Journal of Breast Cancer

Transcription

1 ORIGINAL ARTICLE Journal of Breast Cancer J Breast Cancer 2009 December; 12(4): DOI: /jbc Arm Sentinel Lymph Node Detection for Preserving the Arm Lymphatic System Se Kyung Lee, Jae Hyuck Choi, Hye In Lim, Wan Wook Kim, Sangmin Kim, Jun-Ho Choe, Jeong Eon Lee, Jung-Han Kim, Jee Soo Kim, Seok-Jin Nam, Jung-Hyun Yang Division of Breast and Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Purpose: The objective of arm sentinel lymph node (SLN) detection were to identify the presence of different drainage tracts of the breast and arm lymphatics and eventually to prevent lymphedema after an axillary procedure. Methods: Twenty one patients underwent surgery for breast cancer, with arm SLN detection, from March to July 2008 at Samsung Medical Center. We used the 99 Tc-tin colloid isotope in two patients, blue dye in 18 and green dye in one for the arm SLN detection. Results: Stained and/or hot nodes from the arm lymphatics were identified in 15 of the 21 patients (71.4 %). Among the 15 patients who had the arm SLN identified, one patient had a metastasis at the arm SLN, and another patient had common breast and arm lymphatic drainage. Conclusion: Identification of the arm lymphatic drainage was possible. Since there were cases of common pathway of the arm and breast lymphatics and metastasis of the arm SLN, we cannot conclude that the arm SLN detection was safe and effective. A subsequent study for identifying the presence of two different drainage systems of the breast and arm lymphatics and confirmation of no metastasis at the arm SLN is needed. Key Words: Arm, Breast neoplasms, Lymphedema, Sentinel lymph node biopsy INTRODUCTION Since the sentinel lymph node biopsy (SLNB) technique was first introduced for evaluating the axilla of breast cancer patients, the morbidity associated with axillary dissection has been greatly reduced. However, the rate of lymphedema has ranged from 0% to 13% despite the use of the SLNB,(1-3) and the rates are higher in patients who undergo conventional axillary lymph node dissection (ALND). If there are two independent lymphatic systems, one from the breast (the breast lymphatics) and the other from the arm (the arm lymphatics), and if the metastasis involving the axilla occurs only in the lymph nodes from the breast lymphatics, then mapping and preserving the Correspondence: Jung-Hyun Yang Division of Breast and Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul , Korea Tel: , Fax: drjh.yang@samsung.com Received: February 10, 2009 Accepted: October 10, 2009 arm lymphatics might decrease the likelihood of disrupting the lymphatic drainage of the arm and this could result in decreasing the risk of lymphedema both for ALND and SLNB. Thus, we performed this pilot study to determine if there are two independent lymphatic drainage systems, one from the breast and one from the arm, with no metastasis at the arm sentinel lymph node (SLN; the first drained lymph node by definition). The final goal is to prevent lymphedema by performing arm SLN detection, by preserving the arm lymphatic drainage during ALND or SLNB. METHODS Patients Twenty one patients underwent surgery for breast cancer with arm SLN detection from March to July 2008 at Samsung Medical Center. Among them, 10 patients had SLNB alone and 11 patients required ALND for various reasons (Table 1). 272

2 Arm Sentinel Lymph Node Detection for Preserving the Arm Lymphatic System 273 Table 1. Patients characteristics No. Operation Age BMI Histology Stage Comment Axillary dissection 1 Lt. MRM IDC T1N0 I LN enlargement on preop. w/u 2 Lt. MRM IDC T2N1 IIb LN enlargement on preop. w/u 3 Rt. MRM Mucinous T2N0 IIa LN enlargement on preop. w/u 4 Lt. PM+ALND IDC T1N1 IIa LN enlargement on preop. w/u 5 Lt. MRM IDC T2N0 IIa LN enlargement on preop. w/u 6 Lt. PM+ALND IDC T2N1 IIb SLN: metastasis 7 Lt. PM+ALND IDC ypt1n0 I Neoadjuvant 8 Lt. PM+ALND IDC T2N0 IIa LN enlargement on preop. w/u 9 Rt. MRM IDC T2N1 IIb LN enlargement on preop. w/u 10 Lt. MRM Mucinous T1N0 I Multicentricity, old age 11 Lt. MRM IDC T2N3 IIIc LN enlargement on preop. w/u Breast sentinel lymph 12 Rt. PM+SLNB IDC T1N0 I node biopsy 13 Lt. PM+SLNB IDC T1N0 I 14 