Abstract：
BACKGROUND: Immune checkpoint inhibitors are reportedly effective in treating microsatellite instability (MSI)-high gastric cancer. There are a few case reports of conversion surgery (CS) with nivolumab but none with pembrolizumab. Herein, we describe a patient with MSI-high gastric cancer who was successfully treated with pembrolizumab and underwent CS with a pathological complete response.
METHODS: A 69-year-old man was diagnosed with stage III gastric cancer (T3N2M0) based on contrast-enhanced computed tomography, which revealed a neoplastic lesion and enlarged perigastric lymph nodes in the gastric lesser curvature. The anterior superior lymph node of the common hepatic artery (CHA) was determined to be unresectable due to invasion of the pancreatic head and CHA. Histopathologically, the biopsied tissue showed moderately differentiated adenocarcinoma, then determined to be MSI-high. After three courses of mFOLFOX6 therapy, the patient was diagnosed with progressive disease. Since one course of paclitaxel plus ramucirumab therapy caused grade 3 fatigue, his second-line therapy was switched to pembrolizumab monotherapy. After three courses, the primary tumor and perigastric lymph nodes had shrunk, and it was determined as a partial response. The anterior superior lymph node of the CHA became resectable based on the improvement of infiltration of the pancreatic head and CHA due to shrinkage of the lymph node. Tumor markers remained low; hence, distal gastrectomy plus D2 lymphadenectomy was performed at the end of six courses. Anterior superior lymph node of the CHA was confirmed by intraoperative ultrasonography, and the resection was completed safely. The gross examination of the resected specimen revealed an ulcer scar at the primary tumor site. The histopathological examination showed no viable tumor cell remnants in the primary tumor, which had a grade 3 histological response, and resection margins were negative. The lymph nodes showed mucus retention only in the anterior superior lymph node of the CHA, indicating the presence of metastasis, but no viable tumor cells remained. The patient commenced 6 months of adjuvant pembrolizumab monotherapy 3 months after surgery. Twenty months after surgery, there was no evidence of recurrence.
CONCLUSIONS: Conversion surgery following pembrolizumab monotherapy has a potential utility for the treatment of MSI-high gastric cancer.
METHODS: A 69-year-old man was diagnosed with stage III gastric cancer (T3N2M0) based on contrast-enhanced computed tomography, which revealed a neoplastic lesion and enlarged perigastric lymph nodes in the gastric lesser curvature. The anterior superior lymph node of the common hepatic artery (CHA) was determined to be unresectable due to invasion of the pancreatic head and CHA. Histopathologically, the biopsied tissue showed moderately differentiated adenocarcinoma, then determined to be MSI-high. After three courses of mFOLFOX6 therapy, the patient was diagnosed with progressive disease. Since one course of paclitaxel plus ramucirumab therapy caused grade 3 fatigue, his second-line therapy was switched to pembrolizumab monotherapy. After three courses, the primary tumor and perigastric lymph nodes had shrunk, and it was determined as a partial response. The anterior superior lymph node of the CHA became resectable based on the improvement of infiltration of the pancreatic head and CHA due to shrinkage of the lymph node. Tumor markers remained low; hence, distal gastrectomy plus D2 lymphadenectomy was performed at the end of six courses. Anterior superior lymph node of the CHA was confirmed by intraoperative ultrasonography, and the resection was completed safely. The gross examination of the resected specimen revealed an ulcer scar at the primary tumor site. The histopathological examination showed no viable tumor cell remnants in the primary tumor, which had a grade 3 histological response, and resection margins were negative. The lymph nodes showed mucus retention only in the anterior superior lymph node of the CHA, indicating the presence of metastasis, but no viable tumor cells remained. The patient commenced 6 months of adjuvant pembrolizumab monotherapy 3 months after surgery. Twenty months after surgery, there was no evidence of recurrence.
CONCLUSIONS: Conversion surgery following pembrolizumab monotherapy has a potential utility for the treatment of MSI-high gastric cancer.
摘要：
背景：据报道，免疫检查点抑制剂可有效治疗微卫星不稳定性（MSI）高胃癌。有一些病例报告使用nivolumab进行转换手术（CS），但没有使用pembrolizumab。在这里，我们描述了一名MSI高的胃癌患者,他成功接受了pembrolizumab治疗,并接受了CS治疗,病理完全缓解.
方法：根据对比增强计算机断层扫描，一名69岁男子被诊断为III期胃癌（T3N2M0），显示肿瘤病变和胃小曲的胃周围淋巴结肿大。由于胰头和CHA的侵入，肝总动脉（CHA）的前上淋巴结被确定为不可切除。组织病理学,活检组织显示中分化腺癌，然后确定为MSI高。经过三个疗程的mFOLFOX6治疗，患者被诊断为进行性疾病。由于一个疗程的紫杉醇联合雷莫西单抗治疗引起3级疲劳，他的二线治疗方案改为派博利珠单抗单药治疗.经过三门课程，原发肿瘤和胃周淋巴结缩小,被确定为部分反应。由于淋巴结收缩，胰头和CHA浸润的改善，CHA的前上淋巴结变得可切除。肿瘤标志物仍然很低；因此，在6个疗程结束时进行远端胃切除术加D2淋巴结清扫术.术中超声检查证实CHA的前上淋巴结，手术安全完成.切除标本的大体检查显示，原发肿瘤部位有溃疡疤痕。组织病理学检查显示原发肿瘤中没有活的肿瘤细胞残留，有3级组织学反应，切除边缘均为阴性。淋巴结显示粘液保留仅在CHA的前上淋巴结，表明存在转移，但没有存活的肿瘤细胞.患者在手术后3个月开始6个月的辅助派姆单抗单一疗法。手术20个月后,没有复发的证据.
结论：pembrolizumab单药治疗后的转化手术具有治疗高MSI胃癌的潜在效用。
方法：根据对比增强计算机断层扫描，一名69岁男子被诊断为III期胃癌（T3N2M0），显示肿瘤病变和胃小曲的胃周围淋巴结肿大。由于胰头和CHA的侵入，肝总动脉（CHA）的前上淋巴结被确定为不可切除。组织病理学,活检组织显示中分化腺癌，然后确定为MSI高。经过三个疗程的mFOLFOX6治疗，患者被诊断为进行性疾病。由于一个疗程的紫杉醇联合雷莫西单抗治疗引起3级疲劳，他的二线治疗方案改为派博利珠单抗单药治疗.经过三门课程，原发肿瘤和胃周淋巴结缩小,被确定为部分反应。由于淋巴结收缩，胰头和CHA浸润的改善，CHA的前上淋巴结变得可切除。肿瘤标志物仍然很低；因此，在6个疗程结束时进行远端胃切除术加D2淋巴结清扫术.术中超声检查证实CHA的前上淋巴结，手术安全完成.切除标本的大体检查显示，原发肿瘤部位有溃疡疤痕。组织病理学检查显示原发肿瘤中没有活的肿瘤细胞残留，有3级组织学反应，切除边缘均为阴性。淋巴结显示粘液保留仅在CHA的前上淋巴结，表明存在转移，但没有存活的肿瘤细胞.患者在手术后3个月开始6个月的辅助派姆单抗单一疗法。手术20个月后,没有复发的证据.
结论：pembrolizumab单药治疗后的转化手术具有治疗高MSI胃癌的潜在效用。
