【前沿研究】爱泼斯坦-巴尔病毒阳性的早期胃癌内镜下特征

导 读

Endoscopic Features of Epstein-Barr Virus-Positive Early Gastric Cancer

爱泼斯坦-巴尔病毒阳性的早期胃癌内镜下特征

Background

背景 

Since previous studies reported that Epstein-Barr virus (EBV)-positive early gastric cancers (EGC) has a relatively low frequency of lymph node metastasis, EBV status is expected to be one of clinicopathological factors that could expand the indications for endoscopic resection (ER) for EGC. Identifying the endoscopic features of EBV-positive EGC are therefore quite important, but there are few reports describing these findings.

由于先前的研究报告爱泼斯坦-巴尔病毒（EBV）阳性的早期胃癌（EGC）患者淋巴结转移率相对较低，因此EBV状态有望成为可扩大EGC内镜切除术（ER）适应症的临床病理因素之一。所以，确定EBV阳性的EGC内镜下特征非常重要，但是目前很少有研究描述这些发现。

To clarify the endoscopic features of EBV-positive EGC.

为了阐明EBV阳性EGC的内镜下特征。

Methods

方法 

83 consecutive patients with 94 EBV-positive EGC lesions in naïve stomachs at initial onset who underwent ER or surgical resection at our hospital between April 2006 and December 2018 were included in this study. We retrospectively evaluated the clinicopathological and endoscopic features of these lesions based on the Japanese classification of gastric carcinoma. After identifying lesions suspicious for EBV-positive EGC by HE staining, the EBV-positive status of these lesions were confirmed by in situ hybridization for EBV-encoded RNA (EBER-ISH) in biopsy or resected specimen.

本研究纳入了2006年4月至2018年12月在我院接受ER或手术切除的连续83例患者，这些患者均在胃中发现EBV阳性EGC病变（共94例病变）。根据日本胃癌分类对这些病变的临床病理特征和内镜特征进行回顾性评估。先通过HE染色确定可能为EBV阳性EGC的病变，然后在活检或切除样本中利用EBV编码RNA的原位杂交技术（EBER-ISH）来确认这些病变的EBV阳性状态。

Results

结果 

There were 64 males and 19 females. Mean age was 64.2 (standard deviation 10.9). Preoperative biopsy histological types-tub1 (7)/ tub2 (17)/ por (27)/ mixed type with por component (43). 4 lesions were diagnosed as EBV-positive GC by biopsy specimen. Single lesions (71)/ multiple lesions (12). Tumor location-upper (33)/ middle (46)/ lower third of the stomach (15). Cross-sectional circumference-anterior wall (15)/ posterior wall (33)/ lesser curvature (30)/ greater curvature (16).

男64例，女19例，平均年龄为64.2岁（标准差为10.9）。术前活检的组织学类型为：tub1（7）、tub2（17）、 por（27）和含por成分的混合型（43）。通过活检样本诊断出EBV阳性GC的病变为4个。单发病变71例，多发病变12例。肿瘤位置：胃上部（33）、胃中部（46）、胃下部（15）。横断面观：胃前壁（15）、胃后壁（33）、胃小弯（30）、胃大弯（16）。

Macroscopic types were 0-I (7)/ 0-IIa (6)/ 0-IIc (61)/ 0-IIa+IIc (16)/ 0-IIc+IIa (3)/ other (1). The gastric mucosa atrophy (Kimura-Takemoto Classification) were C-3 (10)/ O-1 (38)/ O-2 (29)/ O-3 (17). The lesions were located on atrophic mucosa (48) or the atrophic boundary (46). Endoscopically, all lesions had redness (100%), 38 lesions (40%) had submucosal tumor (SMT)-like elevation, and 63 lesions (67%) had dot or linear white slough.

肉眼评估的类型为：0-I（7）、0-IIa（6）、0-IIc（61）、0-IIa + IIc（16）、0-IIc + IIa（3）、其他（1）。胃黏膜萎缩（木村-竹本分型）：C-3（10）、O-1（38）、O-2（29）、O-3（17）。病变位于萎缩性黏膜（48）或萎缩边界（46）上。内镜下发现，所有病变均发红（100％），38个病变（40％）有黏膜下肿瘤（SMT）样边缘突起，63个病变（67％）有点状或线状白色凹陷。

28 lesions were treated with ER, 66 by surgical resection. Median tumor size was 20mm (interquartile range; 14-40mm). The invasion depth of tumors: M (34)/ SM1 (≤500μm from muscularis mucosae (MM)) (7)/ SM2 (>500μm from MM) (53). 30 lesions had ulcerations. All lesions were accompanied by lymphocyte infiltration. The proportion of SMT-like elevation was significantly higher in submucosal cancer (35/ 60 = 58%) compared to that in intramucosal cancer (3/ 34 = 9%) (P < 0.01).

28个病变接受内镜切除，66个病变接受手术切除。肿瘤中位大小为20mm（四分位间距，14-40mm）。肿瘤的浸润深度：M（34）、SM1（黏膜下层浸润深度≤500μm）（7）、SM2（黏膜下层浸润深度>500μm）（53）。30个病变有溃疡。所有病变均伴有淋巴细胞浸润。黏膜下癌中SMT样边缘隆起发生率（35/60 = 58％）显著高于黏膜内癌（3/34 = 9％）（P <0.01）。

Conclusion

结论 

Most of EBV-positive EGC were not diagnosed by preoperative biopsy, but major histological types were tub2, por and mixed type with por component. Endoscopically, the EBV-positive lesions often had features such as redness, dot or linear white slough, and SMT-like elevation. Identifying these features can prove useful for endoscopic diagnosis of EBV-positive EGC.

多数EBV阳性的EGC不能通过术前活检得到确诊，但主要的组织学类型为tub2、por和含por成分的混合型。内镜下，EBV阳性的病变通常具有发红、点状或线状白色凹陷和SMT样边缘隆起等特征。识别这些特征有助于EBV阳性EGC的内镜诊断。

Reference:

Osumi H, Kawachi H, Yoshio T, Ida S, Yamamoto N, Horiuchi Y, Ishiyama A, Hirasawa T, Tsuchida T, Hiki N, Takeuchi K, Fujisaki J. Epstein-Barr virus status is a promising biomarker for endoscopic resection in early gastric cancer: proposal of a novel therapeutic strategy. J Gastroenterol. 2019 Sep;54(9):774-783. doi: 10.1007/s00535-019-01562-0. Epub 2019 Mar 2. PMID: 30826866.