Annals of Surgical Oncology Cite Track
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shen, P.
Right arrow Articles by Giuliano, A. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shen, P.
Right arrow Articles by Giuliano, A. E.
Related Collections
Right arrow Diagnosis
Annals of Surgical Oncology 8:241-248 (2001)
© 2001 Society of Surgical Oncology

ORIGINAL ARTICLES

Dermal Versus Intraparenchymal Lymphoscintigraphy of the Breast

Perry Shen, MD, Edwin C. Glass, MD, L. Andrew DiFronzo, MD and Armando E. Giuliano, MD, FACS

From the Joyce Eisenberg Keefer Breast Center, John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, California.

Correspondence: Address correspondence and reprint requests to: Armando E. Giuliano, MD, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404; Fax: 310-449-5259; E-mail: giuliano{at}jwci.org


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background and Objective: Dermal and intraparenchymal (IP) injections of radiocolloid have been used for lymphoscintigraphic identification of the sentinel node (SN) in breast cancer. Because of our institute’s extensive experience with dermal and IP lymphoscintigraphy for melanoma and breast cancer, we compared patterns of lymphatic migration after both types of injections to identify any differences in drainage patterns or SN identification.

Methods: Lymphoscintigrams (n = 31) after dermal injections in 30 patients with primary cutaneous melanoma on the breast were compared with lymphoscintigrams after IP injections in 97 consecutive patients with breast cancer. In each case, 400 µCi of filtered 99mTc-sulfur colloid was injected in four quadrants around the tumor or in the biopsy cavity. All lymphoscintigrams were reviewed for patterns of migration and SN location.

Results: Five of 31 (16%) dermal injections demonstrated bilateral axillary migration (n = 3) or a suprasternal SN (n = 2), neither of which was found with IP injections. Conversely, 3 of 97 (3%) IP injections demonstrated direct supraclavicular (n = 2) or costal margin (n = 1) nodes (P = .006), neither of which was found with dermal injections. Low axillary SNs were noted after 26 (84%) dermal and 93 (96%) IP injections (P = .037). The incidence of extra-axillary SNs was 26% (8 of 31) in the dermal group but only 5% (5 of 97) in the IP group (P = .0027).

Conclusion: There is a significant difference in lymphatic drainage and SN localization between dermal and IP lymphoscintigraphy. This finding has implications for injection techniques when lymphatic mapping of the SN is undertaken to stage a breast carcinoma.

Key Words: Lymphoscintigraphy • Breast cancer • Injection techniques


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The use of lymphoscintigraphy to identify the lymphatic basins draining primary cutaneous melanomas was first reported by Morton’s group in the 1970s.1 In 1992, these investigators published the first study describing preoperative cutaneous lymphoscintigraphy and intraoperative lymphatic mapping with blue dye to identify the regional lymphatic basin draining a cutaneous melanoma and the sentinel lymph node (SN) within that basin.2 The management of malignant melanoma was revolutionized by lymphatic mapping and sentinel lymphadenectomy (LM/SL). Shortly thereafter, Giuliano et al.3 adapted dye-directed lymphatic mapping to breast cancer, and Krag and associates4 reported results of LM/SL in breast cancer using an intraoperative radiocolloid to identify the SN. Since then, various authors have described their experience with LM/SL in breast cancer.5–10

Despite the widespread acceptance of LM/SL for use in staging breast cancer, the specifics of the technique are still evolving. In particular, there is controversy regarding the most appropriate site of injection. The initial reports described peritumoral intraparenchymal (IP) injection of isosulfan blue dye or a radiocolloid to identify the SN. However, recent studies have advocated dermal, subdermal, or subareolar injection as an easier and more convenient method to perform LM/SL with comparable accuracy.6,9,11–13

