背景：氯膦酸二钠（固令）通过抑制肿瘤细胞诱导的破骨细胞骨溶解，来减少骨转移的发生率。方法：本研究为随机双盲、安慰剂对照的多中心临床试验。于1989至2000年间，共入组1069例Ⅰ～Ⅲ期乳腺癌患者，评价了口服氯膦酸二钠的有效性和...背景：氯膦酸二钠（固令）通过抑制肿瘤细胞诱导的破骨细胞骨溶解，来减少骨转移的发生率。方法：本研究为随机双盲、安慰剂对照的多中心临床试验。于1989至2000年间，共入组1069例Ⅰ～Ⅲ期乳腺癌患者，评价了口服氯膦酸二钠的有效性和安全性。入组患者在半年内完成手术、放疗、化疗后，随机分为两组。一组接受氯膦酸二钠（1600mg/天）治疗2年，另一组接受安慰剂两年。本研究的初步结果已于先期发表（Powles et al．JCO，2002），本文报告了未发表的实验相关内容和对Ⅱ／Ⅲ期患者的分析结果。本试验的主要研究终点为5年间第一次骨转移发生时间，次要研究终点为总生存期。这些研究终点用非分层的时序检验和风险比（HR）进行统计分析，可信区间为95％。结果：氯膦酸二钠、安慰剂两组患者的一般状况、疾病特征相似。结果显示2年口服氯膦酸二钠，可降低全组患者骨转移发生风险45％（HR=0．546，P=0．031），5年研究期内降低了全组骨转移发生风险31％（HR=0．692，P=0．043）。对于Ⅱ／Ⅲ期患者，2年氯膦酸二钠口服，也能显著降低骨转移发生风险50％（HR=0．496，P=0．020）；5年研究期内，氯膦酸二钠口服可降低41％的骨转移复发风险（HR=0．592，P=0．009）。口服氯膦酸二钠与安慰剂相比显著提高了患者的总生存率，死亡率下降了23％（HR=0．768，P=0．048），对于Ⅱ／Ⅲ期患者也显著提高了生存率，死亡率下降了26％（HR=0．743，P=0．041）。口服氯膦酸二钠可很好的耐受，轻度到中度的腹泻是最常见的药物不良事件。结论：对于早期可手术乳癌患者，口服氯膦酸二钠较安慰剂组，在5年研究期间，能显著降低药物治疗期和研究期间骨转移的发生率，延长患者的总生存率；对于Ⅱ，Ⅲ期患者，10．5年随诊资料显示，也可提高患者的总生存期。该研究结果显示Ⅱ，Ⅲ期患者，可从口服氯膦酸二纳中，获得更大的益处。展开更多
Background: The treatment of rest pain, ulceration, and gangrene of the leg(severe limb ischaemia) remains controversial. We instigated the BASIL trial to compare the outcome of bypass surgery and balloon angioplasty ...Background: The treatment of rest pain, ulceration, and gangrene of the leg(severe limb ischaemia) remains controversial. We instigated the BASIL trial to compare the outcome of bypass surgery and balloon angioplasty in such patients. Methods: We randomly assigned 452 patients, who presented to 27 UK hospitals with severe limb ischaemia due to infra-inguinal disease, to receive a surgery-first(n=228) or an angioplasty-first(n=224)strategy. The primary endpoint was amputation(of trial leg) free survival. Analysis was by intention to treat. The BASIL trial is registered with the National Research Register(NRR) and as an International Standard Randomised Controlled Trial, number ISRCTN45398889. Findings: The trial ran for 5.5 years, and follow-up finished when patients reached an endpoint(amputation of trial leg above the ankle or death). Seven individuals were lost to follow-up after randomisation(three assigned angioplasty, four surgery); of these, three were lost(one angioplasty, two surgery) during the first year of follow-up. 195(86% ) of 228 patients assigned to bypass surgery and 216(96% ) of 224 to balloon angioplasty underwent an attempt at their allocated intervention at a median(IQR) of 6(3- 16) and 6(2- 20) days after randomisation, respectively. At the end of follow-up, 248(55% ) patients were alive without amputation(of trial leg), 38(8% ) alive with amputation, 36(8% ) dead after amputation, and 130(29% ) dead without amputation. After 6 months, the two strategies did not differ significantly in amputation-free survival(48 vs 60 patients; unadjusted hazard ratio 1.07, 95% CI 0.72- 1.6; adjusted hazard ratio 0.73, 0.49- 1.07). We saw no difference in health- related quality of life between the two strategies, but for the first year the hospital costs associated with a surgery-first strategy were about one third higher than those with an angioplasty-first strategy. Interpretation: In patients presenting with severe limb ischaemia due to infra-inguinal disease and who are suitable for surgery and angioplasty, a bypass-surgery-first and a balloon-angioplasty-first strategy are associated with broadly similar outcomes in terms of amputation-free survival, and in the short-term, surgery is more expensive than angioplasty.展开更多
