Research progress in neoadjuvant and adjuvant therapies for gastric linitis plastica
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摘要: 胃癌是最常见的消化系统恶性肿瘤之一。皮革胃是一种特殊类型的胃癌,大体上呈现为胃壁节段性或弥漫性增厚,镜下可见散在分布的低黏附性肿瘤细胞或印戒细胞,以及弥漫的纤维间质的增生和浸润。皮革胃进展迅速,预后不良。就诊时大部分患者处于进展期,同时伴有隐匿性的腹膜转移,术后中位生存期仅为6~14个月。根治性手术是皮革胃患者最重要的治疗方式,但超过50%的患者在就诊时已丧失根治性手术机会。近年来,以手术为中心的综合治疗模式,包括手术结合术前新辅助治疗、术后辅助治疗等已逐渐应用于皮革胃的治疗,相关分子通路的发现,也为进一步免疫和靶向治疗的研究提供了方向。Abstract: Gastric cancer is globally ranked fifth and fourth in terms of incidence and mortality, respectively. Gastric linitis plastica is a special type of gastric cancer that is macroscopically characterized by segmental or diffuse thickening and gastric wall stiffening. Microscopically, it is characterized by scattered low-adhesion tumor cells or signet-ring cells, in addition to diffuse fibro-stromal proliferation and infiltration. Gastric linitis plastica progressed rapidly and patients with gastric linitis plastica had a poor prognosis. Most patients were at an advanced disease stage with occult peritoneal metastasis at diagnosis. The median postoperative survival duration was only 6–14 months. Radical surgery is the most important treatment approach for patients with gastric linitis plastica. However, more than of half of the patients cannot undergo radical surgery at diagnosis. Recent comprehensive treatment modalities are centered on surgery, including surgery combined with preoperative neoadjuvant therapy or postoperative adjuvant therapy, and are being increasingly applied to treat gastric linitis plastica. The novel discovery of the underlying molecular pathways also provides a direction for further research on immunotherapy and targeted therapy.
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表 1 皮革胃新辅助治疗临床试验汇总
作者 阶段 纳入例数(例) 药物 治疗周期(个) R0切除率(%) PR 不良反应 治疗相关死亡率(%) 生存 Kinoshita等[15] 探索性研究 5 S-1 2 - - - 0 - Kinoshita等[16] Ⅱ期临床试验 55 S-1 2 80.8 32.6 3级:5.4% 0 2年总生存率:60% Iwasaki等[19] Ⅱ临床试验 50 S-1+顺铂 2 66.0 51.0 - 2.0 3年总生存率:4.5%; Iwasaki等[21] Ⅲ临床试验 316 S-1+顺铂 2 - - 3级及以上:19.7% 0.7 3年总生存率:60.9% Hosoda等[24-25] Ⅱ临床试验 40 S-1+多西他赛+顺铂 4 90.0 57.5 0 3年总生存率:77.5%;5年总生存率:69.4% Endo等[27] Ⅱ临床试验 - S-1+多西他赛+奥沙利铂 - - - - - - -
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