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Biomedical subjects

W Duncan

Publications and source records attributed to W Duncan.

At least 37 records · Page 2Linked to original sources
PubMed1994

Production and response of human prostate cancer cell lines to granulocyte macrophage-colony stimulating factor.

Prostate cancer selectively metastasises to skeletal sites, where it normally produces osteoblastic lesions. This study investigated whether haematopoietic growth factors known to be present in the bone environment could be involved in the survival and proliferation of prostate skeletal metastases. To evaluate this hypothesis we investigated the effects of recombinant granulocyte/macrophage colony-stimulating factor (rGM-CSF), recombinant granulocyte colony-stimulating factor (rG-CSF), recombinant erythropoietin (rEPO) and recombinant interleukin-3 (rIL-3) on the growth of 3 human prostate cancer cell lines. Two hormone-insensitive cell lines, PC-3 and DU145, were significantly stimulated by rGM-CSF and rEPO in serum-free medium but their growth was unaffected by incubation with rIL-3 or rG-CSF. A hormone-sensitive cell line, LNCaP, was stimulated only by rGM-CSF. To investigate further the involvement of GM-CSF in prostate cancer, the presence of GM-CSF protein in the 3 prostate cancer cell lines was examined by immunohistochemistry, and analysis of cell line conditioned media was carried out by ELISA and Western blotting. These techniques demonstrated that GM-CSF-like material was produced by both DU145 and PC-3 cells but not by LNCaP. The results from ELISA found that media conditioned by DU145 and PC-3 cells contained 1.7 and 2.5 pg GM-CSF/micrograms protein, respectively, whereas no GM-CSF was detectable in the LNCaP conditioned media. Our results were also confirmed by Western blot analysis demonstrating one single band for DU145 and PC-3 conditioned media which co-migrated along with the standard rGM-CSF band. No bands were associated with the LNCaP conditioned media. The presence of GM-CSF gene transcripts in DU145 and PC-3 cells was established by reverse transcription and polymerase chain reaction of total RNA.

Adenocarcinoma↗
PubMed1994

The influence of transurethral resection of prostate on prognosis of patients with adenocarcinoma of the prostate treated by radical radiotherapy.

Results of 999 patients with carcinoma of the prostate treated with radical radiotherapy were evaluated to assess the impact of pre-treatment transurethral resection of the prostate. (TURP). A total of 427 patients had a needle biopsy and 541 patients had a TURP. In 31 patients the diagnostic procedure could not be ascertained. In patients with stage T1/T2 disease (411) no adverse effect on prognosis was observed following TURP compared with needle biopsy. In patients with stage T3/T4 disease (534) a significantly higher distant relapse rate and cause-specific mortality were observed after TURP but overall survival was similar after TURP and needle biopsy. A significant correlation was observed between the probability of TURP and poorly differentiated cancers. Multivariate analysis which evaluated the influence of age, T stage, histologic differentiation and TURP did not demonstrate diagnostic TURP to be a significant independent prognostic variate for patients with prostate cancer managed by radical radiotherapy.

Adenocarcinoma↗
PubMed1994

An evaluation of the results of neutron therapy trials.

Twenty-five randomised clinical trials have been completed which have investigated the value of fast neutron therapy. The results of these trials are reviewed in terms of the reported rates of local tumour control and late morbidity. The trials have included patients with cancers of the head and neck region, brain, lung, pancreas, cervix, bladder and rectum. None has demonstrated neutrons to be advantageous compared with photons. Two trials of locally advanced prostate cancer have given conflicting results. A trial of mixed schedule therapy has demonstrated improved local tumour control and survival. A trial of neutrons alone for similar stage disease has not shown any therapeutic advantages. It is still claimed that salivary gland tumours may be more effectively treated by neutrons but the clinical trial results are not definitive. Late morbidity after neutron therapy is a persistent cause for concern and often has been unacceptably high. There is no convincing evidence that fast neutrons are either as safe or as effective in cancer control as photon therapy.

Brain Neoplasms↗
PubMed1993

Neutron versus photon irradiation for unresectable salivary gland tumors: final report of an RTOG-MRC randomized clinical trial. Radiation Therapy Oncology Group. Medical Research Council.

