前哨淋巴结活检对382例临床早期宫颈癌盆腔淋巴结转移及预后评估价值
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摘要
目的盆腔淋巴结转移是早期宫颈癌患者预后的独立危险因素。前哨淋巴结活检术(sentinel lymph node biopsy,SLNB)可反映盆腔淋巴结的转移状况,使大多数早期宫颈癌患者避免不必要的盆腔淋巴结清除术,减少了术后并发症,提高了患者的生存质量。本研究探讨联合示踪法定位早期宫颈癌前哨淋巴结(sentinel lymph node,SLN)的可行性与准确性,评估SLNB替代盆腔淋巴结切除的临床价值。方法选取2003-03-01-2018-11-31山东大学附属山东省肿瘤医院妇瘤科收治的ⅠA2～ⅡA2期宫颈癌患者382例,联合使用亚甲蓝和99 Tcm标记的硫胶体示踪,定位并切除SLN,计算SLN检出率、敏感性、符合率、阴性预测值和假阴性率,并对患者进行随访及资料分析。结果 SLN总检出率为97.12%(371/382),261例(70.35%)在双侧盆腔识别SLN。患者肿瘤大小(χ~2=5.529,P=0.021)、浸润深度(χ~2=8.982,P=0.008)、淋巴结转移状态(χ~2=10.101,P=0.005)和FIGO分期(χ~2=9.661,P=0.021)与SLN检出率有关联;肿瘤>4cm(χ~2=4.695,P=0.034)、浸润深度>2/3(χ~2=16.382,P=0.001)、淋巴结阳性(χ~2=27.978,P<0.001)、分期较晚(χ~2=12.114,P=0.016)以及术前放疗(χ~2=4.190,P=0.045)的患者,双侧盆腔SLN检出率降低。SLNB敏感性、符合率、阴性预测值和假阴性率分别为92.77%、98.38%、97.92%和7.23%。宫颈局部肿瘤≤4cm患者假阴性率为4.17%(2/48),≤2cm时未出现假阴性病例。患者1、3、5年总生存率分别为100.00%、94.94%和91.79%,淋巴结阳性、肿瘤>4cm、浸润深度及分期与患者复发率和生存率差异有统计学意义,均P<0.05。结论使用99 Tcm标记的硫胶体和亚甲蓝联合示踪可精准定位SLN,核素作为SLN示踪剂对客观条件以及医生技术熟练程度依赖性较低。宫颈局部肿瘤≤4cm时,SLNB评估盆腔淋巴结转移状况是安全可靠的。
OBJECTIVE Pelvic lymph node metastasis is an independent risk factor for the prognosis of patients with early cervical cancer.Sentinel lymph node biopsy can reflect the metastatic status of pelvic lymph nodes,so that most patients with early cervical cancer avoid unnecessary pelvic lymphadenectomy,reduce postoperative complications and improve the quality of life of patients.This study was to investigate the feasibility and accuracy of combined tracer method for localization of sentinel lymph node(SLN)in early cervical cancer,and to evaluate the clinical value of sentinel lymph node biopsy in replacing pelvic lymph node dissection.METHODS In 2003-03-01-2018-11-31 382 cases ofⅠA2 toⅡA2 cervical cancer patients admitted to the Department of Gynecologic Oncology,Shandong Provincial Cancer Hospital affiliated to Shandong University,combined with methylene blue and 99 Tcmlabeled sulfur colloid tracing,localization and the SLN was excised and the SLN detection rate,sensitivity,coincidence rate,negative predictive value and false negative rate were calculated.The patients were followed up and analyzed.RESULTS The total detection rate of SLN was 97.12%(371/382),and 261(70.35%)patients were recognized SLN in bilateral pelvic cavity.The patient's tumor size(χ2=5.529,P=0.021),depth of invasion(χ2=8.982,P=0.008),lymph node metastasis(χ2=10.101,P=0.005)and FIGO stage(χ2=9.661,P=0.021)had statistically significant differences in SLN detection rates.In patients with tumors>4 cm(χ2=4.695,P=0.034),invasive depth> 2/3(χ2=16.382,P=0.001),lymph node positive(χ2=27.978,P<0.001),late staging(χ2=12.114,P=0.016),and preoperative radiotherapy(χ2=4.190,P=0.045),the detection rate of bilateral pelvic SLN was reduced.The sensitivity,coincidence rate,negative predictive value and false negative rate of SLN biopsy were 92.77%,98.38%,97.92% and 7.23% respectively.The false negative rate of patients with local cervical tumors≤ 4 cm was 4.17%(2/48)and no false negative cases occurred when ≤2 cm.The overall survival rates of patients at 1,3 and 5 years were 100.00%,94.94%,and 91.79%respectively.The lymph node was positive,the tumor was>4 cm,the depth of invasion and staging were statistically different from the recurrence rate and survival rate of patients(P<0.05).CONCLUSIONS The use of 99 Tcm-labeled sulphur colloid and methylene blue combined tracer can accurately locate SLN.As a SLN tracer,nuclides are less dependent on objective conditions and doctors' technical proficiency.When the local cervical tumor is≤4 cm,SLNB is safe and reliable in evaluating pelvic lymph node metastasis.
