胃MALT淋巴瘤缓解后仍需长期随访

德国杜塞尔多夫海因里希•海涅大学的Thomas Wündisch博士及其同事在《胃肠病学》杂志上报告，80%的胃MALT淋巴瘤(GML)患者在幽门螺杆菌根治后可达到缓解，但这些患者发生第二胃癌和淋巴瘤的风险仍显著增高。

研究者对1993年6月~1999年7月入选的120例患者(含63例女性患者，平均年龄62岁)进行了研究，根据安娜堡系统，这些患者患有EI1期胃黏膜相关淋巴组织(MALT)淋巴瘤，淋巴瘤局限于胃的黏膜和黏膜下层，淋巴结未受累。这项多中心研究的受试者接受了幽门螺杆菌根除治疗，包括2周为1个疗程的阿莫西林(每日3次，每次750 mg)和奥美拉唑(每日3次，每次40 mg)治疗。每月进行1次内镜检查，直至达到组织学完全缓解，定义为肉眼淋巴瘤消失并且连续2次活检未发现淋巴瘤，之后每6~12个月进行1次内镜检查。在幽门螺杆菌根治后，患者接受中位数为122个月的随访(范围1~171个月)。

结果显示，120例患者中的96例完成随访者(80%)在根除治疗开始后1~28个月间达到GML完全缓解，其中80%(77/96)保持疾病缓解(Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.06.035])。96例患者中的16例发生组织学残留病变；实际上，这似乎为“持续的组织学残留病变，而非完全缓解，因为显微镜下的病变很小，并且通常仅见于多次活检中的单次切片检查”。对于这些病例采用“观察等待”的方法，除1例患者外，所有其他患者在最后时间点显示再次达到完全缓解，中位二次缓解持续时间为46个月。未见疾病进展。“我们强烈支持这一策略，”研究者写道。总体上，96例GML完全缓解患者的5年生存率为94%，10年生存率为87%。尽管如此，研究者发现，与一般人群相比，这些患者的胃癌发病危险比为8.56795%置信区间(CI)，3.566~20.582；P＜0.001，非霍奇金淋巴瘤的发病危险比为18.621 (95%CI，8.365 ~41.448；P＜10^–6)。所有肿瘤的发病危险比也升高，为1.689，但无统计学意义。研究者认为，尽管治疗相关因素通常与淋巴瘤患者发生第二肿瘤有关，但2周的幽门螺杆菌根治方案不太可能导致长期毒性效应。

研究者总结认为，在任何情况下“为了及时发现再次感染、复发、第二淋巴瘤和早期胃癌，对胃MALT淋巴瘤完全缓解患者应每年进行1次内镜检查，持续终生”。

该研究由德国癌症援助基金会提供的一项基金资助，作者个人无相关利益冲突。

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By: DENISE NAPOLI, Internal Medicine News Digital Network

As many as 80% of gastric MALT lymphoma patients achieve remission after Helicobacter pylori eradication, yet these patients remain at a significantly increased risk for second gastric cancers and lymphomas, reported Dr. Thomas Wündisch and his colleagues in Gastroenterology.

"The clinical consequence of this should be yearly lifelong endoscopic follow-up in all patients with a history of GML [gastric MALT lymphoma] to detect gastric cancer as early as possible," they wrote.

Dr. Wündisch, of Heinrich-Heine-Universität in Düsseldorf, Germany, and his colleagues studied 120 patients (63 female, mean age 62 years) recruited between June 1993 and July 1999 with stage EI1 gastric mucosa–associated lymphoid tissue (MALT) lymphoma according to the Ann Arbor system, where lymphoma is limited to the mucosa and submucosa of the stomach with no lymph node involvement.

Patients in this multicenter study underwent H. pylori eradication therapy consisting of a 2-week course of amoxicillin (750 mg three times daily) and omeprazole (40 mg three times daily).

Endoscopy was performed monthly until complete histologic remission, defined as macroscopic disappearance of lymphoma and absence of lymphoma on biopsy in two consecutive analyses, and then every 6-12 months. Patients were followed for a median of 122 months after H. pylori eradication (range, 1-171 months).

Dr. Wündisch and his colleagues reported that 96 of the 120 patients with complete follow-up (80%) achieved complete GML remission between 1 and 28 months after eradication therapy began, and 80% of them (77/96) remained disease free (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.06.035]).

Histologic residual disease was seen in 16 out of 96 patients; indeed, it was likely "ongoing histological residual disease rather than complete remission, as the microscopic lesions were small and often found only upon examination of serial sections of one of multiple biopsies."

A "watch and wait" approach was used in these cases, and all but one patient showed complete remission again at the last time point, with a median second remission duration of 46 months. There was also no progression.

"We strongly support this strategy," the investigators wrote.

Overall, the 96 patients with complete GML remission had a 5-year survival rate of 94%, and a 10-year survival of 87%.

Nevertheless, the researchers observed a morbidity ratio of 8.567 for gastric cancer among these patients (95% confidence interval, 3.566-20.582; P less than .001) and 18.621 for non-Hodgkin’s lymphoma (95% CI, 8.365-41.448; P less than 10^–6), compared with the general population. The morbidity rate for all cancers was also elevated, at 1.689, but this was not statistically significant.

According to the researchers, although treatment-related factors often contribute to the development of second cancers in patients with lymphoma, the 2-week-long H. pylori regimen employed was unlikely to cause long-term toxic effects.

"Patient-related factors, such as gene polymorphisms, might play a more important role in the development of GML and second cancers in our patients, but these factors have yet to be identified," they said.

In any case, "currently, follow-up of patients without significant comorbidities should extend beyond 5 years for detecting reinfection, relapse, second lymphoma, and early gastric cancer."

The authors stated that the study was funded by a grant from Deutsche Krebshilfe, and they had no personal disclosures.