At our institution, we use IP injection for preoperative lymphoscintigraphy in patients undergoing LM/SL for primary breast carcinoma. Our extensive experience with lymphoscintigraphy in patients with truncal melanomas led us to hypothesize that dermal and parenchymal breast sites have different drainage patterns. We examined this hypothesis by comparing lymphoscintigrams obtained after dermal injection of primary cutaneous melanomas on the breast and after IP injection of primary breast carcinomas. A significant difference in the lymphatic drainage basins produced by dermal versus peritumoral IP injection of radiocolloid might have implications for LM/SL as a staging technique in breast cancer.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Between March 1992 and January 2000, 21 men and 9 women with pathologically confirmed primary cutaneous melanomas on the breast or anterior chest wall underwent preoperative lymphoscintigraphy, LM/SL, and wide local excision of the primary lesion. One patient had two primary melanomas—one over the right breast and one over the left breast, and the lymphoscintigrams for each lesion were considered separately. On the day of surgery, .4 mCi of 99mTc-sulfur colloid (CisUS, Bedford, MA) passed through a 200-nm Millipore filter was injected intradermally through a 27-gauge needle into four quadrants around the biopsy scar. The volume of injectate ranged from .1 to .8 ml. Planar images of the chest and surrounding lymphatic drainage basins were acquired using a scintillation camera and image acquisition times of 1 to 5 minutes. Imaging began immediately after injection and continued sequentially in real time until all SNs were identified. Transit time of the radiocolloid from the injection site to the SNs was usually < 20 minutes after either dermal or IP injection.14,15 A hand-held gamma probe was used to confirm the location of each node. The skin over each probe-identified SN was marked with carbolfuchsin.

Between May 1996 and July 1998, 97 consecutive female patients with a cytologic or tissue diagnosis of invasive breast carcinoma underwent preoperative lymphoscintigraphy on the day of surgery or the day before surgery. The lymphoscintigraphy protocol was similar to that for melanoma patients, except that injection was directed into four quadrants of the parenchyma around the tumor or into four quadrants of the parenchymal wall of the biopsy cavity. Also, a larger volume of injectate (3–8 ml) was used; the exact volume varied with the size of the breast. Specific details regarding our institution’s experience with preoperative breast lymphoscintigraphy have been published elsewhere.14

Each lymphoscintigram was reviewed by the same nuclear medicine physician (ECG), who possessed expertise in both melanoma and breast lymphoscintigraphy for SN localization. The studies were assessed for the overall lymphatic drainage pattern. Based on our experience with over 6000 lymphoscintigrams for melanoma and breast cancer, as well as published anatomic16,17 and lymphatic18 studies of the breast, we determined typical lymphatic drainage patterns for dermal and IP breast injections. Dermal lymphatics of the breast predominantly drain to the ipsilateral axilla but can also drain to the contralateral axilla, intransit nodes, or the suprasternal region. Similarly, IP lymphatics usually drain to the ipsilateral axilla. However, internal mammary (IM) and supraclavicular nodal drainage patterns are not uncommon. Nodal basins observed with one injection technique but not the other were considered discordant. The SN was defined as the first node identified in the first nodal basin to which the radiocolloid drained by lymphoscintigraphy; this was especially pertinent in patients with multiple drainage basins. An axillary SN was the standard low axillary node typically identified on preoperative lymphoscintigrams for breast cancer. An extra-axillary SN was any node not located in the low axilla on lymphoscintigraphy images.

Statistical analysis used a two-tailed Fisher’s exact test for distributions of SNs identified by lymphoscintigraphy. Comparisons of discordant drainage were performed with {chi}2 analysis. Differences were considered significant when the probability of the null hypothesis was <= .05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Table 1 profiles the melanoma and breast cancer study populations. The melanoma group had a preponderance of males, whereas the breast cancer group was entirely female. Primary cutaneous melanomas had a median Breslow thickness of 1.2 mm, which is considered intermediate, and a median Clark level of III. More than 70% of the breast cancer patients had primary tumors <2 cm in diameter. All patients in both groups had clinically negative regional lymph nodes. The rate of SN identification was 100% during both preoperative lymphoscintigraphy and intraoperative lymphatic mapping. Figure 1 shows the distribution of IP and dermal lesions between the two study groups.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Clinicopathologic variables
 


View larger version (48K):
[in this window]
[in a new window]
  		FIG. 1. The distribution of individual intraparenchymal (breast cancer) and dermal (melanoma) lesions in the two study groups.

 
All dermal lymphoscintigrams and almost all (95 of 97) IP lymphoscintigrams showed drainage to the low axillary basin. Nine (29%) dermal and 20 (21%) IP lymphoscintigrams demonstrated more than one lymphatic drainage basin; drainage to multiple basins occurred either sequentially or simultaneously. Three (10%) dermal and 19 (20%) IP lymphoscintigrams showed drainage to the internal mammary (IM) lymph nodes (P = .225). Of the three patients in whom dermal injection revealed IM drainage, one patient had an inner-quadrant primary, one had an areolar lesion, and the third had an outer-quadrant lesion. Similarly, of the 19 patients in whom IP injection showed IM drainage, 6 (32%), 7 (37%), and 6 (32%) had primary lesions in the inner, central/subareolar, and outer quadrants, respectively. Intransit nodes were demonstrated on 1 (3%) dermal and 5 (5%) IP breast lymphoscintigrams. Intramammary nodes were considered intransit. None of these differences were statistically significant.