OBJECTIVE Pelvic lymph node metastasis is an independent risk factor for the prognosis of patients with early cervical cancer.Sentinel lymph node biopsy can reflect the metastatic status of pelvic lymph nodes,so that most patients with early cervical cancer avoid unnecessary pelvic lymphadenectomy,reduce postoperative complications and improve the quality of life of patients.This study was to investigate the feasibility and accuracy of combined tracer method for localization of sentinel lymph node(SLN)in early cervical cancer,and to evaluate the clinical value of sentinel lymph node biopsy in replacing pelvic lymph node dissection.METHODS In 2003-03-01-2018-11-31 382 cases ofⅠA2 toⅡA2 cervical cancer patients admitted to the Department of Gynecologic Oncology,Shandong Provincial Cancer Hospital affiliated to Shandong University,combined with methylene blue and 99 Tcmlabeled sulfur colloid tracing,localization and the SLN was excised and the SLN detection rate,sensitivity,coincidence rate,negative predictive value and false negative rate were calculated.The patients were followed up and analyzed.RESULTS The total detection rate of SLN was 97.12%(371/382),and 261(70.35%)patients were recognized SLN in bilateral pelvic cavity.The patient's tumor size(χ2=5.529,P=0.021),depth of invasion(χ2=8.982,P=0.008),lymph node metastasis(χ2=10.101,P=0.005)and FIGO stage(χ2=9.661,P=0.021)had statistically significant differences in SLN detection rates.In patients with tumors>4 cm(χ2=4.695,P=0.034),invasive depth> 2/3(χ2=16.382,P=0.001),lymph node positive(χ2=27.978,P<0.001),late staging(χ2=12.114,P=0.016),and preoperative radiotherapy(χ2=4.190,P=0.045),the detection rate of bilateral pelvic SLN was reduced.The sensitivity,coincidence rate,negative predictive value and false negative rate of SLN biopsy were 92.77%,98.38%,97.92% and 7.23% respectively.The false negative rate of patients with local cervical tumors≤ 4 cm was 4.17%(2/48)and no false negative cases occurred when ≤2 cm.The overall survival rates of patients at 1,3 and 5 years were 100.00%,94.94%,and 91.79%respectively.The lymph node was positive,the tumor was>4 cm,the depth of invasion and staging were statistically different from the recurrence rate and survival rate of patients(P<0.05).CONCLUSIONS The use of 99 Tcm-labeled sulphur colloid and methylene blue combined tracer can accurately locate SLN.As a SLN tracer,nuclides are less dependent on objective conditions and doctors' technical proficiency.When the local cervical tumor is≤4 cm,SLNB is safe and reliable in evaluating pelvic lymph node metastasis.
引文
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[4] Koh WJ,Greer BE,Abu-Rustum NR,et al.Vulvar cancer,version 1.2017,NCCN clinical practice guidelines in oncology[J].J Natl Compr Canc Netw,2017,15(1):92-120.
[5] Bichakjian CK,Olencki T,Aasi SZ,et al.Basal cell skin cancer,version 1.2016,NCCN clinical practice guidelines in oncology[J].J Natl Compr Canc Netw,2016,14(5):574-597.
[6] Thomaier L,Jager L,Stone R,et al.Risk of empty lymph node packets in sentinel lymph node mapping for endometrial cancer using indocyanine green[J].Int J Gynecol Cancer,2019,29(3):513-517.
[7] Bedyńska M,Szewczyk G,Klepacka T,et al.Sentinel lymph node mapping using indocyanine green in patients with uterine and cervical neoplasms:restrictions of the method[J/OL].Arch Gynecol Obstet,2019 Feb 14.doi:10.1007/s00404-019-05063-6.[Epub ahead of print].
