Originally published as JCO Early Release 10.1200/JCO.2006.08.4228 on May 7 2007

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rodier, J.-F. Articles by Avigdor, S. Search for Related Content PubMed PubMed Citation Articles by Rodier, J.-F. Articles by Avigdor, S. Related Articles Related Articles

Prospective Multicentric Randomized Study Comparing Periareolar and Peritumoral Injection of Radiotracer and Blue Dye for the Detection of Sentinel Lymph Node in Breast Sparing Procedures: FRANSENODE Trial

Jean-François Rodier, Michel Velten, Marc Wilt, Pierre Martel, Gwanaël Ferron, Véronique Vaini-Elies, Hervé Mignotte, Alain Brémond, Jean-Marc Classe, François Dravet, Thierry Routiot, Christine Tunon de Lara, Antoine Avril, Gérard Lorimier, Eric Fondrinier, Gilles Houvenaeghel, Sandrine Avigdor

From the French Comprehensive Cancer Centers of Strasbourg, Toulouse, Lyon, Nantes, Bordeaux, Angers, and Marseille; Axium Clinic of Aix en Provence; Community Hospital of Le Mans; and the Community Hospital of Orléans, Orléans, France

Address reprint requests to Jean-François Rodier, MD, FACS, Department of Surgical Oncology, Paul Strauss Cancer Center, 3 rue de la Porte de l'Hôpital, BP 42 F-67065 Strasbourg Cedex, France; e-mail: jrodier{at}strasbourg.fnclcc.fr

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
Purpose: To determine the optimal injection path for blue dye and radiocolloid for sentinel lymph node (SLN) biopsy in early breast cancer.

Patients and Methods: A prospective randomized multicentric study was initiated to compare the peritumoral (PT) injection site to the periareolar (PA) site in 449 patients.

Results: The detection rate of axillary SLN by lymphoscintigraphy was significantly higher (P = .03) in the PA group (85.2%) than in the PT group (73.2%). Intraoperative detection rate by blue dye and/or gamma probe was similar (99.11%) in both groups. The rate of SLN detection was somewhat higher in the PA group than in the PT group: 95.6% versus 93.8% with blue dye (P = .24) and 98.2% versus 96.0% by probe (P = .16), respectively. The number of SLNs detected by lymphoscintigraphy and by probe was significantly higher in the PA group than in the PT group, 1.5 versus 1.2 (P = .001) and 1.9 versus 1.7 (P = .02). The blue and hot concordance was 95.6% in the PA group and 91.5% in the PT group (P = .08). The mean ex vivo count of the SLN was significantly higher in the PA group than in the PT group (P < .0001).

Conclusion: This study strongly validates the PA injection technique given the high detection rate (99.1%) of SLN and the high concordance (95.6%) between blue dye and the radiotracer, as well as higher significant ex and in vivo counts, improving SLN probe detection.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
One of the most avidly debated issues in lymphatic mapping is where the best place to inject the tracers in patients with breast cancer is. Whereas a consensus exists on how lymphatic mapping should be technically performed in patients with malignant cutaneous melanoma, this is not currently the case in breast cancer.¹ If numerous data are in favor of the combined technique associating injection of lymphotropic dye and radiocolloid, there is still a controversy over their superficial or deep administration in the breast.² In addition, as focused on by Nieweg, ^1,3 several investigators have compared the two techniques in a sequential fashion, first the deep and then superficial. At this time, only one nonrandomized dual tracer, same-site injection study has been published.^4,5 In order to elucidate this key technical point, we initiated a prospective randomized multicentric study comparing periareolar (PA) with peritumoral (PT) injection of blue dye and radioactive colloid in patients with early breast cancer treated with breast-sparing procedures. To our knowledge, the present randomized study is the only one published comparing periareolar with peritumoral injection of a dual tracer in breast cancer patients.

