Tissue glue for PTFE grafts.
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Biomedical subjects
Publications and source records attributed to S Ashley.
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OBJECTIVE: To investigate verbally administered Barthel Index as a measure of functional status in patients with high grade gliomas. BACKGROUND: Barthel Index (BI) is a performance score of activities of daily living which has been validated in patients with neurological disability. While any assessment of quality of life in brain tumour patients should include all the aspects of CNS function we concentrated on measurement of physical performance status and evaluated the role of BI as a measure of palliative effect of treatment in patients with high grade glioma undergoing radiotherapy. METHODS: BI was verbally administered on 504 occasions in 107 patients with high grade glioma. The BI scores were correlated with Karnofsky performance score (KPS), and neurological performance score (NPS) as a measure of inter-index reliability. The BI's prognostic value was assessed using actuarial survival data. RESULTS: BI was sensitive to change and reflected the degree of functional impairment. In patients with high grade glioma BI correlated with KPS, and NPS (R2 = 0.872 and 0.658 respectively). BI score was also of prognostic value in terms of survival. The median survival of patients with functional independence was 9 months with moderate disability 5 months and with severe disability 4 months. CONCLUSION: Verbally administered Barthel Index is easy to use, reliable and sensitive to change and is of prognostic value. It is a useful tool in the management of patients with gliomas, as an objective evaluation of palliative effectiveness of treatment in patients with functional disability.
Eighteen patients with poor risk Ewing's sarcoma (including 11 patients with metastatic disease at presentation) received consolidation therapy of busulphan and melphalan with autologous stem cell rescue. There were nine females. The median age at diagnosis was 14.2 years (range 2.75-30 years). There was one early death due to cytomegalovirus pneumonitis. One patient developed a single generalised convulsion during busulphan therapy. Severe renal toxicity was not encountered. One patient developed veno-occlusive disease of the liver (VOD) which eventually resolved. With a median follow up of 2 years, 13 patients survive including six with initial metastatic disease. We conclude that high-dose busulphan/melphalan is well-tolerated and should be evaluated for efficacy in a larger series of patients with high risk Ewing's sarcoma.
PURPOSE: Histology has been identified as an important prognostic factor in Hodgkin's disease (HD) in adults. Information regarding the impact of histology on outcome in childhood HD is scarce. This study determines the effect of histology on the overall survival (OS) or progression-free survival (PFS) in a national series of children treated in a standardized manner. PATIENTS AND METHODS: The results of treatment of 331 assessable patients, treated between January 1, 1982 and June 30, 1992, in the United Kingdom Children's Cancer Study Group (UKCCSG) Hodgkin's study I were reviewed to evaluate OS, PFS, and deaths according to stage and histology. Treatment was either involved-field radiation alone (stage IA) or chlorambucil, vinblastine, procarbazine, and prednisolone (ChlVPP) chemotherapy with or without mediastinal radiation. All were clinically staged at diagnosis. RESULTS: Nodular sclerosing (NS) HD was the most common histologic subtype (155 of 331 patients [47%]) and was uniformly distributed through all stages. Lymphocyte-depletion (LD) HD was extremely uncommon (< 1%). Mixed-cellularity (MC) HD had the highest relapse rate, but this was only significant (P < .05) in stage I patients who received local irradiation alone. There was no other statistically significant difference in OS and PFS between the various histologic subtypes. Multivariate analysis for PFS and OS confirmed that stage was the most important prognostic factor and that histology did not have an effect after stratification by stage. CONCLUSION: This study demonstrates that with effective multiagent chemotherapy, histologic subtype does not influence outcome. The high relapse rates in stage I MC subtype indicates that MC HD is biologically aggressive and systemic treatment with or without local irradiation may be indicated. The high relapse rate in stage IV patients appeared to be independent of histology.
BACKGROUND: This study was a prospective evaluation of colour duplex imaging for the assessment of distal run-off before femorocrural reconstruction. METHODS: Patients with critical ischaemia who required a distal bypass underwent preoperative run-off assessments using dependent Doppler, arteriography and duplex imaging by a vascular surgeon, radiologist and technologist respectively; each was blinded to the findings of the others. Preoperative data were compared with intraoperative clinical findings and completion flow studies/ arteriograms. RESULTS: Forty-three consecutive patients (33 men, ten women; mean age 78 (range 53-95) years; 12 diabetic) undergoing 44 femorocrural reconstructions for critical ischaemia were assessed. The 30-day primary cumulative graft patency for the series was 86 per cent. Dependent Doppler correctly predicted a suitable run-off vessel in 21 limbs but was indeterminate in four and unrecordable in 19. Arteriography correctly predicted a suitable run-off vessel in 32 cases, but was indeterminate in six and failed to demonstrate run-off in three patients. Arteriography suggested an inferior vessel in three cases. Duplex correctly predicted a suitable run-off vessel for all 44 grafts. CONCLUSION: Duplex imaging is superior to arteriography for preoperative assessment of distal run-off for femorocrural reconstruction.
