Biomedical subjects

S Ashley

Publications and source records attributed to S Ashley.

At least 73 records · Page 4Linked to original sources

PubMed2000

Tourniquets in arterial bypass surgery.

BACKGROUND: successful infra-popliteal bypass depends on precise, atraumatic technique in performing the distal anastomosis. The use of a tourniquet facilitates the distal anastomosis, reducing dissection, avoiding traumatising clamping of the vessels and providing an "uncluttered" operating field. Despite these advantages the technique is under-used. OBJECTIVES: to review the use of tourniquets in arterial reconstruction, with particular reference to safety issues and complications. DESIGN, METHODS AND MATERIALS: a Medline search was performed (last search Feb. 2000), and keywords from relevant papers were used to perform subsequent searches. References were reviewed from each relevant paper. RESULTS: no randomised controlled trials were found. The review details reported use of tourniquets in arterial reconstruction, including techniques, outcomes and potential complications. CONCLUSION: the use of a tourniquet is a safe and effective technique to facilitate arterial reconstruction.

Anastomosis, Surgical↗

PubMed2000

Secondary myelodysplastic syndrome/acute myeloid leukaemia following mitoxantrone-based therapy for breast carcinoma.

Of 1774 patients with breast cancer given mitoxantrone (MTZ) with methotrexate (n = 492) or with methotrexate and mitomycin C (n = 1282), nine developed MDS/AML after a median of 2.5 years. Median duration of survival from diagnosis of MDS/AML was 10 months and six patients died. The crude incidence of developing MDS/AML after MMM or MM chemotherapy was 15 per 100,000 patient years follow-up, while the actuarial risk was 1.1% and 1.6% at 5 and 10 years respectively. MTZ-based regimens carry a 10 x higher risk of subsequent MDS/AML compared to that seen in the general population.

Acute Disease↗

PubMed2000

Serum p53 antibodies: predictors of survival in small-cell lung cancer?

Serum p53 antibodies have been shown to be a poor prognostic marker in resected non-small-cell lung cancer (NSCLC), but studies in small-cell lung cancer (SCLC) have been contradictory. We have studied the incidence of p53 antibodies in a large SCLC cohort treated at one oncology centre and correlated the results with survival. 231 patients (63% male, median age 65), diagnosed and treated for SCLC between 1987 and 1994 at The Royal Marsden Hospital NHS Trust, had sera stored pretreatment. All samples were tested for p53 antibodies (p53-Ab) using a standardized ELISA technique with a selection of strongly ELISA positive, weakly ELISA positive and negative samples being confirmed with immunoprecipitation. 54 patients were positive for p53-Ab (23%). The presence of a high titre of p53-Ab (titre ratio >5) appears to be associated with a survival advantage with a relative risk of death of 1.71 (95% CI: 1.14-2.58) in those without the antibody (P = 0.02). This study, the largest homogeneous group so far looking at p53-Ab in SCLC, suggests that p53 antibody detection may have a role in predicting outcome in this type of cancer.

Adult↗

PubMed2000

Continuous infusional combination chemotherapy in inflammatory breast cancer: a phase II study.

Despite the introduction of systemic chemotherapy, inflammatory breast cancer (IBC) remains a disease with a poor prognosis. We performed this phase II study to evaluate the efficacy of infusional chemotherapy as initial treatment in patients with IBC. Fifty-four patients with newly diagnosed IBC were offered infusional chemotherapy and 34 accepted. The schedule consisted of continuous infusional ECF (bolus epirubicin and cisplatin, substituted by carboplatin or cyclophosphamide in some patients) plus continuous 5-FU, given three weekly for six cycles. Following chemotherapy patients went on to have surgery and/or radiotherapy. The chemotherapy was well tolerated and resulted in an overall response rate of 79% with 35% of patients achieving a complete clinical response. The median response duration, time to progression and overall survival were 12 months (4-89+ months), 12 months (4-89+ months) and 23 months (7-89+ months), respectively. Patients had a 5 year disease free and overall survival of 11% and 29%, respectively. Infusional ECF is well tolerated and achieves a high clinical response rate in patients with IBC, but survival results do not appear to be superior to those achieved with conventional bolus chemotherapy schedules.