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
From October 2001 to January 2003, 459 patients from 10 French institutions (seven comprehensive cancer centers, two community hospitals, and one private clinic) with biopsy-proven T0-T1 invasive breast cancer and clinically negative axilla were enrolled onto this prospective randomized study. Informed written consent was obtained from all patients. All 10 participating surgeons had achieved their learning curve and were certified, having operated in more than 25 cases of breast carcinoma per year. Patient confidentiality was maintained and the trial was approved by the academic institutional review board. The study design is indicated in Figure 1. Exclusion criteria were pregnancy, ductal carcinoma in situ, multicentric tumors, retroareolar and inflammatory tumors, neoadjuvant chemotherapy, and metastatic breast cancer.

View larger version (28K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 1. FRANSENODE study design.

Ten patients were excluded because of peroperative technical problems with the gamma probe; as a result, the analysis was performed on the remaining 449 patients.

Radiotracer Injection and Preoperative Lymphoscintigraphy
We used unfiltered technetium 99 metastable (^m99 Tc)–labeled sulfur colloid (Nanocis, Cis Bio International, Saclay, France), 70% of the particles had a size of between 31 and 180 nm. Patients with unpalpable lesions underwent injection by ultrasound guidance or by needle localization. Eleven to 30 MBq ^m99Tc–labeled sulfur colloid in a volume of 0.2 mL was injected 12 to 24 hours before surgery, either periareolarly or peritumoraly, according to the result of the random assignment. In both cases, a gentle massage was performed at the site of injection for 2 to 3 minutes to improve the diffusion of the radiocolloid.

All patients underwent a preoperative lymphoscintigraphy with a large field of view gamma camera with a high-resolution collimator. The acquisition window was set at 140 keV. Matrix size was 256 x 256. Static images (300 to 600 seconds) were taken from 30 minutes to 2 hours after injection and the next day if necessary. Anterior and oblique anterior images were taken to document the site of the identified draining lymph nodes. All such lymph nodes were marked on the overlying skin with an indelible marker before the patient entered the operating room.

Blue Dye Injection and Surgery
After anesthesia and 10 to 15 minutes before incision, patients were injected, according to the preoperative random assignment results (periareolar or peritumoral area) with 2 mL of Patent Blue Dye (Guerbet, Aulnay-Sous-Bois, France). Full gentle breast massages were performed for 2 to 3 minutes at the injection site. In all patients, the SLN procedure was performed before removal of the breast tumor. Axillary skin was incised and a careful dissection was performed to search for the blue lymphatic channels leading to a blue-stained lymph node.

An intraoperative gamma-detecting probe (Navigator; TYCO, Princeton, NJ) was used to help and guide the dissection and to confirm the site of greater radioactivity previously indicated on the skin before its incision.

SLNs were identified if they were blue, had in vivo radioactive counts at least two times greater than background counts of the axilla, or if they had both characteristics. Radioactive nodes were removed until the background radioactivity of the axilla was lower than 10% of the ex vivo count of the hottest node removed. Extra-axillary SLN, especially internal mammary nodes, were not removed even when detected by preoperative lymphoscintigraphy or by the intraoperative gamma probe.

A level I and II axillary lymph node dissection was performed only if no SLN was identified (by blue dye and/or by probe) or if at least one SLN was positive for tumor metastasis (micro- or macrometastases).

Pathological Evaluation
Lymph nodes were identified as sentinel or nonsentinel. Intraoperative touch imprint cytology or frozen sections were performed. The SLNs were formalin-fixed, paraffin-embedded, and evaluated with hematoxylin and eosin and cytokeratin (KL1, 1:50; Immunotech, Marseille, France) with a negative control. All non-SLNs were evaluated using standard hematoxylin and eosin stained sections. Primary tumors or re-excision specimens were evaluated by routine histology.

Sample Size
Results of a former French study showed that approximately 87% (from 85% to 88%) of SLN were identified after peritumoral injection. To be able to detect an improvement leading to an identification rate of at least 95% in the PA group, at the 5% significance level, 222 patients per group were required to reach a power of 80% (two-sided test). To take into account possible exclusions, we decided to include 460 patients.

Random Assignment
On the day before surgery, random assignment using permuted blocks of eight was performed via a centralized phone call to the coordinating center. Patients were stratified by participating center.

Statistical Analysis
Statistical analyses comparing PA and PT groups, as defined by the randomization, used the Pearson ² test and the Wilcoxon rank sum test.

