Tropism of drug targeting lymph nodes and drug concentration after regional injection of paclitaxel-nano carbon in patients with esophageal cancer: A prospective non-randomized controlled study_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

CAI Jie ¹ , LIU Xin ² , WANG Wenping ¹ , HU Weipeng ¹ , YANG Yushang ¹ , ZHANG Li ² ,  CHEN Longqi ¹

1. Department of Thoracic Surgery, West China Hospital of Sichuan University, Chengdu, 610041, P.R.China;
2. Department of Thoracic Surgery, the Second Affiliated Hospital, Kunming Medical University, Kunming, 650000, P.R.China;

Corresponding author：

CHEN Longqi, Email: drchenlq@gmail.com

Keywords：

Esophageal cancer; lymphatic chemotherapy; paclitaxel; drug concentration

DOI：

10.7507/1007-4848.201712044

Video：

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Objective To compare the distribution of drug concentration in lymph nodes and blood between lymphatic chemotherapy and single drug chemotherapy and to study if nano carbon can enhance the number of lymph node dissection. Methods From June 2015 to February 2016, 80 patients with esophageal cancer in the Department of Thoracic Surgery, West China Hospital were enrolled and they were divided into two groups: a lymphatic chemotherapy with paclitaxel (LCP) group and a paclitaxel alone (PTX) group. There were 35 males and 5 females with an average age of 60.63±8.78 years in the LCP group, and 30 males and 10 females with an average age of 62.13±7.89 years in the the PTX group. We observed the incidence rate of complications after operation, the number of lymph node dissection and the rate of lymph node metastasis. The drug concentration in the blood and lymph nodes between the two groups was compared. Results The postoperative morbidity did not increase in the both groups, which did not have adverse drug reactions such as bone marrow suppression, gastrointestinal reaction and so on. The concentration of chemotherapy drug in lymph nodes in the LCP group was higher than that in the PTX group. The LCP group collected 771 lymph nodes, and the average number was 19.27±7.77 for each patient; the PTX group collected 658 lymph nodes, and the average number was 16.45±7.12 for each patient; but the difference between two groups was not statistically significant (P>0.05). Conclusion Nano carbon carriers can effectively improve the drug concentration in lymph nodes after the local injection of chemotherapy drugs. The use of nano carbon tracer in the operation to improve lymph node dissection may not have significance.

Citation： CAI Jie, LIU Xin, WANG Wenping, HU Weipeng, YANG Yushang, ZHANG Li, CHEN Longqi. Tropism of drug targeting lymph nodes and drug concentration after regional injection of paclitaxel-nano carbon in patients with esophageal cancer: A prospective non-randomized controlled study. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2018, 25(11): 929-934. doi: 10.7507/1007-4848.201712044 Copy

