William Phillips;Kathleen Weiss;Christopher Digesu;Ritu Gill;Emanuele Mazzola;Hisashi Tsukada;Lana Schumacher;Yolonda Colson;
Annals of Surgery. Publish Ahead of Print():, JULY 09, 2020
DOI: 10.1097/SLA.0000000000004176 PMID: 32657925 Issn Print: 0003-4932
Publication Date: July 09, 2020
AbstractObjective: To examine technical-, patient-, tumor-, and treatment-related factors associated with NIR guided SLN identification.目的：探索性研究影響近紅外顯像引導下前哨淋巴結顯像的技術要點、患者特徵、腫瘤、治療相關因素。
Background: Missed nodal disease correlates with recurrence in early stage NSCLC. NIR-guided SLN mapping may improve staging and outcomes through identification of occult nodal disease.背景：未檢出的淋巴結轉移與早期肺癌復發相關。近紅外顯像引導下的前哨淋巴結顯像通過確定隱匿性淋巴結轉移或可提高分期準確性和長期預後。
Methods: Retrospective analysis of 2 phase I clinical trials investigating NIR-guided SLN mapping utilizing ICG in patients with surgically resectable NSCLC.方法：回顧性分析2項I期臨床試驗以探索外科可切除NSCLC使用ICG行近紅外顯像引導下淋巴結顯像的影響因素。
Results: In total, 66 patients underwent NIR-guided SLN mapping and lymphadenectomy after peritumoral ICG injection. There was significantly increased likelihood of SLN identification with injection dose ≥1 mg compared to <1 mg (65.2% vs 35.0%, P = 0.05), lung ventilation after injection (65.2% vs 35.0%, P = 0.05), and albumin dissolvent (68.1%) compared to fresh frozen plasma (28.6%) and sterile water (20.0%) (P = 0.01). In patients receiving the optimized ICG injection, there was significantly increased likelihood of SLN identification with radiologically solid nodules compared to sub-solid nodules (77.4% vs 33.3%, P = 0.04) and anatomic resection compared to wedge resection (88.2% vs 52.2%, P = 0.04). Disease-free and overall survival are 100% in those with a histologically negative SLN identified (n = 25) compared to 73.6% (P = 0.02) and 63.6% (P = 0.01) in patients with node negative NSCLC established via routine lymphadenectomy alone (n = 22).結果：總計66例患者於瘤周注射ICG後，接受了近紅外前哨淋巴結顯像和淋巴結清掃術。前哨淋巴結顯像率在注射劑量≥1mg組顯著優於＜1mg組(65.2% vs 35.0%, P = 0.05)，注射後進行肺通氣成像更好(65.2% vs 35.0%, P = 0.05)，ICG溶於白蛋白(68.1%)中注射較溶於新鮮冰凍血漿(28.6%)或蒸餾水(20.0%) (P = 0.01)更好。在接受了理想的ICG注射後，影像學實性結節的顯像顯著好於亞實性結節(77.4% vs 33.3%, P = 0.04)，行解剖性切除組顯像顯著好於楔形切除組(88.2% vs 52.2%, P = 0.04)。DFS和OS在前哨淋巴結確證為陰性組(n = 25)均為100%,而通過常規淋巴結清掃術確證為淋巴結陰性組(n = 22)NSCLC患者的DFS和OS分別為73.6%(P = 0.02)、63.6%。
Conclusions: SLN(s) are more reliably identified with ICG dose ≥1 mg, albumin dissolvent, post-injection lung ventilation, radiologically solid nodules, and anatomic resections. To date, N0 status when established via NIR SLN mapping seems to be associated with decreased recurrence and improved survival after surgery for NSCLC.結論：前哨淋巴結檢出率在注射劑量≥1mg、溶於白蛋白、注射後行肺通氣、影像學實性結節、解剖性切除術中更高。目前通過NIR SLN活檢或可降低NSCLC手術後復發並提高遠期生存。
兩項試驗簡潔明了，先探索影響前哨淋巴結檢出的影響因素，後探索前哨淋巴結檢出在早期NSCLC預後的價值。
FIGURE 1. Stratification of patients for analysis of (1) SLN success rate by technical-factors; (2) SLN success rate by patient-, tumor-, and treatment-related factors in patients receiving optimized ICG injection; and (3) Recurrence in patients with node-negative NSCLC (aIncludes 17 patients with SLN identified despite nonoptimized ICG injection). ICG indicates indocyanine green; NIR, near-infrared; NSCLC, non-small cell lung cancer; SLN, sentinel lymph node.
很明顯注射劑量≥1mg、注射後肺通氣、溶於25%白蛋白更有助於顯像。
—討論—
推薦用於ICG淋巴結顯像的方式有：注射劑量≥1mg、注射後肺通氣、溶於白蛋白。本研究於2009年開始，一做就是十餘年，可見ICG在肺癌前哨淋巴結顯像中實在不算強項。小樣本量下的數據存在潛在偏倚，個人考慮如果能告訴我們整個尋找前哨淋巴結的時間會更加有參考意義吧。若要以這種方式尋找早期N0患者恐不是一種較為理想的方式。
針對這個話題上個月剛發了一篇薈萃分析，結論是The use of ICG in SLNB for NSCLC, while promising, is far from ready for routine clinical practice.
吲哚菁綠ICG太熟悉了，有人用它找結節，有人用它找平面。但其在肺部手術應用於淋巴結清掃還是步履維艱啊，肺內各個段間的發育變異較大，且肺部淋巴引流錯綜複雜，想要便捷檢出前哨淋巴結屬實不易。NIR ICG要想達到在乳腺外科和胃部腫瘤般的應用效果，恐怕還有很長的路要走。