乳腺癌前哨淋巴结活检在临床的应用探讨
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摘要
目的:研究前哨淋巴结活检术(SLNB)在乳腺癌中的最佳定位方法及其临床应用的意义。
方法:采用美兰染色及美兰联合核素淋巴显像的方法对132例早期乳腺癌患者(其中美兰法50例,联合法82例)行前哨淋巴结活检术(SLNB)。分析两种示踪方法对前哨淋巴结(SLN)识别的检出率及其影响因素。对3例SLN病理阴性而腋窝淋巴结病理阳性患者的SLN再次多层连续切片和免疫组织化学(CK-19)病理检查。
结果:1、132例患者行前哨淋巴结活检术,成功检出115例,检出率87.1%,总共检出前哨淋巴结245枚,其中1枚者38人、2枚者57人、3枚者15人、4枚者5人,平均2.1枚。2、美兰组、联合组SLN的识别成功率分别为78.0%、92.7%;准确率分别为94.9%、98.7% ;假阴性率为22.2%、4.5%;美兰组与联合组在SLN的识别成功率上存在显著性差异(P<0.05)。3、两种方法SLN识别成功率与原发肿瘤的大小、肿瘤所在的象限、病理类型无关(P>0.05),与学习曲线、患者的年龄显著相关(P<0.05)。
结论:(1)联合组较美兰组有更高的SLN识别成功率;(2)经过学习曲线后和对较年轻的患者,SLN识别成功率增加;(3)SLN可预测乳腺癌腋窝淋巴结转移状况;(4)SLN在早期乳腺癌患者可替代常规ALND。
Objectives: To research the method of lymphatic mapping and the meaning of the clinical study of sentinel lymph node biopsy in the patients with breast cancer.
Methods: To analize the identification of sentinel lymph node and the influential factors, the one hundred and thirty-two patients with breast cancer were carried out sentinel lymph node biopsy using either methylene blue or 99mTc-DX and methylene blue. The sentinel lymph nodes that were negative firstly while axillary lymph nodes were positive were stained with the multilap continuous slice and immunohistochemical by monoclonal antibody CK-19 . Then modified radical mastectomy and simple breast surgery be carried out.
Results: 1. There are 132 cases of patients with sentinel lymph node biopsy, 115 cases of successful detection.The detection rate is 87.1%, a total of 245 sentinel lymph nodes were detected, of which one in 38 people, two in 57 people, three in 15 people, 4 in 5, mean is 2.1. 2、SLN succeed rates were 78.0% and 92.7%,respectively. The accuracy rates of SLN were 94.9% and 98.7% . the false negative were 22.2% and 4.5% in the two groups ,respectively.There are obviously difference between blue dye group and the combination group about success rates(P<0.05).2、The success rate of SLN is irrelevate with the size of primary tumour, tumor location, clinic pathologic types(P>0.05),while the study curve and the age of patients were independent factors significantly correlated with the success rate of SLN in our study (P<0.05).
Conclusions: 1.The success rate of SLN in combination group is obviously higher than blue dye group. 2.After the study curve and among the younger patients the identification rate was higher. 3.SLN maybe can predict the axillary lymph node status of the early stage breast cancer. 4. ALND would be replaced by SLN among the patients whose SLN(s) have not tumor metastasis in their early stage breast cancer.