A logistic regression analysis was planned to take into account the influence of center, age, body mass index, tumor size and location and, of course, site of injection on the detection rate of SLN.

Two-sided P values .05 were considered as statistically significant. All the analyses were performed with SAS statistical software version 9.1 (SAS Institute Inc, Cary, NC).

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
The baseline characteristics of the 449 eligible patients are indicated in Table 1.

View larger version (13K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 2. Sentinel lymph node (SLN) detection rates according to site of injection (2 test, P = .28). PA, periareolar; PT, peritumoral.

The SLN was blue in 94.7% (425 of 449), hot in 97.1% (436 of 449), blue-hot in 92.6% of cases (416 of 449; Table 4). The blue and hot observed concordance was 91.5% in the PT group (205 of 224) and 95.6% in the PA group (215 of 225; P = .08).

The overall blue and hot concordance rate for the positive sentinel nodes was 94.5% (155 of 164), by group, 96.2% in the PA group (76 of 79) and 92.9% in the PT group (79 of 85), respectively.

No adverse peroperative effect (especially anaphylactic reaction after blue dye injection) occurred. No postoperative morbidity, or axillary recurrence, was observed (median follow-up, 48.4 months; range, 41 to 57) at the date of point (July 1, 2006).

Given the high detection rate, and the very few discrepancies among participating centers on this point, the results of the logistic regression analysis were very similar to those of the univariate analysis and no interaction was detected (Table A1, online only).

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
The first description of SLN biopsy for breast cancer using the combined technique included the peritumoral injection of blue dye or radioisotope instead of the intradermal injection that is used in malignant cutaneous melanoma.^6,7 Subsequently, Nieweg classified injection sites of lymphatic mapping agents in breast cancer into two categories: deep (peritumoral, subtumoral, intratumoral) and superficial (intradermal, subdermal, periareolar, subareolar).² The lack of consensus regarding the optimal site for injection is manifest given the great number of studies (Tables A2 and A3, online only) comparing the different approaches.

Peritumoral injection was the initial and most widely studied method. Deep tracer administration was promoted by northern European teams, with a SLN identification rate of 97.2% and a false-negative rate of 3.1%.^8-10 This sort of administration relies on the parenchymal lymphatic system draining mainly to axillary nodes but also to extra-axillary nodes in up to 27% of patients leading to changes in the therapeutic management in 17% of the cases after removal and histologic assessment.⁸ However, this approach has been criticized especially in nonpalpable and multicentric tumors and also in upper outer quadrant lesions because of the shine through phenomenon.²

The four superficial injection techniques are based on the assumption that the breast parenchyma and the overlying skin drain to a common axillary node because of their common embryological origin.^10-14

The difference between intradermal and subdermal injection is that the former raises a dermal skin wheal, whereas the second does not, despite the fact that it is performed beneath the skin into the subcutaneous tissue.^15,16

Advocated by several investigators, intradermal as compared with intraparenchymal injection has numerous advantages including ease of injection, shorter time between injection and sentinel node identification, and increased radiotracer nodal uptake (hotter sentinel node), resulting in improved nodal identification rates.^15,17,18 Nevertheless, intradermal injection allows almost exclusive identification of axillary nodes, and only on rare occasions, of nonaxillary nodes.

In a study comparing two different radiocolloid injection techniques—intradermal and intradermal plus deep injection—of a radiocolloid, Koizumi improved both the axillary and the internal mammary SLN detection rate (1.5% v 15.1%) with the latter procedure.¹⁹ Interestingly, in a prospective randomized trial comparing intradermal, intraparenchymal, and subareolar radiocolloid injection, Povoski demonstrated a greater frequency of pre- and peroperative SLN identification and a decreased time to first identify the SLN on a preoperative lymphoscintigraphy and to harvest the first SLN during the operation.²⁰ The blue dye was unvaryingly injected intraparenchymally in all the 399 patients. Therefore this study could not be strictly considered as a dual tracer-same site injection study, as was the FRANSENODE trial, except in the case of the PT group.

In a retrospective, nonrandomized 116 case study comparing intradermal with subdermal radioisotope injection, Motomura reported both a significantly higher detection rate and a lymphoscintigraphy success rate in the intradermal injection group.¹⁶ The false-negative rates (9.5% and 5.3%, respectively) were not significantly different in the two groups.

