|
|
ORIGINAL ARTICLE |
|
Year : 2014 | Volume
: 4
| Issue : 1 | Page : 6-10 |
|
Assessment of the efficacy and safety of methylene blue dye for sentinel lymph node mapping in early breast cancer with clinically negative axilla
Arindam Mukherjee, Suman Kharkwal, KS Charak
Department of Surgery, Employees' State Insurance Post Graduate Institute of Medical Sciences and Research, New Delhi, India
Date of Web Publication | 14-Jul-2014 |
Correspondence Address: Suman Kharkwal Chief Medical Officer, 229, Pocket V, Mayur Vihar, New Delhi - 110 091 India
Source of Support: None, Conflict of Interest: None | Check |
DOI: 10.4103/2278-9596.136689
Background : The benefits of sentinel lymph node (SLN) biopsy in breast cancer patients with clinically negative axillary nodes are now well established. SLN biopsy has been performed using different techniques including injection of isosulfan blue dye (IBD), radioactive colloid, and methylene blue. The aim of this study was to assess the safety and efficacy of methylene blue dye (MBD) as a mapping agent for SLN biopsy in axillary node negative breast carcinoma. Materials and Methods: Between February 2010-2012, a total of 27 female patients of 18 years and above, with established diagnosis of breast carcinoma with clinically negative ipsilateral axillary lymph nodes were studied. After induction of anesthesia, 5 ml of 1% methylene blue was infiltrated into the subareolar tissue on the affected side. The lymph nodes receiving the blue dye were excised as the SLN. Modified radical mastectomy (MRM) was completed and the excised breast with the axillary tissue was sent for histopathological examination to correlate with the findings of the SLN biopsy. Results: The incidence of breast cancer was highest at 41-50 years. Of 27 cases, SLN was identified in 24 cases using MBD. The identification rate was 88.9%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 81.8, 100, 100, and 86.7%, respectively. Conclusion: This study confirms the safety and efficacy of methylene blue as a mapping agent for SLN biopsy in axillary node negative breast cancer. Keywords: Breast cancer, methylene blue dye, sentinel lymph node biopsy
How to cite this article: Mukherjee A, Kharkwal S, Charak K S. Assessment of the efficacy and safety of methylene blue dye for sentinel lymph node mapping in early breast cancer with clinically negative axilla. Arch Int Surg 2014;4:6-10 |
How to cite this URL: Mukherjee A, Kharkwal S, Charak K S. Assessment of the efficacy and safety of methylene blue dye for sentinel lymph node mapping in early breast cancer with clinically negative axilla. Arch Int Surg [serial online] 2014 [cited 2024 Mar 29];4:6-10. Available from: https://www.archintsurg.org/text.asp?2014/4/1/6/136689 |
Introduction | | |
Surgical treatment of breast cancer has evolved from Halsted's radical mastectomy to breast conserving surgery. Similarly, surgical treatment of regional lymph nodes has also become less extensive. Axillary lymph node dissection (ALND) was standard of care for a long time and considered necessary for locoregional control and staging purposes. [1],[2] Although ALND came with substantial morbidity [1],[3] and the majority of the ALND patients were "node negative", various studies reported ALND has no effect on disease-free and overall survivals. [4] There has been a trend recently to be less radical in cancer treatment without compromising the principles of surgical oncology. The relatively recent method of sentinel lymph node (SLN) mapping is a step to achieve that end.
SLN biopsy has been performed using different techniques including injection of isosulfan blue dye (IBD), patent blue (PB), radioactive colloid, fluorescence-guided SLN biopsy using indocyanine green, combination of blue dye and radioactive colloid, and so forth. Methylene blue dye (MBD) is a recent addition to this list.
Isosulfan blue is costly and is known to cause hypersensitivity reactions. IBD and PB were associated with significant number of allergic reaction (0.1-3%), [5],[6],[7],[8],[9],[10] some of which are life threatening. [11] The techniques like fluorescence-guided SLN biopsy using indocyanine green are not widely available, are costly, and are still being studied. Preoperative lymphoscintigraphy facilitates intraoperative identification of axillary nodes, but there are concerns about limited availability and cost of radio colloids as well as exposure of healthcare professionals to radiation.
