Hayashi Hirokatsu, Yasufuku Itaru, Higashi Toshiya, Chikaishi Wakana, Yokoi Ryoma, Fukada Masahiro, Sato Yuta, Asai Ryuichi, Tajima Jesse Yu, Saigo Chiemi, Makiyama Akitaka, Tanaka Yoshihiro, Okumura Naoki, Murase Katsutoshi, Takahashi Takao, Futamura Manabu, Takeuchi Tamotsu, Matsuhashi Nobuhisa
Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City, 501-1194, Japan.
United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu City, 501-1194, Japan.
Surg Case Rep. 2023 May 22;9(1):87. doi: 10.1186/s40792-023-01660-5.
Late recurrence of gastric cancer at 10 years post-gastrectomy is extremely rare, and the underlying mechanism remains unclear. We report a para-aortic lymph node metastasis case that recurred 12 years postoperatively.
A 44-year-old woman pathologically diagnosed with moderately to poorly differentiated adenocarcinoma with pT2(SS)pN2cM0pStageIIIA according to the Japanese Classification of Gastric Carcinoma (the 13th Edition) underwent laparoscopic distal gastrectomy with D1 + lymph node dissection. She received adjuvant chemotherapy with tegafur-uracil (400 mg/day) for 2 years. At postoperative year (POY) 5, a swollen lymph node was detected in the No.16b1lat lymph node station. However, positron emission tomography (PET) revealed normal uptake, and the levels of tumor markers were within normal limits; hence, the possibility of metastasis was considered low, and the patient was placed under observation. At POY 12, computed tomography revealed an enlargement of the No.16b1lat lymph node station, and PET showed abnormal uptake. Endoscopic ultrasound-guided fine-needle aspiration revealed a moderately differentiated adenocarcinoma. Hence, a diagnosis of recurrence of gastric cancer was made. The patient underwent para-aortic nodal dissection (PAND) of No.16b1lat & int stations. Immunochemical staining results also suggested the recurrence of gastric cancer. However, the expression of CD44 variant 9 (CD44v9), a cancer stem cell marker for gastric adenocarcinoma, was attenuated in the recurrent lesions compared with that in the primary lesions. Postoperatively, she received chemotherapy with tegafur-gimeracil-oteracil (80 mg/day) for 1 year. Bone metastasis was observed at POY 4 after PAND, and the IHC analysis showed a HER2 score of 3 + in a needle biopsy specimen of bone metastasis. The expression of CD44v9 was slightly positive. The patient is being treated with chemotherapy with FOLFOX + trastuzumab.
A defense mechanism against reactive oxygen species has been reported as a mechanism causing recurrence of CD44v9-positive gastric cancer. Consequently, CD44v9-positive gastric cancer grows in metastatic organs, repeatedly self-renews, and proliferates to form recurrent lesions. In the present case, the degree of CD44v9 staining in recurrent lesions was suggested to be related to the recurrence time.
胃癌胃切除术后10年出现晚期复发极为罕见，其潜在机制尚不清楚。我们报告1例术后12年出现的主动脉旁淋巴结转移病例。
一名44岁女性，根据日本胃癌分类（第13版）病理诊断为中低分化腺癌，pT2(SS)pN2cM0pⅢA期，接受了腹腔镜远端胃癌切除术及D1+淋巴结清扫。她接受了替加氟-尿嘧啶（400mg/天）辅助化疗2年。术后第5年，在第16b1lat淋巴结站发现一个肿大淋巴结。然而，正电子发射断层扫描（PET）显示摄取正常，肿瘤标志物水平在正常范围内；因此，转移可能性被认为较低，患者接受观察。术后第12年，计算机断层扫描显示第16b1lat淋巴结站肿大，PET显示摄取异常。超声内镜引导下细针穿刺活检显示为中分化腺癌。因此，诊断为胃癌复发。患者接受了第16b1lat和int站的主动脉旁淋巴结清扫术（PAND）。免疫组化染色结果也提示胃癌复发。然而，与原发灶相比，复发灶中胃癌干细胞标志物CD44变异体9（CD44v9）的表达减弱。术后，她接受了替加氟-吉美嘧啶-奥替拉西（80mg/天）化疗1年。PAND术后第4年观察到骨转移，免疫组化分析显示骨转移针吸活检标本中HER2评分为3+。CD44v9的表达呈弱阳性。患者正在接受FOLFOX联合曲妥珠单抗化疗。
据报道，一种针对活性氧的防御机制是导致CD44v9阳性胃癌复发的机制。因此，CD44v9阳性胃癌在转移器官中生长，反复自我更新并增殖形成复发灶。在本病例中，复发灶中CD44v9染色程度提示与复发时间有关。
