DISCUSSION


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Currently, the implementation of modern surgical techniques for patients with breast cancer seeks to minimize the risk of treatment-associated morbidities, particularly lymphedema,8,32,33 with a subsequent decline in ALND practice after positive SLNB for micrometastases or isolated tumor cells, suggesting that ALND is more prognostic than therapeutic.34

Lymphedema develops when the rate of production of lymphatic fluid exceeds the capacity of lymph transport. It is characterized by lymphatic fluid accumulation in the interstitial space (edema), which often occurs in the extremities.35,36 Once established, lymphedema is incurable, and it is difficult to diagnose, especially in the early stages.12 Without a correct diagnosis, treatment begins late and at a more advanced stage of the disease. Immediate treatment leads to rapid improvement and also prevents the progression of the disease to the chronic phase.16,23 The concern of patients regarding lymphedema development was reported by McLaughlin et al34 who found that 50% of patients who underwent SLNB versus 75% of patients who underwent ALND were concerned about the development of this disease. Despite reports showing that the concerns of patients who underwent SLNB are unfounded due to the low risk of developing lymphedema, preventive measures should be taken because, although low, the risk exists. Several factors are attributed to the development of lymphedema after the SLNB and ALND procedures, such as the rupture of lymphatic vessels of the arm;19,20,37 the fact that the sentinel lymph node draining to the breast and upper limb is the same and that its removal disrupts lymphatic drainage;38 obesity;20,21 poor surgical techniques;39 low educational level; advanced stage of disease; infections; number of lymph nodes involved; associated comorbidities; trauma; time after surgery;36 anatomical peculiarities of the lymphatic system, which vary among patients;35 and combination with adjuvant radiotherapy.40,41

Nuclear medicine technology plays an important role in evaluating the pattern of lymphatic drainage.42,43 The lymphatic system is complex, and its imaging remains a challenge. First, the lymphatic system is not an organ but connects different structures of small lymphatic capillaries to main ducts through lymph nodes and valves. Each of these structures can be visualized separately in images. Second, the lymphatic system can comprise a variety of diseases, including neoplasias and infectious diseases.16,18,44 Studies using LS to evaluate the lymphatic circulation of the arm immediately after surgical treatment in patients with breast cancer (ALND and SLNB) were not found in the literature, so comparisons with this study could not be performed. This study was able to evaluate the lymphatic route in the early and delayed phases of scintigraphy in both groups. The delayed LS images (WBS) were more significant in identifying the differences in the lymphatic alterations between the ALND and SLNB groups. It is possible that a larger sample might generate a significant difference.

Using LS, Celebioglu et al35 qualitatively and quantitatively compared the operated and nonoperated upper limbs of patients who underwent ALND and SLNB, where the second examination was 2–3 years after surgery and radiotherapy. The authors found a difference in the ALND group, where patients had dermal backflow and decreased accumulation of radiotracer in the axilla, while there was no difference in the SLNB group. In this study, dermal backflow was not visualized in any patient, most likely due to the short interval between the surgery and the LS. An attempt to maintain the lymphatic flow through alternative routes was identified. Additionally, more axillary lymph nodes were observed in the SLNB group, obviously due to the preservation of the axilla in this group. In contrast, a greater number of extra-axillary lymph nodes, especially in the cubital and deltoid regions, were observed in the ALND group. This finding is most likely due to damage to the normal lymphatic circulation, with flow redirected to alternative routes of deeper lymphatic chains, confirming the study conducted by Sarri et al29 comparing lymphatic drainage before and after ALND. These findings show an attempt to maintain the lymphatic flow of the upper limb after more aggressive surgeries. Lymphoscintigraphies performed at longer intervals after surgery (a minimum of 6 months after) may clarify the impact of these findings. Further studies should be conducted at such intervals to try to better elucidate these points.

CONCLUSION

In conclusion, the data from this study showed lymphatic damage, with the lymphatic flow from the axilla being redirected to alternative routes in the ALND group in early postoperative breast surgery.

Acknowledgments

The authors thank the Teaching and Research Institute of Barretos Cancer Hospital, Brazil, and all patients who gave their consents to participate in this study.

Disclosure

The authors report no conflicts of interest in this work.


Almir José Sarri,Rogério Dias,Carla Elaine Laurienzo,Mônica Carboni Pereira Gonçalves,Daniel Spadoto Dias,Sonia Marta Moriguchi4
1Department of Physical Therapy, Barretos Cancer Hospital, Barretos, 2Department of Obstetrics, Gynaecology and Mastology, Botucatu Medical School, São Paulo State University – UNESP, Botucatu,3Department of Nuclear Medicine, Barretos Cancer Hospital, Barretos, 4Department of Tropical Diseases and Diagnostic Imaging, Botucatu Medical School, São Paulo State University – UNESP, Botucatu, São Paulo, Brazil  


References

1. Cidon EU, Perea C, Lopez-Lara F. Life after breast cancer: dealing with lymphoedema. Clin Med Insights Oncol. 2011;5:9–14.