Objective. In the past 15 years there have been tremendous advances in endoscopic management of chronic pancreatitis (CP). However, the value of endoscopic pancreatic stenting is still debatable. Material and methods....Objective. In the past 15 years there have been tremendous advances in endoscopic management of chronic pancreatitis (CP). However, the value of endoscopic pancreatic stenting is still debatable. Material and methods. In 98 patients suffering from symptomatic CP (84 M, 14 F, 49 ±12, age range 23-83 years) endotherapy including temporary stenting of the pancreatic duct was performed. After final stent removal, indicating the primary end-point of endotherapy, 96 patients were followed for 35 ±28 (8 days-111) months. All data were assessed retrospectively. Results. As well as other endoscopic procedures, a total of 358 prostheses were inserted in the pancreatic duct and left in place for 3 ±1(1 day-11) months. Total stent treatment time was 10 ±10 (6 days-49) months. At 46 ±27 (4-111) months after limited endotherapy, 57 patients had no need for secondary intervention, two-thirds were even without further pain sensations. In 22 patients, surgical treatment and in 17 patients further endoscopic therapy became necessary, which was significantly correlated with continued alcohol consumption. Conclusions. Temporary stent placement as a part of interventional endoscopic therapy in CP shows a high rate of technical and long-term clinical success, with no need for secondary treatment in a remarkable number of patients. Continued cessation of alcohol consumption supports the treatment benefit significantly.展开更多
文摘总生存期(overall survival,OS)是转移性结直肠癌(metastatic colorectal cancer,m CRC)临床试验的主要研究终点,被认为是"金标准"。因为mCRC患者的OS较十年前有明显延长,OS作为临床试验的主要研究终点和评价疗效都受到挑战。在1999年前的单纯化疗时代,无进展生存期(progression-free survival,PFS)被认为是OS的可靠替代终点,由于有效后线治疗的增加,PFS对OS的影响越来越小,其替代性降低;在含靶向药物方案中,尤其是抗血管生成药物治疗中,PFS和OS的相关性也下降。疾病控制时间(duration of disease control,DDC)和治疗策略失败时间(time to failure of strategy,TFS)等新的研究终点逐步显示替代OS的可能性。文章对以上内容进行综述,希望对临床试验的设计和解读提供参考。
文摘背景：氯膦酸二钠（固令）通过抑制肿瘤细胞诱导的破骨细胞骨溶解，来减少骨转移的发生率。方法：本研究为随机双盲、安慰剂对照的多中心临床试验。于1989至2000年间，共入组1069例Ⅰ～Ⅲ期乳腺癌患者，评价了口服氯膦酸二钠的有效性和安全性。入组患者在半年内完成手术、放疗、化疗后，随机分为两组。一组接受氯膦酸二钠（1600mg/天）治疗2年，另一组接受安慰剂两年。本研究的初步结果已于先期发表（Powles et al．JCO，2002），本文报告了未发表的实验相关内容和对Ⅱ／Ⅲ期患者的分析结果。本试验的主要研究终点为5年间第一次骨转移发生时间，次要研究终点为总生存期。这些研究终点用非分层的时序检验和风险比（HR）进行统计分析，可信区间为95％。结果：氯膦酸二钠、安慰剂两组患者的一般状况、疾病特征相似。结果显示2年口服氯膦酸二钠，可降低全组患者骨转移发生风险45％（HR=0．546，P=0．031），5年研究期内降低了全组骨转移发生风险31％（HR=0．692，P=0．043）。对于Ⅱ／Ⅲ期患者，2年氯膦酸二钠口服，也能显著降低骨转移发生风险50％（HR=0．496，P=0．020）；5年研究期内，氯膦酸二钠口服可降低41％的骨转移复发风险（HR=0．592，P=0．009）。口服氯膦酸二钠与安慰剂相比显著提高了患者的总生存率，死亡率下降了23％（HR=0．768，P=0．048），对于Ⅱ／Ⅲ期患者也显著提高了生存率，死亡率下降了26％（HR=0．743，P=0．041）。口服氯膦酸二钠可很好的耐受，轻度到中度的腹泻是最常见的药物不良事件。结论：对于早期可手术乳癌患者，口服氯膦酸二钠较安慰剂组，在5年研究期间，能显著降低药物治疗期和研究期间骨转移的发生率，延长患者的总生存率；对于Ⅱ，Ⅲ期患者，10．5年随诊资料显示，也可提高患者的总生存期。该研究结果显示Ⅱ，Ⅲ期患者，可从口服氯膦酸二纳中，获得更大的益处。