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2.	Blom RL, Lagarde SM, van Oudenaarde K, et al. Survival after recurrent esophageal carcinoma has not improved over the past 18 years. Ann Surg Oncol, 2013, 20(8): 2693-2698.
3.	de Manzoni G, Pedrazzani C, Pasini F, et al. Pattern of recurrence after surgery in adenocarcinoma of the gastro-oesophageal junction. Eur J Surg Oncol, 2003, 29(6): 506-510.
4.	Thomson IG, Smithers BM, Gotley DC, et al. Thoracoscopic-assisted esophagectomy for esophageal cancer: analysis of patterns and prognostic factors for recurrence. Ann Surg, 2010, 252(2): 281-291.
5.	Sánchez-Pernaute A, Pérez Aguirre E, Hernando Trancho F, et al. Recurrence pattern of esophageal cancer after esophagectomy with two-field lymphadenectomy. Rev Esp Enferm Dig, 2003, 95(3): 197-201.
6.	Li CL, Zhang FL, Wang YD, et al. Characteristics of recurrence after radical esophagectomy with two-field lymph node dissection for thoracic esophageal cancer. Oncol Lett, 2013, 5(1): 355-359.
7.	Ninomiya I, Okamoto K, Tsukada T, et al. Recurrence patterns and risk factors following thoracoscopic esophagectomy with radical lymph node dissection for thoracic esophageal squamous cell carcinoma. Mol Clin Oncol, 2016, 4(2): 278-284.
8.	Rizk NP, Ishwaran H, Rice TW, et al. Optimum lymphadenectomy for esophageal cancer. Ann Surg, 2010, 251(1): 46-50.
9.	Ma GW, Situ DR, Ma QL, et al. Three-field vs two-field lymph node dissection for esophageal cancer: a meta-analysis. World J Gastroenterol, 2014, 20(47): 18022-18030.
10.	孟强, 孟荣贵, 崔龙, 等. 直肠癌术前淋巴化疗安全性分析. 中华消化外科杂志, 2008, 7(2): 137-139.
11.	Pérez-Herrero E, Fernández-Medarde A. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy. Eur J Pharm Biopharm, 2015, 93: 52-79.
12.	Sze MF, McKay G. An adsorption diffusion model for removal of para-chlorophenol by activated carbon derived from bituminous coal. Environ Pollut, 2010, 158(5): 1669-1674.
13.	Valberg PA, Long CM, Sax SN. Integrating studies on carcinogenic risk of carbon black: epidemiology, animal exposures, and mechanism of action. J Occup Environ Med, 2006, 48(12): 1291-1307.
14.	李伟. 纳米炭吸附紫杉醇对胃癌淋巴结内肿瘤细胞凋亡、Bcl-2及P16表达的研究. 泸州医学院, 2010.
15.	李伟, 徐亮, 姬俊成, 等. 胃癌周围注射不同比例紫杉醇与纳米炭后引流区淋巴结药物浓度观察. 中国普通外科杂志, 2013, 22(12): 1646-1650.
16.	李伟, 曾晓华, 徐发良, 等. 纳米炭吸附多西紫杉醇在乳腺癌区域淋巴化疗中的临床研究. 重庆医学, 2015, 44(7): 907-909.
17.	郑希, 袁勇, 胡杨, 等. 食管癌术中淋巴结化疗的临床研究. 中华肿瘤防治杂志, 2017, 24(5): 307-311.
18.	程科, 庄競, 李保东, 等. 纳米碳淋巴示踪剂在腹腔镜辅助下进展期胃癌根治术中的应用及评价. 中国普外基础与临床杂志, 2016, 23(12): 1460-1463.
19.	段绪伟, 李真龙, 许坚. 纳米碳示踪剂在甲状腺癌根治术中的应用. 中国普通外科杂志, 2015, 24(5): 638-642.
20.	葛现才, 张勤, 徐宪辉, 等. 纳米碳示踪技术在结肠癌根治术淋巴结清扫中应用价值研究. 中国实用外科杂志, 2016, 36(8): 904-906.
21.	刘珊, 蒋永新, 陈芸, 等. 纳米碳示踪非小细胞肺癌淋巴结清除临床应用研究. 中华肿瘤防治杂志, 2015, 22(17): 1393-1396.
22.	杨志芳, 岳瑞雪, 朱智, 等. 纳米碳在cN0期甲状腺乳头状癌中央区淋巴结清扫手术中的应用. 中国普外基础与临床杂志, 2013, 20(9): 976-980.
23.	Kelsen DP, Ginsberg R, Pajak TF, et al. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med, 1998, 339(27): 1979-1984.
24.	Guo F, Mao X, Wang J, et al. Gemcitabine adsorbed onto carbon particles increases drug concentrations at the injection site and in the regional lymph nodes in an animal experiment and a clinical study. J Int Med Res, 2011, 39(6): 2217-2227.
25.	Yang Q, Wang XD, Chen J, et al. A clinical study on regional lymphatic chemotherapy using an activated carbon nanoparticle-epirubicin in patients with breast cancer. Tumour Biol, 2012, 33(6): 2341-2348.
26.	Wang J, Yu JC, Kang WM, et al. Prognostic significance of intraoperative chemotherapy and extensive lymphadenectomy in patients with node-negative gastric cancer. J Surg Oncol, 2012, 105(4): 400-404.
27.	侯俊民. 紫杉醇对人食管癌细胞作用的体外实验研究. 南京医科大学, 2001.
28.	何丽. 多烯紫杉醇对人食管癌细胞的放射增敏作用及其机制的实验研究. 河北医科大学, 2012.
29.	王卫强. 紫杉醇脂质体对人食管鳞癌细胞系体外抗瘤作用的研究. 河北医科大学, 2013.
30.	彭玮丹, 张杰, 曹云新, 等. 紫杉醇诱导食管癌细胞的细胞周期阻断与细胞凋亡. 中国药理学通报, 1998, 14(5): 402-406.
31.	孟强, 李会晨, 崔龙, 等. 消化道恶性肿瘤淋巴化疗的现状. 中国实用外科杂志, 2006, 26(2): 145-147.
32.	顾蔚, 王天翔. 胃癌纳米炭载体淋巴化疗的研究现状及前景. 外科理论与实践, 2007, 12(4): 398-400.
33.	张李, 王晓娜, 丁学伟, 等. 纳米炭吸附丝裂霉素C腹腔化疗的实验研究. 中华肿瘤防治杂志, 2008, 15(7): 503-506.
34.	Natsugoe S, Aikou T, Shimada M, et al. Loco-regional treatment for esophageal cancer with bleomycin adsorbed to activated carbon particles. Anticancer Res, 1993, 13(5C): 1785-1787.
35.	Ortner MA, Taha AA, Schreiber S, et al. Endoscopic injection of mitomycin adsorbed on carbon particles for advanced esophageal cancer: a pilot study. Endoscopy, 2004, 36(5): 421-425.
36.	许天文, 林建清, 郭启祥, 等. 顺铂纳米炭示踪剂在食管癌手术中的应用. 中华实验外科杂志, 2015, 32(12): 3209-3210.

1. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65(2): 87-108.
2. Blom RL, Lagarde SM, van Oudenaarde K, et al. Survival after recurrent esophageal carcinoma has not improved over the past 18 years. Ann Surg Oncol, 2013, 20(8): 2693-2698.
3. de Manzoni G, Pedrazzani C, Pasini F, et al. Pattern of recurrence after surgery in adenocarcinoma of the gastro-oesophageal junction. Eur J Surg Oncol, 2003, 29(6): 506-510.
4. Thomson IG, Smithers BM, Gotley DC, et al. Thoracoscopic-assisted esophagectomy for esophageal cancer: analysis of patterns and prognostic factors for recurrence. Ann Surg, 2010, 252(2): 281-291.
5. Sánchez-Pernaute A, Pérez Aguirre E, Hernando Trancho F, et al. Recurrence pattern of esophageal cancer after esophagectomy with two-field lymphadenectomy. Rev Esp Enferm Dig, 2003, 95(3): 197-201.
6. Li CL, Zhang FL, Wang YD, et al. Characteristics of recurrence after radical esophagectomy with two-field lymph node dissection for thoracic esophageal cancer. Oncol Lett, 2013, 5(1): 355-359.
7. Ninomiya I, Okamoto K, Tsukada T, et al. Recurrence patterns and risk factors following thoracoscopic esophagectomy with radical lymph node dissection for thoracic esophageal squamous cell carcinoma. Mol Clin Oncol, 2016, 4(2): 278-284.
8. Rizk NP, Ishwaran H, Rice TW, et al. Optimum lymphadenectomy for esophageal cancer. Ann Surg, 2010, 251(1): 46-50.
9. Ma GW, Situ DR, Ma QL, et al. Three-field vs two-field lymph node dissection for esophageal cancer: a meta-analysis. World J Gastroenterol, 2014, 20(47): 18022-18030.
10. 孟强, 孟荣贵, 崔龙, 等. 直肠癌术前淋巴化疗安全性分析. 中华消化外科杂志, 2008, 7(2): 137-139.
11. Pérez-Herrero E, Fernández-Medarde A. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy. Eur J Pharm Biopharm, 2015, 93: 52-79.
12. Sze MF, McKay G. An adsorption diffusion model for removal of para-chlorophenol by activated carbon derived from bituminous coal. Environ Pollut, 2010, 158(5): 1669-1674.
13. Valberg PA, Long CM, Sax SN. Integrating studies on carcinogenic risk of carbon black: epidemiology, animal exposures, and mechanism of action. J Occup Environ Med, 2006, 48(12): 1291-1307.
14. 李伟. 纳米炭吸附紫杉醇对胃癌淋巴结内肿瘤细胞凋亡、Bcl-2及P16表达的研究. 泸州医学院, 2010.
15. 李伟, 徐亮, 姬俊成, 等. 胃癌周围注射不同比例紫杉醇与纳米炭后引流区淋巴结药物浓度观察. 中国普通外科杂志, 2013, 22(12): 1646-1650.
16. 李伟, 曾晓华, 徐发良, 等. 纳米炭吸附多西紫杉醇在乳腺癌区域淋巴化疗中的临床研究. 重庆医学, 2015, 44(7): 907-909.
17. 郑希, 袁勇, 胡杨, 等. 食管癌术中淋巴结化疗的临床研究. 中华肿瘤防治杂志, 2017, 24(5): 307-311.