[8] Niikura H,Okamoto S,Otsuki T,et al.Prospective study of sentinel lymph node biopsy without further pelvic lymphadenectomy in patients with sentinel lymph.node-negative cervical cancer[J].Int J Gynecol Cancer,2012,22(7):1244-1250.
[9] Yahata H,Kobayashi H,Sonoda K,et al.Prognostic outcome and complications of sentinel lymph node navigation surgery for early-stage cervical cancer[J].Int J Clin Oncol,2018,23(6):1167-1172.
[10] Du XL,Sheng XG,Jiang T,et al.Sentinel lymph node biopsy as guidance for radical trachelectomy in young patients with early stage cervical cancer[J].BMC Cancer,2011,11:157.
[11] Yamashita T,Katayama H,Kato Y,et al.Management of pelvic lymph nodes by sentinel node navigation surgery in the treatment of invasive cervical cancer[J].Int J Gynecol Cancer,2009,19(6):1113-1118.
[12] Kadkhodayan S,Hasanzadeh M,Treglia G,et al.Sentinel node biopsy for lymph nodal staging of uterine cervix cancer:a systematic review and meta-analysis of the pertinent literature[J].Eur J Surg Oncol,2015,41(1):1-20.
[13] Buda A,Crivellaro C,Elisei F,et al.Impact of indocyanine green for sentinel lymph node mapping ine arly stage endometrial and cervical cancer:comparison with conventional radiotracer 99mTc and/or blue dye[J].Ann Surg Oncol,2016,23(7):2183-2191.
[14] Eriksson AG,Montovano M,Beavis A,et al.Impact of obesity on sentinel lymph node mapping in patients with newly diagnosed uterine cancer undergoing robotic surgery[J].Ann Surg Oncol,2016,23(8):2522-2528.
[15] Salvo G,Ramirez PT,Levenback CF,et al.Sensitivity and negative predictive value for sentinel lymph node biopsy in women with early-stage cervical cancer[J].Gynecol Oncol,2017,145(1):96-101.
[16] Tax C,Rovers MM,de Graaf C,et al.The sentinel node procedure in early stage cervical cancer,taking the next step;a diagnostic review[J].Gynecol Oncol,2015,139(3):559-567.
[17] Harlow SP,Krag DN,Julian TB,et al.Prerandomization Surgical Training for the National Surgical Adjuvant Breast and Bowel Project(NSABP)B-32trial:a randomized phaseⅢclinical trial to compare sentinel node resection to conventional axillary dissection in clinically node-negative breast cancer[J].Ann Surg,2005,241(1):48-54.
[18] Lyman GH,Giuliano AE,Somerfield MR,et al.American society of clinical oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer[J].J Clin Oncol,2005,23(30):7703-7720.
[19] Sawai K,Nakajima H,Ohe S,et al.Sentinel lymph node biopsy and low axillary node sampling for breast cancer[J].Nihon Geka Gakkai Zasshi,2002,103(11):825-830.
[20]楼寒梅,朱滔,邵峰,等.早期宫颈癌前哨淋巴结及非前哨淋巴结微转移的检测及其临床意义[J].中华肿瘤杂志,2013,35(6):434-438.
[21] Soergel P,Kirschke J,Klapdor R,et al.Sentinel lymphadenectomy in cervical cancer using near infrared fluorescence from indocyanine green combined with technetium-99m-nanocolloid[J].Lasers Surg Med,2018,50(10):994-1001.
[22] Lennox GK.Can sentinel lymph node biopsy replace pelvic lymphadenectomy for early cervical cancer?[J].Gynecol Oncol,2017,144(1):16-20.
[2] Fuchs J,Hamann MF,Schulenburg F,et al.Sentinel lymph node biopsy for penile carcinoma:Assessment of reliability[J].Urologe A,2013,52(10):1447-1450.
[3] Goetz MP,Gradishar WJ,Anderson BO,et al.NCCN guidelines insights:breast cancer,version 3.2018[J].J Natl Compr Canc Netw,2019,17(2):118-126.
[4] Koh WJ,Greer BE,Abu-Rustum NR,et al.Vulvar cancer,version 1.2017,NCCN clinical practice guidelines in oncology[J].J Natl Compr Canc Netw,2017,15(1):92-120.