Interest in central injections (subareolar, periareolar) have been recently outlined.^14,21-26 For subareolar injection, tracers are directly administrated underneath the nipple areolar complex. For the periareolar technique, the injection is performed in the dermis or subdermis around the edge of the areola.²⁵ Originally described by Sappey and confirmed by studies using dual tracer injection, there is a common anatomic connection between the subareolar lymphatic plexus (Sappey's plexus), the dermis of the skin, and the breast parenchyma draining to the same axillary nodes.²⁷

The subareolar injection of blue dye was first reported by Kern with a 98% identification rate and 0% false negative rate in 40 patients.²⁸ The success rate of identifying a sentinel node by subareolar lymphoscintigraphy was 90% and 50% by intraparenchymal lymphoscintigraphy (P = .009).²⁹ The visualization time was 59% shorter in the subareolar injection group (P < .001). In the first dual tracer study of 185 patients (blue dye and radiocolloid injected in the subareolar site), the same author observed a 98.4% identification rate, a false-negative rate of 0%, and an accuracy of 100%.^4,5 In addition, 98.9% of blue nodes were hot and 95.1% of hot nodes were blue.

In a small series of 38 cases, Smith reported an identification rate of 94.7% and of 100% after peritumoral and subareolar injection, and a false-negative rate of 20% and 0%, respectively.²¹ Klimberg compared subareolar with peritumoral injection of radiocolloid, in addition to peritumoral injection of blue dye.³⁰ The identification rates were 100% and 94.7%, and the false negative rates were 0% and 20%, respectively. The nonrandomized study of Bauer compared peritumoral and subareolar injection with both blue dye and radioisotope.³¹ Identification rates were 95% and 97% and the isotope blue dye concordance rates were 87% and 90%, respectively. All these data suggest that delivery of mapping agents in the subareolar and peritumoral location identifies similar lymph nodes. The advantages of the subareolar injection include less pain, rapid radiotracer uptake, the avoidance of radioisotope overlapping with tumors of the upper quadrants, and the ability to inject impalpable lesions without the need for additional preoperative imaging. Another advantage is that this technique can be performed in patients with previous biopsy cavity or with multifocal tumors. The drawbacks include lack of reliable internal mammary lymph node mapping and significant temporary but prolonged skin tattooing of the nipple areolar complex with blue dye.

Validation of central (subareolar and periareolar) injection techniques were demonstrated in 2004 by Chagpar and McMasters in a prospective multicentric study of 3,961 patients with clinical stage I and II breast cancers using blue dye alone or radiocolloid plus blue dye and involving more than 300 surgeons.²⁵ Subareolar and periareolar radioactive colloid injection techniques were associated with sentinel node identification rates of 99.3% and 95.6% respectively, and with false-negative rates of 8.3% and 8.9%, respectively. As initially suggested by Borgstein in a study of functional lymphatic anatomy, periareolar injection appeared ideally suited to identification of the principal (axillary) metastasis route in early breast cancer.⁷ According to Borgstein's data, sentinel nodes were always found in the same relative anatomic location in the lower axilla.⁷ The only possible disadvantage of the periareolar injection lies in its inability to permit detection of accessory lymphatic pathways, especially internal mammary chains. More recently, in a nonrandomized study, Pelosi reported identification rates with the periareolar technique of 98.3% and 95.0%, respectively, for radiotracer and blue dye in a subgroup of 59 cases.³² The blue dye radiotracer concordance was 100%. Similarly, also on a nonrandomized basis, Shimazu compared periareolar (n = 52) with peritumoral (n = 41) injection of radiocolloid, combined with peritumoral injection of blue dye.³³ The success rate of lymphoscintigraphy was significantly higher in the periareolar group (90%) than in the peritumoral group (51%; P < .001). The detection rate of the sentinel node by radiotracer only was significantly higher in the periareolar group (98%) than in the peritumoral group (85%; P < .05). Moreover, the detection rate by the combination of radiotracer and blue dye was also significantly higher in the periareolar group (100%) than in the peritumoral group (90%; P < .05).³³ As observed in our study, the sentinel node appeared more radioactive after periareolar administration of radiotracer with a significantly higher mean ex vivo count (117 v 51 in the peritumoral group) allowing for easier detection, especially during the learning phase. No significant difference in the residual count of the axillary basin was observed.

