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W Duncan

Publications and source records attributed to W Duncan.

At least 19 recordsLinked to original sources
PubMed2005

Preoperative radiotherapy for esophageal carcinoma.

BACKGROUND: The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. OBJECTIVES: This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery and whether or not any pre-defined patient subgroups benefit more or less from preoperative radiotherapy SEARCH STRATEGY: MEDLINE and CancerLit searches were supplemented by information from trial registers and by hand searching relevant meeting proceedings and by discussion with relevant trialists, organisations and industry. The search strategy was run again in MEDLINE, EMBASE and the Cochrane Library on 30th April 2001, two years after original publication. No new trials were found. The search strategy was re-run August 2002 and August 2003 on MEDLINE, EMBASE , CancerLit and The Cochrane Library, and July 2004 and 2005 on MEDLINE, EMBASE and the Cochrane Library. No new relevant trials were identified on any of these occasions. SELECTION CRITERIA: Trials were eligible for inclusion in this meta-analysis provided they randomized patients with potentially resectable carcinoma of the esophagus (of any histological type) to receive radiotherapy or no radiotherapy prior to surgery. Trials must have used a randomization method which precluded prior knowledge of treatment assignment and completed accrual by December 1993, to ensure sufficient follow-up by the time of the first analysis (September 1995). DATA COLLECTION AND ANALYSIS: A quantitative meta-analysis using updated data from individual patients from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials. This approach was used to assess whether preoperative radiotherapy improves overall survival and whether it is differentially effective in patients defined by age, sex and tumour location. MAIN RESULTS: With a median follow-up of 9 years, in a group patients with mostly squamous carcinomas, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p=0.062). No clear differences in the size of the effect by sex, age or tumor location were apparent. AUTHORS' CONCLUSIONS: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients (90% power, 5% significance level) would be needed to reliably detect such an improvement (from 15 to 20%).

Esophageal Neoplasms↗
PubMed2000

Preoperative radiotherapy for esophageal carcinoma. Oeosphageal Cancer Collaborative Group.

BACKGROUND: The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. OBJECTIVES: This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery and whether or not any pre-defined patient subgroups benefit more or less from preoperative radiotherapy SEARCH STRATEGY: Medline and CancerLit searches were supplemented by information from trial registers and by hand searching relevant meeting proceedings and by discussion with relevant trialists, organisations and industry. SELECTION CRITERIA: Trials were eligible for inclusion in this meta-analysis provided they randomized patients with potentially resectable carcinoma of the esophagus (of any histological type) to receive radiotherapy or no radiotherapy prior to surgery. Trials must have used a randomization method which precluded prior knowledge of treatment assignment and completed accrual by December 1993, to ensure sufficient follow-up by the time of the first analysis (September 1995). DATA COLLECTION AND ANALYSIS: A quantitative meta-analysis using updated data from individual patients from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials. This approach was used to assess whether preoperative radiotherapy improves overall survival and whether it is differentially effective in patients defined by age, sex and tumour location. MAIN RESULTS: With a median follow-up of 9 years, in a group patients with mostly squamous carcinomas, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p=0.062). No clear differences in the size of the effect by sex, age or tumor location were apparent. REVIEWER'S CONCLUSIONS: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients (90% power, 5% significance level) would be needed to reliably detect such an improvement (from 15 to 20%).

Esophageal Neoplasms↗
PubMed2000

Zidovudine (AZT) versus AZT plus didanosine (ddI) versus AZT plus zalcitabine (ddC) in HIV infected adults.