Journal Article↗

PubMed2000

Magnetic resonance spectroscopy in the evaluation of neurotoxicity following cranial irradiation for childhood cancer.

In order to evaluate the role of proton MR spectroscopy (1H-MRS) in the diagnosis and assessment of long-term radiation-related neurotoxicity, 14 children who had received cranial irradiation for the treatment of childhood leukaemia (n = 6) or brain tumours (n = 8) underwent 1H-MRS, MRI and neuropsychological assessment. Short-term effects at 2 months following treatment were studied in a further three patients. MRI abnormalities were observed in nine patients. No statistically significant differences between patients and controls (n = 17) were seen in any of the calculated 1H-MRS metabolite ratios, in any of the three patient groups. On multivariate logistic regression analysis there was a correlation between the choline/water ratio and a low IQ. It is concluded that any systematic radiation-induced changes in the 1H MRS metabolites must be below the detection threshold of this study.

Adolescent↗

PubMed1999

The incidence of cerebrovascular accidents in patients with pituitary adenoma.

BACKGROUND AND PURPOSE: Patients with pituitary adenomas are effectively treated with a combination of surgery, radiotherapy, and medical therapy. Nevertheless, long-term studies suggest increased mortality that is independent of tumor control, with cerebrovascular accidents (CVA) as the major contributing cause. The purpose of this study was to define the frequency of CVAs in a cohort of patients with pituitary adenoma and identify potential predisposing factors. PATIENTS AND METHODS: A cohort of 331 United Kingdom (UK) residents with pituitary adenoma treated at the Royal Marsden Hospital (RMH) between 1962 and 1986 was studied. The frequency of CVA was assessed from RMH and referring hospital records and clinicians, by postal questionnaire of referring hospitals and general practitioners, and by examination of all death certificates. The data were analyzed by actuarial methods, and risk factors were assessed by multivariate analysis. The data were compared to the incidence of CVA in the general population using a published UK population cohort. RESULTS: Sixty-four of 331 patients developed CVA after primary treatment of pituitary adenoma. The actuarial incidence of CVA was 4% (95% CI: 2-7%) at 5 years, 11% (95% CI: 8-14%) at 10 years, and 21% (95% CI: 16-28%) at 20 years measured from the date of radiotherapy. The relative risk of CVA compared to the general population in the UK was 4.1. Age was an independent predictive factor for CVA. However, the relative risk in comparison to the general population was independent of age. The relative risk of developing CVA was higher in women compared to men, in patients undergoing debulking surgery compared to less radical procedures, and in patients diagnosed and treated in the 1980s compared to previous decades. The dose of radiotherapy was an additional independent prognostic factor on multivariate analysis. CONCLUSION: Patients with pituitary adenoma treated with surgery and radiotherapy have a significantly increased risk of CVA compared to the general population. The factors which may contribute to the increased risk include the presence of pituitary adenoma and consequent endocrine disturbances and the treatment, particularly the extent of surgery and the dose of radiotherapy. When assessing the value of treatment strategies, it is therefore important to include not only intermediate endpoints of tumor and hormonal control, but also late toxicity, including the incidence of CVA and overall survival as the primary endpoint. The potential predisposing factors for CVA need further elucidation to develop treatment strategies with lower risk and consequently, reduced mortality.

Adenoma↗

PubMed1999

Modifying radical radiotherapy in high grade gliomas; shortening the treatment time through acceleration.