Of the 31 dermal lymphoscintigrams, 5 (16%) displayed drainage patterns not found with IP injection (Table 2). Three of these dermal lymphoscintigrams (10%) demonstrated simultaneous drainage to ipsilateral and contralateral axillae from an inner-quadrant lesion (n = 2) or a central breast lesion, and two (6%) displayed suprasternal lymphatic drainage to paratracheal nodes from an inner-quadrant or a central breast primary. Of the 97 IP lymphoscintigrams, 3 (3%) demonstrated drainage patterns not associated with dermal injection (Table 2). Specifically, 2 (2%) showed drainage to supraclavicular nodes from an inner-quadrant or outer-quadrant primary, and 1 (1%) to a costal margin node from an inner-quadrant lesion. This difference in discordant lymphatic drainage between the two injection sites was statistically significant (P = .006).


View this table:
[in this window]
[in a new window]
  		TABLE 2. Eight patients with discordant drainage demonstrated by lymphoscintigraphy after dermal or intraparenchymal injection of the breast
 
An axillary SN, defined as the first lymph node receiving drainage, was identified in 84% (26 of 31) of dermal and 96% (93 of 97) of IP studies (P = .037). Because the SN is defined as the first node of the first lymphatic basin identified on lymphoscintigraphy, this is not a comparison of overall lymphatic drainage to specific basins, which was reported earlier. Extra-axillary SNs were identified in 26% (8 of 31) of dermal and 5% (5 of 97) of IP lymphoscintigrams (P = .0027). Of the eight studies showing extra-axillary SNs identified by dermal injection, five represented inner-quadrant primary lesions that drained to two contralateral axillary SNs, one suprasternal SN, one IM SN, and one apical axillary SN, respectively; the three remaining melanomas were overlying the central portion of the breast and drained to one contralateral axillary SN, one suprasternal SN, and one IM SN, respectively. All three patients with a contralateral axillary SN also had a low axillary SN because of simultaneous primary migration of radiocolloid; the remaining cases of extra-axillary SNs identified by dermal injection did not have concomitant axillary drainage. The lymphoscintigrams in Fig. 2 show extra-axillary SNs identified by dermal injection. Of the five IP lymphoscintigrams demonstrating extra-axillary SNs, one study after an outer-quadrant injection and one study after a central breast injection demonstrated simultaneous drainage to an ipsilateral low axillary SN and an IM SN. On the other three lymphoscintigrams, outer-quadrant, inner-quadrant, and central primary lesions each drained exclusively to an IM SN. The lymphoscintigrams in Fig. 3 show extra-axillary SNs identified after IP injection.



View larger version (17K):
[in this window]
[in a new window]
  		FIG. 2. Lymphoscintigrams showing extra-axillary sentinel nodes (SNs) after dermal injection. (A) Bilateral axillary SN after an inner-quadrant injection. (B) An apical axillary SN of atypical location after an inner-quadrant injection. (C) An internal mammary SN after an inner-quadrant injection.

 


View larger version (19K):
[in this window]
[in a new window]
  		FIG. 3. Lymphoscintigrams showing extra-axillary sentinel nodes (SNs) after intraparenchymal injections. (A) An internal mammary SN after an outer-quadrant injection. (B) Simultaneous migration to an internal mammary SN and a low axillary SN after a central breast injection.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Table 3 summarizes published reports of LM/SL after IP, dermal, subdermal, or subareolar injection of a primary breast cancer. Using a peritumoral IP injection of blue dye alone, Giuliano et al.3 reported a 94% rate of SN identification with no false-negatives. In another study from the same institution, Glass and associates15 identified an axillary SN in 99% of preoperative lymphoscintigrams obtained after peritumoral injection of radiocolloid. The multicenter study of Krag and associates4 reported a 93% rate of intraoperative SN identification after peritumoral IP injection of radiocolloid; preoperative lymphoscintigraphy was not performed. These investigators reported a 5% and .2% incidence of IM and supraclavicular "hot spots," respectively, which differs markedly from our 20% and 2% incidence of IM and supraclavicular lymphatic drainage in patients undergoing IP injection and dynamic real-time scanning. This difference could relate to variations in the duration of monitoring after injection. These reports illustrate and document the importance of axillary drainage after IP injection of breast tissue.


