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Published online before print December 29, 2003, 10.1148/radiol.2302021380

(Radiology 2004;230:543.)

A more recent version of this article appeared on February 1, 2004
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© RSNA, 2003

Breast Imaging

Breast Sentinel Lymph Node Mapping at CT Lymphography with Iopamidol: Preliminary Experience1

Kazuyoshi Suga, MD, Yue Yuan, MD, Munemasa Okada, MD, Naofumi Matsunaga, MD, Akira Tangoku, MD, Shigeru Yamamoto, MD and Masaaki Oka, MD

1 From the Departments of Radiology (K.S., Y.Y., M. Okada, N.M.) and Second Surgery (A.T., S.Y., M. Oka), Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan. Received October 30, 2002; revision requested January 7, 2003; final revision received July 12; accepted August 22. Address correspondence to K.S. (e-mail: sugar@po.cc.yamaguchi-u.ac.jp).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
PURPOSE: To evaluate sentinel lymph node (SLN) mapping with interstitial computed tomographic (CT) lymphography with small volumes of iopamidol for direction of SLN biopsy in breast cancer.

MATERIALS AND METHODS: Thin-section transverse and three-dimensional CT images that included the breast and axilla were acquired at multi–detector row helical CT in 17 patients with operable breast cancer before subcutaneous injection of 2 mL of undiluted iopamidol into peritumoral and periareolar areas and 1–5 minutes after massage of injection sites. Location and size of SLNs were assessed at CT lymphography and were compared with SLNs at standard axillary lymph node dissection with blue dye staining.

RESULTS: CT lymphography allowed localization of SLNs in all patients by means of visualization of a direct connection between an SLN and its afferent lymphatic vessels draining from the injection sites. Afferent vessels were joined and drained into a single axillary SLN, except in four patients with two or three SLNs, including a parasternal one. SLNs did not enhance because of rerouting of lymph flow in four patients. At surgery, SLNs that were stained or not stained with blue dye were easily found with CT lymphographic guidance. Tumoral infiltration was not evident in any resected nodes, except for infiltration in one patient with micrometastasis in SLN alone and infiltration in four patients with massive metastasis in both SLN and distant nodes.

CONCLUSION: Because preoperative CT lymphography–guided SLN mapping provides SLN position with detailed lymphatic anatomy, it may be useful for the direction of breast SLN biopsy.

© RSNA, 2003

Index terms: Breast neoplasms, CT, 00.1211 • Computed tomography (CT), contrast enhancement, 997.12912, 00.1211 • Lymphatic system, biopsy, 997.1261 • Lymphatic system, CT, 997.12912, 997.12915, 997.12917


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Breast tumors are considered to drain in a logical way through the lymphatic system from the first to upper levels. The tumoral status of the first lymph node (sentinel lymph node [SLN]) encountered by lymphatic vessels draining from a tumor appears to reflect the tumoral status of the entire lymphatic drainage basin (1–17). The SLN is most likely the first to be affected by metastases, and a negative SLN makes it highly unlikely that other nodes are affected. On the basis of this concept, breast SLN biopsy is performed to identify node-positive patients who require axillary dissection and to spare node-negative patients from such surgery (2,4–21). At present, local practice for breast SLN biopsy includes lymphoscintigraphic and/or vital blue dye–staining methods that have favorable results for SLN mapping (2,4–21). However, there are some disadvantages and potential pitfalls in SLN mapping with these methods (4,14–21). For example, the injected tracer may fail to migrate from the injection site, depending on the radiocolloid particle size; the blue dye–stained lymphatic vessels and/or nodes may not be readily apparent in the fatty axilla; there is a risk of labeling non-SLNs because of further migration of radiocolloids and blue dye to the subsequent distant nodes; the lymph nodes with the highest radioactivity and blue dye staining are not necessarily defined as SLNs; and in the primary SLN with extensive tumoral infiltration, markers may not accumulate because of lymph flow rerouting.

