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Effects of autotransplanted lymph node fragments on the lymphatic system in the pig model

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Abstract

Secondary lymphedema often develops after removal of lymph nodes in combination with radiation therapy, in particular in patients with breast cancer, inguinal cancer, cervical cancer and melanoma. No convincing treatment for the prevention and therapy of acquired lymphedema exists so far, therefore we wanted to show the reintegration of transplanted avascular lymph node fragments in the lymphatic system and positive effects of the transplanted fragments on the restoration of the lymphatic flow in this study. A total of 26 minipigs underwent lymphadenectomy of both groins. A minimum of one lymph node was retransplanted. The lymph nodes were cut into small pieces and retransplanted in the left groin (n = 17) or in both groins (n = 9). Different retransplantation techniques were investigated, transplantation of large versus small fragments, with and without capsule. The lymph flow was evaluated 5 and 8 months after surgery, using SPECT/CT and Berlin Blue. The results were confirmed by dissection. The lymph node transplants were assessed histologically. In contrast to the lymph flow in the transplanted groin, the lymph flow in the non-transplanted groin was often malfunctioning. Large lymph node fragments were found reintegrated in the lymphatic system more often than small slices of lymph node fragments. About 5 months after surgery impairment of lymph flow was seen especially after retransplantation of small slices of lymph node fragments. In seven out of eight minipigs a dermal backflow developed in the non-transplanted groin, 8 months after surgery. Only one minipig of these groups developed dermal backflow in both groins. All lymph node fragments showed an organized structure histologically. Autologous lymph node transplantation has positive effects on the regeneration of lymph vessels and restoration of lymph flow after lymphadenectomy.

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References

  1. Hadamitzky C, Pabst R (2008) Acquired lymphedema: an urgent need for adequate animal models. Cancer Res 68:343–345. doi:10.1158/0008-5472.CAN-07-2454

    Article  CAS  PubMed  Google Scholar 

  2. Lawenda BD, Mondry TE, Johnstone PA (2009) Lymphedema: a primer on the identification and management of a chronic condition in oncologic treatment. CA Cancer J Clin 59:8–24. doi:10.3322/caac.20001

    Article  PubMed  Google Scholar 

  3. Mortimer PS (1998) The pathophysiology of lymphedema. Cancer 83:2798–2802. doi:10.1002/(SICI)1097-0142(19981215)83:12B+<2798::AID-CNCR28>3.0.CO;2-E

    Article  CAS  PubMed  Google Scholar 

  4. Szuba A, Strauss W, Sirsikar SP et al (2002) Quantitative radionuclide lymphoscintigraphy predicts outcome of manual lymphatic therapy in breast cancer-related lymphedema of the upper extremity. Nucl Med Commun 23:1171–1175. doi:10.1097/00006231-200212000-00004

    Article  CAS  PubMed  Google Scholar 

  5. Brorson H, Svensson H, Norrgren K et al (1998) Liposuction reduces arm lymphedema without significantly altering the already impaired lymph transport. Lymphology 31:156–172

    CAS  PubMed  Google Scholar 

  6. Ryan TJ (1995) Lymphatics and adipose tissue. Clin Dermatol 13:493–498. doi:10.1016/0738-081X(95)00092-T

    Article  CAS  PubMed  Google Scholar 

  7. Burak WE, Hollenbeck ST, Zervos EE et al (2002) Sentinel lymph node biopsy results in less postoperative morbidity compared with axillary lymph node dissection for breast cancer. Am J Surg 183:23–27. doi:10.1016/S0002-9610(01)00848-0

    Article  PubMed  Google Scholar 

  8. Kwan W, Jackson J, Weir LM et al (2002) Chronic arm morbidity after curative breast cancer treatment: prevalence and impact on quality of life. J Clin Oncol 20:4242–4248. doi:10.1200/JCO.2002.09.018

    Article  PubMed  Google Scholar 

  9. Meneses KD, McNees MP (2007) Upper extremity lymphedema after treatment for breast cancer: a review of the literature. Ostomy Wound Manage 53:16–29

    PubMed  Google Scholar 

  10. Brennan MJ, Miller LT (1998) Overview of treatment options and review of the current role and use of compression garments, intermittent pumps, and exercise in the management of lymphedema. Cancer 83:2821–2827. doi:10.1002/(SICI)1097-0142(19981215)83:12B+<2821::AID-CNCR33>3.0.CO;2-G

    Article  CAS  PubMed  Google Scholar 

  11. Mortimer PS (1997) Therapy approaches for lymphedema. Angiology 48:87–91. doi:10.1177/000331979704800114

    Article  CAS  PubMed  Google Scholar 

  12. Rockson SG (2001) Lymphedema. Am J Med 110:288–295. doi:10.1016/S0002-9343(00)00727-0

    Article  CAS  PubMed  Google Scholar 

  13. Campisi C, Davini D, Bellini C et al (2006) Is there a role for microsurgery in the prevention of arm lymphedema secondary to breast cancer treatment? Microsurgery 26:70–72. doi:10.1002/micr.20215

    Article  CAS  PubMed  Google Scholar 

  14. Filippetti M, Santoro E, Graziano F et al (1994) Modern therapeutic approaches to postmastectomy brachial lymphedema. Microsurgery 15:604–610. doi:10.1002/micr.1920150816

    Article  CAS  PubMed  Google Scholar 

  15. Weiss M, Baumeister RG, Hahn K (2002) Post-therapeutic lymphedema: scintigraphy before and after autologous lymph vessel transplantation: 8 years of long-term follow-up. Clin Nucl Med 27:788–792. doi:10.1097/00003072-200211000-00007