BACKGROUND: Zidovudine (AZT) monotherapy was the first antiretroviral drug to be tested widely. The next two drugs to be developed were didanosine (ddI) and zalcitabine (ddC). OBJECTIVES: To assess the effects of zidovudine (AZT), zidovudine plus didanosine (ddI) and zidovudine plus zalcitabine (ddC) on HIV disease progression and survival. SEARCH STRATEGY: Investigators and pharmaceutical companies were contacted, and MEDLINE searches were supplemented by searching conference abstracts. SELECTION CRITERIA: Randomised controlled trials comparing any two of AZT plus ddI, AZT plus ddC or AZT alone in participants with or without AIDS which collected information on deaths and new AIDS events. DATA COLLECTION AND ANALYSIS: Individual patient data with, wherever possible, follow-up obtained beyond that previously published were obtained and checked for internal consistency and consistency with any published reports; any apparent discrepancies were resolved with the trialists. Time to death and to disease progression (defined as a new AIDS-defining event or prior death) were analysed on an intention to treat basis, stratified to avoid direct comparisons between participants in different trials. MAIN RESULTS: Six trials were included in the meta-analysis. During a median follow-up of 29 months, 2904 individuals progressed, of whom 1850 died. The addition of ddI to AZT delayed both progression (RR 0.74; 95% CI 0.67 to 0.82, P<0.0001) and death (RR 0.72; 95% CI 0.64 to 0.82, P<0.0001). Likewise, the addition of ddC to AZT also delayed progression (RR 0. 86; 95% CI 0.78 to 0.94, P=0.001) and death (RR 0.87; 95% CI 0.77 to 0.98, P=0.02). After 3 years the estimated percentages alive and without a new AIDS event were 53% for AZT+ddI, 49% for AZT+ddC and 44% for AZT alone; the percentages alive were 68%, 63% and 59% respectively. Five of the six trials involved randomised comparisons of AZT+ddI versus AZT+ddC: in these, the AZT+ddI regimen had greater effects on disease progression (P=0.004) and death (P=0.009). REVIEWER'S CONCLUSIONS: The use of ddI and, to a lesser extent, ddC delayed both HIV disease progression and death, at least when added to AZT.

Adult↗
PubMed2000

Immediate versus deferred zidovudine (AZT) in asymptomatic or mildly symptomatic HIV infected adults.

BACKGROUND: Zidovudine (AZT) monotherapy was the first antiretroviral drug to be tested widely. Subsequent trials in asymptomatic or early symptomatic HIV infection indicated short-term delays in disease progression with AZT, but not improved survival. OBJECTIVES: To assess the effects of immediate versus deferred zidovudine (AZT) on HIV disease progression and survival. SEARCH STRATEGY: Investigators and pharmaceutical companies were contacted, and MEDLINE searches were supplemented by searching conference abstracts. SELECTION CRITERIA: Randomised controlled trials comparing immediate versus deferred AZT in participants without AIDS which prospectively collected deaths and new AIDS events. DATA COLLECTION AND ANALYSIS: Individual patient data with, wherever possible, follow-up obtained beyond that previously published was obtained and checked for internal consistency and consistency with any published reports; any apparent discrepancies were resolved with the trialists. Time to death and to disease progression (defined as a new AIDS-defining event or prior death) were analysed on an intention to treat basis, stratified to avoid direct comparisons between participants in different trials. MAIN RESULTS: Nine trials were included in the meta-analysis. During a median follow-up of 50 months, 1908 individuals developed disease progression, of whom 1351 died. In the deferred group, 61% started antiretroviral therapy (median time to therapy 28 months, which was AZT monotherapy in 94%). During the first year of follow-up immediate AZT halved the rate of disease progression (P<0.0001), increasing the probability of AIDS-free survival at one year from 96% to 98%, but this early benefit did not persist: after 6 years AIDS-free survival was 54% in both groups, and at no time was there any difference in overall survival, which at 6 years was 64% with immediate and 65% with deferred AZT (rate ratio [RR] 1.04, 95% confidence interval [CI] 0. 94 to 1.15). REVIEWER'S CONCLUSIONS: Although immediate use of AZT halved disease progression during the first year, this effect was not sustained, and there was no improvement in survival in the short or long term.

Anti-HIV Agents↗
PubMed1999

Totally laparoscopic abdominal aortic aneurysm repair.

On the basis of our previous animal and clinical experience with laparoscopic intra-abdominal vascular reconstructions, and due to the prevalence of abdominal aortic aneurysms (AAA), we have recently broadened our scope to tackle more difficult aortic surgery laparoscopically. We present a case report of our first clinical experience with laparoscopic AAA repair using specialized laparoscopic vascular instrumentation. The patient was an 84-year-old hypertensive male with a 7-cm asymptomatic infrarenal abdominal aortic aneurysm that was discovered incidentally. He presented with postcoronary artery bypass grafting and had moderate chronic obstructive pulmonary disease (COPD). A spiral computed tomograph (CT) angiogram revealed an adequate infrarenal neck and aneurysmal involvement of the proximal iliac arteries. An eight-port transabdominal technique was used with the patient in the supine position. Proximal and distal control was achieved without difficulty. The aneurysm was excluded using endoscopic stapling devices, and an aortobiiliac reconstruction was performed with a 16 x 9-mm bifurcated dacron graft. Estimated blood loss was 1000 ml, and the operative time was approximately 7 hours. The patient was ambulating without assistance on postoperative day 3. Total hospitalization was 7 days (delayed secondarily to postoperative ileus). Minimal quantities of narcotics were required for analgesia. At 6-months follow-up, the patient has palpable peripheral pulses and no complications related to surgery. This case report shows that a completely laparoscopic approach to the abdominal aortic aneurysm is possible using instrumentation specifically designed for laparoscopic vascular surgery. The exact role that laparoscopic techniques will hold in vascular surgery remains to be determined because these procedures are time consuming and technically difficult.