PURPOSE: To evaluate the efficacy and toxicity of accelerated radiotherapy in patients with primary high grade glioma, where acceleration is used as a means of delivering a shortened course of radical radiotherapy. PATIENTS AND METHODS: Two-hundred and eleven patients with primary high grade glioma were treated at the Royal Marsden NHS Trust between 1987 and 1997 with accelerated radiotherapy (55 Gy in 34 fractions twice daily), to planning target volume (PTV) defined as enhancing tumour and a 3 cm margin. All had histologically confirmed high grade glioma (53 anaplastic astrocytoma, 137 glioblastoma multiforme, 4 gliosarcoma, 5 gemistocytic astrocytoma, 12 high grade astrocytoma not otherwise specified). The mean Karnofsky performance status (KPS) was 90 and median age was 54 years (range 19-77). RESULTS: Of 211 patients entered, 201 were able to complete radiotherapy; 39 patients (19%) had deterioration in KPS during radiotherapy and this was transient in 11. Median survival of 211 patients was 10 months with 1 year, 2 year, and 3 year survival probabilities of 38%, 14%, and 8% respectively. Age and extent of excision were independent prognostic factors for survival. Previous comparison to matched cohort receiving 60 Gy in 30 daily fractions did not demonstrate significant survival difference. CONCLUSION: Accelerated radiotherapy is a feasible treatment approach for patients with high grade glioma. The survival and functional outcome are comparable to conventional radiotherapy and the treatment is without serious acute toxicity. While acceleration of conventional dose irradiation could be tested in randomised studies, it is unlikely this approach would result in a clinically meaningful survival benefit. Accelerated radiotherapy therefore remains one of the ways of delivering radical irradiation in patients with high grade glioma. However, it adds complexity to what is a palliative treatment regimen and the rationale and advisability should be re-examined, particularly in terms of impact on quality of life, true patient preference, and health economic considerations.

Adult↗

PubMed1999

Selective avoidance of lymphatic radiotherapy in the conservative management of women with early breast cancer.

BACKGROUND AND PURPOSE: Until recently, elective treatment of the lymphatic pathways in women with early invasive breast cancer was assumed to impact on quality of life rather than on overall survival. In a multidisciplinary breast clinic these considerations underpinned a policy of observation of the lymphatic pathways if axillary lymph nodes were not palpably enlarged and if recommendations for adjuvant systemic therapy did not depend on knowledge of pathological node status. This paper evaluates the long-term outcome of the observation policy in terms of lymphatic morbidity due to cancer recurrence. MATERIAL AND METHODS: Seven hundred and fifty-nine patients with operable breast cancer and suitable for breast conserving surgery were seen between January 1984 and December 1994. Of these, 291 (38.3%) were recommended a policy of observation to the lymphatic pathways. The case records of these patients were reviewed to record regional relapse patterns and morbidity. RESULTS: At a median follow up of 60 months, 32/291 (11%) patients suffered ipsilateral lymphatic relapse at some stage prior to death or last follow up, representing a 22% actuarial 10-year risk of lymphatic relapse. Metastases coincided with, or preceded, lymphatic relapse in 8/32 (25%) patients. Eighteen out of 32 (56%) patients suffered symptoms of lymphatic relapse prior to death or last follow up, despite subsequent surgery, radiotherapy and/or systemic therapies. The absolute risk of symptomatic ipsilateral lymphatic relapse in the observation group was 18/291 (6.2%), representing an actuarial 10-year risk of 17%. CONCLUSION: A policy of observation on the axilla with deferred treatment of lymphatic relapse has benefited 273/291 (94%) patients, but at the expense of cancer-related regional morbidity in 18 (6%) patients. We conclude that the cancer-related morbidity suffered by a minority of patients and the strengthening evidence of an overall survival benefit conferred by elective local-regional therapy favours a policy of elective treatment of the lymphatic pathways in the routine setting.

Actuarial Analysis↗

PubMed1999

Lymphatic relapse in women with early breast cancer: a difficult management problem.

The aim of this study was to review the ability to control symptoms of regional lymphatic relapse in women with early breast cancer. A retrospective study was made of 759 consecutive women presenting with stage 1 or 2 breast cancer treated by breast conserving surgery and radiotherapy between June 1984 and December 1994, 291 (38.3%) of whom were managed by a policy of observation on the lymphatic pathways. Patterns of lymphatic relapse, relapse management and morbidity caused by recurrent malignancy were reviewed from the case notes. The overall rate of relapse in the ipsilateral axilla and/or supraclavicular fossa was 76/759 (10%) at any time prior to death or last follow-up. 34 of 65 patients who relapsed in the axilla did so despite prior axillary surgery and/or radiotherapy. 41 of 76 patients with regional recurrence presented with symptoms, including lymphoedema, arm pain or sensory motor changes. These symptoms were poorly controlled by palliative surgery, radiotherapy or systemic therapy in 23 cases, including 12 who progressed to arm paralysis. Symptomatic control of patients with regional lymphatic relapse can be very difficult, even in women under regular surveillance in a multidisciplinary breast cancer clinic.