2. Hashim D, Boffetta P, La Vecchia C, et al. The global decrease in cancer mortality: trends and disparities. Ann Oncol. 2016;27(5):926–933.

3. Noguchi M. Axillary reverse mapping for breast cancer. Breast Cancer Res Treat. 2010;119(3):529–535.

4. Yildiz R, Urkan M, Hancerliogullari O, et al. Comparison of five different popular scoring systems to predict nonsentinel lymph node status in patients with metastatic sentinel lymph nodes: a tertiary care center experience. Springerplus. 2015;4:651.

5. Maaskant-Braat AJ, de Bruijn SZ, Woensdregt K, Pijpers H, Voogd AC, Nieuwenhuijzen GA. Lymphatic mapping after previous breast surgery. Breast. 2012;21(4):444–448.

6. Rebegea L, Firescu D, Dumitru M, Anghel R. The incidence and risk factors for occurrence of arm lymphedema after treatment of breast cancer. Chirurgia (Bucur). 2015;110(1):33–37.

7. Aerts PD, De Vries J, Van der Steeg AF, Roukema JA. The relationship between morbidity after axillary surgery and long-term quality of life in breast cancer patients: the role of anxiety. Eur J Surg Oncol. 2011;37(4):344–349.

8. Cho Y, Do J, Jung S, Kwon O, Jeon JY. Effects of a physical therapy program combined with manual lymphatic drainage on shoulder function, quality of life, lymphedema incidence, and pain in breast cancer patients with axillary web syndrome following axillary dissection. Support Care Cancer. 2016;24(5):2047–2057.

9. Krag DN, Weaver DL, Alex JC, Fairbank JT. Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. Surg Oncol. 1993;2(6):335–339; discussion 340.

10. Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg. 1994;220(3):391–398; discussion 398–401.

11. Morrow M. Progress in the surgical management of breast cancer: Present and future. Breast. 2015;24(Suppl 2):S2–S5.

12. Pesce C, Morrow M. The need for lymph node dissection in nonmetastatic breast cancer. Annu Rev Med. 2013;64:119–129.

13. Rao R. The evolution of axillary staging in breast cancer. Mo Med. 2015;112(5):385–388.

14. Rubio IT. Sentinel lymph node biopsy after neoadjuvant treatment in breast cancer: Work in progress. Eur J Surg Oncol. 2016;42(3):326–332.

15. Ahmed M, Rubio IT, Kovacs T, Klimberg VS, Douek M. Systematic review of axillary reverse mapping in breast cancer. Br J Surg. 2016;103(3):170–178.

16. Szuba A, Shin WS, Strauss HW, Rockson S. The third circulation: radionuclide lymphoscintigraphy in the evaluation of lymphedema. J Nucl Med. 2003;44(1):43–57.

17. Bourgeois P, Leduc O, Leduc A. Imaging techniques in the management and prevention of posttherapeutic upper limb edemas. Cancer. 1998;83(12 Suppl American):2805–2813.

18. Ellis S. Structure and function of the lymphatic system: an overview. Br J Community Nurs. 2006;11(4):S4–S6.

19. De Gournay E, Guyomard A, Coutant C, et al. Impact of sentinel node biopsy on long-term quality of life in breast cancer patients. Br J Cancer. 2013;109(11):2783–2791.

20. Helyer LK, Varnic M, Le LW, Leong W, McCready D. Obesity is a risk factor for developing postoperative lymphedema in breast cancer patients. Breast J. 2010;16(1):48–54.

21. Mehrara BJ, Greene AK. Lymphedema and obesity: is there a link? Plast Reconstr Surg. 2014;134(1):154e–160e.

22. Ezzo J, Manheimer E, McNeely ML, et al. Manual lymphatic drainage for lymphedema following breast cancer treatment. Cochrane Database Syst Rev. 2015;5:CD003475.

23. Lahtinen T, Seppala J, Viren T, Johansson K. Experimental and analytical comparisons of tissue dielectric constant (TDC) and bioimpedance spectroscopy (BIS) in assessment of early arm lymphedema in breast cancer patients after axillary surgery and radiotherapy. Lymphat Res Biol. 2015;13(3):176–185.

24. Kibar S, Dalyan Aras M, Unsal Delialioglu S. The risk factors and prevalence of upper extremity impairments and an analysis of effects of lymphoedema and other impairments on the quality of life of breast cancer patients. Eur J Cancer Care (Engl). Epub 2016 Jan 13.