方法:采用美兰染色及美兰联合核素淋巴显像的方法对132例早期乳腺癌患者(其中美兰法50例,联合法82例)行前哨淋巴结活检术(SLNB)。分析两种示踪方法对前哨淋巴结(SLN)识别的检出率及其影响因素。对3例SLN病理阴性而腋窝淋巴结病理阳性患者的SLN再次多层连续切片和免疫组织化学(CK-19)病理检查。
结果:1、132例患者行前哨淋巴结活检术,成功检出115例,检出率87.1%,总共检出前哨淋巴结245枚,其中1枚者38人、2枚者57人、3枚者15人、4枚者5人,平均2.1枚。2、美兰组、联合组SLN的识别成功率分别为78.0%、92.7%;准确率分别为94.9%、98.7% ;假阴性率为22.2%、4.5%;美兰组与联合组在SLN的识别成功率上存在显著性差异(P<0.05)。3、两种方法SLN识别成功率与原发肿瘤的大小、肿瘤所在的象限、病理类型无关(P>0.05),与学习曲线、患者的年龄显著相关(P<0.05)。
结论:(1)联合组较美兰组有更高的SLN识别成功率;(2)经过学习曲线后和对较年轻的患者,SLN识别成功率增加;(3)SLN可预测乳腺癌腋窝淋巴结转移状况;(4)SLN在早期乳腺癌患者可替代常规ALND。
Objectives: To research the method of lymphatic mapping and the meaning of the clinical study of sentinel lymph node biopsy in the patients with breast cancer.
Methods: To analize the identification of sentinel lymph node and the influential factors, the one hundred and thirty-two patients with breast cancer were carried out sentinel lymph node biopsy using either methylene blue or 99mTc-DX and methylene blue. The sentinel lymph nodes that were negative firstly while axillary lymph nodes were positive were stained with the multilap continuous slice and immunohistochemical by monoclonal antibody CK-19 . Then modified radical mastectomy and simple breast surgery be carried out.
Results: 1. There are 132 cases of patients with sentinel lymph node biopsy, 115 cases of successful detection.The detection rate is 87.1%, a total of 245 sentinel lymph nodes were detected, of which one in 38 people, two in 57 people, three in 15 people, 4 in 5, mean is 2.1. 2、SLN succeed rates were 78.0% and 92.7%,respectively. The accuracy rates of SLN were 94.9% and 98.7% . the false negative were 22.2% and 4.5% in the two groups ,respectively.There are obviously difference between blue dye group and the combination group about success rates(P<0.05).2、The success rate of SLN is irrelevate with the size of primary tumour, tumor location, clinic pathologic types(P>0.05),while the study curve and the age of patients were independent factors significantly correlated with the success rate of SLN in our study (P<0.05).
Conclusions: 1.The success rate of SLN in combination group is obviously higher than blue dye group. 2.After the study curve and among the younger patients the identification rate was higher. 3.SLN maybe can predict the axillary lymph node status of the early stage breast cancer. 4. ALND would be replaced by SLN among the patients whose SLN(s) have not tumor metastasis in their early stage breast cancer.
引文
1. Kootstra J, Hoekstra-Weebers JE, Rietman H, et al. Quality of life after sentinel lymph node biopsy or axillary lymph node dissection in stage I/II breast cancer patients: a prospective longitudinal study[J]. Ann Surg Oncol. 2008;15(9):2533-2541.
2. Zhao YS, Pang D, Wang F, et al. Nipple aspirate fluid collection, related factors and relationship between carcinoembryonic antigen in nipple aspirate fluid and breast diseases in women in Harbin, PRC[J]. Cancer Epidemiol Biomarkers Prev. 2009;18(3):732-738.
3. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer[J]. N Engl J Med. 2002;347(16):1227-1232.
4. Moghimi M, Ghoddosi I, Rahimabadi AE, et al. Accuracy of sentinel node biopsy in breast cancer patients with a high prevalence of axillary metastases[J]. Scand J Surg. 2009;98(1):30-33.
5. Takei H, Kurosumi M, Yoshida T, et al. Current trends of sentinel lymph node biopsy for breast cancer--a surgeon's perspective[J]. Breast Cancer. 2007;14(4):362-370.
6. Yen RF, Kuo WH, Lien HC, et al. Radio-guided sentinel lymph node biopsy using periareolar injection technique for patients with early breast cancer[J]. J Formos Med Assoc. 2007;106(1):44-50.
7. Gulec SA, Moffat FL, Carroll RG, et al. Sentinel lymph node localization in early breast cancer[J]. J Nucl Med. 1998;39(8):1388-1393.
8. Poletti P, Fenaroli P, Milesi A, et al. Axillary recurrence in sentinel lymph node-negative breast cancer patients[J]. Ann Oncol. 2008;19(11):1842-1846.