Recently, we proposed the potential use of interstitial computed tomographic (CT) lymphography with subcutaneous injection of the commercially available low-osmolar nonionic contrast medium iopamidol for SLN mapping in animals and healthy volunteers (22,23). This technique may address the previously mentioned disadvantages of the scintigraphic and blue dye–staining methods because with it clear visualization of the direct connection between the primary SLN and its afferent lymphatic channel and the detailed anatomy of breast lymphatic pathways is possible on a cross-sectional basis. The purpose of our present study was to evaluate SLN mapping with interstitial CT lymphography by using small volumes of iopamidol for the direction of SLN biopsy in patients with operable breast cancer.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patient Population
With the approval of the local ethics committee and informed consent provided, a total of 17 patients who were 38–71 years old (mean age, 50.7 years) and had operable unilateral invasive breast cancer were enrolled in this study. Only two of those patients had palpable axillary lymph nodes. All the patients had undergone thin-section contrast material–enhanced breast CT and/or magnetic resonance (MR) imaging to evaluate the details of tumoral morphology prior to undergoing CT lymphography as part of this study. Preoperative diagnosis of breast cancer was obtained with ultrasonography-guided fine-needle aspiration biopsy. Each patient underwent CT lymphography within 7 days before surgery in combination with preoperative routine contrast-enhanced abdominal and/or thoracic CT examinations to evaluate distant metastases. These simultaneous CT examinations could be performed because only focal enhancement of breast lymphatic pathways did not interrupt the performance of the subsequent contrast-enhanced CT examinations. Breast-conserving surgery was then performed in 10 of these patients; modified radical mastectomy, combined with standard axillary lymph node dissection, was performed in the remaining seven patients.

CT Lymphography
Interstitial CT lymphography was performed by using a multi–detector row helical CT scanner with four rows of 0.5-mm detectors (Siemens Voulme Zoom; Siemens-Asahi Medical, Tokyo, Japan). Each patient was placed in the supine position, with the arms positioned upward but bent at the elbow with the hands at the side of the cranium. This position is similar to the surgical position. After induction of local anesthesia with subcutaneous injection of a total of 0.2 mL of 2% lidocaine hydrochloride, 2 mL of iopamidol (Iopamiron 370; Nippon Shering, Osaka, Japan) was subcutaneously injected into the peritumoral and periareolar areas with a 26-gauge 5/8-inch hypodermic needle attached to a tuberculin syringe.

There were a total of 15 possible radiologists (including K.S., Y.Y., M. Okada) and six possible surgeons (including A.T., S.Y.) who could inject the contrast agent at the CT examination time. One of these radiologists and one of these surgeons performed the contrast agent injection. In several cases with small nonpalpable tumors with an ill-defined margin on the precontrast CT images, the peritumoral site was localized by referring to the previously obtained thin-section contrast-enhanced breast CT and/or MR images. Iopamidol was commercially supplied with a disposable syringe containing 100 mL of solution. This contrast agent had a molecular weight of 777.09 Da, and the solute had an iodine concentration of 370 mg/mL, osmolarity of 780 mOsm/kg (less than three times the osmolarity of physiologic saline [~300 mOsm/kg]), viscosity of 9.1 mPa/sec, and pH of 6.5–7.5. After administration of iopamidol, the injection sites were gently massaged for 30 seconds to facilitate the migration of this contrast agent to the draining lymphatic vessels (4,8).

Contiguous 2-mm-thick CT images that included the breast and axilla were obtained prior to administration of the contrast agent and at 1, 3, and 5 minutes after 30 seconds of gentle massage of the injection sites. The CT scanning was performed at 120 kV and 330 mA, with a 45-cm field of view, a 512 x 512 matrix, a section spacing of 5 mm, and a table speed of 1.53 mm/0.5 sec. The number of sections ranged between 36 and 40, and the acquisition time ranged from 22 to 25 seconds. During CT image acquisition, each patient was placed in the same position if possible, and breath hold was performed at a tidal inspiration level. The transverse CT images were reconstructed with a 0.5-mm pitch and section thickness of 0.3 mm. Three-dimensional (3D) CT images were then reconstructed from the postcontrast CT images at each time point by using maximum intensity projection and/or surface-rendering techniques. With CT image guidance and the consensus of two observers (K.S., A.T.), the skin location overlying the identified SLN was labeled by using a painting pen.

The contrast material injection was painless because a local anesthetic was used in all patients, but temporary swelling at the injection site occurred. CT lymphography was completed within 15 minutes in all patients. After CT lymphography, each patient underwent routine contrast-enhanced abdominal and/or thoracic CT to evaluate distant metastases by using 96 mL of the contrast agent that remained in the syringe that contained 100 mL of iopamidol (4 mL was already injected). Consequently, no additional cost except for image recording and administration of local anesthetic was required for CT lymphography.

Surgery
After SLN biopsy, all patients underwent standard axillary lymph node dissection that included the anatomic boundaries of levels I–II; level I nodes are located lateral to or below the lower border of the pectoralis minor muscle, and level II nodes are located deep to or behind this muscle (8,14). At SLN biopsy, the surgeons referred to lymphatic pathways and nodal anatomy at CT lymphography during surgery, and a blue dye–staining method was also combined with this technique to search for the SLN. A total of 4–5 mL of 5% patent blue dye solute was injected into the four points around breast tumors. In patients with multiple SLNs that were seen as draining from tumoral and periareolar areas on the preoperative CT lymphographic scan, 3–4 mL of blue dye was additionally injected in the periareolar area (8,14) by one of the surgeons of the team. SLN biopsy was started within 10 minutes after a 30-second gentle massage of the sites where the blue dye was injected.