MBD is more economical than isosulfan blue, does not cause hypersensitivity reactions or any other significant complications and, most importantly, is as good as, and possibly better than, isosulfan blue at SLN mapping. [5],[12] Thus, MBD as a single agent is well suited to surgeons in developing countries to offer the important technique of SLN biopsy without significantly compromising the quality of the test. [13]
The aim of this study was to analyze the safety and success rate of MBD for SLN identification in the management of early breast cancer in the prospective series of 27 patients.
Materials and Methods | | |
This study was conducted in Employees' State Insurance Post Graduate Institute of Medical Sciences and Research (ESI PGIMSR), New Delhi. Twenty-seven patients with confirmed fine needle aspiration cytological diagnosis of breast cancer who were undergoing planned mastectomy and axillary nodal clearance were enrolled in this study between February 2010-2012 after prior approval and informed consent. We selected patients with tumor size not more than 5 cm and clinically negative axillary lymph nodes. We excluded patients with palpable axillary lymph nodes, patients with distant metastases, patients with previous breast surgery, radiotherapy or chemotherapy, and patients with known allergy to MBD and those who refused consent for the use of MBD. All patients were informed of the procedure and consent was taken before surgery. Institutional ethical committee clearance was also obtained.
Procedure
All selected patients planned for modified radical mastectomy (MRM), after induction of anesthesia, were infiltrated with 5 ml of 1% methylene blue into the subareolar tissue on the affected side. [14],[15] No massage was done. SLN were looked for after the superior flap was raised. The lymph node or nodes receiving the blue dye were taken as the SLN. Immediately following their identification the lymph nodes were excised. The excised lymph nodes were sliced into 2-3 transverse sections, depending on their size. Imprint smear was made and stained using Giemsa stain. Following this, the lymph nodes were sent for histopathological examination.
MRM was completed along with ALND in all cases. The excised breast with the axillary tissue was sent for histopathological examination to correlate with the findings of the SLN biopsy.
Statistical methods used
Descriptive statistics was analyzed with Statistical Package for the Social Sciences (SPSS) version 17.0 software. Continuous variables were presented as mean ± standard deviation (SD) and categorical variables as frequencies and percentages. The association between the histopathology of SLN and MRM axillary specimen was analyzed using Fisher's exact test. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were also calculated. A P < 0.05 was taken as significant.
Results | | |
The age of patients with breast carcinoma in the study ranged from 33 to 70 years. The median age was 45 years. The incidence of breast cancer was maximum in the age group of 41-50 years. The next common age group was 31-40 years. The most commonly affected site was the outer upper quadrant (44.4%, n = 12) followed by the lower outer quadrant (22.2%, n = 6), lower inner quadrant (18.5%, n = 5), and the upper inner quadrant (14.8%, n = 4).
SLN was successfully identified in 24 patients (88.9%) using MBD. In three patients (11.1%), SLNB failed as the dye failed to reach the axilla [Table 1], [Figure 1]. Of the 24 patients in whom SLN was identified, imprint cytology showed tumor metastases to SLN in nine patients, whereas it was negative for 15 patients. The results of imprint cytology and histopathology of the SLN were similar in all the cases where SLN was identified [Table 2], [Figure 2]. | Figure 1: Showing the SLN identification rate. SLN = Sentinel lymph node
Click here to view |
Histopathology of the MRM axillary specimen showed tumor metastases into axilla in 11 patients and showed no nodal metastases in the remaining 16 patients. There were two cases in which the imprint cytology and histopathological examination of the SLN were negative for tumor metastases but the histopathological examination of the MRM specimen was positive for nodal metastases. The comparison between histopathology of SLN and MRM axillary specimens is shown in [Table 3] and [Figure 3] and [Figure 4]. The sensitivity, specificity, PPV, and NPV of SLN identification were 81.8, 100, 100, and 86.7%, respectively [Table 4]. | Table 3: Sensitivity, specificity, positive predictive value and negative predictive value of SLN identification
Click here to view |
| Table 4: Showing the comparison between histopathology of the SLN and the MRTable 4: Showing the comparison between histopathology of the SLN and the MRM axillary specimenM axillary specimen
Click here to view |
| Figure 3: Showing blue lymphatic mapping (arrow) after injection of methylene blue dye
Click here to view |
There were no local complications observed with any of the patients including blue discoloration of the urine. None of the patients had any primary or delayed hypersensitivity reaction to MBD.