Adult↗

PubMed1999

Local therapy and other factors influencing site of relapse in patients with localised Ewing's sarcoma. United Kingdom Children's Cancer Study Group (UKCCSG).

Relapse patterns have been documented in 191 children with localised Ewing's sarcoma treated with the United Kingdom Children's Cancer Group (UKCCSG) Ewing's Tumour regimen ET2. All received chemotherapy comprising ifosfamide, vincristine, doxorubicin and actinomycin D. Local treatment modality was excision and or radiotherapy depending on tumour site and response to primary chemotherapy. Although not strictly comparable, due to the clinical indications used for each modality, local relapse rates were very low and were similar, irrespective of the type of local treatment modality: radiotherapy (3/56), surgery (7/114) or a combination (0/20). Combined relapse (local + distant) rates were similarly low irrespective of the type of local therapy: radiotherapy (4/56), surgery (4/114) or a combination (0/20). Overall survival was lower in females (P = < 0.04), older children (P = < 0.002) and those with primaries at sites other than long bones (P = < 0.02). It is concluded that with effective intensive chemotherapy combined with either radiotherapy or surgery, local control in this study was excellent at sites other than the pelvis. Preventing distant relapse, predominantly to lung and bone, remains the major challenge.

Adolescent↗

PubMed1999

Local relapse in primary breast cancer patients with unexcised positive surgical margins after lumpectomy, radiotherapy and chemoendocrine therapy.

BACKGROUND: Inadequate surgical excision with residual involvement of resection margins by tumour after breast conservation results in increased local recurrence rates. To reduce this risk positive margins are, therefore, usually excised. Systemic treatment with tamoxifen or chemotherapy reduces local recurrence, along with radiotherapy. However, no studies to date have examined the correlation between chemoendocrine treatment, together with radiotherapy, and local relapse in patients with unexcised involved resection margins, having had breast conservation treatment. PATIENTS AND METHODS: The histopathology reports were reviewed of 184 patients who were treated from June 1991 to August 1995 within our randomised study of neoadjuvant versus adjuvant chemoendocrine therapy with mitozantrone and methotrexate (2M) +/- mitomycin-C (3M) and tamoxifen, used concurrently with radiation following conservation surgical treatment. Histological resection margin was considered positive if ductal carcinoma in situ (DCIS) or invasive carcinoma was present microscopically less than 1 mm from the excision margin. RESULTS: Although 38% of patients had unexcised microscopically involved margins, local relapse rate as first site of relapse was only 1.9% after a median follow up of 57 months. There was no difference in distant relapse (P = 0.2) and survival (P = 0.5) between the positive and negative margins groups. CONCLUSIONS: The presence of positive unexcised margins does not have a significant effect on outcome in patients who are treated with chemoendocrine therapy together with radiotherapy. Further clinical trials are required.

Adult↗

PubMed1999

A high incidence of vertebral fracture in women with breast cancer.

Because treatment for breast cancer may adversely affect skeletal metabolism, we investigated vertebral fracture risk in women with non-metastatic breast cancer. The prevalence of vertebral fracture was similar in women at the time of first diagnosis to that in an age-matched sample of the general population. The incidence of vertebral fracture, however, was nearly five times greater than normal in women from the time of first diagnosis [odds ratio (OR), 4.7; 95% confidence interval (95% CI), 2.3-9.9], and 20-fold higher in women with soft-tissue metastases without evidence of skeletal metastases (OR, 22.7; 95% CI, 9.1-57.1). We conclude that vertebral fracture risk is markedly increased in women with breast cancer.