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The results are presented of a prospective study of acute skin toxicity in 197 patients with early stage breast cancer, who were treated by conservative surgery and postoperative radiotherapy. We have examined the factors determining the severity of the acute skin reaction with particular reference to the degree of dry or moist desquamation at the completion of treatment. One hundred and ten patients had treatment with radiotherapy alone. The remaining 87 received synchronous chemotherapy with breast irradiation, using either the 3M or the 2M regimen, consisting of mitoxantrone and methotrexate, with (3M) or without Mitomycin-C (2M). Patients were analysed according to both the severity and the site of the skin reaction, age, dose, dose variation across the central outline, treatment technique, beam energy, field separation and breast size. A univariate analysis of these results, which has been presented as an odds ratio of the likelihood of developing a moderate or severe reaction in comparison with those scored as mild, has shown that several factors are associated with an increase in the acute skin reaction. These include the use of the semi-supine technique (odds ratio (OR) = 7.3 (95% CI 3.7-14.6)), beam energy (60Co: 6-10 MV photons OR = 5.9 (95% CI 2.6-13.4)), field separation (> or = 20 cm: < 20 cm OR = 4.1 (95% CI 2.2-7.8)), dose variation across the central outline (> or = 10%: < 10% OR = 9.7 (95% CI 2.6-36.4)), inclusion of the axilla (OR = 4.6 (95% CI 2.4-8.9)), and bust size (bra cup size C and D: A and B OR = 4.6 (95% CI 2.7-11.9)). Using multivariate logistic regression, the technique of radiation delivery and bust size were shown to be independently significant variables affecting acute skin reaction. In view of the high correlation between variables (e.g. radiotherapy technique and beam energy) it is still not possible to specify with definite certainty which is the primary variable causing the skin reaction. However 20/57 (35%) of patients treated by the semisupine technique sustained a severe skin reaction, with > 10% dry or moist desquamation in the treatment field. This compares with only 6/140 (4%) patients treated by the supine method. A possible mechanism by which treatment using the semisupine technique may enhance acute toxicity is discussed. We conclude that there are both treatment and patient related factors that will increase the acute skin reaction after breast irradiation.
One hundred and ninety-seven patients with early stage breast cancer, who were treated initially with conservative surgery, were evaluated prospectively for acute toxicity after completing post-operative irradiation. Eighty-seven of these patients had synchronous chemotherapy with the 3M regimen (mitoxantrone, methotrexate and Mitomycin-C) during radiotherapy. The results indicate that patients receiving chemotherapy and radiotherapy (CRT) showed no significant difference in acute skin toxicity (AST) when compared with those treated with radiotherapy alone (RTO), with an odds ratio (OR = 0.6) and 95% confidence intervals (0.3-1.1) of developing either a moderate or severe, compared with a mild, skin reaction. Even after controlling for other confounding factors, such as treatment technique and beam energy, patients treated with the supine technique using 6-10 MV photons still displayed no significant difference in AST, with 12/74 (16%) patients in the CRT group and 14/66 (21%) in the RTO group developing a moderate or severe skin reaction (OR = 0.7 (95% CI 0.3-1.7)). Four of the 87 patients treated with CRT developed symptomatic acute radiation pneumonitis, three of whom were found to have > 3 cm of lung length on their simulator or check films. The volume of lung included within the treatment field was found to be statistically significant (P = 0.005) in predicting the onset of radiation pneumonitis in the CRT group. None of these patients has suffered any symptomatic late lung toxicity. We conclude that synchronous chemotherapy and radiotherapy, when using the 3M regimen, is feasible for patients having adjuvant treatment for early stage breast carcinoma and there is no significant increase in AST. However, it is associated with an increase in acute radiation pneumonitis when a significant volume of lung is included within the radiation treatment field.