Discussion | | |
In this study, 5 ml of 1% MBD was given intraparenchymal subareolarly after induction of anesthesia. Breast massage was avoided in this study as its safety is controversial. [16],[17],[18] MBD was found to be safe and none of our patients developed any allergic or anaphylactic reaction, which is in accordance with most published series. [19],[20],[21]
In all 27 patients injected with MBD in the subareolar region, no necrotic skin lesions were observed. This is in contrast with most of the published data. [22],[23],[24] Saha et al., reported 7% cases of skin necrosis after injection of 1% MBD. [25] There were no cases of blue discoloration of urine, and subareolar injection of MBD was never associated with bladder irritation in our patients.
In the present study, SLN was identified in 24 patients. There were three cases in which SLN could not be identified using MBD. The identification rate was 88.9%. This could be due to faulty injection technique or inability of the MBD to reach the axilla. SLN identification rate improved subsequently with the number of cases. In comparison, previous studies reported the SLN identification with MBD ranging from 65-94 %. [26],[27],[28],[29]
Imprint cytology and histopathology of the SLN showed that of the 24 lymph nodes identified 15 of them were negative and nine of them were positive for tumor metastases. The results of imprint cytology and histopathology of the SLN were similar in all the cases where SLN was identified.
On comparing the results of the SLN biopsy and histopathology of the MRM specimen, P <0.001 is obtained, which suggests that our results are statistically significant. Axillary dissection of 24 patients with positive SLNs showed that two cases in which SLN was negative for tumor metastases but the histopathology of axilla was positive. The rate of false-negative result best defines the accuracy of SLN biopsy. In our study, false-negative results were seen in two of the patients (8%), which is comparable with those of other published studies. [30],[31]
Conclusion | | |
MBD is safe for SLN identification in early breast cancer and the technique of subareolar intraparenchymal injection of dilute MBD without massage increases the technical success and maintains low rate of complication. MBD is safe, cheap, and widely available in most of the hospitals. Therefore, with no extra cost to the patient and institution, the option of SLN biopsy can be offered to poor patients in developing countries, which can drastically reduce the morbidity associated with ALND. SLN biopsy with MBD is an effective method. However, it is not an absolute index of freedom from node metastases and should be combined with intraoperative assessment and other investigations.
References | | |
1. | Mansel RE, Fallowfield L, Kissin M, Goyal A, Newcombe RG, Dixon JM, et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: The ALMANAC Trial. J Natl Cancer Inst 2006;98:599-609. |
2. | Samphao S, Eremin JM, El-Sheemy M, Eremin O. Management of the axilla in women with breast cancer: Current clinical practice and a new selective targeted approach. Ann Surg Oncol 2008;15:1282-96. |
3. | Petrek JA, Heelan MC. Incidence of breast carcinoma-related lymphedema. Cancer 1998;83:2776-81. |
4. | Pepels MJ, Vestjens JH, de Boer M, Smidt M, van Diest PJ, Borm GF, et al. Safety of avoiding routine use of axillary dissection in early stage breast cancer: A systematic review. Breast Cancer Res Treat 2011;125:301-13. |
5. | Thevarajah S, Huston TL, Simmons RM. A comparison of the adverse reactions associated with isosulfan blue versus methylene blue dye in sentinel lymph node biopsy for breast cancer. Am J Surg 2005;189:236-9. Mostafa A, Carpenter R. Anaphylaxis to patent blue dye during sentinel lymph node biopsy for breast cancer. Eur J Surg Oncol 2001;27:610. |
6. | Mostafa A, Carpenter R. Anaphylaxis to patent blue dye during sentinel lymph node biopsy for breast cancer. Eur J Surg Oncol 2001;27:610. |
7. | Mullan MH, Deacock SJ, Quiney NF, Kissin MW. Anaphylaxis to patent blue dye during sentinel lymph node biopsy for breast cancer. Eur J Surg Oncol 2001;27:218-9. |