Administration, Oral↗

PubMed1999

Pre-operative chemotherapy in early stage resectable non-small-cell lung cancer: a randomized feasibility study justifying a multicentre phase III trial.

Surgical resection offers the best chance for cure for early stage non-small-cell lung cancer (NSCLC, stage I, II, IIIA), but the 5-year survival rates are only moderate, with systemic relapse being the major cause of death. Pre-operative (neo-adjuvant) chemotherapy has shown promise in small trials restricted to stage IIIA patients. We believe similar trials are now appropriate in all stages of operable lung cancer. A feasibility study was performed in 22 patients with early stage (IB, II, IIIA) resectable NSCLC; randomized to either three cycles of chemotherapy [mitomycin-C 8 mg m(-2), vinblastine 6 mg m(-2) and cisplatin 50 mg m(-2) (MVP)] followed by surgery (n = 11), or to surgery alone. Of 40 eligible patients, 22 agreed to participate (feasibility 55%) and all complied with the full treatment schedule. All symptomatic patients achieved either complete (50%) or partial (50%) relief of tumour-related symptoms with pre-operative chemotherapy. Fifty-five per cent achieved objective tumour response, and a further 27% minor tumour shrinkage; none had progressive disease. Partial pathological response was seen in 50%. No severe (WHO grade III-IV) toxicities occurred. No significant deterioration in quality of life was detected during chemotherapy. Pre-operative MVP chemotherapy is feasible in early stage NSCLC, and this study has now been initiated as a UK-wide Medical Research Council phase III trial.

Adult↗

PubMed1999

Estimation of mortality and morbidity risk in vascular surgery using POSSUM and the Portsmouth predictor equation.

BACKGROUND: The Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (POSSUM) is a simple scoring system previously validated in general surgical patients which enables estimation of the risk of complications and death after operation. The Portsmouth predictor equation (P-POSSUM) is a modification that may result in more accurate prediction of death than POSSUM. The aim of this study was to test the validity of POSSUM and P-POSSUM in patients undergoing major arterial surgery in a specialist unit. METHODS: Physiological and operative severity scores in 221 patients undergoing elective and emergency arterial surgery in a pure vascular practice under a single consultant were recorded prospectively. Observed morbidity and mortality rates were compared with the rates predicted by POSSUM and P-POSSUM using a linear method of analysis. RESULTS: The POSSUM equation overestimated deaths with this analysis but the mortality rate estimated by P-POSSUM was not significantly different from the observed death rate. The risk of morbidity predicted by POSSUM was not significantly different from the observed complication rate. CONCLUSION: The POSSUM methodology combined with the P-POSSUM adjustment for death allows satisfactory prediction of mortality and morbidity rates in patients undergoing vascular surgery.

Humans↗

PubMed1999

A study testing the routine use of ultrasound measurements when selecting the electron energy for breast boost radiotherapy.

The determination of the depth of the tumour bed within the breast requiring an electron therapy boost dose is generally judged clinically and can be inconsistent between individual radiotherapists. High frequency ultrasound provides a reproducible, safe and quick method of measuring this depth. In order to improve current working practice at the Royal Marsden NHS Trust the routine use of ultrasound when planning breast boost radiotherapy was established. Fifty-three early stage postoperative breast cancer patients had both clinical and ultrasound assessments of boost depth performed. These measurements were converted into electron energy and compared. Measurements ranged from 0.8 cm to 4.9 cm and electron energy from 4 MeV to 15 MeV. As a direct result of the ultrasound measurements taken, 60% of patients had their electron energy changed from that chosen by the clinically assessed measurement. Overall, the energy was as likely to be increased as decreased. Breast size did not influence the need for change but patients with small breasts never required an increase in the energy from that chosen clinically. It was concluded that the use of ultrasound, once integrated into the planning process, can improve accuracy when selecting electron energy for patients receiving breast boost irradiation.

Breast Neoplasms↗

PubMed1999

Ruptured abdominal aortic aneurysms: selecting patients for surgery.