PURPOSE: To compare the efficacy of fast neutron radiotherapy versus conventional photon and/or electron radiotherapy for unresectable, malignant salivary gland tumors a randomized clinical trial comparing was sponsored by the Radiation Therapy Oncology Group in the United States and the Medical Research Council in Great Britain. METHODS AND MATERIALS: Eligibility criteria included either inoperable primary or recurrent major or minor salivary gland tumors. Patients were stratified by surgical status (primary vs. recurrent), tumor size (less than or greater than 5 cm), and histology (squamous or malignant mixed versus other). After a total of 32 patients were entered onto this study, it appeared that the group receiving fast neutron radiotherapy had a significantly improved local/regional control rate and also a borderline improvement in survival and the study was stopped earlier than planned for ethical reasons. Twenty-five patients were study-eligible and analyzable. RESULTS: Ten-year follow-up data for this study is presented. On an actuarial basis, there continues to be a statistically-significant p = 0.009) but there is no improvement in overall survival (15% vs. 25%, p = n.s.). Patterns of failure are analyzed and it is shown that distant metastases account for the majority of failures on the neutron arm and local/regional failures account for the majority of failures on the photon arm. Long-term, treatment-related morbidity is analyzed and while the incidence of morbidity graded "severe" was greater on the neutron arm, there was no significant difference in "life-threatening" complications. This work is placed in the context of other series of malignant salivary gland tumors treated with definitive radiotherapy. CONCLUSIONS: Fast neutron radiotherapy appears to be the treatment-of-choice for patients with inoperable primary of recurrent malignant salivary gland tumors.

Adult↗
PubMed1993

Results of a policy of surveillance in stage I testicular seminoma.

PURPOSE: To determine what proportion of patients with Stage I testicular seminoma will be cured with orchidectomy alone. METHODS AND MATERIALS: From August 1984 to December 1991 148 patients with Stage I testicular seminoma were entered on a prospective study of surveillance following orchidectomy. The eligibility criteria included a normal chest X ray, lymphogram, computed tomography (CT) of the abdomen and pelvis, and normal post-orchidectomy tumor markers (AFP and BHCG). Patients were followed with a clinical assessment (markers, chest X ray and CT abdomen and pelvis) at 4 to 6 monthly intervals. RESULTS: With a median follow-up of 47 months (range 7-87 months), the actuarial relapse-free rate was 81% at 5 years. Twenty-three patients have relapsed with a median time to relapse of 15 months (range 2-61 months). Four patients (17%) relapsed at 4 or more years from diagnosis. Twenty-one of the 23 relapses occurred in the paraaortic lymph nodes, one patient relapsed in the mediastinum and ipsilateral inguinal nodes and one patient had an isolated ipsilateral inguinal node relapse. Nineteen patients were treated for relapse with external beam radiation therapy of which three developed a second relapse and were salvaged with chemotherapy. Four patients were treated for first relapse with chemotherapy and one developed a second relapse and died of disease. Age at diagnosis was the only prognostic factor for relapse, with patients age < or = 34 having an actuarial relapse-free rate at 5 years of 70% in contrast to a 91% relapse-free rate in those > 34 years of age. CONCLUSIONS: We recommend that surveillance in Stage I testicular seminoma should only be performed in a study setting until further data regarding the risk of late relapse and the efficacy of salvage chemotherapy is available.

Adult↗
PubMed1993

Carcinoma of the prostate: results of radical radiotherapy (1970-1985).