[5] Bichakjian CK,Olencki T,Aasi SZ,et al.Basal cell skin cancer,version 1.2016,NCCN clinical practice guidelines in oncology[J].J Natl Compr Canc Netw,2016,14(5):574-597.
[6] Thomaier L,Jager L,Stone R,et al.Risk of empty lymph node packets in sentinel lymph node mapping for endometrial cancer using indocyanine green[J].Int J Gynecol Cancer,2019,29(3):513-517.
[7] Bedyńska M,Szewczyk G,Klepacka T,et al.Sentinel lymph node mapping using indocyanine green in patients with uterine and cervical neoplasms:restrictions of the method[J/OL].Arch Gynecol Obstet,2019 Feb 14.doi:10.1007/s00404-019-05063-6.[Epub ahead of print].
[8] Niikura H,Okamoto S,Otsuki T,et al.Prospective study of sentinel lymph node biopsy without further pelvic lymphadenectomy in patients with sentinel lymph.node-negative cervical cancer[J].Int J Gynecol Cancer,2012,22(7):1244-1250.
[9] Yahata H,Kobayashi H,Sonoda K,et al.Prognostic outcome and complications of sentinel lymph node navigation surgery for early-stage cervical cancer[J].Int J Clin Oncol,2018,23(6):1167-1172.
[10] Du XL,Sheng XG,Jiang T,et al.Sentinel lymph node biopsy as guidance for radical trachelectomy in young patients with early stage cervical cancer[J].BMC Cancer,2011,11:157.
[11] Yamashita T,Katayama H,Kato Y,et al.Management of pelvic lymph nodes by sentinel node navigation surgery in the treatment of invasive cervical cancer[J].Int J Gynecol Cancer,2009,19(6):1113-1118.
[12] Kadkhodayan S,Hasanzadeh M,Treglia G,et al.Sentinel node biopsy for lymph nodal staging of uterine cervix cancer:a systematic review and meta-analysis of the pertinent literature[J].Eur J Surg Oncol,2015,41(1):1-20.
[13] Buda A,Crivellaro C,Elisei F,et al.Impact of indocyanine green for sentinel lymph node mapping ine arly stage endometrial and cervical cancer:comparison with conventional radiotracer 99mTc and/or blue dye[J].Ann Surg Oncol,2016,23(7):2183-2191.
[14] Eriksson AG,Montovano M,Beavis A,et al.Impact of obesity on sentinel lymph node mapping in patients with newly diagnosed uterine cancer undergoing robotic surgery[J].Ann Surg Oncol,2016,23(8):2522-2528.
[15] Salvo G,Ramirez PT,Levenback CF,et al.Sensitivity and negative predictive value for sentinel lymph node biopsy in women with early-stage cervical cancer[J].Gynecol Oncol,2017,145(1):96-101.
[16] Tax C,Rovers MM,de Graaf C,et al.The sentinel node procedure in early stage cervical cancer,taking the next step;a diagnostic review[J].Gynecol Oncol,2015,139(3):559-567.
[17] Harlow SP,Krag DN,Julian TB,et al.Prerandomization Surgical Training for the National Surgical Adjuvant Breast and Bowel Project(NSABP)B-32trial:a randomized phaseⅢclinical trial to compare sentinel node resection to conventional axillary dissection in clinically node-negative breast cancer[J].Ann Surg,2005,241(1):48-54.
[18] Lyman GH,Giuliano AE,Somerfield MR,et al.American society of clinical oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer[J].J Clin Oncol,2005,23(30):7703-7720.
[19] Sawai K,Nakajima H,Ohe S,et al.Sentinel lymph node biopsy and low axillary node sampling for breast cancer[J].Nihon Geka Gakkai Zasshi,2002,103(11):825-830.
[20]楼寒梅,朱滔,邵峰,等.早期宫颈癌前哨淋巴结及非前哨淋巴结微转移的检测及其临床意义[J].中华肿瘤杂志,2013,35(6):434-438.
[21] Soergel P,Kirschke J,Klapdor R,et al.Sentinel lymphadenectomy in cervical cancer using near infrared fluorescence from indocyanine green combined with technetium-99m-nanocolloid[J].Lasers Surg Med,2018,50(10):994-1001.
[22] Lennox GK.Can sentinel lymph node biopsy replace pelvic lymphadenectomy for early cervical cancer?[J].Gynecol Oncol,2017,144(1):16-20.