Conclusion
Although the false-negative rate could not be definitively assessed in this randomized, prospective, multicentric study, we believe that its results strongly validate the PA technique given the high detection rate of SLN (99.11%) and the high concordance (95.56%) between blue dye and radiotracer. Technically simple, the PA injection can be confidently privileged, especially in nonpalpable (T0) and/or upper outer quadrant lesions mainly for the prevention of the shine through phenomenon. Higher significant ex vivo and in vivo counts in SLN detected after PA injection of a radioisotope may make it easier to learn the technique, especially by less experienced colleagues.

	AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
The authors indicated no potential conflicts of interest.

	AUTHOR CONTRIBUTIONS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
Conception and design: Jean-François Rodier, Michel Velten

Administrative support: Michel Velten

Provision of study materials or patients: Jean-François Rodier, Marc Wilt, Pierre Martel, Gwanaël Ferron, Véronique Vaini-Elies, Hervé Mignotte, Alain Brémond, Jean-Marc Classe, François Dravet, Thierry Routiot, Christine Tunon de Lara, Antoine Avril, Gérard Lorimier, Eric Fondrinier, Gilles Houvenaeghel, Sandrine Avigdor

Collection and assembly of data: Jean-François Rodier, Michel Velten, Pierre Martel, Gwanaël Ferron, Véronique Vaini-Elies, Hervé Mignotte, Alain Brémond, Jean-Marc Classe, François Dravet, Thierry Routiot, Christine Tunon de Lara, Antoine Avril, Gérard Lorimier, Eric Fondrinier, Gilles Houvenaeghel, Sandrine Avigdor

Data analysis and interpretation: Jean-François Rodier, Michel Velten

Manuscript writing: Jean-François Rodier, Michel Velten

Final approval of manuscript: Jean-François Rodier, Michel Velten, Marc Wilt, Pierre Martel, Gwanaël Ferron, Véronique Vaini-Elies, Hervé Mignotte, Alain Brémond, Jean-Marc Classe, François Dravet, Thierry Routiot, Christine Tunon de Lara, Antoine Avril, Gérard Lorimier, Eric Fondrinier, Gilles Houvenaeghel, Sandrine Avigdor

	Appendix

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 

	ACKNOWLEDGMENTS

 
We thank the following nuclear physicians and pathologists for their dedicated participation to the trial: Olivier Schneegans, Gérard Ott, Jean-Pierre Ghnassia, Strasbourg; Frédéric Courbon, Véronique Maisongrosse, Toulouse; Sophie Cosculluela, Henri-Pierre Sanchez, Aix-en-Provence; Isabelle Treilleux, Francesco Giammarile, Lyon; Marie-France, Longchamps, Louis-Rémy DeYbarlucea, Le Mans; Françoise Bonichon, Gaëtan Mac Grogan, Isabelle DeMascarel, Jean-Michel Coindre, Bordeaux; Jocelyne Jacquemier, Marseille; Isabelle Brenot-Rossi, Marseille; Patrick Michenet, Fabienne Therain, Orléans; Olivier Morel, Véronique Vérrièle, Angers. We also thank Gabrielle Blanché and Alexandre Bernard for their expert assistance for database maintenance, Josiane Marrel and Marie-José Trunzer for their assistance, and Liane Acito-Khan who advised the authors in the preparation of the manuscript.

	NOTES

 
published online ahead of print at www.jco.org on July 23, 2007.

Supported by grants from the Ligue Nationale Contre le Cancer and the Féderation Nationale des Centres de Lutte Contre le Cancer.