18. 程科, 庄競, 李保东, 等. 纳米碳淋巴示踪剂在腹腔镜辅助下进展期胃癌根治术中的应用及评价. 中国普外基础与临床杂志, 2016, 23(12): 1460-1463.
19. 段绪伟, 李真龙, 许坚. 纳米碳示踪剂在甲状腺癌根治术中的应用. 中国普通外科杂志, 2015, 24(5): 638-642.
20. 葛现才, 张勤, 徐宪辉, 等. 纳米碳示踪技术在结肠癌根治术淋巴结清扫中应用价值研究. 中国实用外科杂志, 2016, 36(8): 904-906.
21. 刘珊, 蒋永新, 陈芸, 等. 纳米碳示踪非小细胞肺癌淋巴结清除临床应用研究. 中华肿瘤防治杂志, 2015, 22(17): 1393-1396.
22. 杨志芳, 岳瑞雪, 朱智, 等. 纳米碳在cN0期甲状腺乳头状癌中央区淋巴结清扫手术中的应用. 中国普外基础与临床杂志, 2013, 20(9): 976-980.
23. Kelsen DP, Ginsberg R, Pajak TF, et al. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med, 1998, 339(27): 1979-1984.
24. Guo F, Mao X, Wang J, et al. Gemcitabine adsorbed onto carbon particles increases drug concentrations at the injection site and in the regional lymph nodes in an animal experiment and a clinical study. J Int Med Res, 2011, 39(6): 2217-2227.
25. Yang Q, Wang XD, Chen J, et al. A clinical study on regional lymphatic chemotherapy using an activated carbon nanoparticle-epirubicin in patients with breast cancer. Tumour Biol, 2012, 33(6): 2341-2348.
26. Wang J, Yu JC, Kang WM, et al. Prognostic significance of intraoperative chemotherapy and extensive lymphadenectomy in patients with node-negative gastric cancer. J Surg Oncol, 2012, 105(4): 400-404.
27. 侯俊民. 紫杉醇对人食管癌细胞作用的体外实验研究. 南京医科大学, 2001.
28. 何丽. 多烯紫杉醇对人食管癌细胞的放射增敏作用及其机制的实验研究. 河北医科大学, 2012.
29. 王卫强. 紫杉醇脂质体对人食管鳞癌细胞系体外抗瘤作用的研究. 河北医科大学, 2013.
30. 彭玮丹, 张杰, 曹云新, 等. 紫杉醇诱导食管癌细胞的细胞周期阻断与细胞凋亡. 中国药理学通报, 1998, 14(5): 402-406.
31. 孟强, 李会晨, 崔龙, 等. 消化道恶性肿瘤淋巴化疗的现状. 中国实用外科杂志, 2006, 26(2): 145-147.
32. 顾蔚, 王天翔. 胃癌纳米炭载体淋巴化疗的研究现状及前景. 外科理论与实践, 2007, 12(4): 398-400.
33. 张李, 王晓娜, 丁学伟, 等. 纳米炭吸附丝裂霉素C腹腔化疗的实验研究. 中华肿瘤防治杂志, 2008, 15(7): 503-506.
34. Natsugoe S, Aikou T, Shimada M, et al. Loco-regional treatment for esophageal cancer with bleomycin adsorbed to activated carbon particles. Anticancer Res, 1993, 13(5C): 1785-1787.
35. Ortner MA, Taha AA, Schreiber S, et al. Endoscopic injection of mitomycin adsorbed on carbon particles for advanced esophageal cancer: a pilot study. Endoscopy, 2004, 36(5): 421-425.
36. 许天文, 林建清, 郭启祥, 等. 顺铂纳米炭示踪剂在食管癌手术中的应用. 中华实验外科杂志, 2015, 32(12): 3209-3210.

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Tropism of drug targeting lymph nodes and drug concentration after regional injection of paclitaxel-nano carbon in patients with esophageal cancer: A prospective non-randomized controlled study

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