PURPOSE: To determine the outcome and prognostic factors in patients with localized carcinoma of the prostate treated with external beam radiation therapy. METHODS AND MATERIALS: A retrospective review of 999 patients with histologically confirmed adenocarcinoma of the prostate treated radically with megavoltage irradiation at the Princess Margaret Hospital between 1970 and 1985. Prognostic factors were analyzed using recursive partitioning method. RESULTS: Overall survival at 5 and 10 years were 69.8% and 40.1% for the whole group. The cause-specific survival rates were 78.9% and 53.5%, respectively. The cause-specific survival rates were significantly different at 10 years by T stage, T1 being 79.0%, T2 66.0%, T3 55% and T4 22%. The overall clinical local control rates was 77% in the first 5 years following treatment. There was no statistically significant difference in the local control rates of T1 and T2 stage disease at 5 years, the combined rate being 88%. Significant differences were observed between other stages, being 76% for T3 and 55% for T4. At 10 years the control rate for T1 tumours was maintained for T1 stage disease (92%) but was significantly reduced for other stages, T2 75%, T3 67% and for T4 37%. In the whole group 33.5% of patients had distant metastases in the first 5 years. The distant relapse rates at 10 years were significantly different by T stage, being 20% for T1, 33% for T2, 55% for T3 and 87% for T4. Multivariate analysis demonstrated that only T stage and histological grade were independent prognostic covariates for cause-specific survival. Age was the only other independent variate in terms of overall survival. The late radiation related morbidity was 2.3% overall; 1.3% affecting rectum and recto-sigmoid and 1.0% arising in the bladder. CONCLUSION: In terms of survival the results of radiotherapy of intracapsular disease were excellent, but they were less satisfactory in patients with direct extracapsular extension. The assessment of local control was difficult and may have reflected more the lack of local disease progression rather than true local tumor control. The treatment was well tolerated and there were few serious late complications.

Adenocarcinoma↗
PubMed1993

Patterns of palliative radiotherapy in Canada.

A questionnaire study was performed to determine patterns of radiotherapy practice across Canada and the relationship of age, work-load, resources, intent and aims of therapy on departmental policy; 99 returns were analysed. Three case scenarios were given: Brain metastases were treated typically without a simulation as a parallel pair with palliative intent to 2000 cGy in 5 fractions; for locally advanced lung cancer most patients were simulated, but 40% we deemed 'radical' and there was a bimodal pattern of dose fractionation (the age of the radiation oncologist appeared to influence this and geographical differences were also notable); bony metastases from breast cancer were typically simulated as a single field using 2000-2500 cGy in 5 fractions and always considered palliative. Work-load and resources are likely to influence patterns of care. For example, over 20% felt that treatment choice was suboptimal, largely due to lack of radiation technologists and megavoltage equipment. The implications of these determinants on palliative care are discussed. Objective criteria and definitions are required to allow satisfactory workload measurements and comparisons to be made.

Bone Neoplasms↗
PubMed1992

Low dose preoperative radiotherapy for carcinoma of the oesophagus: results of a randomized clinical trial.

One-hundred-and-seventy-six patients with potentially operable squamous cell carcinoma or adenocarcinoma of the middle or lower thirds of the oesophagus were randomly assigned to preoperative radiotherapy or surgery alone. Patients assigned to the radiotherapy arm received 20 Gy in 10 treatments over 2 weeks, using parallel opposed 4 MV beams. The preoperative radiotherapy was not associated with any significant acute morbidity or any increase in operative complications. The median survival of the overall group of 176 patients was 8 months, and the 5-year survival was 13%. There was no significant difference in the survival of the 90 patients who received preoperative radiotherapy and the 86 who were managed by surgery alone. Proportional hazards analysis identified lymph node involvement, high tumour grade and male sex as significant adverse prognostic features, but the treatment option assigned had no prognostic significance. It was concluded that low dose preoperative radiotherapy offered no advantage over surgery alone.

Adenocarcinoma↗
PubMed1992

Surveillance after orchidectomy for patients with clinical stage I nonseminomatous testis tumors.

PURPOSE: This study was designed to determine the proportion of patients with clinical stage I nonseminomatous germ cell tumors of the testis (NSGCTT) managed with surveillance after orchidectomy who have more advanced disease and, therefore, require further treatment, the time to progression, the sites of progression, and the efficacy of treatment delayed until progression was recognized. PATIENTS AND METHODS: One hundred five patients were observed prospectively without further treatment after orchidectomy and full clinical staging. Treatment was given immediately upon detection of marker-positive, clinical, or radiologic evidence of disease. RESULTS: Thirty-seven patients (35.2%) have required further therapy for disease progression, occurring from 2 to 21 months after diagnosis. Thirty-six patients have been successfully treated. Overall, 104 patients (99%) remain alive and free of disease at 12 to 121 months after orchidectomy. Progression occurred in the retroperitoneum in 25 of 37 patients who developed further disease on surveillance. The presence of vascular invasion in the primary tumor was predictive of an increased risk of progression. CONCLUSION: Surveillance is a valid alternative to immediate retroperitoneal lymph node dissection in patients with clinical stage I NSGCTT but should be recommended only under the close supervision of physicians experienced in the diagnosis and treatment of testicular cancer.

Adolescent↗
PubMed1992

Differentiation of side chain isomers of ring-substituted amphetamines using gas chromatography/infrared/mass spectrometry (GC/IR/MS).

Common analytical methods used for identifying samples obtained from clandestine laboratories were evaluated for their ability to differentiate between possible amphetamine isomers and homologs. A series of ring-substituted (4-methyl, 4-methoxy, and 3,4-methylenedioxy) amphetamine and N-methylphenethylamine isomers was analyzed using color tests, thin-layer chromatography, gas chromatography/mass spectrometry (GC/MS) and GC/infrared (GC/IR). The N-acetyl derivatives of the isomers were analyzed using GC/IR/MS. GC/IR/MS readily differentiated the 4-methylphenylalkylamine isomers. MS and IR spectra were also obtained for each pair of the 4-methoxyphenylalkylamine isomers and the 3,4-methylenedioxyphenylalkylamine isomers, but differentiation via GC/IR/MS was difficult. The N-acetyl derivatives of each pair of isomers could be readily differentiated using GC/IR/MS. Good library researchable spectra for N-acetylamphetamine could be obtained for IR identification with 10 ng (on-column) and MS identification with 2 ng. The spectrometrically independent IR and MS data obtained for the N-acetyl derivatives indicated that the combination of GC/IR/MS can add a significant level of confidence in the analysis of ring-substituted arylalkylamines.

Amphetamines↗
PubMed1991

Bladder cancer: long-term follow-up results of patients treated with radical radiation.

Carcinoma of the bladder is commonly treated for cure with external beam radiation. Whilst short-term results are associated with a good chance of disease control there is little information about the long-term results of such therapy. We present a retrospective review of the Princess Margaret Hospital experience in treating transitional cell carcinoma of the bladder and emphasis on the long-term follow-up of patients treated with radiotherapy (XRT). Between 1972 and 1980, 355 patients were treated with a radical course of external beam radiation. The overall survival was 20% at 10 years and the cause-specific survival was 32%. Radiation treatment resulted in a long-term bladder preservation in at least 25% of patients. The majority of long-term survivors without evidence of relapse were patients with T1 (solitary tumours), T2 and T3a tumours. This subgroup represents patients with disease favourable for treatment with radiation. Factors affecting response to the XRT and survival included T stage and tumour bulk. Radiation complications were frequent and were usually associated with local disease recurrence.

Adult↗
PubMed1991

An assessment of combined tumour markers in patients with seminoma: placental alkaline phosphatase (PLAP), lactate dehydrogenase (LD) and beta human chorionic gonadotrophin (beta HCG).

We have assessed the tumour markers placental alkaline phosphatase (PLAP), lactate dehydrogenase (LD), and human chorionic gonadotrophin (beta HCG) using 2,000 serum samples from 286 patients with seminoma. The ROC curves show that no one marker performs adequately for the detection of disease either at initial staging or during follow-up. We used a Markov model heuristically to devise strategies, in which marker results were assessed in combination, which might be useful in clinical practice. We found that the best strategy was to consider a test result abnormal only if either the beta HCG was greater than 6 Ul-1 or the LD was greater than 400 U l-1 and the PLAP level was greater than 60 U l-1. This will detect about 50% of patients with disease and the false-positive rate is 2%. In practical terms this means that PLAP need only be estimated in patients whose beta HCG is less than 6 IU l-1 and whose LD is greater than 400 U l-1.

Alkaline Phosphatase↗
PubMed1990

Fast neutron treatment for squamous cell carcinoma of the head and neck: final report of Edinburgh randomised trial.