The aims of this study were to determine the effects of the bisphosphonate, clodronate, on the incidence of skeletal metastases and associated morbidity in women with advanced breast cancer. 133 women with recurrent breast cancer, but no evidence of skeletal metastases, were randomly allocated to receive clodronate 1600 mg daily by mouth or an identical placebo for 3 years under double-blind conditions at two clinical oncology centers in the UK and Canada. Main outcome measures included the occurrence of skeletal metastases, as judged by sequential bone scans and radiographs, and the morbidity associated with skeletal metastases comprising the incidence of hypercalcemia, vertebral, and nonvertebral fractures, and bone pain assessed by the requirements for skeletal radiotherapy. The number of patients developing skeletal metastases was lower in clodronate-treated patients than with placebo (15 vs. 19), but was not significantly different. The number of skeletal metastases was significantly lower with clodronate treatment than with placebo (32 vs. 63; p < 0.005). The complications of skeletal disease were fewer by 26% in clodronate-treated patients compared to controls (p < 0.01). Compared to placebo, significant effects in favor of clodronate were observed for vertebral deformities (29%) and nonvertebral fractures (75%), but the event frequency of each was low. There was a small (22%) but nonsignificant treatment effect on the requirements for radiotherapy and hypercalcemia (39%). There was no effect of clodronate on survival. We conclude that clodronate by mouth significantly decreases the number and complications of skeletal metastases in women with advanced breast cancer.
The palliation of cancer-related breathlessness is challenging and complex. An open pilot study was conducted, exploring the safety and efficacy of acupuncture in 20 patients who were breathless at rest and whose breathlessness was directly related to primary or secondary malignancy. Sternal and LI4 acupuncture points were used. Outcome measures included pulse, respiratory rate, oxygen saturation and patient-rated visual analogue scales of breathlessness, pain, anxiety and relaxation. At each time point the mean values of the variables were calculated and compared to their pretreatment levels (Student's t-test). Seventy per cent (14/20) of patients reported marked symptomatic benefit from treatment; there were significant changes in VAS scores of breathlessness, relaxation and anxiety at least up to 6 hours post acupuncture which were measured to be maximal at 90 minutes (p < 0.005, p < 0.001, respectively). There was a significant reduction in respiratory rate, which was sustained for 90 minutes post acupuncture (p < 0.02). The therapeutic value of acupuncture in the management of breathlessness requires further evaluation.
PURPOSE: Tamoxifen is an effective treatment for metastatic and primary breast cancer and is now being evaluated as a chemoprevention agent in healthy women. Any long-term effects on estrogen-sensitive tissues such as bone may have important therapeutic implications. METHODS: We measured bone mineral density (BMD) in the lumbar spine and hip using dual-energy x-ray absorptiometry (DXA) in premenopausal and postmenopausal healthy women who participated in our placebo-controlled tamoxifen chemoprevention of breast cancer trial. RESULTS: BMD data are now available from 179 women for this analysis. In premenopausal women, BMD decreased progressively in the lumbar spine (P < .001) and in the hip (P < .05) for women on tamoxifen, but not those on placebo. The mean annual loss in lumbar BMD per year over the 3-year study period in tamoxifen-treated compliant women who remained premenopausal throughout the study period was 1.44% (1.88% calculated on an intent-to-treat basis) compared with a small gain of 0.24% per annum for women on placebo (P < .001). Tamoxifen had the opposite effect in postmenopausal women. The mean annual increase in BMD for women on tamoxifen was 1.17% in the spine (P < .005) and 1.71% in the hip (P < .001) compared with a noninsignificant loss for women on placebo. CONCLUSION: These results indicate that tamoxifen treatment is associated with a significant loss of BMD in premenopausal women, whereas it prevents bone loss in postmenopausal women. These adverse and beneficial effects of tamoxifen should be considered in the assessment of the therapeutic benefits for both the adjuvant treatment and the chemoprevention of breast cancer.
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The increasing use of neoadjuvant chemotherapy and endocrine therapy in the management of breast cancer has lead us to evaluate and optimise the standard technique of cytocentrifugation of a single fine needle aspirate (FNA) taken from a breast tumour in-vivo, to determine a range of both immunocytochemical and flow cytometric factors which are predictive of response to primary medical therapy. Some of these factors are also of prognostic significance in early stage disease. An analysis of the cellularity and immunocytochemical staining characteristics of FNAs obtained from a series of 206 patients with palpable breast cancers indicate that in a sample of 46 cases it is possible to measure oestrogen receptor, progesterone receptor and c-erbB-2 providing over 400 cells per slide are obtained, with material obtained in a single FNA prepared by cytocentrifugation, using standard immunocytochemical methods. The staining results obtained were comparable to those obtained using frozen or paraffin embedded tissue sections taken from the same tumour. In addition an estimate of the proliferation indices could be made by flow cytometric analysis of the residual cell suspension fluid with measurement of DNA index and S-phase fraction in 131/164 (80%) and 110/164 (67%) of cases respectively. Providing all FNAs obtained for cytocentrifugation were taken at first presentation rather than immediately following a standard FNA, then it was possible to obtain adequately cellular (> 400 cells/slide) samples in 96 out of 126 (75%) of the last cohort of breast aspirates. These effects may be independent of T stage but not histological type as patients with lobular tumours only produced cellular aspirates in 1/7 (14%) of cases.(ABSTRACT TRUNCATED AT 250 WORDS)
One hundred and sixteen patients with high grade glioma were entered into a prospective phase two study and treated with accelerated radiotherapy from 1988 to 1993. In this cohort of patients we analysed speech deficit as a subdivision of global functional status in terms of incidence, category and prognosis for survival. Forty three patients (37%) had a speech deficit at presentation. Eighty percent of these had a component of expressive dysphasia, associated with considerable degree of awareness and distress. The overall median survival was 9.5 months. On univariate analysis, median survival in patients with speech difficulties (6 months) was worse than patients with normal speech (10.5 months) (log rang p = 0.005). Multivariate analysis established independent significance from age, Karnofsky Performance Status (KPS), gender, histological grade, extent of surgery and seizures. This paper highlights the importance of assessing individual categories of functional disability which in patients with high grade glioma include mobility, cognitive function and communication. Each of these factors may seriously affect an individual's activities of daily living, hence quality of life and separate analysis has a number of clinical implications. Firstly, with over a third of patients suffering speech difficulties, adequate speech therapy facilities should be freely available to score the degree of deficit, devise coping strategies and institute communication therapy. Secondly, an understanding of prognostic factors aids the critical analysis of phase two studies and the design and stratification of future prospective trials which should include an analysis of speech deficit. Thirdly, separating individual patients into good and bad prognostic groups can assist strategic management decisions.
This is a retrospective review of stages I and II low grade nodal non-Hodgkin's lymphoma (NHL) seen at the Royal Marsden Hospital and treated with radiotherapy alone. From January 1970 to December 1989, 58 patients were treated. The Ann Arbor staging system was modified to subdivide stage II into localised and extensive disease, with localised disease representing no more than two contiguous regions. There were 40 stage I patients and 18 stage II patients (eight localised and 10 extensive). Volume of the radiotherapy was involved field only in 30 patients and extended fields in 28 patients. The median dose was 40 Gy in 20 fractions. The pattern of relapse was assessed as being systemic or within the standard volume. Survival and progression-free survival (PFS) were calculated. Prognostic variables of age, histology, stage and radiotherapy volume were analysed by multivariate analysis. The 5- and 10-year PFS for the total group were 59 and 43%, and corresponding OS figures were 93 and 79%. Age less than 60 years was a predictor of improved survival but not for PFS and we found no significance in histology, stage or extent of radiotherapy field for the other variables. All relapses occurred with disease outside the original volume, with three patients also relapsing in-field. Treatment of this disease produced an OS at 10 years of 79%. The plateau on the PFS plot suggested that some patients are cured. Young age was the only prognostic factor found for survival. Relapse is most frequently outside the treated volume. Our current treatment policy for stage I and II low grade NHL is involved field radiotherapy to a dose of 35 Gy in 20 fraction over 4 weeks.
A pilot study of continuous infusional 5-fluorouracil 200 mg m-2 per 24 h by ambulatory pump and Hickman line for the entire treatment cycle with mitomycin C 8 mg m-2 i.v. on day 1 and cisplatin 75 mg m-2 i.v. on day 1, both repeated every 28 days, was carried out in 31 previously untreated patients with advanced non-small-cell lung cancer (NSCLC). Of 31 patients assessable for response, one attained a complete remission and eight a partial remission, an overall response rate of 29%. Haematological toxicity was minimal, with only 3% of patients developing WHO grade III/IV neutropenia and 13% grade III/IV thrombocytopenia. Significant side-effects included moderate to severe emesis (41%), mucositis (34%), diarrhoea (31%) and palmar-plantar syndrome (14%). Seven patients (23%) had Hickman line complications requiring line removal. Continuous infusional chemotherapy with this regimen is active in advanced non-small-cell lung cancer, but its complexity and associated treatment toxicity offer little advantage over equally active but simpler and less toxic cisplatin-based regimens.