In the cases of breast-conserving surgery, a skin incision was made at the axilla along the axillary fold by referring to the external marker preoperatively placed on the CT lymphographic scan, and the blue dye–stained lymphatic tract connected to the SLN was pursued carefully. We traced any blue dye–stained lymphatic vessels first toward the breast, as we searched for the SLN in the axillary tail, and then we searched higher into the axilla, with care observed to preserve the lymphatic vessels intact until their nodes were identified and all SLNs stained with or not stained with blue dye were removed. In the cases of mastectomy, the SLN biopsy was similarly performed through the skin incision made at the anterior chest wall for the mastectomy. The location of each SLN was compared with the skin surface marker placed on the preoperative CT lymphographic scan. After SLN biopsy, complete axillary node dissection was performed in every patient. After measurement of the sizes of the resected nodes, including the SLN, by one of the surgeons of the team, serially sectioned specimens of all these SLNs and other distant nodes were separately sent to the laboratory for pathologic examination.

Image Interpretation
Before surgery, the first lymph node (ie, SLN) directly draining from the injection site in each patient was independently localized by each of two observers (K.S., A.T.) on the image viewer unit (Yokogawa-GE Medical, Tokyo, Japan) connected to the CT system. These observers had 21 and 17 years experience, respectively, in the reading of breast CT images. This independent interpretation was performed to investigate the consistency between the different observers. In addition, the size of the identified SLN (the maximum diameter of this node on consecutive postcontrast CT images) was measured.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
The CT lymphographic scans showed excellent enhancement of the drainage lymphatic pathways from the injection sites as early as on the first postcontrast images in all patients (Figs 1–4). The oval lymph nodes with greater diameters than those of the lymphatic vessels were easily identified on the transverse images. These lymphatic pathways were consistently enhanced throughout the examination time, although the lymphatic enhancement appeared to slightly decrease after the peak enhancement on the first or second postcontrast images. In 13 of 17 patients, regardless of the breast quadrant of the primary tumors, the lymphatic vessels from the peritumoral and periareolar areas were draining toward the axilla and joined, and then drained into, a single common axillary SLN at axillary level I (Fig 1). However, the remaining four patients had multiple SLNs directly draining from the different lymphatic routes; three patients had two (n = 2) or three (n = 1) axillary SLNs at level I (Fig 2), and one patient had one axillary SLN at level I and one parasternal SLN (Fig 3). Lymphatic connections between the peritumoral and periareolar areas were also visualized in 15 of 17 patients. The different angle views of the 3D CT image sets provided a comprehensive anatomy of these lymphatic pathways. The localization of each SLN was always consistent between the two observers (Figs 1–4). Overall, along the drainage lymphatic vessels from the injection sites, a total of 22 SLNs were identified in these 17 patients (Table). The diameter of these SLNs ranged from 3.4 to 36.4 mm (mean diameter, 7.5 mm ± 7.5 [SD]).



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  		Figure 1a. Patient 4. Images in patient with 28 x 20-mm breast tumor in left lower outer quadrant. (a) Transverse first postcontrast CT images. (b) Corresponding 3D CT lymphographic images. Left: Surface rendering. Right: Maximum intensity projection. Lymphatic pathways are substantially enhanced with interstitially injected iopamidol. Drainage lymphatic vessels (long arrows) from peritumoral and periareolar injection sites (arrowheads) drain into single axillary SLN at level I (short arrows). Several distant nodes (curved arrows) up to axillary level II also show enhancement. P = periareolar area, T = tumor site.

 


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  		Figure 1b. Patient 4. Images in patient with 28 x 20-mm breast tumor in left lower outer quadrant. (a) Transverse first postcontrast CT images. (b) Corresponding 3D CT lymphographic images. Left: Surface rendering. Right: Maximum intensity projection. Lymphatic pathways are substantially enhanced with interstitially injected iopamidol. Drainage lymphatic vessels (long arrows) from peritumoral and periareolar injection sites (arrowheads) drain into single axillary SLN at level I (short arrows). Several distant nodes (curved arrows) up to axillary level II also show enhancement. P = periareolar area, T = tumor site.

 


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  		Figure 2a. Patient 7. Images in a patient with 12 x 11-mm breast tumor in the right lower outer quadrant. (a) Transverse first postcontrast CT images. (b) Corresponding 3D CT lymphographic images. Top left: Maximum intensity projection 3D image. Bottom left: Surface-rendered image. Right: Maximum intensity projection 3D image. Drainage lymphatic vessels (long arrows) from peritumoral and periareolar sites (arrowheads) appear to drain into two axillary SLNs at level I (short arrows). Different angle views of the surface-rendered and maximum intensity projection 3D images clearly show that lymphatic vessels drain into two axillary SLNs. Keys are the same as for Figure 1.

 


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  		Figure 2b. Patient 7. Images in a patient with 12 x 11-mm breast tumor in the right lower outer quadrant. (a) Transverse first postcontrast CT images. (b) Corresponding 3D CT lymphographic images. Top left: Maximum intensity projection 3D image. Bottom left: Surface-rendered image. Right: Maximum intensity projection 3D image. Drainage lymphatic vessels (long arrows) from peritumoral and periareolar sites (arrowheads) appear to drain into two axillary SLNs at level I (short arrows). Different angle views of the surface-rendered and maximum intensity projection 3D images clearly show that lymphatic vessels drain into two axillary SLNs. Keys are the same as for Figure 1.

 


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  		Figure 3a. Patient 9. Images in a patient with 16 x 14-mm breast tumor in the right upper inner quadrant. (a) Transverse first postcontrast CT images. (b) Corresponding 3D CT lymphographic images. Although drainage lymphatic vessels (long arrows) from the periareolar site (arrowhead P) drain into the axillary SLN at level I (short arrows), those from the peritumoral site (arrowhead T) drain into the parasternal SLN (short arrows). Different angle views of the maximum intensity projection 3D CT images clearly show the lymphatic vessels draining into the axillary and parasternal areas (long arrows). Keys are the same as for Figure 1.

 


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  		Figure 3b. Patient 9. Images in a patient with 16 x 14-mm breast tumor in the right upper inner quadrant. (a) Transverse first postcontrast CT images. (b) Corresponding 3D CT lymphographic images. Although drainage lymphatic vessels (long arrows) from the periareolar site (arrowhead P) drain into the axillary SLN at level I (short arrows), those from the peritumoral site (arrowhead T) drain into the parasternal SLN (short arrows). Different angle views of the maximum intensity projection 3D CT images clearly show the lymphatic vessels draining into the axillary and parasternal areas (long arrows). Keys are the same as for Figure 1.

 


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  		Figure 4a. Patient 17. Images in a patient with 35 x 34-mm breast tumor in right upper outer quadrant. (a) Transverse first postcontrast CT images. (b) Corresponding 3D CT lymphographic images. These images show that drainage lymphatic vessels (long arrows) from peritumoral and periareolar sites (arrowheads) drain into a single axillary SLN at level I (short arrow); however, this SLN (*) is not enhanced. Instead, the subsequent distant node was enhanced (curved arrow). In this case, the histologic findings of this SLN revealed marked tumoral infiltration. Keys are the same as for Figure 1.

 


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  		Figure 4b. Patient 17. Images in a patient with 35 x 34-mm breast tumor in right upper outer quadrant. (a) Transverse first postcontrast CT images. (b) Corresponding 3D CT lymphographic images. These images show that drainage lymphatic vessels (long arrows) from peritumoral and periareolar sites (arrowheads) drain into a single axillary SLN at level I (short arrow); however, this SLN (*) is not enhanced. Instead, the subsequent distant node was enhanced (curved arrow). In this case, the histologic findings of this SLN revealed marked tumoral infiltration. Keys are the same as for Figure 1.

 

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  		Data about Tumor and SLN

 
At surgery, the SLN could be easily identified and resected with the guidance of the skin surface marker and CT lymphography in all patients, including three with a large fatty axilla. The routes of the blue dye–stained draining lymphatic vessels appeared consistent with those observed on the preoperative CT lymphographic scan. In the four cases with multiple SLNs, including one parasternal SLN, the corresponding SLN could be found along the blue dye–stained lymphatic vessels. The SLN was usually most intensely stained with blue dye, although one to three other blue dye–stained distant nodes were simultaneously found in each patient. However, in the four patients with an unenhanced SLN on the CT lymphographic scan, the SLN and other distant nodes did not show any blue stain. Overall, in each patient, a total of 16–25 lymph nodes that included the preoperatively marked SLN were resected (Table). The diameter (mean, 7.7 mm ± 7.4; range, 3.2–36.5 mm) of each resected SLN (n = 22) was almost consistent with that measured on CT images.

