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抗反流手术联合消融治疗 Barrett 食管的长期疗效:临床与分子生物学研究。

Long-term results of ablation with antireflux surgery for Barrett's esophagus: a clinical and molecular biologic study.

机构信息

Division of General Thoracic and Esophageal Surgery, Helsinki University Central Hospital, Haartmaninkatu 4, PO Box 340, 00029 HUS Helsinki, Finland.

出版信息

Surg Endosc. 2012 Jul;26(7):1892-7. doi: 10.1007/s00464-011-2121-3. Epub 2012 Jan 5.

DOI:10.1007/s00464-011-2121-3
PMID:22219010
Abstract

BACKGROUND

The initial results from ablation therapy for metaplastic/dysplastic Barrett's esophagus (BE) are promising, but the results of extended follow-up evaluation are seldom reported.

METHODS

Neodymium:yttrium-aluminum-garnet laser ablation and successful antireflux surgery for 18 patients with metaplastic BE primarily resulted in the total histologic eradication of BE in 15 patients (83%). After antireflux surgery, the healing of gastroesophageal reflux disease (GERD) was objectively verified in all the patients. At late follow-up evaluation, endoscopy, conventional histology, molecular oxidative stress analyses in comparison with normal control conditions (8-hydroxydeoxyguanosine [8-OHdG], superoxide dismutase [SOD], glutathione [GSH], myeloperoxydase [MP]), and immunohistochemistry (p53, and Cdx2, caudal-related homeobox gene 2, marking intestinal differentiation) of the neosquamous epithelium were performed.

RESULTS

At the end of the follow-up period (range, 3-15 years; mean, 8 years), intestinal metaplasia without dysplasia was detected histologically in eight patients (44%). Six patients had macroscopic BE (mean length, 3.5 cm; range 1-10 cm). The neosquamous epithelium was histologically normal, with no underlying columnar tissue. The fundoplication was endoscopically normal in 14 patients (82%). The 8-OHdG level was higher in the neosquamous epithelium than in the control conditions in the distal esophagus (4.3 vs. 0.52; P = 0.0002) and the proximal esophagus (1.8 vs. 0.95; P = 0.006). Likewise, SOD activity was higher in the neosquamous epithelium (0.38 vs. 0.12; P = 0.0005), whereas MP activity and GSH levels remained normal. Three patients showed slight nuclear p53 expression (typical in normal inflammatory reactions), whereas Cdx2 positivity was confined to one case with recurrent intestinal metaplasia.

CONCLUSIONS

The neosquamous mucosa, generated by the ablation of BE and the treatment of GERD with fundoplication, was stable during long-term follow-up evaluation in two-thirds of the patients with initial eradication. It had normal p53 expression and no Cdx2 protein expression. The oxidative stress of the neosquamous esophagus remained high, although the clinical significance of this is unclear.

摘要

背景

消融治疗对化生/发育不良 Barrett 食管(BE)的初始结果很有前景,但扩展随访评估的结果很少报道。

方法

对 18 例化生 BE 患者进行钕:钇-铝-石榴石激光消融和成功的抗反流手术,结果 15 例(83%)患者的 BE 组织学完全消除。抗反流手术后,所有患者均客观证实胃食管反流病(GERD)愈合。在晚期随访评估中,进行内镜检查、常规组织学检查、分子氧化应激分析(与正常对照条件相比 8-羟基脱氧鸟苷[8-OHdG]、超氧化物歧化酶[SOD]、谷胱甘肽[GSH]、髓过氧化物酶[MP])和免疫组织化学(p53 和 Cdx2,尾相关同源盒基因 2,标记肠分化)。

结果

在随访期末(范围 3-15 年;平均 8 年),8 例患者(44%)组织学上检测到无异型增生的肠化生。6 例患者有肉眼可见的 BE(平均长度 3.5cm;范围 1-10cm)。新的鳞状上皮组织学正常,无柱状组织。14 例患者(82%)内镜下胃底折叠术正常。远端食管(4.3 vs. 0.52;P=0.0002)和近端食管(1.8 vs. 0.95;P=0.006)的 8-OHdG 水平在新的鳞状上皮中高于对照条件。同样,SOD 活性在新的鳞状上皮中更高(0.38 vs. 0.12;P=0.0005),而 MP 活性和 GSH 水平保持正常。3 例患者有轻微的核 p53 表达(在正常炎症反应中典型),而 Cdx2 阳性仅局限于 1 例有复发性肠化生的患者。

结论

在最初根除的三分之二患者中,通过 BE 消融和胃底折叠术治疗 GERD 生成的新的鳞状黏膜在长期随访评估中是稳定的。它有正常的 p53 表达,没有 Cdx2 蛋白表达。新的食管鳞状上皮的氧化应激仍然很高,尽管其临床意义尚不清楚。

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Acid and bile salt-induced CDX2 expression differs in esophageal squamous cells from patients with and without Barrett's esophagus.酸和胆汁盐诱导的 CDX2 表达在有无 Barrett 食管的食管鳞状细胞中不同。
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Predictors of progression in Barrett's esophagus: current knowledge and future directions.
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Am J Gastroenterol. 2010 Jul;105(7):1490-1502. doi: 10.1038/ajg.2010.2. Epub 2010 Jan 26.
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Properties of the neosquamous epithelium after radiofrequency ablation of Barrett's esophagus containing neoplasia.含肿瘤的Barrett食管经射频消融后新生鳞状上皮的特性。
Am J Gastroenterol. 2009 Jun;104(6):1366-73. doi: 10.1038/ajg.2009.88. Epub 2009 Apr 21.
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N Engl J Med. 2009 May 28;360(22):2277-88. doi: 10.1056/NEJMoa0808145.
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