Presented at the 4th Annual International Sentinel Node Congress, December 3-6, 2004, Los Angeles, CA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
1. Nieweg OE, Estourgie SH, Van Rijk MJ, et al: Rationale for superficial injection techniques in lymphatic mapping in breast cancer patients. J Surg Oncol 87:153-156, 2004[CrossRef][Medline]

2. Celliers L, Mann GB: Alternative sites of injection for sentinel lymph node biopsy in breast cancer. Anz J Surg 73:600-604, 2003[CrossRef][Medline]

3. Nieweg OE, Tanis PJ: Intradermal radioisotope injection optimises sentinel lymph node identification in breast cancer. Eur J Surg Oncol 30:708-709, 2004[CrossRef][Medline]

4. Kern KA: Concordance and validation study of sentinel lymph node biopsy for breast cancer using subareolar injection of blue dye and Technetium99m sulfur colloid. J Am Coll Surg 195:467-475, 2002[CrossRef][Medline]

5. Kern KA: Breast lymphatic mapping using blue dye and radiocolloid. J Am Coll Surg 194:681-683, 2002[Medline]

6. Roumen RMH, Geuskens LM, Valkenburg JGH: In search of the true sentinel node by different injection techniques in breast cancer patients. Eur J Surg Oncol 25:347-351, 1999[CrossRef][Medline]

7. Borgstein P, Meijer S, Pijpers RJ, et al: Functional lymphatic anatomy for sentinel node in breast cancer: Echoes from the past and the periareolar blue method. Ann Surg 232:81-89, 2000[CrossRef][Medline]

8. Nieweg OE, Estourgie SH, Valdès Olmos RA, et al: Lymphatic mapping with tracer administration into the primary breast cancer. Eur J Surg Oncol 29:95-97, 2003[CrossRef][Medline]

9. Leppänen E, Leidenius M, Krogerus L, et al: The effect of patient and tumor characteristics on visualization of sentinel nodes after a single intratumoral injection of Tc 99m labeled human albumin colloid in breast cancer. Eur J Surg Oncol 28:821-826, 2002[CrossRef][Medline]

10. Doting MHE, Jansen L, Nieweg OE, et al: Lymphatic mapping with intralesional tracer administration in breast carcinoma patients. Cancer 88:2546-2552, 2000[CrossRef][Medline]

11. Shen P, Glass EC, Di Fronzo LA, et al: Dermal versus intraparenchymal lymphoscintigraphy of the breast. Ann Surg Oncol 8:241-248, 2001[Abstract/Free Full Text]

12. Linehan DC, Hill ADK, Akhurst T: Intradermal radiocolloid and intraparenchymal blue dye injection optimize sentinel node identification in breast cancer patients. Ann Surg Oncol 6:450-454, 1999[Abstract]

13. Boolbol SK, Fey JV, Borgen PI, et al: Intradermal isotope injection: A highly accurate method of lymphatic mapping in breast cancer. Ann Surg Oncol 8:20-24, 2001[Abstract/Free Full Text]

14. Layeeque R, Kepple J, Henry-Tillman SH, et al: Intra operative subareolar radioisotope injection for immediate sentinel lymph node biopsy. Ann Surg 239:841-848, 2004[CrossRef][Medline]

15. McMasters KM, Wong SL, Martin RCG, et al: Dermal injection of radioactive colloid is superior to peritumoral injection for breast cancer sentinel lymph node biopsy: Results of a multi-institutional study. Ann Surg 233:676-687, 2001[CrossRef][Medline]

16. Motomura K, Komoike Y, Hasegawa, et al: Intradermal radioisotope injection is superior to subdermal injection for the identification of the sentinel node in breast cancer. J Surg Oncol 82:91-97, 2003[CrossRef][Medline]

17. Lin KM, Patel TH, Ray A, et al: Intradermal radioisotope is superior to peritumoral blue dye or radioisotope in identifying breast cancer sentinel nodes. J Am Coll Surg 199:561-566, 2004[CrossRef][Medline]

18. Martin RCG, Derossis AM, Fey J, et al: Intradermal isotope injection is superior to intramammary in sentinel node biopsy for breast cancer. Surgery 130:432-438, 2001[CrossRef][Medline]

19. Koizumi M, Koyama M, Yamashita T, et al: Experience with intradermal and intradermal-plus-deep injection in the radioguided sentinel node biopsy of early breast cancer patients. Eur J Surg Oncol 32:738-742, 2006[CrossRef][Medline]