OBJECTIVES: Mortality from ruptured abdominal aortic aneurysm (RAAA) remains high. Despite this, withholding surgery on poor-prognosis patients with RAAA may create a difficult dilemma for the surgeon. Hardman et al. identified five independent, preoperative risk factors associated with mortality and proposed a model for preoperative patient selection. The aim of this study was to test the validity of the same model in an independent series of RAAA patients. METHODS: A consecutive series of patients undergoing surgery for RAAA was analysed retrospectively by case-note review. Thirty-day operative mortality and the presence of the five risk factors: age (> 76 years), creatinine (Cr) (> 190 mumol/l), haemoglobin (Hb) (< 9 g/dl), loss of consciousness and electrocardiographic (ECG) evidence of ischaemia were recorded for each patient. RESULTS: Complete data sets existed for 69 patients (mean age: 73 years, range: 38-86 years, male to female ratio: 6:1). Operative mortality was 43%. The cumulative effect of 0, 1 and 2 risk factors on mortality was 18%, 28% and 48%, respectively. All patients with three or more risk factors died (eight patients). CONCLUSIONS: These results lend support to the validity of the model. The potential to avoid surgery in patients with little or no chance of survival would spare unnecessary suffering, reduce operative mortality and enhance use of scarce resources.

Adult↗

PubMed1999

Radiotherapy in the treatment of benign meningioma of the skull base.

OBJECT: This study was undertaken to assess the long-term efficacy and toxicity of conventional fractionated external-beam radiation in the treatment of benign skull base meningioma. METHODS: This is a retrospective study of 82 patients with histologically verified benign skull base meningioma treated by surgery followed by fractionated external-beam radiation at the Royal Marsden Hospital between 1962 and 1992. The 5- and 10-year progression-free survival (PFS) rates were 92% and 83%, respectively, with the site of disease being the only independent prognostic factor for tumor control according to multivariate analysis. The 10-year PFS rate for patients with sphenoid ridge meningiomas was 69% compared with 90% for those with tumors in the parasellar region. The overall 10-year survival rate was 71%, with performance status and patient age found to be significant independent prognostic factors. Six patients had worsening vision, which was due to cataract in five cases and retinopathy in one. There were no recorded cases of cranial nerve neuropathy. CONCLUSIONS: The excellent long-term tumor control and length of survival with minimal toxicity associated with conventional external-beam radiation should serve as a baseline for evaluation of new treatment strategies such as radiosurgery and skull base surgery.

Adolescent↗

PubMed1998

Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial.

BACKGROUND: Tamoxifen, a drug with antioestrogenic effects, is predicted to prevent the occurrence of breast cancer. We have undertaken a trial of tamoxifen in healthy women who are at increased risk of breast cancer because of family history. We report a planned interim analysis. METHODS: Between October, 1986, and April, 1996, we accrued 2494 healthy women aged between 30 and 70 with a family history of breast cancer. They have been randomised (double blind) to receive tamoxifen 20 mg per day orally or placebo for up to 8 years. Follow-up included clinical assessment, annual mammography, and assessment of toxicity and compliance. The primary endpoint was the occurrence of breast cancer, which was analysed on an intention-to-treat basis with a survival curve. FINDINGS: With a median follow-up of 70 months, 2471 women (tamoxifen 1238, placebo 1233) were suitable for analysis. The groups were evenly matched at baseline, and compliance was good. The overall frequency of breast cancer is the same for women on tamoxifen or placebo (tamoxifen 34, placebo 36, relative risk 1.06 [95% CI 0.7-1.7], p=0.8). Participants who were already on hormone-replacement therapy when they entered the study had an increased risk of breast cancer compared with non-users. Those participants who started such therapy while on trial had a significantly reduced risk. The safety profile of tamoxifen was as expected. INTERPRETATION: We have been unable to show any effect of tamoxifen on breast-cancer incidence in healthy women, contrary to the report from the NSABP-P1 study showing a 45% reduction in healthy women given tamoxifen versus placebo. Differences in the study populations for the two trials may underlie these conflicting findings: eligibility in our trial was based predominantly on a strong family history of breast cancer whereas in the NSABP trial was mostly based on non-genetic risk factors. The importance of oestrogen promotion may vary between such populations.

Adult↗