8. | Kuerer HM, Wayne JD, Ross MI. Anaphylaxis during breast cancer lymphatic mapping. Surgery 2001;129:119-20. |
9. | Raut CP, Daley MD, Hunt KK, Akins J, Ross MI, Singletary SE, et al. Anaphylactoid reactions to isosulfan blue dye during breast cancer lymphatic mapping in patients given preoperative prophylaxis. J Clin Oncol 2004;22:567-8. |
10. | Wilke LG, McCall LM, Posther KE, Whitworth PW, Reintgen DS, Leitch AM, et al. Surgical complications associated with sentinel lymph node biopsy: Results from a prospective international cooperative group trial. Ann Surg Oncol 2006;13:491-500. |
11. | Dewachter P, Mouton-Faivre C, Benhaijoub A, Abel-Decollogne F, Mertes PM. Anaphylactic reaction to patent blue V after sentinel lymph node biopsy. Acta Anaesthesiol Scand 2006;50:245-7. |
12. | Simmons R, Thevarajah S, Brennan MB, Christos P, Osborne M. Methylene blue dye as an alternative to isosulfan blue dye for sentinel lymph node localization. Ann Surg Oncol 2003;10:242-7. |
13. | East JM, Valentine CS, Kanchev E, Blake GO. Sentinel lymph node biopsy for breast cancer using methylene blue manifests a short learning curve among experienced surgeons: A prospective tabular cumulative sum (CUSUM) analysis. BMC Surg 2009;9:2. |
14. | Klimberg VS, Rubio IT, Henry R, Cowan C, Colvert M, Korourian S: Subareolar versus peritumoral injection for location of the sentinel lymph node. Ann Surg 1999;229:860-4. |
15. | Kern KA. Sentinel lymph node mapping in breast cancer using subareolar injection of blue dye. J Am Coll Surg 1999;189:539-45. |
16. | Rosser RJ. Sentinel lymph nodes and post injection massage: It is premature to reject caution. J Am Coll Surg 2001;193:338-9. |
17. | Shenoy V, Ravichadran D, Ralphs DN. Is massage following dye injection necessary in sentinel node biopsy in breast cancer? Breast 2002;11:273-4. |
18. | Turner R, Giuliano AE. Does breast massage push tumour cells into sentinel nodes? Am J Surg Pathol 2005;29:1254-5; author reply 1255-6. |
19. | Aydogan F, Celik V, Uras C, Salihoglu Z, Topuz U. A comparison of the adverse reactions associated with isosulfan blue versus methylene blue dye in sentinel lymph node biopsy for breast cancer. Am J Surg 2008;195:277-8. |
20. | Varghese P, Abdel-Rahman AT, Akberali S, Mostafa A, Gattuso JM, Carpenter R. Methylene blue dye - a safe and effective alternative for sentinel lymph node localization. Breast J 2008;14:61-7. |
21. | Zakaria S, Hoskin TL, Degnim AC. Safety and technical success of methylene blue dye for lymphatic mapping in breast cancer. Am J Surg 2008;196:228-33. |
22. | Stradling B, Aranha G, Gabram S. Adverse skin lesions after methylene blue injections for sentinel lymph node localization. Am J Surg 2002;184:350-2. |
23. | Nour A. Efficacy of methylene blue dye in localization of sentinel lymph node in breast cancer patients. Breast J 2004;10:388-91. |
24. | Salhab M, Al Sarakbi W, Mokbel K. Skin and fat necrosis of the breast following methylene blue dye injection for sentinel node biopsy in a patient with breast cancer. Int Semin Surg Oncol 2005;2:26. |
25. | Saha S, Sirop SJ, Fritz P. Comparative analysis of sentinel lymph node mapping in breast cancer by 1% lymphazurin vs. 1% methylene blue: a prospective study. J Clin Oncol; ASCO Annual Meeting Proceedings (Post-Meeting Edition) 2008;26:570. |
26. | Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg 1994;220:391-8. |
27. | Laurie SA, Khan DA, Gruchalla RS, Peters G. Anaphylaxis to isosulphan blue. Ann Allergy Asthma Immunol 2002; 88:64-6. |
28. | Bass SS, Cox CE, Ku NN, Berman C, Reintgen DS. The role of sentinel lymph node biopsy in breast cancer. J Am Coll Surg 1999;189:183-94. |
29. | Giuliano AE, Jones RC, Brennan M, Statman R. Sentinel lymphadenectomy in breast cancer. J Clin Oncol 1997; 15:2345-50. |
30. | Veronesi U, Paganelli G, Galimberti V, Viale G, Zurrida S, Bedoni M, et al. Sentinel- node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes. Lancet 1997;349:1864-7. |
31. | O'Hea BJ, Hill AD, El-Shirbiny AM, Yeh SD, Rosen PP, Coit DG, et al. Sentinel lymph node biopsy in breast cancer: Initial experience at Memorial Sloan-Kettering Cancer Centre. J Am Coll Surg 1998;186:423-7. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]
|