20. Povoski SP, Olsen JO, Young DC, et al: Prospective randomized clinical trial comparing intradermal, intraparenchymal, and subareolar injection routes for sentinel lymph node mapping and biopsy in breast cancer. Ann Surg Oncol 13:1412-1421, 2006[Abstract/Free Full Text]

21. Smith LF, Cross MJ, Klimberg VS: Subareolar injection is a better technique for sentinel lymph node biopsy. Am J Surg 180:434-438, 2000[CrossRef][Medline]

22. Donahue EJ: Sentinel node imaging and biopsy in breast cancer patients. Am J Surg 182:426-428, 2001[CrossRef][Medline]

23. Tuttle TM, Colbert M, Christensen R, et al: Subareolar injection of 99mTc facilitates sentinel lymph node identification. Ann Surg Oncol 9:77-81, 2002[Abstract/Free Full Text]

24. Yoshida K, Yamamoto N, Imanaka N, et al: Will subareolar injection be a standard technique for sentinel lymph node biopsy. Breast Cancer 9:319-322, 2002[Medline]

25. Chagpar A, Martin RC, Chao C, et al: Validation of subareolar and periareolar injection techniques for breast sentinel lymph node biopsy. Arch Surg 139:614-620, 2004[Abstract/Free Full Text]

26. Ellis RL, Seifert PJ, Neal CE: Periareolar injection for localization of sentinel nodes in breast cancer patients. Breast J 10:94-100, 2004[CrossRef][Medline]

27. Sappey MPC: Injection preparation et conservation des vaisseaux lymphatiques. Thèse Médecine N° 241, Paris, Rignoux imprimeur de la Faculté de Médecine, 1834

28. Kern KA: Sentinel lymph node mapping in breast cancer using subareolar injection of blue dye. J Am Coll Surg 189:539-545, 1999[CrossRef][Medline]

29. Kern KA, Rosenberg RJ: Preoperative lymphoscintigraphy during lymphatic mapping for breast cancer: Improved sentinel node imaging using subareolar injection of Technetium 99m sulfur colloid. J Am Coll Surg 191:479-489, 2000[CrossRef][Medline]

30. Klimberg VS, Rubio IT, Henry R, et al: Subareolar versus peritumoral injection for location of the sentinel lymph node. Ann Surg 229:860-865, 1999[CrossRef][Medline]

31. Bauer TW, Spitz FR, Callans LS, et al: Subareolar and peritumoral injection identify similar sentinel nodes for breast cancer. Ann Surg Oncol 9:169-176, 2002[Abstract/Free Full Text]

32. Pelosi E, Bello M, Giors M, et al: Sentinel lymph node detection in patients with early breast cancer: Comparison of periareolar and subdermal/peritumoral injection techniques. J Nucl Med 45:220-225, 2004[Abstract/Free Full Text]

33. Shimazu K, Tamaki Y, Taguchi T, et al: Comparison between periareolar and peritumoral injection of radiotracer for sentinel lymph node biopsy in patients with breast cancer. Surgery 131:277-286, 2002[CrossRef][Medline]

Submitted October 2, 2006; accepted February 28, 2007.

Related Articles

• Surgical Complications Associated With Sentinel Lymph Node Dissection (SLND) Plus Axillary Lymph Node Dissection Compared With SLND Alone in the American College of Surgeons Oncology Group Trial Z0011
  Anthony Lucci, Linda Mackie McCall, Peter D. Beitsch, Patrick W. Whitworth, Douglas S. Reintgen, Peter W. Blumencranz, A. Marilyn Leitch, Sukumal Saha, Kelly K. Hunt, and Armando E. Giuliano
  JCO 2007 25: 3657-3663 [Abstract] [Full Text]
• Doctor, What Are My Chances of Having a Positive Sentinel Node? A Validated Nomogram for Risk Estimation
  José Luiz B. Bevilacqua, Michael W. Kattan, Jane V. Fey, Hiram S. Cody, III, Patrick I. Borgen, and Kimberly J. Van Zee
  JCO 2007 25: 3670-3679 [Abstract] [Full Text]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rodier, J.-F. Articles by Avigdor, S. Search for Related Content PubMed PubMed Citation Articles by Rodier, J.-F. Articles by Avigdor, S. Related Articles Related Articles