal extent was measured by endoscopic ultrasonography and confirmed at operation, with division of the lymph node harvest into anatomical sites according to the Japanese classification of oesophageal cancer. RESULTS: There were 21 men and five women, with a mean age of 64 (range 42-78) years; seven patients were lymph node negative in both the mediastinal and abdominal fields. Six patients had nodal metastases more than 2 cm above the tumour and all had extensive involvement of other nodes at the level of the tumour or below, with 7, 7, 9, 12, 15 and 18 nodes positive. There were no patients in whom nodes above the tumour contained metastases while those at the level or below were clear. CONCLUSIONS: Dissection of proximal lymph nodes along the recurrent laryngeal nerve chains in patients with adenocarcinoma of the oesophagus is not warranted. Lymphatic spread above the level of the tumour occurs in association with extensive lymph node involvement elsewhere and removal of proximal nodes from difficult locations is not warranted as a means of improving staging or survival.

Journal Article↗
PubMed2000

Endoscopic ultrasonography in the evaluation of idiopathic acute pancreatitis.

BACKGROUND: 'Idiopathic' pancreatitis may be diagnosed when gallstones are excluded by transabdominal ultrasonography and less common causes are not implicated by history or other investigations. Transabdominal ultrasonography may not, however, detect small stones responsible for acute pancreatitis. The aim of this study was to determine if endoscopic ultrasonography (EUS) is able to identify undetected gallstones in cases of 'idiopathic' pancreatitis. METHODS: Consecutive patients presenting with 'idiopathic' pancreatitis were assessed using EUS for the presence of gallstones or other potential causes of the attack. A control group was also imaged. RESULTS: Forty-four patients with 'idiopathic' pancreatitis were assessed. Ten had suffered earlier attacks of pancreatitis before this study. EUS revealed proven pathology in 18 patients. Unconfirmed pathology was evident in 14. No abnormality was seen in only nine patients. EUS failed in one patient and there were two possible false-positive results. CONCLUSION: EUS is able to identify significant pathology in patients in whom a diagnosis of 'idiopathic' pancreatitis has been made following standard investigations. Patients with untreated gallstones are at risk of recurrent attacks. Idiopathic pancreatitis should not be diagnosed unless EUS has been performed.

Acute Disease↗
PubMed1999

Amplification of cyclin D1 and MDM-2 in oesophageal carcinoma.

AIMS: This study investigated amplification of the cyclin D1 and MDM-2 genes, and overexpression of the cyclin D1 gene product, in oesophageal carcinoma. METHODS: Paired tumour and normal DNA samples from 26 oesophageal adenocarcinomas and 19 squamous cell carcinomas were analysed by Southern blotting with specific DNA probes for cyclin D1 and MDM-2, and for a control gene (alpha-lactalbumin). The cyclin D1 and MDM-2 gene copy numbers were calculated for each tumour. Expression of the cyclin D1 gene was assessed by immunohistochemical analysis of its protein product. RESULTS: Cyclin D1 gene amplification (by a factor of between two and six) was identified in seven tumours (16%). MDM-2 gene amplification (by a factor of between two and 11) was identified in 10 tumours (22%). Overexpression of cyclin D1 protein was identified in eight tumours and was significantly associated with gene amplification (P=0.04; Fisher's exact test), and with early T stage (P=0.01; Fisher's exact test). CONCLUSIONS: Cyclin D1 and MDM-2 amplification and cyclin D1 overexpression occur, although infrequently, in the development of oesophageal carcinoma. Cyclin D1 overexpression may influence tumour behaviour, causing the disease to present at an earlier T stage. The mechanism for this effect is unclear, and warrants further investigation.

Adenocarcinoma↗
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↗