9. Kathleen M, Erb MD, Thomas B, et al. Completion of Axillary Dissection for a Positive Sentinel Node: Necessary or Not?[J]. Curr Oncol Rep. 2009;11(1):15–20.
10. Lee JH, Ryu KW, Kim CG, et al. Sentinel node biopsy using dye and isotope double tracers in early gastric cancer[J].Ann Surg Oncol. 2006;13(9):1168-1174.
11. Fournier K,Schiller A,Perry RR,et a1. Micrometastals in the sentinel lymph node of breast cancer does not mandate completion axillarv dissection[J]. Ann Surg. 2004;239:859-865.
12. Mathelin C, Salvador S, Croce S, et al. Optimization of sentinel lymph node biopsy in breast cancer using an operative gamma camera[J]. World J Surg Oncol. 2007;5:132-137.
13. Namwongprom S, Boonyaprapa S, Ekmahachai M, et al. Breast lymphoscintigraphy for sentinel node identification in breast cancers with clinically-negative axillary nodes[J]. Singapore Med J. 2005; 46(12):688-672.
14. Sato K, Tamaki K, Takeuchi H, et al. Management of the axilla in breast cancer: a comparative study between sentinel lymph node biopsy and four-node sampling procedure[J]. Jpn J Clin Oncol. 2001;31(7):318-321.
15. Fleissig A, Fallowfield LJ, Langridge CI, et al. Postoperative arm morbidity and quality of life. Results of the ALMA-NAC randomised trial comparing sentinel node biopsy with standardaxillary treatment in the management of patients with early breast cancer[J]. Breast Cancer Res Treat. 2006;95(3):279-293.
16. Veronesi U, Paganelli G, Viale G, etal. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer[J]. N Engl J Med. 2003;349(6): 546-553.
17. 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.
18. Morton DL,Cochran AJ,Thomspon JF,et al.Sentinel node biopsy for early-stage melanoma:accuracy and morbidity in MSLT-I,an internat-ional multicenter trial[J].Ann surg,2005;242(3):302-311.
19. Fraile M,Rull FJ. Sentinel lymph node biopsy as a practical alternative to axillary lymph node dissection in breast cancer patients;an approach to its validity[J].Ann Oncol, 2000;11(6):701-705.
20. Takei H, Suemasu K, Kurosumi M, et al. Added Value of the Presence of Blue Nodes or Hot Nodes in Sentinel Lymph Node Biopsy of Breast Cancer[J]. Breast Cancer. 2006;13(2): 175-179.
21. Takahashi M, Sasa M, Hirose C, et al. Clinical efficacy and problems with CT lymphography in identifying the sentinel node in breast cancer[J]. World J Surg Oncol. 2008; 6:57-72.
22. Giuliano AE, Kirgan DM, Guenther JM, et al. Lymphatic mapping and sentinel lymphadenectomy for breast cancer[J].Ann Surg. 1994;220(3):391-398.
23. Filippakis GM, Zografos G. Contraindications of sentinel lymph node biopsy: are there any really[J]? World J Surg Oncol. 2007;29:5-10.
24. East JM, Valentine CS, Kanchev E, et al. Sentinel lymph node biopsy for breast cancer using methylene blue dye manifests a short learning curve among experienced surgeons: a prospective tabular cumulative sum (CUSUM) analysis[J]. BMC Surg. 2009;27(9):2-5.
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34 Chagpar AB, Scoggins CR, Martin RC,et al. Are 3 sentinel nodes sufficient[J]? Arch Surg. 2007;142(5):456-460.
35 Mathelin C, Salvador S, Croce S, et al. Optimization of sentinel lymph node biopsy in breast cancer using an operative gamma camera[J]. World J Surg Oncol. 2007;5:132-137.
36 Lo YF, Hsueh S, Ma SY, et al. Radioguided sentinel lymph node biopsy in early breast cancer: experience at Chang Gung Memorial Hospital[J]. Chang Gung Med J. 2006 ;29(5):458-467.