Aged↗
PubMed1998

Preoperative radiotherapy in esophageal carcinoma: a meta-analysis using individual patient data (Oesophageal Cancer Collaborative Group).

PURPOSE: The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery. METHODS AND MATERIALS: This quantitative meta-analysis included updated individual patient data from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials. RESULTS: With a median follow-up of 9 years, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p = 0.062). No clear differences in the size of the effect by sex, age, or tumor location were apparent. CONCLUSION: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients would be needed to reliably detect such an improvement (15-->20%).

Carcinoma↗
PubMed1998

Transoesophageal echocardiographic assessment of obstruction to the pulmonary venous pathway in children with Mustard or Senning repair.

The morphology and mechanism of obstruction to the pulmonary venous pathway in patients following either Mustard or Senning repair of complete transposition was assessed using transoesophageal echocardiography. Seven patients underwent catheterization and complete transoesophageal study in both transverse and longitudinal planes, followed by balloon dilation of the obstructed venous pathway in five of seven under transoesophageal echocardiography guidance. A complete scan of both systemic and venous pathway was obtained in all patients. Four patients with a Mustard repair were found to have a 'tubular' baffle, with stenosis resulting from a discrete wedge of tissue arising from the atrial free wall in association with fibrous adhesions to the baffle. In the three patients with a Senning repair the intra-atrial baffle showed a characteristic 'peaked' appearance, with stenosis of the venous pathway stenosis related directly to contracture of the patch used to augment the atrial free wall. The mechanism of obstruction appears to be inherent to the different surgical techniques. Indwelling transoesophageal echocardiography provided immediate haemodynamic and morphologic assessment of the efficacy of dilation of the obstructed venous pathway.

Adolescent↗
PubMed1998

Aortic cusp prolapse in ventricular septal defect and its association with aortic regurgitation--appropriate timing of surgical repair and outcomes.

OBJECTIVES: To determine the appropriate indications and timing for surgery in children with either a perimembranous or a subarterial type of ventricular septal defect (VSD) associated with aortic cusp prolapse. DESIGN: Retrospective review of children with VSD and associated aortic cusp prolapse with or without aortic regurgitation. This review was based on data obtained from clinical findings, two-dimensional echocardiography, cardiac catheterization and angiocardiography. SETTING: Tertiary health care facility with two-dimensional and colour Doppler echocardiographic and cardiac surgery facilities, and a catheterization laboratory. PATIENTS: Forty-eight patients were found to have perimembranous or subarterial VSDs in association with aortic cusp prolapse with or without aortic regurgitation. INTERVENTIONS: All 48 patients had high resolution two-dimensional and colour Doppler echocardiography. Of the 19 patients who underwent surgical closure of their VSD, five also had an aortic valvuloplasty and one had an aortic valve replacement. Cardiac catheterization was performed in 16 of the 19 surgical patients and 12 of the 29 nonsurgical patients. MEASUREMENTS AND MAIN RESULTS: Annual clinical and echocardiographic assessments in the nonsurgical group did not demonstrate increasing aortic insufficiency. Two children in the nonsurgical group showed spontaneous resolution of aortic insufficiency. In the surgical group, four children with VSD and clinical aortic insufficiency had surgery at less than five years of age; two were found to be regurgitant-free, one had trivial clinical aortic insufficiency and the other had echocardiography-only insufficiency. Of the seven surgical patients older than five years with VSD and clinical aortic insufficiency, four were found to be regurgitant-free, one had echocardiography-only regurgitation and two were unchanged. Two children undergoing surgery with VSD and no aortic insufficiency had postoperative echocardiography-only regurgitation, presumably related to cusp deformity from presurgical prolapse. Children with large VSDs with or without aortic cusp prolapse required surgery for indications of shunt size and pulmonary resistance. CONCLUSIONS: For children with small perimembranous VSDs and cusp prolapse, surgery is indicated only if there is clinical evidence of aortic regurgitation and progressive left ventricular enlargement.

Aortic Valve Insufficiency↗
PubMed1997

Prostate specific antigen levels during radical radiation therapy and the prediction of outcome in localized carcinoma of the prostate.

There has been substantial interest in the effect of radiation therapy upon serum prostate specific antigen (PSA) levels in patients managed by radiation therapy and their ability to predict the eventual outcome. At our institute, an observational prospective longitudinal study was begun in 1989 to identify prognostic factors for biochemical relapse from among several variables, including PSA levels measured prior to treatment, during treatment, and post-treatment, and to summarize what happens to PSA levels over the course of treatment with radical radiation therapy. A total of 142 patients with adenocarcinoma of the prostate (T1-4, N0, M0) were radically irradiated (6-7 weeks) between February 1989 and January 1991. Serum PSA levels were recorded weekly during radiation therapy in 117 patients. Of these 117, weekly PSA measurements ranged in completeness from 95 to 113 cases. A number of statistical tests were performed on the data with investigative/ exploratory intent. There were 60 biochemical relapses documented in the whole group of 142 patients, with a maximum follow-up of 4.6 years and median follow-up of 3.3 years. Of the candidate prognostic variables tested by univariate analysis, the following emerged as statistically significant (i.e. P < 0.05): each of the four pretreatment factors (absolute PSA value, dichotomous PSA (normal versus above normal), T category and Gleason score); the treatment variables namely, the end-of-treatment PSA, the slope of PSA, and the absolute change in PSA from pretreatment to the end of treatment; and, among post-treatment variables, the first follow-up PSA, the absolute change in PSA from pretreatment to first follow-up, and the return to normal of an above-normal pretreatment PSA by first follow-up. The majority of these factors were then subjected to multivariate Cox proportional hazards (PH) regression analyses. The end-of-treatment PSA and T category were consistently identified as independently statistically significant factors associated with biochemical relapse. The Gleason score was selected less consistently, and never when defined on a categorical scale. Therefore, using a Cox PH model with the variables of end-of-treatment PSA and T category, both defined on a categorical scale, we developed three prognostic groups with good, intermediate and poor prognoses (chi 2 TREND = 40.7; P < 0.0001). Their 3-year biochemical relapse-free rates, for example, were: 91%, (standard error (SE) 5%); 64% (SE 9%); and 24% (SE 6%), respectively. However, substitution of the baseline value of PSA, which was also strongly associated with outcome, and using the data from all 142 patients, provided similarly distinct prognostic groups (chi 2 TREND = 41.6; P < 0.0001), with corresponding 3-year relapse-free rates of: 92% (SE 4%); 79% (SE 7%); and 30% (SE 6%). Mean weekly PSA levels measured during treatment were found to have a negatively sloping or decreasing tendency. A statistically significant decrease in PSA occurred from pretreatment to the end of treatment (t116 = 7.5; P < 0.0001); the geometric mean of the ratio of end-of-treatment PSA to PSA at pretreatment was 0.7 (95% CI 0.6-0.8). The end-of-treatment PSA and T category emerged as independently statistically significant prognostic variables predicting biochemical relapse. Using the fitted Cox PH model with these two variables, three distinct prognostic groups were identified. The results using pretreatment PSA instead of end-of-treatment PSA produced similarly distinct prognostic groups. Mean weekly PSA levels measured during treatment exhibited a decreasing tendency, and a statistically significant decrease in PSa from pretreatment to the end of treatment was observed.

Adenocarcinoma↗
PubMed1996

Adverse effect of treatment gaps in the outcome of radiotherapy for laryngeal cancer.

BACKGROUND AND PURPOSE: A correlation has been demonstrated between unplanned prolongation of radiotherapy and increased local relapse. This review was performed to assess the importance of overall time on the outcome of curative radiotherapy of larynx cancer. MATERIALS AND METHODS: Retrospective analysis was performed of 383 patients with laryngeal cancer managed by elective radiotherapy between 1976-1988 in the Department of Clinical Oncology, University of Edinburgh, Western General Hospital, Edinburgh All cancers were confirmed histologically to be squamous cell carcinomas. All subjects received radiotherapy in 20 daily fractions (except Saturdays and Sundays), employing individual beam direction techniques and computer dose distribution calculations. Main outcome measures were complete resolution of the cancer in the irradiated volume; local relapse; survival and cause-specific survival rates. RESULTS: Radiotherapy was completed without any unplanned interruption (28 +/- 2 days) in 230/383 (60%) of patients. A statistically significant two-fold increase in local relapse rates was observed when treatment was given in 31 days or more. There also was a statistically significant four-fold increase in laryngeal cancer deaths when the treatment time exceeded 30 days. CONCLUSIONS: In patients with laryngeal cancer, accelerated repopulation of cancer cells probably occurs after the start of radiotherapy. When the overall treatment time is 4 weeks or less, gaps at weekends are not detrimental. However, long holiday periods or gaps in treatment longer than 4 days increase the risk of laryngeal cancer relapse and cancer-related mortality. Significant gaps in treatment should be avoided. If treatment has to be prolonged, additional radiation dose should be prescribed to compensate for increased tumour cell proliferation.