View this table:
[in this window]
[in a new window]
  		TABLE 3. Reports of sentinel lymphadenectomy followed by axillary lymph node dissection in patients with breast cancer
 
There are two published reports of LM/SL in breast cancer after dermal injection of blue dye plus IP injection of a radioisotope. All procedures were followed by completion axillary lymph node dissection (ALND) to determine the false-negative rate. The report from Borgstein’s group11 included only 25 patients but had a 100% SN identification rate and no false negatives. In a study of 58 patients, Van der Ent et al.10 identified only 86% of SNs and reported a 4% false-negative rate. In the 31 dermal and 97 IP lymphoscintigrams reviewed for our study, the SN identification rate was 100%.

Two recent studies compared dermal and IP injections of radioisotope in breast cancer patients undergoing preoperative lymphoscintigraphy followed by LM/SL. Investigators from Memorial Sloan-Kettering Cancer Center reported on 200 patients: half received an IP injection of sulfur colloid and half received a dermal injection of sulfur colloid.12 The SN identification rates were 97% for the dermal group and 78% for the IP group. No patients in either group demonstrated IM nodal drainage. Roumen and associates19 performed sequential IP and dermal lymphoscintigraphy in each of 99 breast cancer patients. SN localization rates were 65% after dermal injection but 86% after IP injection. The incidence of IM drainage was 11% after IP injection and zero after dermal injection.

Subdermal injection of radioisotope has been advocated in two separate breast cancer studies from the European Institute of Oncology in Milan, Italy. Veronesi et al.6 used subdermal injection to achieve an SN identification rate of 98%, with a 5% false-negative rate. Cicco and associates20 found no significant difference between subdermal and IP injection techniques to identify the SN, although they observed that IP injection produced delayed and faint images. These findings are not consistent with our experience: SN identification at our institution approaches 100% for both dermal and IP injections; the median time to localize a SN is approximately 10 minutes after dermal injection and approximately 20 minutes after IP injection.14,15 Kern9 reported a series of 40 patients who underwent completion ALND after LM/SL using subareolar injection. He reported a 98% SN identification rate with no false-negatives. In a study of 69 patients, Klimberg and associates13 reported SN identification rates of 94% with subareolar injection and 90% with peritumoral injection. No extra-axillary SNs were identified in any of these studies. These reports document the high success rate for identifying the SN using alternative injection techniques, but they do not indicate whether the same patterns of migration can be expected after different methods of injection.

Previous studies have questioned the similarity of lymphatic drainage patterns from the skin and parenchyma of the breast. Uren et al.16 reported a 35% incidence of lymphatic drainage to IM nodes after IP lymphoscintigraphy, and also noted no evidence of IM drainage in 62 patients with melanomas of the breast and anterior chest who underwent lymphoscintigraphy with 99mTc-antimony sulfide.21 Nieweg and associates22 stated that the skin of the breast does not drain to the IM nodes of melanoma patients. They conjectured that a dermal injection for breast cancer was further away from the primary than a peritumoral IP injection and could potentially cross a lymphatic watershed, draining an area that did not include the malignancy.

Before the present study was initiated, one concern was that the cutaneous lymphatic drainage of the breast might not target the IM nodal basin; however, our study demonstrated a 10% incidence of IM drainage on 31 cutaneous lymphoscintigrams. This rate was less than the 20% incidence observed on the 97 IP lymphoscintigrams, but not significantly different (P = .225). However, the amount of discordant lymphatic drainage in the dermal group was significantly higher on {chi}2 analysis. This finding is consistent with the suggestion that the skin is more richly supplied with lymph channels than is breast tissue,16 and it is supported by different observed migration times.14,15 Other reports have not documented the same incidence of extra-axillary drainage after dermal injection over the breast; however, at our institution, lymphoscintigraphic images are monitored continuously after injection by the nuclear medicine physician in real time until nodal localization occurs. This continuous monitoring might demonstrate extra-axillary nodal basins that would be missed on static images obtained at preset delayed intervals.