37 Moghimi M, Ghoddosi I, Rahimabadi AE,et al. Accuracy of sentinel node biopsy in breast cancer patients with a high prevalence ofaxillary metastases[J]. Scand J Surg. 2009;98(1):30-33.
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39 Choi YJ, Yun HR, Yoo KE, et al. Intraoperative examination of sentinel lymph nodes by ultrarapid immunohistochemistry in breast cancer[J]. Jpn J Clin Oncol. 2006;36(8):489-493.
40 Compton CC. Colorectal carcinoma: Diagnostic,prognos-tic,and molecular features[J]. Modern Pathol.2003;16(4):376-381.
41 Dowlatshahi K, Fan M, Snider HC, et al. Lymph node micrometases from breast carcinoma: reviewing the dilemma[J]. Cancer.1997;80:1188-1197.
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7 Cody HS. Clinical aspects of sentinel node biopsy[J]. Breast Cancer Res. 2001;3(2):104-108.
8 Filippakis GM, Zografos G. Contraindications of sentinel lymph node biopsy: are there any really[J]. World J Surg Oncol. 2007;29:5-10
9 Ferrari A, Dionigi P, Rovera F, et al. Multifocality and multicentricity are not contraindications for sentinel lymph node biopsy in breast cancer surgery[J]. World J Surg Oncol. 2006;4:79-84.
10 Weaver DL, Ashikaga T, Harlovo SP, et al. Pathologic analysis of sentinel and nonsentinel lymph nodes in breast carcinoma[J].Cancer.2000;88(5):1099-1107.
11 Kumar R, Jana S, Heiba SI, et al. Retrospective analysis of sentinel node localization in multifo-cal, multicentric, palpable, or nonpalpable breast cancer[J].J Nucl Med.2003;44(1):7-10.
12 East JM, Valentine CS, Kanchev E, et al. Sentinel lymph node biopsy for breast cancer using methylene blue dye manifests a short learning curve among experienced sur-geons:a prospective tabular cumulative sum(CUSUM) analysis[J]. BMC Surg.2009;9:2-9.
13 Compton CC. Colorectal carcinoma:Diagnostic, prognos-tic, andmolecular features[J].Modern Pathol.2003;16(4):376-388..
14 Ono T, Minamiya Y, Ito M, et al. Sentinel node mapping and micrometastasis in patients with clinical stage IA non-small cell lung cancer[J]. .Interact Cardiovasc Thorac Surg. 2009;9(4):659-661.
15 Dowlatshahi K, Fan M, Snider HC, et al. Lymph node micrometases from breast carcinoma: reviewing the dilemma[J]. Cancer.1997;80:1188-1197.
16 Hauspy J, Beiner M, Harley I, et al. Sentinel lymph node in vulvar cancer[J]. Cancer. 2007;110(5):1015-1023.
17 Kelder W, Braat AE, Karrenbeld A, et al. The sentinel node procedure in colon carcinoma: a multi-centre study in The Netherlands[J]. Int J Colorectal Dis. 2007;22(12):1509-1514.
18 Cahill RA.What's wrong with sentinel node mapping in colon cancer[J]? World J Gastroenterol. 2007;13(47):6291-6294.
19 Phan GQ, Messina JL, Sondak VK, et al. Sentinel lymph node biopsy for melanoma: indications and rationale. Cancer Control. 2009;16(3):234-239.
20 Balch CM, Cascinelli N. Sentinel-node biopsy in melanoma[J]. N Engl J Med 2006; 355: 1370-1371.
21 Lyman GH, Giuliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinellymph node biopsy in early-stage breast cancer[J]. J Clin Oncol.2005;23:7703-7720.
22 Moghimi M, Ghoddosi I, Rahimabadi AE, et al. Accuracy of sentinel node biopsy in breast cancer patients with a high prevalence of axillary metastases[J]. Scand J Surg. 2009;98(1):30-33.
23 Poletti P, Fenaroli P, Milesi A, et al. Axillary recurrence in sentinel lymph node-negative breast cancer patients[J]. Ann Oncol. 2008;19(11):1842-1846.