Rt. PM+SLNB IDC T1N0 I 15 Rt. PM+SLNB IDC T1N0 I 16 Rt. PM+SLNB DCIS TisN Rt. PM+SLNB IDC T1N0 I 18 Lt. PM+SLNB IDC T1N0 I 19 Lt. PM+SLNB IDC T1N0 I 20 Rt. TM+SLNB DCIS TisN Rt. PM+SLNB IDC T1N0 I MRM=modified radical mastectomy; TM=total mastectomy; PM=partial mastectomy; ALND=axillary lymph node dissection; SLNB=sentinel lymph node biopsy; IDC=invasive ductal carcinoma; DCIS=ductal carcinoma in situ; BMI=body mass index; w/u=work-up. Arm sentinel node detection For mapping the arm lymphatics, we used the 99 Tc-tin colloid isotope in two patients, blue dye (0.8% indigocarmine, 2-3 ml) in 18 patients and green dye (1% indocyanine green [ICG], 2.5 ml) in one patient. With using the 99 Tc-tin colloid isotope, we preoperatively injected 4 mci of the isotope at the 2nd and 3rd inter-digital spaces and we assessed the lymphoscintigraphy after one to two hours. A gamma probe also was used to intraoperatively locate the signals. The dyes were intraoperatively injected at the inner side of the upper arm along the medial intermuscular groove 5 to 10 min before the incision. After an injection of blue or green dye in the upper arm or after an injection of the isotope in the hand, the surgeon performed the SLNB or ALND to identify the arm and/or breast SLN. The lymph node which took the armside injected materials (dye or isotope) defined as an arm sentinel lymph node. For the cases that we could find the SLN in the breast lymphatics and/or the arm lymphatics, we removed them separately, and we examined them for the presence of metastases. We thought that the union of the substances which injected in the arm and breast side resulted from common pathway of breast and arm lymphatics. Breast sentinel node detection In the case of doing breast sentinel lymph node biopsy, we routinely preoperatively inject 0.5 mci of 99 Tc-tin colloid isotope in the subareolar lymphatic plexus. The lymphoscintigraphy is obtained one to three hours after the injection. Only the isotope was used for the first eight cases for detecting a breast SLN. To increase the specificity for breast SLN detection, we adopted the triple method of checking for which the isotope and two different dyes (blue and green) are used (Tables 2, 3).(4) RESULTS Clinical characteristics of the patients Among the 21 arm SLN detention patients, 10 patients underwent breast SLNB, another 10 patients underwent ALND and one patient underwent both SLNB and ALND (due to metastasis of breast SLN). The mean age of the patients was 49.5±11.3. The mean body mass index (BMI)

3 274 Se Kyung Lee, et al. of these patients was 22.6±3.1. There were 19 cases of invasive carcinomas and two cases of ductal carcinoma in situ. The invasive tumors were subclassified as ductal (17 patients) and mucinous (2 patients) carcinoma (Table 1). Arm sentinel lymph node detection Stained and/or hot nodes from the arm lymphatics were identified in 15 out of 21 patients (71.4%). The mean Table 2. Detection methods Breast side Arm side No. Patients planned for No Isotope 2 cases axillary dissection (n=10) No Blue dye 8 cases Patients planned for Isotope Blue dye 8 cases breast SLNB (n=11) Isotope & Blue dye 2 cases green dye Isotope & Green dye 1 case blue dye SLNB=sentinel lymph node biopsy. number of dissected arm SLNs was 1.3 (range, 1-2). There was no statistically significant correlation between the detection of arm SLN and the detection method, age, BMI, histology, or cancer stage probably due to small sample size. Location and pathway of arm sentinel lymph node detection The arm SLN is located at various regions from similar location of breast SLN to near the axillary vein. All arm SLNs were located between the second intercostobracheal nerve and axillary vein, usually within 3 cm from the axillary vein and lateral side to central group lymph nodes. Among the 15 patients in whom an arm SLN was identified, one patient had metastasis at the arm SLN, and another patient had a common breast and arm lymphatic drainage system (Table 3). There were no serious complications except for prolonged arm tattooing. Table 3. Arm sentinel node detection No. Op. procedure Detection method Arm SLN No. of SLN Detection method Breast SLN No. of SLN Metastasis