Morton Donald L, Hoon Dave S B, Cochran Alistair J, Turner Roderick R, Essner Richard, Takeuchi Hiroya, Wanek Leslie A, Glass Edwin, Foshag Leland J, Hsueh Eddy C, Bilchik Anton J, Elashoff David, Elashoff Robert
Roy E Coats Research Laboratories of the John Wayne Cancer Insstitute at Saint John's Health Center, Santa Monica, CA 90404, USA.
Ann Surg. 2003 Oct;238(4):538-49; discussion 549-50. doi: 10.1097/01.sla.0000086543.45557.cb.
Lymphatic mapping and sentinel lymphadenectomy (LM/SL) have been applied to virtually all solid neoplasms since our original description of LM/SL for melanoma. Our objectives were to determine the diagnostic and therapeutic utility of LM/SL, investigate carbon dye for mapping the microanatomy of lymphatic flow within the sentinel node (SN), and determine the prognostic accuracy of molecular assessment of the SN.
Since 1985, 1599 patients with AJCC Stage I/II melanoma have been treated by LM/SL at our institution and 4590 have been treated by wide excision (WE) without nodal staging. We examined the incidence of clinical nodal recurrence after WE alone, the incidence of subclinical nodal metastases found by LM/SL, and the incidence of nodal recurrence in basins with histopathology-negative SNs.
In 1514 LM/SL patients with a primary of known Breslow thickness, the incidence of metastasis in nodes claimed to be sentinel was 7.3%, 19.7%, 33.2%, and 39.7% for primary lesions </=1.0, 1.01-2.0, 2.01-4.0, and >4.0 mm, respectively. In 3652 WE-only patients, the corresponding rates of nodal recurrence were 12.0%, 32.0%, 34.4%, and 30.1%. Thus, LM/SL detected only 60% of expected nodal metastases from primary melanomas <2.01 mm. Forty of 1599 (3.1%) patients developed recurrence in basins with immunohistochemistry (IH)-negative SNs. To determine whether nonrandom intranodal distribution of tumor cells could explain missed SN metastases, we coinjected carbon particles and blue dye during LM/SL in 166 patients: 25 (16%) patients had nodal metastases, all of which were found only in nodal subsectors containing carbon particles. When paraffin-embedded SNs from a subset of 162 IH-negative patients were re-examined by quantitative multimarker reverse-transcriptase polymerase chain reaction (qRT) assay, 49 (30%) gave positive signals. These patients had a significantly higher risk of disease recurrence and death than did patients whose IH and qRT results were negative (p < 0.0001). Comparison of 287 prognostically matched pairs of patients who underwent immediate (after LM/SL) versus delayed (after observation) dissection of nodal metastases revealed 5-, 10-, and 15-year survival rates of 73%, 69%, and 69% versus 51%, 37%, and 32%, respectively (P < or = 0.001).
SN assessment based on intranodal compartmentalization of lymphatic flow (carbon dye mapping) should increase the accuracy of IH and, in combination with multimarker qRT assessment, will allow confident identification of most patients for whom surgery alone is curative. Our data suggest a significant therapeutic benefit for immediate dissection based on identification of a tumor-involved SN.
自从我们最初描述用于黑色素瘤的淋巴绘图和前哨淋巴结切除术（LM/SL）以来，LM/SL已几乎应用于所有实体肿瘤。我们的目的是确定LM/SL的诊断和治疗效用，研究碳染料用于绘制前哨淋巴结（SN）内淋巴引流的微观解剖结构，并确定SN分子评估的预后准确性。
自1985年以来，1599例美国癌症联合委员会（AJCC）I/II期黑色素瘤患者在我们机构接受了LM/SL治疗，4590例患者接受了未进行淋巴结分期的广泛切除（WE）。我们检查了单纯WE后临床淋巴结复发的发生率、LM/SL发现的亚临床淋巴结转移的发生率，以及组织病理学SN阴性的区域淋巴结复发的发生率。
在1514例已知Breslow厚度原发灶的LM/SL患者中，对于原发灶≤1.0、1.01 - 2.0、2.01 - 4.0和>4.0 mm的患者，声称是前哨的淋巴结中转移的发生率分别为7.3%、19.7%、33.2%和39.7%。在3652例仅接受WE的患者中，相应的淋巴结复发率分别为12.0%、32.0%、34.4%和30.1%。因此，LM/SL仅检测到<2.01 mm原发性黑色素瘤预期淋巴结转移的60%。1599例（3.1%）患者中有40例在免疫组织化学（IH）阴性的SN区域发生复发。为了确定肿瘤细胞的非随机结内分布是否可以解释漏诊的SN转移，我们在166例患者的LM/SL过程中同时注射了碳颗粒和蓝色染料：25例（16%）患者有淋巴结转移，所有转移均仅在含有碳颗粒的结内亚区域发现。当通过定量多标记逆转录聚合酶链反应（qRT）检测对162例IH阴性患者的一部分石蜡包埋SN进行重新检查时，49例（30%）给出阳性信号。这些患者疾病复发和死亡的风险明显高于IH和qRT结果均为阴性的患者（p < 0.0001）。对287对预后匹配的患者进行比较，这些患者在发现淋巴结转移后立即（LM/SL后）与延迟（观察后）进行淋巴结清扫，结果显示5年、10年和十五年生存率分别为73%、69%和69%，而延迟清扫组分别为51%、37%和32%（P≤0.001）。
基于淋巴引流的结内分区（碳染料绘图）的SN评估应提高IH准确性，并且与多标记qRT评估相结合，将能够可靠地识别大多数仅通过手术即可治愈的患者。我们的数据表明，基于识别出有肿瘤累及的SN进行立即清扫具有显著的治疗益处。