24 Louis-Sylvestre C, Clough K, Asselain B,et al. Axillary treatment in conservative management of operable breast cancer:dissection or radiotherapy?Results of a randomizedstudy with 15 years of follow-up[J].J Clin Oncol.2004;22(1):97-101.
25 Yuan SH, Liang XF, Jia WH, et al. Molecular diagnosis of sentinel lymph node metastases in cervical cancer using squamous cell carcinoma antigen[J]. Clin Cancer Res. 2008;14(17):5571-5578.
26 Rhim CC, Park JS, Bae SN, et al. Sentinel node biopsy as an indicator for pelvic nodes dissection in early stage cervical cancer[J]. J Korean Med Sci. 2002;17(4):507-511.
27 Bohanes T, Neoral C, Aujesky R,et al. Sentinel lymph node in esophageal cancer before neoadjuvant therapy[J]. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub.2005;149(1):145-147.
28 Saikawa Y, Otani Y, Kitagawa Y, et al. Interim results of sentinel node biopsy during laparoscopic gastrectomy:possible role in function-preserving surgery for early cancer[J].World J Surg.2006;30(11):1962-1968.
29 Liu CG, Lu P, Lu Y, et al. Distribution of solitary lymph nodes in primary gastric cancer: a retrospective study and clinical implications[J].World J Gastroenterol. 2007;13(35):4776-4780.
30 Minamiya Y, Ito M, Hosono Y, et al. Subpleural injection of tracer improves detection of mediastinal sentinel lymph nodes in non-small cell lung cancer[J]. Eur J Cardiothorac Surg 2007;32:770-775.
31 Roh JL, Park CI. Sentinel lymph node biopsy as guidance for central neck dissection in patients with papillary thyroid carcinoma[J]. Cancer. 2008;113(7):1527-1531.
32 Atula T, Shoaib T, Ross GL, et al. How many sentinel nodes should be harvested in oral squamous cell carcinoma[J]? Eur Arch Otorhinolaryngol. 2008;265(1)l:19-23.
33 Janetschek G, Jeschke S, Leeb K, et al. Sentinel lymph node dissection for localized prostate cancer[J] Actas Urol Esp. 2007;31(6):686-692.
34 Chagpar AB, Scoggins CR, Martin RC, et al. Are 3 sentinel nodes sufficient[J]? Arch Surg. 2007;142(5):456-460.
35 Mathelin C, Salvador S, Croce S, et al. Optimization of sentinel lymph node biopsy in breast cancer using an operative gamma camera[J]. World J Surg Oncol. 2007;5:132-135.
36 Lo YF, Hsueh S, Ma SY, et al. Radioguided sentinel lymph node biopsy in early breast cancer: experience at Chang Gung Memorial Hospital[J]. Chang Gung Med J. 2006 ;29(5):458-467.
37 Barranger E,Coutant C,Cortez A,et al.Sentinel node biopsy is reliable in early-stage cervical cancer but not in localy advanced disease[J].Ann Oncol.2005;16(8):1237-1242.
38 Namwongprom S, Boonyaprapa S, Ekmahachai M, et al. Breast lymphoscintigraphy for sentinel node identification in breast cancers with clinically-negative axillary nodes[J]. Singapore Med J. 2005; 46(12):688-672
39 Choi YJ, Yun HR, Yoo KE, et al. Intraoperative examination of sentinel lymph nodes by ultrarapid immunohistochemistry in breast cancer[J]. Jpn J Clin Oncol. 2006 ;36(8):489-493.
2. Zhao YS, Pang D, Wang F, et al. Nipple aspirate fluid collection, related factors and relationship between carcinoembryonic antigen in nipple aspirate fluid and breast diseases in women in Harbin, PRC[J]. Cancer Epidemiol Biomarkers Prev. 2009;18(3):732-738.
3. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer[J]. N Engl J Med. 2002;347(16):1227-1232.