OBJECTIVE: To compare neutron treatment and megavoltage (photon) radiotherapy in locally advanced squamous cell carcinoma of the head and neck. DESIGN: Randomised trial of patients stratified by site of primary tumour and presence or absence of lymph node metastases. Follow up of patients after treatment. SETTING: Department of clinical oncology, Western General Hospital, Edinburgh. PATIENTS: 165 Patients with untreated, histologically proved squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx. All patients completed treatment, and no patient was lost to follow up. INTERVENTION: Treatment with either neutrons or photons. MAIN OUTCOME MEASURES: Disease state and morbidity (scored with the system of the European Organisation for Research on Treatment of Cancer) at each visit during follow up. RESULTS: Of the 165 patients, 85 were randomised to receive neutron treatment and 80 to receive photon treatment. Minimum follow up was five years. Local control of cancer remained similar in the two groups, being achieved in 37 (44%) patients after neutron treatment and 36 (45%) after photon treatment. Five year and actuarial 10 year survival rates were 24% (20/85) and 14% respectively in the group treated with neutrons and 34% (27/80) and 30% respectively in the group treated with photons. Five year survival rates without local disease were 19% (16/85) and 30% (24/80) respectively. Necrosis was more common after neutron treatment than after photon treatment. Seven patients in the neutron group who developed necrosis died whereas no deaths were associated with photon treatment. CONCLUSION: Rates of long term local control were similar in the two groups. Necrosis related to radiation was more common in patients treated with neutrons, and the mortality related to treatment was significantly higher in these patients.

Carcinoma, Squamous Cell↗
PubMed1990

Is placental alkaline phosphatase (PLAP) a useful marker for seminoma?

The usefulness of placental alkaline phosphatase (PLAP) as a tumour marker was assessed in 1578 serum samples from 236 patients with seminoma. Smoking habits were known for all but 7 patients (22 samples). Smoking was associated with significantly higher mean levels of PLAP in disease-free patients (28.8 [S.E. 2.1] U/l vs. 15.9 [1.3] U/l in non-smokers). Mean PLAP levels were higher in patients with active disease (78.6 [23.5] U/l in non-smokers and 47.2 [18.5] U/l in smokers). The median values showed a similar trend. However, there was considerable overlap between the various groups and differences between mean and median values indicated that PLAP values were distributed asymmetrically. The predictive value of PLAP as a tumour marker was consequently much less than superficial inspection of these values might suggest. In 97 patients on surveillance, only 2 out of 11 patients who relapsed had elevated PLAP at the time of clinically detectable relapse. With the upper limit of normal PLAP quoted by our laboratory (35 U/l), specificity and sensitivity were, respectively, 88% and 45% (all patients) and 96% and 47% (non-smokers). The sensitivity and specificity of PLAP were assessed in more detail for a series of threshold values (normal vs. abnormal) with a graphical method. Only in non-smokers did PLAP seem useful and even in this group the positive predictive value of an "abnormal" test may be low; less than 50% in clinically relevant circumstances. Serum PLAP assay cannot usefully stand alone as a marker for seminoma and its routine estimation contributes little to follow-up.

Adult↗
PubMed1990

Use of biological glue to control pulmonary air leaks.

Biological glue is a natural adhesive generated by the interaction between fibrinogen (pre-glue) and thrombin to produce fibrin. The pre-glue is prepared from a single donor (to avoid the problems of pooled plasma) and stored as cryoprecipitate. Before being used it is thawed, dissolved in saline, and activated into an adhesive by the addition of topical thrombin. Biological glue was used prophylactically to prevent air leaks from bronchial suture lines and raw lung surfaces after pulmonary resections in six patients. In addition two new methods of using biological glue have been developed for the control of persisting air leaks. In selective intrabronchial tamponade the glue is instilled into the bronchial tree through a flexible bronchoscope, and in therapeutic pleurodesis it is instilled into the pleural cavity through a chest drainage tube. The air leaks were resolved in all cases. Seven procedures using selective intrabronchial tamponade were carried out in six patients. Four were immediately successful but three were not and required further interventions. Therapeutic pleurodesis alone was successfully carried out in one patient and as an adjunct to selective intrabronchial tamponade on two occasions. A thoracotomy was eventually needed in one of the seven patients.

Bronchi↗