25. Bulley C, Gaal S, Coutts F, et al. Comparison of breast cancer-related lymphedema (upper limb swelling) prevalence estimated using objective and subjective criteria and relationship with quality of life. Biomed Res Int. 2013;2013:807569.

26. Stuiver MM, ten Tusscher MR, Agasi-Idenburg CS, et al. Conservative interventions for preventing clinically detectable upper-limb lymphoedema in patients who are at risk of developing lymphoedema after breast cancer therapy. Cochrane Database Syst Rev. 2015;2:CD009765.

27. Ridner SH, Dietrich MS, Kidd N. Breast cancer treatment-related lymphedema self-care: education, practices, symptoms, and quality of life. Support Care Cancer. 2011;19(5):631–637.

28. Munn LL, Padera TP. Imaging the lymphatic system. Microvasc Res. 2014;96:55–63.

29. Sarri AJ, Moriguchi SM, Dias R, et al. Physiotherapeutic stimulation: Early prevention of lymphedema following axillary lymph node dissection for breast cancer treatment. Exp Ther Med. 2010;1(1):147–152.

30. Yamamoto T, Matsuda N, Doi K, et al. The earliest finding of indocyanine green lymphography in asymptomatic limbs of lower extremity lymphedema patients secondary to cancer treatment: the modified dermal backflow stage and concept of subclinical lymphedema. Plast Reconstr Surg. 2011;128(4):314e–321e.

31. Akita S, Mitsukawa N, Rikihisa N, et al. Early diagnosis and risk factors for lymphedema following lymph node dissection for gynecologic cancer. Plast Reconstr Surg. 2013;131(2):283–290.

32. Kootstra JJ, Hoekstra-Weebers JE, Rietman JS, et al. A longitudinal comparison of arm morbidity in stage I–II breast cancer patients treated with sentinel lymph node biopsy, sentinel lymph node biopsy followed by completion lymph node dissection, or axillary lymph node dissection. Ann Surg Oncol. 2010;17(9):2384–2394.

33. Noguchi M. Axillary reverse mapping for preventing lymphedema in axillary lymph node dissection and/or sentinel lymph node biopsy. Breast Cancer. 2010;17(3):155–157.

34. McLaughlin SA, Bagaria S, Gibson T, et al. Trends in risk reduction practices for the prevention of lymphedema in the first 12 months after breast cancer surgery. J Am Coll Surg. 2013;216(3):380–389; quiz 511–513.

35. Celebioglu F, Perbeck L, Frisell J, Grondal E, Svensson L, Danielsson R. Lymph drainage studied by lymphoscintigraphy in the arms after sentinel node biopsy compared with axillary lymph node dissection following conservative breast cancer surgery. Acta Radiol. 2007;48(5):488–495.

36. Shahpar H, Atieh A, Maryam A, et al. Risk factors of lymph edema in breast cancer patients. Int J Breast Cancer. 2013;2013:641818.

37. Noguchi M, Yokoi M, Nakano Y. Axillary reverse mapping with indocyanine fluorescence imaging in patients with breast cancer. J Surg Oncol. 2010;101(3):217–221.

38. Britton TB, Solanki CK, Pinder SE, Mortimer PS, Peters AM, Purushotham AD. Lymphatic drainage pathways of the breast and the upper limb. Nucl Med Commun. 2009;30(6):427–430.

39. Unsal MG, Dural AC, Celik MF, et al. The adaptation process of a teaching and research hospital to changing trends in modern breast surgery. Ulus Cerrahi Derg. 2015;31(1):34–38.

40. Cheville AL, Brinkmann DH, Ward SB, et al. The addition of SPECT/CT lymphoscintigraphy to breast cancer radiation planning spares lymph nodes critical for arm drainage. Int J Radiat Oncol Biol Phys. 2013;85(4):971–977.

41. Donker M, Slaets L, van Tienhoven G, Rutgers EJ. Okselklierdissectie versus okselbestraling bij borstkankerpatiënten met een positieve schildwachtklier. [Axillary lymph node dissection versus axillary radiotherapy in patients with a positive sentinel node: the AMAROS trial]. Ned Tijdschr Geneeskd. 2015;159:A9302. Dutch.

42. Giammarile F, Alazraki N, Aarsvold JN, et al. The EANM and SNMMI practice guideline for lymphoscintigraphy and sentinel node localization in breast cancer. Eur J Nucl Med Mol Imaging. 2013;40(12):1932–1947.

43. Uren RF. Lymphatic drainage of the skin. Ann Surg Oncol. 2004;11(3 Suppl):179S–185S.

44. Choi I, Lee S, Hong YK. The new era of the lymphatic system: no longer secondary to the blood vascular system. Cold Spring Harb Perspect Med. 2012;2(4):a006445.

Source: OncoTargets and Therapy.
Originally published March 6, 2017.