Metastasis Comment Axillary dissection 1 Lt. MRM Isotope 2 0 No - - (n=11) 2 Lt. MRM Isotope 1 1 No - - Arm SLN: metastasis* 3 Rt. MRM Indigocarmine 0 - No - - Failed 4 Lt. PM+ALND Indigocarmine 1 0 No Lt. MRM Indigocarmine 2 0 No Lt. PM+ALND Indigocarmine 1 0 Isotope 1 (3) Yes Breast SLN: metastasis 7 Lt. PM+ALND Indigocarmine 0 - No - - Failed 8 Lt. PM+ALND Indigocarmine 0 - No - - Failed 9 Rt. MRM Indigocarmine 1 0 No Lt. MRM Indigocarmine 0 - No - - Failed 11 Lt. MRM Indigocarmine 1 0 No Breast sentinel lymph 12 Rt. PM+SLNB Indigocarmine 1 0 Isotope 1 (4) No node biopsy (n=10) 13 Lt. PM+SLNB Indigocarmine 1 0 Isotope 2 (2) No Common pathway 14 Rt. PM+SLNB Indigocarmine 1 0 Isotope 1 (2) No 15 Rt. PM+SLNB Indigocarmine 2 0 Isotope 2 (4) No 16 Rt. PM+SLNB Indigocarmine 0 - Isotope 1 (3) No Failed 17 Rt. PM+SLNB Indigocarmine 1 0 Isotope 1 (4) No 18 Lt. PM+SLNB ICG 1 0 Isotope, 3 (4) No Triple method Indigocarmine 19 Lt. PM+SLNB Indigocarmine 1 0 Isotope, ICG 2 (0) No Triple method 20 Rt. TM+SLNB Indigocarmine 2 0 Isotope 3 (2) No 21 Rt. PM+SLNB Indigocarmine 0 - Isotope, ICG 1 (4) No Failed, Triple method MRM=modified radical mastectomy; TM=total mastectomy; PM=partial mastectomy; ALND=axillary lymph node dissection; SLNB=sentinel lymph node biopsy; SLN=sentinel lymph node; ICG=indocyanine green. *There was metastasis of the arm sentinel lymph node which was detected by radioisotope; Common pathway of arm lymphatics and breast lymphatics.

4 Arm Sentinel Lymph Node Detection for Preserving the Arm Lymphatic System 275 DISCUSSION The status of the axillary lymph nodes is an important prognostic factor for the treatment of breast cancer. ALND has been widely adopted to identify the exact lymph node status; in addition, SLNB has become a standard treatment method for early stage breast cancers. Lymphedema remains one of the most serious complications of ALND and this occurs in 13% to 52% of the patients with the variations occurring due to the definition and methods of determining lymphedema, the length of follow-up, the number of positive lymph nodes, the use of postoperative irradiation, the body habitus and the BMI.(4-7) Although SLNB has been shown to have a lower morbidity rate than that of ALND, the rate of postoperative lymphedema with SLNB alone has ranged from 0% to 13% with an average of approximately 7%.(1-3) Although many factors influence the development of lymphedema, the best way and the first step to prevent lymphedema is to preserve the arm lymphatic drainage. Some investigators have suggested that arm lymphatic mapping is helpful to identify and preserve the arm lymphatics. Thompson et al. refers to this new procedure as axillary reverse mapping (ARM) because identification of the arm lymphatics is for preservation, not removal.(8) This is the reverse concept of SLNB where we seek to identify the SLN for removal. Other investigators refer to the arm lymphatics as lymphatic arm drainage (LAD) and they recommend considering the physiology, removing only those nodes draining the breast and leaving in place the lymph nodes involved in the LAD.(9) Prior investigators have shown that this technique is feasible, and they have reported the detection rate for the arm lymphatics or lymph nodes to be 61-71%. In our study, the detection rate for the arm SLN was 71.4%. To find the role of arm SLN detection in the cases of doing breast SLNB, we also tried the arm SLN detection in the patients which underwent the breast SLNB simultaneously. In our institute, we are performing the biopsy of a suspicious palpable LN as an integral part of SLNB to lower the false negative rate of SLNB.(10,11) Although Given that the excision of palpable LNs may reduce the false negative rate of SLNB, lymphedema rate would be increased. However, if we could define some palpable nodes as an arm SLNs, it would be helpful to reduce the occurrence of lymphedema by preserving a palpable arm SLN which could be misinterpreted as a breast SLN even though it is palpable. Interestingly, most of the arm SLNs were palpable in this study. The anatomy of the relationship between the arm and breast lymphatics has not yet been defined. It is assumed that there is a different lymphatic drainage system for the arm and breast lymphatic drainage to the axilla. Evaluation of the lymphatic systems is difficult because of the scarcity of detection methods, the small lymphatic channels and the difficult accessibility. Hama et al.