    Article  PubMed  Google Scholar 

  16. Damstra RJ, Voesten HG, van Schelven WD, et al (2008) Lymphatic venous anastomosis (LVA) for treatment of secondary arm lymphedema. A prospective study of 11 LVA procedures in 10 patients with breast cancer related lymphedema and a critical review of the literature. Breast Cancer Res Treat 113:199–206. doi:10.1007/s10549-008-9932-5

    Article  PubMed  Google Scholar 

  17. Brorson H, Ohlin K, Olsson G et al (2006) Adipose tissue dominates chronic arm lymphedema following breast cancer: an analysis using volume rendered CT images. Lymphat Res Biol 4:199–210. doi:10.1089/lrb.2006.4404

    Article  PubMed  Google Scholar 

  18. Tammela T, Saaristo A, Holopainen T et al (2007) Therapeutic differentiation and maturation of lymphatic vessels after lymph node dissection and transplantation. Nat Med 13:1458–1466. doi:10.1038/nm1689

    Article  CAS  PubMed  Google Scholar 

  19. Lammermann T, Sixt M (2008) The microanatomy of T-cell responses. Immunol Rev 221:26–43. doi:10.1111/j.1600-065X.2008.00592.x

    Article  PubMed  Google Scholar 

  20. Szuba A, Pyszel A, Jedrzejuk D et al (2007) Presence of functional axillary lymph nodes and lymph drainage within arms in women with and without breast cancer-related lymphedema. Lymphology 40:81–86

    CAS  PubMed  Google Scholar 

  21. Blum KS, Radtke C, Knapp WH et al (2007) SPECT-CT: a valuable method to document the regeneration of lymphatics and autotransplanted lymph node fragments. Eur J Nucl Med Mol Imaging 34:1861–1867. doi:10.1007/s00259-007-0458-6

    Article  CAS  PubMed  Google Scholar 

  22. Cheville AL, Das I, Srinivas S, et al (2009) A pilot study to assess the utility of SPECT/CT-based lymph node imaging to localize lymph nodes that drain the arm in patients undergoing treatment for breast cancer. Breast Cancer Res Treat. doi:10.1007/s10549-008-0283-z

    PubMed  Google Scholar 

  23. Fu K, Izquierdo R, Vandevender D et al (1998) Transplantation of lymph node fragments in a rabbit ear lymphedema model: a new method for restoring the lymphatic pathway. Plast Reconstr Surg 101:134–141. doi:10.1097/00006534-199801000-00022

    Article  CAS  PubMed  Google Scholar 

  24. Weissleder H, Weissleder R (1988) Lymphedema: evaluation of qualitative and quantitative lymphoscintigraphy in 238 patients. Radiology 167:729–735

    CAS  PubMed  Google Scholar 

  25. Herd-Smith A, Russo A, Muraca MG et al (2001) Prognostic factors for lymphedema after primary treatment of breast carcinoma. Cancer 92:1783–1787. doi:10.1002/1097-0142(20011001)92:7<1783::AID-CNCR1694>3.0.CO;2-G

    Article  CAS  PubMed  Google Scholar 

  26. Petrek JA, Senie RT, Peters M et al (2001) Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis. Cancer 92:1368–1377. doi:10.1002/1097-0142(20010915)92:6<1368::AID-CNCR1459>3.0.CO;2-9

    Article  CAS  PubMed  Google Scholar 

  27. Becker C, Assouad J, Riquet M et al (2006) Postmastectomy lymphedema: long-term results following microsurgical lymph node transplantation. Ann Surg 243:313–315. doi:10.1097/01.sla.0000201258.10304.16

    Article  PubMed  Google Scholar 

  28. Saharinen P, Tammela T, Karkkainen MJ et al (2004) Lymphatic vasculature: development, molecular regulation and role in tumor metastasis and inflammation. Trends Immunol 25:387–395. doi:10.1016/j.it.2004.05.003

    Article  CAS  PubMed  Google Scholar 

  29. Blum KS, Pabst R (2006) Keystones in lymph node development. J Anat 209:585–595. doi:10.1111/j.1469-7580.2006.00650.x

    Article  CAS  PubMed  Google Scholar 

  30. Porter CJ, Charman SA (2000) Lymphatic transport of proteins after subcutaneous administration. J Pharm Sci 89:297–310. doi:10.1002/(SICI)1520-6017(200003)89:3<297::AID-JPS2>3.0.CO;2-P

    Article  CAS  PubMed  Google Scholar 

  31. Adair TH, Guyton AC (1983) Modification of lymph by lymph nodes II. Effect of increased lymph node venous blood pressure. Am J Physiol 245:H616–H622

    CAS  PubMed  Google Scholar 

Download references

Acknowledgment

The excellent technical assistance of Andrea Herden and Karin Westermann and the polishing of the English by Sheila Fryk are gratefully acknowledged. This study was partly supported by the German Research Foundation (Cluster of Excellence “From Regenerative Biology to Reconstructive Therapy, REBIRTH”).

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Authors and Affiliations

  1. Institute of Diagnostic and Interventional Neuroradiology, OE 8210, Medical School of Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    K. S. Blum

  2. Institute of Functional and Applied Anatomy, Medical School of Hannover, Hannover, Germany

    K. S. Blum, C. Hadamitzky & R. Pabst

  3. Clinic for Nuclear Medicine, Medical School of Hannover, Hannover, Germany

    K. F. Gratz

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  1. K. S. Blum
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  2. C. Hadamitzky
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  3. K. F. Gratz
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  4. R. Pabst
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Correspondence to K. S. Blum.

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Blum, K.S., Hadamitzky, C., Gratz, K.F. et al. Effects of autotransplanted lymph node fragments on the lymphatic system in the pig model. Breast Cancer Res Treat 120, 59–66 (2010). https://doi.org/10.1007/s10549-009-0367-4

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  • DOI: https://doi.org/10.1007/s10549-009-0367-4

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