个别患者在射频消融后罹患食管癌

堪萨斯城退伍军人事务部医疗中心的Mohammad Titi 博士在9月刊《胃肠病学》杂志上报告，已知有3例Barrett食管患者在接受射频消融(RFA)治疗后发生了恶变，包括2例腺癌和1例亚鳞状上皮高级别发育异常(Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.04.051])。

作者称，这一发现提示需要“定期对新生鳞状上皮进行活检以严密监测，即使在成功消融去除肠上皮化生病灶之后也不能放松警惕”。

除了这3例射频消融“成功”后发生亚鳞状上皮肿瘤的患者之外，迄今尚未得到其他类似病例的报告。

据作者介绍，第1例患者年龄65岁，在接受2年监测后被发现罹患黏膜内腺癌并接受了食管切除术，切缘为高级别发育异常阳性。该患者此前接受了3次RFA治疗，“发育异常和肠上皮化生已被完全清除”，在随后2年内进行了5次监测性活检，均未得到肠上皮化生的内镜下或组织学证据。“大约在RFA后2年时，对连接部上方2 cm处的新生鳞状上皮进行监测性活检，结果显示为亚鳞状细胞肠上皮化生的高级别发育异常。”

第2例患者年龄59岁，有10年的Barrett食管病史，因被发现局灶性高级别发育异常而接受了2次RFA治疗，发育异常和肠上皮化生被完全清除，术后3个月时监测结果仍正常。“RFA后6个月时监测性内镜检查显示，新生鳞状上皮正常，但胃食管连接部上方1 cm处活检发现了亚鳞状细胞腺癌。当时淋巴结为阴性。”

第3例患者年龄76岁，患有Barrett食管伴局灶性高级别发育异常，初始接受了内镜下黏膜切除术(EMR)，继而进行了4次RFA治疗，发育异常和肠上皮化生被完全清除。间隔3个月的前2次监测性内镜检查均未发现肠上皮化生的证据，但RFA后9个月时的第3次监测性内镜检查发现，胃食管连接部上方新生鳞状上皮处出现了一个结节性区域，距离此前EMR部位约1 cm。活检证实为亚鳞状细胞腺癌，该患者随后接受了食管切除术。

作者表示，这3例患者在被发现罹患肿瘤时均正在服用质子泵抑制剂2次/d。

 “这篇报告证明，进行任何消融治疗——包括RFA——之时都需谨记：即使成功切除了肿物和肠上皮化生，部分患者仍可能发生高级别发育异常或癌症。谨慎的应对策略是消融治疗后1年内每3个月进行1次监测，第2年内每6个月监测1次，此后每年监测1次。这篇报告还提示，对所有Barrett食管患者都进行消融治疗未必合理。”

作者报告称无相关利益冲突，也未获得任何资金支持。

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By: DENISE NAPOLI, Internal Medicine News Digital Network

Two cases of adenocarcinoma and one case of subsquamous high-grade dysplasia have been reported after radiofrequency ablation for Barrett’s esophagus, wrote Dr. Mohammad Titi and colleagues in the September issue of Gastroenterology.

The findings point to a need for "continued meticulous surveillance with biopsies of neosquamous epithelium, even after apparently successful eradication of intestinal metaplasia," the authors wrote.

The three cases of subsquamous neoplasia following "successful" radiofrequency ablation (RFA) are the only cases reported to date, said Dr. Titi of the Veterans Affairs Medical Center, Kansas City, Mo., and colleagues (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.04.051]).

The first case detailed by the investigators occurred in a 65-year-old patient with Barrett’s esophagus who had been undergoing surveillance for 2 years. An intramucosal adenocarcinoma was detected, and the patient underwent esophagectomy. The margins were positive for high-grade dysplasia.

RFA was performed in three sessions, "leading to complete eradication of dysplasia and intestinal metaplasia," the authors wrote, and for 2 years and over five surveillance biopsies, no endoscopic or histologic evidence of intestinal metaplasia was seen.

"Finally, almost two years post RFA, surveillance biopsies from the neosquamous epithelium 2 cm above surgical anastomosis showed subsquamous intestinal metaplasia with high-grade dysplasia."

In the second case, a 59-year-old patient with a 10-year Barrett’s history was found to have focal high-grade dysplasia and underwent two RFA sessions with complete eradication of dysplasia and intestinal metaplasia. Surveillance at 3 months was normal.

"Surveillance endoscopy at 6 months post RFA showed normal neosquamous epithelium; however, biopsies 1 cm above the gastroesophageal junction revealed subsquamous adenocarcinoma," wrote the authors. The patient underwent esophagectomy, revealing residual subsquamous carcinoma. The lymph nodes were negative.

The third and final case was a 76-year-old Barrett’s patient with focal, high-grade dysplasia initially treated with endoscopic mucosal resection (EMR) followed by four sessions of RFA, with complete eradication of dysplasia and intestinal metaplasia.

Two surveillance endoscopies at 3-month intervals showed no evidence of intestinal metaplasia. "The third surveillance endoscopy per protocol was at 9 months post RFA, and showed a nodular area in the neosquamous epithelium above the gastroesophageal junction, 1 cm distal to the site of previous EMR." Biopsies confirmed subsquamous adenocarcinoma; the patient underwent esophagectomy.

According to the authors, all patients were on twice-daily proton pump inhibitor therapy at the time of neoplasia occurrence. All patients underwent surveillance biopsies per the Seattle protocol.

"This report illustrates an important fact that must be remembered about any ablative therapy, including RFA: High-grade dysplasia or cancer can develop in some patients even after apparently successful eradication of neoplasia and intestinal metaplasia," the authors wrote.

"A prudent approach is performing surveillance every 3 months for the first year post ablation; every 6 months for the next year; and then annually," they wrote. "These reports should also temper our enthusiasm to apply ablation to all patients with Barrett’s esophagus."

The authors stated that they had no conflicts of interest related to this report, and no grant support.