Morton and associates2 defined the SN as the lymph node most likely to contain metastatic melanoma. The SN concept holds that the lymphatic effluent of a tumor drains initially to one or two lymph nodes before other nodes receive tumoral drainage.23 Intuitively, the first regional site of lymphatic drainage from a primary tumor should also be the most likely site of tumor cells metastasizing from the primary. In our study, if more than one nodal basin was identified, the first dominant node in the first nodal basin receiving lymphatic drainage was considered the SN. Using this definition, there was a significant difference in the incidence of low axillary and extra-axillary SNs between the dermal and IP groups. In addition, the locations of the extra-axillary nodal basins differed. These findings support the concept that complex drainage patterns to more than one node or more than one nodal basin are more common in patients undergoing cutaneous lymphoscintigraphy than IP lymphoscintigraphy.24

Almost all studies of preoperative lymphoscintigraphy for breast cancer focus on the identification of an axillary SN. Currently, there is no consensus regarding the sampling of extra-axillary SNs. Few reports document IM drainage in breast lymphoscintigraphy, much less LM/SL for IM SNs. This may be because anatomic studies have documented that 75% to 100% of the lymphatic drainage of the breast is to the ipsilateral axillary node.15,25 Even though studies have shown that up to 20% to 30% of breast cancer patients can have metastatic disease to the IM nodes, it is often in conjunction with axillary disease.19,20 Early anatomic studies of the lymphatic drainage of the breast found that 29% to 34% of patients possessed both axillary and IM nodal metastases, whereas only 4% to 5% of patients had IM disease exclusively.26 Morrow and Foster27 reported a 10% incidence of isolated IM metastases in over 3500 patients with tumor-negative axillary nodes. In their multicenter validation study of probe-directed LM/SL in breast cancer, Krag et al.4 reported that only 3% of tumor-positive SNs were in nonaxillary locations. A recent follow-up study by Borgstein and associates28 examined SN targeting with peritumoral radiocolloid and intradermal blue dye. They reported a 15% incidence of IM drainage by preoperative lymphoscintigraphy. Although some of the IM nodes were biopsied, the authors did not indicate the sequence of lymphatic drainage between axillary and IM basins, whether all patients with IM drainage underwent biopsy of parasternal nodes, or whether biopsied IM nodes were blue-stained.

Despite these findings, there is evidence that the importance of IM nodal metastases might be understated. Veronesi et al.29 reported a 9% rate of initial spread to the IM nodes in the absence of axillary involvement. A prospective randomized study by Lacour et al.30 in 1983 found that adding IM nodal dissection to radical mastectomy did not impact overall or disease-free survival. However, these studies were performed without the benefit of preoperative lymphoscintigraphy, so it could not be ascertained prospectively whether or not the primary tumor drained to the IM nodal basin. If the breast cancer did not drain to the IM nodes, then removing or irradiating them would obviously offer no benefit. Veronesi et al.31 recently reported that, although dissection of the IM nodes did not affect overall survival of breast cancer patients, it yielded significant prognostic information. There are no prospective randomized studies examining the effect of IM SN dissection on patient outcome, and at this point, it is still unclear whether an IM SN should be sampled. Nevertheless, staging and treatment of the occasional patient with isolated spread to IM or other nonaxillary nodes requires identification of such a priori.

Our results must be considered in the context of intrinsic design limitations. First, our study groups represented two histologically different malignancies that have different biologies and patterns of spread. Not surprisingly, the melanoma patients were predominantly male, whereas the breast cancer patients were all female, and there was a significant difference in the median age between the two groups. Because of the retrospective nature of this study, confirmation of each tumor site location was based only on review of the medical chart. In addition, the volume of injectate was much smaller for the dermal group than the IP group. Although this difference might be seen as a confounding factor, the dermis has a much richer lymphatic distribution than breast parenchymal tissue16 and requires less volume to generate activity that will be picked up by the scintillation camera. For this reason, a larger volume of sulfur colloid for dermal injection might have produced an even more discordant lymphatic drainage pattern compared with the IP technique.