(11) showed in a mouse model two different drainage systems by performing two-color spectral fluorescence lymphangiography. Previous studies about the arm SLN also reported that there were variations in the location of lymphatics from arm.(8,9) They both showed the absence of concordance of the arm and breast lymphatic drainage. However, other researchers that performed cadaver studies have reported that the main sentry node in the axilla had the same drainage from the upper limb and the anterior upper torso.(12,13) In addition, in a study of the arm sentinel by Boneti et al.,(14) common pathway of the blue arm lymphatics with the breast lymphatics together with a hot SLN was observed in five (3.9%) patients, although these lymph nodes in the five patients did not contain metastases. In our study, there were two cases of common pathway of the arm and breast SLN, and the arm SLN in one case showed a breast cancer metastasis. Therefore, detection of the arm SLN should be tested in future studies with a larger number of patients and long-term follow up because of the risk of missing a positive axillary node when preserving the arm SLN. A previous report on detecting the arm SLN showed that lymphazurin (isosulfan blue dye)(8) and patent blue dye (9) could be used for detecting the arm SLN. For the cases that underwent simultaneous breast SLNB and arm SLNB in a previous report, isotope was additionally used for the detection of the breast SLN. We attempted several methods for detecting the arm SLN with using isotope

5 276 Se Kyung Lee, et al. and other dyes (indigocarmine, ICG) because of the risk of severe skin reactions, including necrosis and dermolysis, for the cases with injecting methylene blue dye into the subcutaneous tissue or dermis and due to the difficulty with obtaining lymphazurin (Table 2). This is the first report of a triple detection method being used for increasing the detection rate of the sentinel lymph node. This method was used in three cases. Blue dye for the arm lymphatic drainage and green dye and isotope for the breast SLNB were used in two cases. This method can be applied with other combinations of using an isotope for the arm SLN and blue and green dyes for the breast SLN. Although differentiation of these colors was very difficult, it was possible to differentiate the blue and green dye-stained lymph nodes. Some reports have suggested that using fluorescence imaging for sentinel node biopsy may be effective.(15,16) Kitai et al. reported a high detection rate (94%) with using indocyanine green fluorescence imaging. This approach may help in the differentiation between a green dye stained SLN (the breast SLN) and a blue dye stained SLN (the arm SLN).(16) The site of dye injection in the arm was the upper inner area. A previous study also chose this area for the injection site of blue dye. This site was chosen simply because it had the most rapid drainage (average flow 2.0 cm/ min),(17) and the site also easily hid the tattoo. There was no severe systemic allergic reaction to the employed dyes. After 5 months of follow-up, the blue stain was resolving. In one report that used patent blue dye, the blue stain either disappeared or it was resolving after 2 yr.(9) In a report with using lymphazurin, the skin coloration lasted from 1 week to 6 months.(8) A small dose, another site of the arm or another method such as an isotope should be considered as alternative methods that can be used to avoid prolonged tattooing. We used an isotope method for detecting the arm SLN in 2 cases. Our study is limited by the small number of patients and the relative inexperience with the procedure we used. Identification and preservation of the arm lymphatic drainage is a novel procedure. Identification and preservation of the arm lymphatic drainage is more difficult than simple biopsy and detection of a SLN, and it likely requires a longer learning curve than that for breast SLNB. The previously reported results for the identification rate and the dissection of lymphatic drainage (71% vs 47%) suggest this discrepancy.(9) In our preliminary study, metastasis to the arm SLN and a case with common lymphatic drainage posed difficulty for the concept of two separate lymphatic drainage systems. Therefore, the usefulness and safety of arm sentinel lymph node biopsy remains unclear. Nos et al. recently reported on three patients who had breast metastasis in their arms sentinel nodes.(18) We also found the presence of metastasis in an arm SLN. In addition, we introduced the first triple detection method. CONCLUSION Identifying the arm sentinel lymphatic drainage is possible. Because there were cases of common pathway of the arm and breast lymphatics and metastasis of the arm SLN, we cannot conclude that the arm SLN detection was safe and effective. A subsequent study is needed for the identification of the presence of two different drainage systems of the breast and arm lymphatics and for confirming the absence of metastasis at the arm SLN. REFERENCES 1. Sakorafas GH, Peros G, Cataliotti L, Vlastos G. Lymphedema following axillary lymph node dissection for breast cancer. Surg Oncol 2006; 15: 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: Schrenk P, Rieger R, Shamiyeh A, Wayand W. Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma. Cancer 2000;88: Soran A, D Angelo G, Begovic M, Ardic F, Harlak A, Samuel Wieand H, et al. Breast cancer-related lymphedema--what are the significant predictors and how they affect the severity of lymphedema? Breast J 2006;12: Ververs JM, Roumen RM, Vingerhoets AJ, Vreugdenhil G, Coebergh JW, Crommelin MA, et al. Risk, severity and predictors of physical and psychological morbidity after axillary lymph node dissection for breast cancer. Eur J Cancer 2001;37: Petrek JA, Senie RT, Peters M, Rosen PP. Lymphedema in a cohort

6 Arm Sentinel Lymph Node Detection for Preserving the Arm Lymphatic System 277 of breast carcinoma survivors 20 years after diagnosis. Cancer 2001; 92: 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 AL- MANAC Trial. J Natl Cancer Inst 2006;98: Thompson M, Korourian S, Henry-Tillman R, Adkins L, Mumford S, Westbrook KC, et al. Axillary reverse mapping (ARM): a new concept to identify and enhance lymphatic preservation. Ann Surg Oncol 2007;14: Nos C, Lesieur B, Clough KB, Lecuru F. Blue dye injection in the arm in order to conserve the lymphatic drainage of the arm in breast cancer patients requiring an axillary dissection. Ann Surg Oncol 2007; 14: Carmon M, Olsha O, Rivkin L, Spira RM, Golomb E. Intraoperative palpation for clinically suspicious axillary sentinel lymph nodes reduces the false-negative rate of sentinel lymph node biopsy in breast cancer. Breast J 2006;12: Hama Y, Koyama Y, Urano Y, Choyke PL, Kobayashi H. Simultaneous two-color spectral fluorescence lymphangiography with near infrared quantum dots to map two lymphatic flows from the breast and the upper extremity. Breast Cancer Res Treat 2007;103: Suami H, O Neill JK, Pan WR, Taylor GI. Superficial lymphatic system of the upper torso: preliminary radiographic results in human cadavers. Plast Reconstr Surg 2008;121: Suami H, Taylor GI, Pan WR. The lymphatic territories of the upper limb: anatomical study and clinical implications. Plast Reconstr Surg 2007;119: Boneti C, Korourian S, Bland K, Cox K, Adkins LL, Henry-Tillman RS, et al. Axillary reverse mapping: mapping and preserving arm lymphatics may be important in preventing lymphedema during sentinel lymph node biopsy. J Am Coll Surg 2008;206: Sevick-Muraca EM, Sharma R, Rasmussen JC, Marshall MV, Wendt JA, Pham HQ, et al. Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study. Radiology 2008;246: Kitai T, Inomoto T, Miwa M, Shikayama T. Fluorescence navigation with indocyanine green for detecting sentinel lymph nodes in breast cancer. Breast Cancer 2005;12: Uren RF, Hawman-Giles R, Thompson JF. Variation in cutaneous lymphatic flow rates. Ann Surg Oncol 1997;4: Nos C, Kaufmann G, Clough KB, Collignon MA, Zerbib E, Cusumano P, et al. Combined axillary reverse mapping (ARM) technique for breast cancer patients requiring axillary dissection. Ann Surg Oncol 2008;15: