Purpose: To assess the baseline variation in global renal and tumour blood flow, blood volume and extraction fraction, and changes in these parameters related to the acute physiological effects of a single dose of a n...Purpose: To assess the baseline variation in global renal and tumour blood flow, blood volume and extraction fraction, and changes in these parameters related to the acute physiological effects of a single dose of a non selective inhibitor of nitric oxide synthase, L-NNA. Materials & Methods: Ethical approval and informed consent were obtained for this Phase I clinical study. Patients with advanced solid tumours refractory to conventional therapy were recruited and given L-NNA intravenously at two different dose levels. Volumetric perfusion CT scans were carried out at 1, 24, 48 & 72 hours post L-NNA. Blood pressures were taken at regular interval for 6 hours after LNNA. Results: L-NNA was well tolerated by the four patients who received it. Blood flow (BF) and blood volume (BV) in both tumour and kidney were reduced post L-NNA administration (renal BF—20%;renal BV—19.7%;tumour BF—16.9%;tumour BV—18.6%), though the effect was more sustained in tumour vasculature. A negative correlation was found between the change in systemic blood pressure and vascular supply to the tumour within 1 hour following L-NNA (p 0.0001). Differences in response to L-NNA by separate target lesions in the same patient were observed. Conclusion: The differential effect of L-NNA on tumour and renal blood flow, and the absence of any significant toxicity in this small cohort of patients permit further dose escalation of L-NNA in future early phase trials. The predictive value of blood pressure change in relation to the acute effect of L-NNA on tumour vasculature deserves further evaluation.展开更多
结直肠癌(结肠、直肠或大肠癌症)是英国第4位最常见恶性肿瘤,每年新诊断患者超过42000例1。近年生存率有所提高,目前5年生存率约为60%2。本文对英国国家健康与临床优选研究所(National Institute for Health and Care Excellence,NICE)...结直肠癌(结肠、直肠或大肠癌症)是英国第4位最常见恶性肿瘤,每年新诊断患者超过42000例1。近年生存率有所提高,目前5年生存率约为60%2。本文对英国国家健康与临床优选研究所(National Institute for Health and Care Excellence,NICE)结直肠癌诊断和治疗指南更新推荐进行总结3。更新聚焦于结直肠癌的治疗,反映该领域的最新研究证据。展开更多
The management of metastatic bladder cancer is palliative.Best outcomes are achieved in those who are fit enough for systemic therapies.The place of radiotherapy in these patients is mainly for symptom control,in part...The management of metastatic bladder cancer is palliative.Best outcomes are achieved in those who are fit enough for systemic therapies.The place of radiotherapy in these patients is mainly for symptom control,in particular haematuria.However,a small proportion,especially those with oligometastases,will benefit from more radical treatment.In this review,we look at the evidence currently available for radiotherapy in this setting.展开更多
文摘Purpose: To assess the baseline variation in global renal and tumour blood flow, blood volume and extraction fraction, and changes in these parameters related to the acute physiological effects of a single dose of a non selective inhibitor of nitric oxide synthase, L-NNA. Materials & Methods: Ethical approval and informed consent were obtained for this Phase I clinical study. Patients with advanced solid tumours refractory to conventional therapy were recruited and given L-NNA intravenously at two different dose levels. Volumetric perfusion CT scans were carried out at 1, 24, 48 & 72 hours post L-NNA. Blood pressures were taken at regular interval for 6 hours after LNNA. Results: L-NNA was well tolerated by the four patients who received it. Blood flow (BF) and blood volume (BV) in both tumour and kidney were reduced post L-NNA administration (renal BF—20%;renal BV—19.7%;tumour BF—16.9%;tumour BV—18.6%), though the effect was more sustained in tumour vasculature. A negative correlation was found between the change in systemic blood pressure and vascular supply to the tumour within 1 hour following L-NNA (p 0.0001). Differences in response to L-NNA by separate target lesions in the same patient were observed. Conclusion: The differential effect of L-NNA on tumour and renal blood flow, and the absence of any significant toxicity in this small cohort of patients permit further dose escalation of L-NNA in future early phase trials. The predictive value of blood pressure change in relation to the acute effect of L-NNA on tumour vasculature deserves further evaluation.
文摘结直肠癌(结肠、直肠或大肠癌症)是英国第4位最常见恶性肿瘤,每年新诊断患者超过42000例1。近年生存率有所提高,目前5年生存率约为60%2。本文对英国国家健康与临床优选研究所(National Institute for Health and Care Excellence,NICE)结直肠癌诊断和治疗指南更新推荐进行总结3。更新聚焦于结直肠癌的治疗,反映该领域的最新研究证据。
基金Peter Hoskin is supported by the NIHR Manchester Biomedical Research Centre.
文摘The management of metastatic bladder cancer is palliative.Best outcomes are achieved in those who are fit enough for systemic therapies.The place of radiotherapy in these patients is mainly for symptom control,in particular haematuria.However,a small proportion,especially those with oligometastases,will benefit from more radical treatment.In this review,we look at the evidence currently available for radiotherapy in this setting.