4. Moghimi M, Ghoddosi I, Rahimabadi AE, et al. Accuracy of sentinel node biopsy in breast cancer patients with a high prevalence of axillary metastases[J]. Scand J Surg. 2009;98(1):30-33.
5. Takei H, Kurosumi M, Yoshida T, et al. Current trends of sentinel lymph node biopsy for breast cancer--a surgeon's perspective[J]. Breast Cancer. 2007;14(4):362-370.
6. Yen RF, Kuo WH, Lien HC, et al. Radio-guided sentinel lymph node biopsy using periareolar injection technique for patients with early breast cancer[J]. J Formos Med Assoc. 2007;106(1):44-50.
7. Gulec SA, Moffat FL, Carroll RG, et al. Sentinel lymph node localization in early breast cancer[J]. J Nucl Med. 1998;39(8):1388-1393.
8. Poletti P, Fenaroli P, Milesi A, et al. Axillary recurrence in sentinel lymph node-negative breast cancer patients[J]. Ann Oncol. 2008;19(11):1842-1846.
9. Kathleen M, Erb MD, Thomas B, et al. Completion of Axillary Dissection for a Positive Sentinel Node: Necessary or Not?[J]. Curr Oncol Rep. 2009;11(1):15–20.
10. Lee JH, Ryu KW, Kim CG, et al. Sentinel node biopsy using dye and isotope double tracers in early gastric cancer[J].Ann Surg Oncol. 2006;13(9):1168-1174.
11. Fournier K,Schiller A,Perry RR,et a1. Micrometastals in the sentinel lymph node of breast cancer does not mandate completion axillarv dissection[J]. Ann Surg. 2004;239:859-865.
12. Mathelin C, Salvador S, Croce S, et al. Optimization of sentinel lymph node biopsy in breast cancer using an operative gamma camera[J]. World J Surg Oncol. 2007;5:132-137.
13. Namwongprom S, Boonyaprapa S, Ekmahachai M, et al. Breast lymphoscintigraphy for sentinel node identification in breast cancers with clinically-negative axillary nodes[J]. Singapore Med J. 2005; 46(12):688-672.
14. Sato K, Tamaki K, Takeuchi H, et al. Management of the axilla in breast cancer: a comparative study between sentinel lymph node biopsy and four-node sampling procedure[J]. Jpn J Clin Oncol. 2001;31(7):318-321.
15. Fleissig A, Fallowfield LJ, Langridge CI, et al. Postoperative arm morbidity and quality of life. Results of the ALMA-NAC randomised trial comparing sentinel node biopsy with standardaxillary treatment in the management of patients with early breast cancer[J]. Breast Cancer Res Treat. 2006;95(3):279-293.
16. Veronesi U, Paganelli G, Viale G, etal. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer[J]. N Engl J Med. 2003;349(6): 546-553.
17. 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.
18. Morton DL,Cochran AJ,Thomspon JF,et al.Sentinel node biopsy for early-stage melanoma:accuracy and morbidity in MSLT-I,an internat-ional multicenter trial[J].Ann surg,2005;242(3):302-311.
19. Fraile M,Rull FJ. Sentinel lymph node biopsy as a practical alternative to axillary lymph node dissection in breast cancer patients;an approach to its validity[J].Ann Oncol, 2000;11(6):701-705.
20. Takei H, Suemasu K, Kurosumi M, et al. Added Value of the Presence of Blue Nodes or Hot Nodes in Sentinel Lymph Node Biopsy of Breast Cancer[J]. Breast Cancer. 2006;13(2): 175-179.
21. Takahashi M, Sasa M, Hirose C, et al. Clinical efficacy and problems with CT lymphography in identifying the sentinel node in breast cancer[J]. World J Surg Oncol. 2008; 6:57-72.
22. Giuliano AE, Kirgan DM, Guenther JM, et al. Lymphatic mapping and sentinel lymphadenectomy for breast cancer[J].Ann Surg. 1994;220(3):391-398.
23. Filippakis GM, Zografos G. Contraindications of sentinel lymph node biopsy: are there any really[J]? World J Surg Oncol. 2007;29:5-10.
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