Results of our study suggest that the incidence of typical low axillary SNs identified during preoperative lymphoscintigraphy significantly varies with the injection technique. This could potentially result in sampling differences that might affect the staging of the disease and rates of recurrence. Current published reports, including ours, do not have sufficient power and were not designed to discern any small clinical differences between different injection techniques. Based on large, published clinical series supported by pathologic confirmation,3,4 it is reasonable to expect that peritumoral IP injections in the breast yield lymphoscintigrams that correctly map the expected lymphatic drainage of a primary breast tumor. Investigators who propose changes in an established technique must assume the burden of proving efficacy. Thus, if a different injection technique is to be used for LM/SL, it must be followed by completion ALND to determine the rate of false-negative SNs.


   Acknowledgments
 
Supported by funding from the Leslie and Susan Gonda (Goldschmied) Foundation (Los Angeles, CA), the Ben B. and Joyce E. Eisenberg Foundation (Los Angeles, CA), the Associates for Breast and Prostate Cancer Studies (Santa Monica, CA), and the Fashion Footwear Association of New York (New York City, NY).


   Footnotes
 
Presented at the Society of Surgical Oncology Annual Meeting, New Orleans, Louisiana, March 16–19, 2000.

Received for publication September 7, 2000. Accepted for publication December 4, 2000.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Robinson DS, Samkple WF, Fee JH, et al. Regional lymphatic drainage in primary malignant melanoma of the trunk determined by colloidal gold scanning. Surg Forum 1977; 28: 147–8.[Medline]
  2. Morton DL, Wen D-R, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992; 127: 392–9.[Abstract]
  3. Giuliano AE, Jones RC, Brennan M, Statman R. Sentinel lymphadenectomy in breast cancer. J Clin Oncol 1997; 15: 2345–50.[Abstract/Free Full Text]
  4. Krag D, Weaver D, Ashikaga T, et al. The sentinel node in breast cancer: a multicenter validation study. N Engl J Med 1998; 339: 941–6.[Abstract/Free Full Text]
  5. Roumen RMH, Valkenburg JGM, Geuskens LM. Lymphoscintigraphy and feasibility of sentinel node biopsy in 83 patients with primary breast cancer. Eur J Surg Oncol 1997; 23: 495–502.[CrossRef][Medline]
  6. Veronesi U, Paganelli G, Galimberti V, et al. Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes. Lancet 1977; 349: 1864–7.
  7. Borgstein PJ, Pijpers R, Comans EF, et al. Sentinel lymph node biopsy in breast cancer: guidelines and pitfalls of lymphoscintigraphy and gamma probe detection. J Am Coll Surg 1998; 186: 275–83.[CrossRef][Medline]
  8. Cox CE, Pendas S, Cox JM, et al. Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer. Ann Surg 1998; 227: 645–53.[CrossRef][Medline]
  9. Kern K. Sentinel lymph node mapping in breast cancer using subareolar injection of blue dye. J Am Coll Surg 1999; 189: 539–45.[CrossRef][Medline]
  10. Van der Ent FWC, Kengen RAM, van der Pol HAG, Hoofwijk AGM. Sentinel node biopsy in 70 unselected patients with breast cancer: increased feasibility by using 10 mCi radiocolloid in combination with a blue dye tracer. Eur J Surg Oncol 1999; 25: 24–9.[CrossRef][Medline]
  11. Borgstein PJ, Meijer S, Pijpers R. Intradermal blue dye to identify sentinel lymph node in breast cancer. Lancet 1997; 349: 1668–9.[Medline]
  12. Linehan DC, Hill ADK, Akhurst T, et al. Intradermal radiocolloid and intraparenchymal blue dye injection optimize sentinel node identification in breast cancer patients. Ann Surg Oncol 1999; 6: 450–4.[Abstract]
  13. Klimberg VS, Rubio IT, Henry R, et al. Subareolar versus peritumoral injection for location of the sentinel lymph node. Ann Surg 1999; 229: 860–5.[CrossRef][Medline]
  14. Haigh PI, Hansen NM, Giuliano AE, et al. Factors affecting sentinel node localization during preoperative breast lymphoscintigraphy. J Nucl Med 2000; 41: 1682–8.[Abstract/Free Full Text]
  15. Glass EC, Essner R, Morton DL. Kinetics of three lymphoscintigraphy agents in patients with cutaneous melanoma. J Nucl Med 1998; 39: 1185–90.[Abstract/Free Full Text]
  16. Uren RF, Howman-Giles RB, Thompson JF, et al. Mammary lymphoscintigraphy in breast cancer. J Nucl Med 1995; 36: 1775–80.[Abstract/Free Full Text]
  17. Vendrell-Torne E, Setoain-Quinquer J, Domenech-Torne FM. Study of normal mammary lymphatic drainage using radioactive isotopes. J Nucl Med 1972; 13: 801–5.[Free Full Text]
  18. Thompson JF, Uren RF, Shaw HM, et al. Location of sentinel lymph nodes in patients with cutaneous melanoma: new insights into lymphatic anatomy. J Am Coll Surg 1999; 189: 195–206.[CrossRef][Medline]
  19. 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 1999; 25: 347–51.[CrossRef][Medline]
  20. Cicco CD, Cremonesi M, Luini A, et al. Lymphoscintigraphy and radioguided biopsy of the sentinel axillary node in breast cancer. J Nucl Med 1998; 39: 2080–4.[Abstract/Free Full Text]
  21. Uren RF, Thompson JF, Howman-Giles R. Sentinel lymph node biopsy in breast cancer. Lancet 1998; 352: 1471–3.
  22. Nieweg OE, Jansen L, Olmos RAV, et al. Lymphatic mapping and sentinel lymph node biopsy in breast cancer. Eur J Nucl Med 1999; 26(Suppl): S11–S16.[CrossRef][Medline]
  23. Glass EC, Essner R, Giuliano AE. Sentinel node localization in breast cancer. Semin Nucl Med 1999; 29: 57–68.[CrossRef][Medline]
  24. Bennett LR, Lago G. Cutaneous lymphoscintigraphy in malignant melanoma. Semin Nucl Med 1983; 13: 61–9.[CrossRef][Medline]
  25. Turner-Warwick RT. The lymphatics of the breast. Br J Surg 1959; 46: 574–82.[Medline]
  26. Hultborn KA, Larsson LG, Ragnhult I. The lymph drainage from the breast to the axillary and parasternal lymph nodes, studied with the aid of colloidal AU198. Acta Radiol 1955; 43: 52–64.
  27. Morrow M, Foster RS. Staging of breast cancer: a new rationale for internal mammary node biopsy. Arch Surg 1981; 116: 748–51.[Abstract]
  28. Borgstein PJ, Meijer S, Pijpers RJ, van Diest PJ. Functional lymphatic anatomy for sentinel node biopsy in breast cancer; echoes from the past and the periareolar blue method. Ann Surg 2000; 232: 81–9.[CrossRef][Medline]
  29. Veronesi U, Cascinelli N, Greco N, et al. Prognosis of breast cancer patients after mastectomy and dissection of internal mammary nodes. Ann Surg 1985; 202: 702–7.[Medline]
  30. Lacour J, Le M, Caceres E, et al. Radical mastectomy versus radical mastectomy plus internal mammary dissection. Cancer 1983; 51: 1941–3.[CrossRef][Medline]
  31. Veronesi U, Marubini E, Mariani L, et al. The dissection of internal mammary nodes does not improve the survival of breast cancer patients. 30-year results of a randomised trial. Eur J Cancer 1999; 35: 1320–5.



