AIM： To establish whether there are fundamental differences in the biochemistries of adenocarcinomas of the gastroesophageal junction （GEJ） and the squamous cell carcinomas of the lower third of the esophagus （LTE...AIM： To establish whether there are fundamental differences in the biochemistries of adenocarcinomas of the gastroesophageal junction （GEJ） and the squamous cell carcinomas of the lower third of the esophagus （LTE）. METHODS： Between February 1, 1997 and February 1, 2000, we obtained tissue samples at the moment of resection from 54 patients for biochemical analysis. The full set of data could be comprehensively analyzed in 47 of 54 patients＇ samples （81%）. Of these, 29 were adenocarcinomas of the GEJ Siewert type Ⅰ （n = 8）, type Ⅱ （n = 12）, type Ⅲ （n = 9）, and 18 presented as squamous cell carcinomas of the LTE. We evaluated the mean values of 11-lysosomal enzyme and 1-cytosol protease activities of the tumorous and surrounding mucosae as well as their relative activities, measured as the ratio of activity in tumor and normal tissues from the same patient. These data were further analyzed to establish the correlation with tumor localization, TNM stage （lymph-node involvement）, histological type （papillary, signet-ring cell, tubular）, state of differentiation （good, moderate, poor）, and survival （≤24 or ≥24 mo）. RESULTS： In adenocarcinomas, the activity of α-mannosidase （AMAN）, cathepsin B （CB） and dipeptidyl-peptidase Ⅰ （DPP Ⅰ） increased significantly as compared to the normal gastric mucosa. In squamous cell carcinomas of the esophagus, we also found a significant difference in the activity of cathepsin L and tripeptidyl-peptidase Ⅰ in addition to these three. There was a statistical correlation of AMAN, CB, and DPP Ⅰ activity between the level of differentiation of adenocarcinomas of the GEJ and lymph node involvement,because tumors with no lymph node metastases histologically confirmed as well-differentiated, showed a significantly lower activity. The differences in CB and DPP Ⅰ activity correlated well with the differences in survival rates, since the CB and DPP Ⅰ values of those who died within 24 mo following surgical interve展开更多
对于局部进展期可切除的胃或胃食管结合部腺癌(gastric or gastroesophageal junction adenocarcinoma,GC/GEJC),联合新辅助/辅助化疗和免疫检查点抑制剂的获益尚不清楚。KEYNOTE-585研究的期中分析结果 报告了新辅助/辅助帕博利珠单抗...对于局部进展期可切除的胃或胃食管结合部腺癌(gastric or gastroesophageal junction adenocarcinoma,GC/GEJC),联合新辅助/辅助化疗和免疫检查点抑制剂的获益尚不清楚。KEYNOTE-585研究的期中分析结果 报告了新辅助/辅助帕博利珠单抗联合化疗在局部进展期可切除GC/GEJC患者中的疗效及安全性。研究者在24个国家的143个中心进行了一项随机双盲、安慰剂对照3期临床研究。研究招募了年龄≥18岁、既往未经治疗且可切除的局部进展期GC/GEJC患者(≥T_(3)或N+)。研究分为两个队列,主要队列纳入804例,FLOT队列纳入203例。患者入组后按1∶1随机分为试验组和对照组,并基于地区(亚洲vs非亚洲)、肿瘤分期(Ⅱ vs Ⅲ vs Ⅳa)、化疗方案(XP/FP vs FLOT)进行分层。主要终点设置为病理完全缓解率、无事件生存期、总生存期以及安全性(FLOT队列)。该研究已在ClinicalTrial.gov注册(编号NCT03221426),目前已完成招募。在2017年10月9日至2021年1月25日期间,1 007例患者1∶1随机纳入帕博利珠单抗+化疗组(n=502)和安慰剂+化疗组(n=505)。主要队列中位随访47.7个月后,帕博利珠单抗+化疗组相比安慰剂+化疗组病理完全缓解率显著提升10.9%(P<0.001);无事件生存期有所增加但未达到预设统计学显著水平[44.4个月(95%CI:33.0~NR) vs 25.3个月(95%CI:20.6~33.9),HR=0.81,95%CI:0.67~0.99,P=0.019 8];总生存期无明显获益(60.7个月vs 58.0个月,HR=0.90,95%CI:0.73~1.12,P=0.174)。此外,两组安全性事件方面相似,包括3级及以上不良事件(78%vs 74%)和治疗相关严重不良事件(26% vs 24%)发生率。在未经治疗的局部进展期GC/GEJC患者中,新辅助/辅助帕博利珠单抗联合化疗可显著提高pCR率,但未能显著转化为EFS/OS生存获益。展开更多
文摘AIM： To establish whether there are fundamental differences in the biochemistries of adenocarcinomas of the gastroesophageal junction （GEJ） and the squamous cell carcinomas of the lower third of the esophagus （LTE）. METHODS： Between February 1, 1997 and February 1, 2000, we obtained tissue samples at the moment of resection from 54 patients for biochemical analysis. The full set of data could be comprehensively analyzed in 47 of 54 patients＇ samples （81%）. Of these, 29 were adenocarcinomas of the GEJ Siewert type Ⅰ （n = 8）, type Ⅱ （n = 12）, type Ⅲ （n = 9）, and 18 presented as squamous cell carcinomas of the LTE. We evaluated the mean values of 11-lysosomal enzyme and 1-cytosol protease activities of the tumorous and surrounding mucosae as well as their relative activities, measured as the ratio of activity in tumor and normal tissues from the same patient. These data were further analyzed to establish the correlation with tumor localization, TNM stage （lymph-node involvement）, histological type （papillary, signet-ring cell, tubular）, state of differentiation （good, moderate, poor）, and survival （≤24 or ≥24 mo）. RESULTS： In adenocarcinomas, the activity of α-mannosidase （AMAN）, cathepsin B （CB） and dipeptidyl-peptidase Ⅰ （DPP Ⅰ） increased significantly as compared to the normal gastric mucosa. In squamous cell carcinomas of the esophagus, we also found a significant difference in the activity of cathepsin L and tripeptidyl-peptidase Ⅰ in addition to these three. There was a statistical correlation of AMAN, CB, and DPP Ⅰ activity between the level of differentiation of adenocarcinomas of the GEJ and lymph node involvement,because tumors with no lymph node metastases histologically confirmed as well-differentiated, showed a significantly lower activity. The differences in CB and DPP Ⅰ activity correlated well with the differences in survival rates, since the CB and DPP Ⅰ values of those who died within 24 mo following surgical interve
文摘对于局部进展期可切除的胃或胃食管结合部腺癌(gastric or gastroesophageal junction adenocarcinoma,GC/GEJC),联合新辅助/辅助化疗和免疫检查点抑制剂的获益尚不清楚。KEYNOTE-585研究的期中分析结果 报告了新辅助/辅助帕博利珠单抗联合化疗在局部进展期可切除GC/GEJC患者中的疗效及安全性。研究者在24个国家的143个中心进行了一项随机双盲、安慰剂对照3期临床研究。研究招募了年龄≥18岁、既往未经治疗且可切除的局部进展期GC/GEJC患者(≥T_(3)或N+)。研究分为两个队列,主要队列纳入804例,FLOT队列纳入203例。患者入组后按1∶1随机分为试验组和对照组,并基于地区(亚洲vs非亚洲)、肿瘤分期(Ⅱ vs Ⅲ vs Ⅳa)、化疗方案(XP/FP vs FLOT)进行分层。主要终点设置为病理完全缓解率、无事件生存期、总生存期以及安全性(FLOT队列)。该研究已在ClinicalTrial.gov注册(编号NCT03221426),目前已完成招募。在2017年10月9日至2021年1月25日期间,1 007例患者1∶1随机纳入帕博利珠单抗+化疗组(n=502)和安慰剂+化疗组(n=505)。主要队列中位随访47.7个月后,帕博利珠单抗+化疗组相比安慰剂+化疗组病理完全缓解率显著提升10.9%(P<0.001);无事件生存期有所增加但未达到预设统计学显著水平[44.4个月(95%CI:33.0~NR) vs 25.3个月(95%CI:20.6~33.9),HR=0.81,95%CI:0.67~0.99,P=0.019 8];总生存期无明显获益(60.7个月vs 58.0个月,HR=0.90,95%CI:0.73~1.12,P=0.174)。此外,两组安全性事件方面相似,包括3级及以上不良事件(78%vs 74%)和治疗相关严重不良事件(26% vs 24%)发生率。在未经治疗的局部进展期GC/GEJC患者中,新辅助/辅助帕博利珠单抗联合化疗可显著提高pCR率,但未能显著转化为EFS/OS生存获益。