文摘Background: The treatment of rest pain, ulceration, and gangrene of the leg(severe limb ischaemia) remains controversial. We instigated the BASIL trial to compare the outcome of bypass surgery and balloon angioplasty in such patients. Methods: We randomly assigned 452 patients, who presented to 27 UK hospitals with severe limb ischaemia due to infra-inguinal disease, to receive a surgery-first(n=228) or an angioplasty-first(n=224)strategy. The primary endpoint was amputation(of trial leg) free survival. Analysis was by intention to treat. The BASIL trial is registered with the National Research Register(NRR) and as an International Standard Randomised Controlled Trial, number ISRCTN45398889. Findings: The trial ran for 5.5 years, and follow-up finished when patients reached an endpoint(amputation of trial leg above the ankle or death). Seven individuals were lost to follow-up after randomisation(three assigned angioplasty, four surgery); of these, three were lost(one angioplasty, two surgery) during the first year of follow-up. 195(86% ) of 228 patients assigned to bypass surgery and 216(96% ) of 224 to balloon angioplasty underwent an attempt at their allocated intervention at a median(IQR) of 6(3- 16) and 6(2- 20) days after randomisation, respectively. At the end of follow-up, 248(55% ) patients were alive without amputation(of trial leg), 38(8% ) alive with amputation, 36(8% ) dead after amputation, and 130(29% ) dead without amputation. After 6 months, the two strategies did not differ significantly in amputation-free survival(48 vs 60 patients; unadjusted hazard ratio 1.07, 95% CI 0.72- 1.6; adjusted hazard ratio 0.73, 0.49- 1.07). We saw no difference in health- related quality of life between the two strategies, but for the first year the hospital costs associated with a surgery-first strategy were about one third higher than those with an angioplasty-first strategy. Interpretation: In patients presenting with severe limb ischaemia due to infra-inguinal disease and who are suitable for surgery and angioplasty, a bypass-surgery-first and a balloon-angioplasty-first strategy are associated with broadly similar outcomes in terms of amputation-free survival, and in the short-term, surgery is more expensive than angioplasty.
文摘Objective. In the past 15 years there have been tremendous advances in endoscopic management of chronic pancreatitis (CP). However, the value of endoscopic pancreatic stenting is still debatable. Material and methods. In 98 patients suffering from symptomatic CP (84 M, 14 F, 49 ±12, age range 23-83 years) endotherapy including temporary stenting of the pancreatic duct was performed. After final stent removal, indicating the primary end-point of endotherapy, 96 patients were followed for 35 ±28 (8 days-111) months. All data were assessed retrospectively. Results. As well as other endoscopic procedures, a total of 358 prostheses were inserted in the pancreatic duct and left in place for 3 ±1(1 day-11) months. Total stent treatment time was 10 ±10 (6 days-49) months. At 46 ±27 (4-111) months after limited endotherapy, 57 patients had no need for secondary intervention, two-thirds were even without further pain sensations. In 22 patients, surgical treatment and in 17 patients further endoscopic therapy became necessary, which was significantly correlated with continued alcohol consumption. Conclusions. Temporary stent placement as a part of interventional endoscopic therapy in CP shows a high rate of technical and long-term clinical success, with no need for secondary treatment in a remarkable number of patients. Continued cessation of alcohol consumption supports the treatment benefit significantly.