Carcinoma, Squamous Cell↗
PubMed1996

Report on consensus conference on colorectal cancer: Royal College of Surgeons of Edinburgh 1993.

Colorectal cancer is the second commonest cause of death from cancer in Scotland. Recent developments in molecular biology, pre-symptomatic diagnosis, surgery and adjuvant treatment suggest that a substantial reduction in mortality is achievable. Some fear that major changes to the organisation of the NHS could undermine future attempts to coordinate major cancer screening studies or multicentre adjuvant trials. In contrast, others argue that a sharp focus on cost and benefits could encourage the development of clear guidelines based on a consensus of good practice. Thus, the time seems right for a consensus conference and this article summarises the outcome of such a recent conference held in Scotland. A group of 80 surgeons, radiation oncologists and medical oncologists were invited as a representative cross-section of clinicians with an interest in colorectal cancer. Seventy per cent of those attending were surgeons. A series of expert presentations were used to lead discussion in four sessions devoted respectively to epidemiology and screening, influence of surgical factors and outcome, the role of adjuvant therapy and planning for the future. Full discussion from delegates was encouraged and computer-collated, key-pad responses allowed documentation of the opinions of the audience in respect of pre-defined questions. For statistical purposes we have assumed that a consensus had been reached when there was a statistically significant difference (Chi-square) between the observed response from clinicians and the null hypothesis, i.e. a 50/50 split.

Aftercare↗
PubMed1995

Radical radiotherapy for localized adenocarcinoma of the prostate. A report of 191 cases.

OBJECTIVE: To assess the results of radiotherapy in the treatment of localized prostate cancer. End points for assessment were survival, local control, development of metastases, and the toxicity of therapy. MATERIALS AND METHODS: The case notes of 191 patients who were treated with radical radiotherapy between 1982 and 1992 were reviewed. The pathology of 130 patients was reviewed by a single pathologist. A multivariate analysis was performed to identify significant prognostic factors with regard to survival and relapse. RESULTS: One-hundred and eighty-two patients were assessable. The minimum length of follow-up was one year (median = 40 months). The actuarial cause-specific 5 and 10 year survival rates were 63% and 35% respectively. Local progression occurred in 41% of patients with 37% developing metastases. Multivariate statistical analysis demonstrated that T stage and Gleason Score were significant predictors for survival. Late complications were usually mild, with only 4% developing serious bladder toxicity. CONCLUSION: Radical radiotherapy has a role in the curative treatment of prostate cancer. Survival is significantly related to T stage at the time of presentation, and to the Gleason Score of the tumour. Survival in this series was not as good as the best surgical series, but it is still not clear which patients should receive radiotherapy and which surgery as their primary management.

Actuarial Analysis↗
PubMed1995

Radiotherapy for stages I and II testicular seminoma: results and morbidity in 238 patients.

We have undertaken a retrospective analysis of 238 patients with Stages I and II seminoma of the testis treated with radiotherapy in Edinburgh between 1974 and 1989. There were five deaths from seminoma. Cause-specific survival for the whole group at 2 and 5 years was 99.2% and 98.1%, respectively. Cause-specific survival at 2 and 5 years by stage (Royal Marsden staging classification) was: Stage I, 99.5% and 98.7% and Stage II, 98.1% and 96.1%. Fourteen (5.9%) patients relapsed (one after treatment for his second testicular seminoma). Eight were given successful salvage treatment, five died of seminoma and one died of intercurrent disease. 13 (5.5%) patients developed World Health Organisation (WHO) grade 3 gastrointestinal or haematological toxicity and two developed grade 4 gastrointestinal toxicity as a result of abdominal radiotherapy. 22 patients (9.2%) developed problems ascribed to late morbidity of abdominal radiotherapy including 18 with peptic ulcer disease. Contralateral testicular tumours occurred in seven (2.9%) patients and five (2.1%) patients developed malignancies at other sites.

Adolescent↗