This article has been cited by other articles:


Home page
 Ann. Surg. Oncol.Home page
I. M. C. van der Ploeg, B. B. R. Kroon, N. Antonini, R. A. V. Olmos, E. J. T. Rutgers, and O. E. Nieweg
Axillary and Extra-axillary Lymph Node Recurrences after a Tumor-Negative Sentinel Node Biopsy for Breast Cancer Using Intralesional Tracer Administration
Ann. Surg. Oncol., April 1, 2008; 15(4): 1025 - 1031.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J.-F. Rodier, M. Velten, M. Wilt, P. Martel, G. Ferron, V. Vaini-Elies, H. Mignotte, A. Bremond, J.-M. Classe, F. Dravet, et al.
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
J. Clin. Oncol., August 20, 2007; 25(24): 3664 - 3669.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
S. H. Estourgie, P. J. Tanis, O. E. Nieweg, R. A. Valdes Olmos, E. J. Th. Rutgers, and B. B. R. Kroon
Should the Hunt for Internal Mammary Chain Sentinel Nodes Begin? An Evaluation of 150 Breast Cancer Patients
Ann. Surg. Oncol., October 1, 2003; 10(8): 935 - 941.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shen, P.
Right arrow Articles by Giuliano, A. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shen, P.
Right arrow Articles by Giuliano, A. E.
Related Collections
Right arrow Diagnosis

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS