定义胰腺神经内分泌肿瘤淋巴结清扫术的作用：美国神经内分泌肿瘤研究组对 695 例患者的 8 个机构研究。
Defining the Role of Lymphadenectomy for Pancreatic Neuroendocrine Tumors: An Eight-Institution Study of 695 Patients from the US Neuroendocrine Tumor Study Group.
机构信息
Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
出版信息
Ann Surg Oncol. 2019 Aug;26(8):2517-2524. doi: 10.1245/s10434-019-07367-y. Epub 2019 Apr 19.
BACKGROUND
Preoperative factors that reliably predict lymph node (LN) metastases in pancreatic neuroendocrine tumors (PanNETs) are unclear. The number of LNs needed to accurately stage PanNETs has not been defined.
METHODS
Patients who underwent curative-intent resection of non-functional PanNETs at eight institutions from 2000 to 2016 were analyzed. Preoperative factors associated with LN metastases were identified. A procedure-specific target for LN retrieval to accurately stage patients was determined.
RESULTS
Of 695 patients who underwent resection, 33% of tumors were proximal (head/uncinate) and 67% were distal (neck/body/tail). Twenty-six percent of patients (n = 158) had LN-positive disease, which was associated with a worse 5-year recurrence-free survival (RFS; 60% vs. 86%; p < 0.001). The increasing number of positive LNs was not associated with worse RFS. Preoperative factors associated with positive LNs included tumor size ≥ 2 cm (odds ratio [OR] 6.6; p < 0.001), proximal location (OR 2.5; p < 0.001), moderate versus well-differentiation (OR 2.1; p = 0.006), and Ki-67 ≥ 3% (OR 3.1; p < 0.001). LN metastases were also present in tumors without these risk factors: < 2 cm (9%), distal location (19%), well-differentiated (23%), and Ki-67 < 3% (16%). Median LN retrieval was 13 for pancreatoduodenectomy (PD), but only 9 for distal pancreatectomy (DP). Given that PD routinely includes a complete regional lymphadenectomy, a minimum number of LNs to accurately stage patients was not identified. However, for DP, removal of less than seven LNs failed to discriminate 5-year RFS between LN-positive and LN-negative patients (less than seven LNs: 72% vs. 83%, p = 0.198; seven or more LNs: 67% vs. 86%; p = 0.002).
CONCLUSIONS
Tumor size ≥ 2 cm, proximal location, moderate differentiation, and Ki-67 ≥ 3% are preoperative factors that predict LN positivity in resected non-functional PanNETs. Given the 9-23% incidence of LN metastases in patients without such risk factors, routine regional lymphadenectomy should be considered. PD inherently includes sufficient LN retrieval, while DP should aim to remove seven or more LNs for accurate staging.
背景
目前尚不清楚哪些术前因素可可靠预测胰腺神经内分泌肿瘤（PanNETs）的淋巴结（LN）转移。尚无明确需要获取多少枚 LN 才能准确分期 PanNETs。
方法
分析了 2000 年至 2016 年 8 家机构行根治性切除术的非功能性 PanNETs 患者，确定了与 LN 转移相关的术前因素。确定获取 LN 的特定目标，以准确分期患者。
结果
695 例接受切除术的患者中，33%的肿瘤位于胰头/钩突（近端），67%的肿瘤位于胰颈/体/尾（远端）。26%的患者（n=158）存在 LN 阳性疾病，其 5 年无复发生存率（RFS）较差（60% vs. 86%；p<0.001）。阳性 LN 数量的增加与 RFS 无显著相关性。与 LN 阳性相关的术前因素包括肿瘤直径≥2cm（优势比[OR]6.6；p<0.001）、位于近端（OR 2.5；p<0.001）、中-低分化（OR 2.1；p=0.006）和 Ki-67≥3%（OR 3.1；p<0.001）。无上述风险因素的肿瘤中也存在 LN 转移：肿瘤直径<2cm（9%）、位于远端（19%）、高分化（23%）和 Ki-67<3%（16%）。胰十二指肠切除术（PD）的 LN 平均检出量为 13 枚，但远端胰腺切除术（DP）仅为 9 枚。由于 PD 通常包括完整的区域淋巴结清扫术，因此未确定准确分期患者所需的最小 LN 检出量。然而，DP 切除少于 7 枚 LN 无法区分 LN 阳性和 LN 阴性患者的 5 年 RFS（少于 7 枚 LN：72% vs. 83%，p=0.198；7 枚或更多 LN：67% vs. 86%；p=0.002）。
结论
肿瘤直径≥2cm、位于近端、中-低分化和 Ki-67≥3%是预测切除的非功能性 PanNETs 发生 LN 阳性的术前因素。鉴于无上述风险因素的患者中 LN 转移的发生率为 9%~23%，应考虑常规行区域淋巴结清扫术。PD 固有地包含足够的 LN 检出量，而 DP 应切除 7 枚或更多 LN 以进行准确分期。
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