The histologic analysis revealed no metastases in any of the resected SLNs and distant nodes in 12 of 17 patients (Figs 1–3). However, one patient with a well-enhanced SLN at CT lymphography had micrometastasis (<2 mm in diameter) in the serially sectioned specimen of this SLN. In the four patients with unenhanced SLNs and lymph flow rerouting at CT lymphography, the SLNs were almost entirely replaced by tumoral tissue, with multiple positive distant nodes (Fig 4).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
REFERENCES
 
By means of quick and sufficient visualization of the direct connection between the SLN and its afferent lymphatic vessels with detailed cross-sectional lymphatic anatomy, CT lymphography allowed accurate localization of the SLN. CT lymphography allowed accurate localization even in the patients with lymph flow rerouting toward the subsequent distant nodes and in those with multiple SLNs, including a parasternal one. The topographic 3D CT images facilitated comprehensive perception of the anatomy of the lymphatic pathway and provided the correct location of the SLNs. At surgery, the SLNs marked by using the CT lymphographic scan could be easily identified, and the locations and the draining lymphatic routes of the SLNs were consistent with those assessed at CT lymphography. Thus, this technique appears to have an excellent potential in preoperative SLN mapping for breast SLN biopsy.

To date, although gamma probe– and vital dye–guided SLN mapping have shown favorable results (1–21), there are some disadvantages and potential pitfalls in SLN biopsy with these methods (4,8,14–21). Lymphoscintigraphy has the disadvantages of poor spatial resolution and the lack of accurate anatomic landmarks and geometry. Intraoperative external gamma probe counting requires some skill for accurate identification of the SLN (2,4,8,12,20,21). Visualization of the draining lymphatic pathway is poor in some cases, because of slow lymphatic migration of radiocolloids or because of the radiocolloid particle size (8,11). Sufficient nodal uptake of radiocolloid may be interrupted by impaired phagocytosis capacity of macrophages (8,11). The blue dye–stained lymphatic vessels and/or nodes may not be readily apparent in the fatty axilla (4,8,17). Spillover of the blue dye and radiotracer from SLN to the subsequent distant nodes may increase the number of stained or labeled non-SLNs. Several blue dye–stained lymph nodes other than the primary SLN identified by using CT lymphography were often found at surgery in the present patients (4,8,16,17). The lymph nodes with the highest radioactivity and blue dye staining are not necessarily defined as the primary SLN (7,16,19,20). As seen in four of the present patients, in the primary SLN there may not be any accumulation of markers because of mechanical obstruction from extensive tumoral infiltration, and alternative nodes may become SLNs because of lymph flow rerouting (8,20). Furthermore, gamma probe–directed SLN mapping may be difficult when the SLN is close to the injection site because of shine-through radioactivity (7,8,20,21).

The ability of CT lymphography to allow effective visualization of breast lymphatic drainage with detailed anatomy may eliminate the potential pitfalls of the scintigraphic and blue dye–staining methods. The excellent visualization of the direct connection between the first lymph node and its afferent lymphatic vessels is of value for determining the true SLN even when subsequent distant nodes are variably enhanced because of spillover of iopamidol, as was frequently observed in the present patients. This ability is also of value for detection of multiple SLNs, as demonstrated in several patients in the present study. Findings of previous studies with scintigraphy and blue dye also demonstrated the presence of multiple SLNs in some patients (4,8,14).

For SLN biopsy, accurate differentiation between SLN and distant nodes is important, since focusing on just one or a few SLNs for extensive histologic evaluation increases accuracy (2,4,12,14). Since CT lymphography allowed accurate recognition of the unenhanced primary SLN and lymph flow rerouting in the present four patients, the detailed lymphatic anatomy provided by this technique may contribute to accurate localization of the true SLN in cases with lymph flow rerouting caused by gross SLN metastases. CT lymphography is rather sensitive to imaging of small structures surrounded by fatty tissues, and preoperative CT lymphography–guided SLN mapping may help in the detection of SLN in the fatty axilla, since an SLN survey with blue dye often is not easy because of obliteration with adipose tissue (8,14,16).

Currently, relative changes in lymph node position before and during surgery might make CT lymphography less effective, especially for the SLN located deep in the fatty axilla. Placement of a radiopaque internal marker for the identified SLN may allow accurate localization of this SLN and preoperative SLN mapping at any convenient time, even in hospitals without a nuclear medicine department. Although the multi–detector row helical CT unit contributed to quick acquisition and excellent quality of the 3D images of the small lymphatic vessels, CT lymphographic scans may be obtained even with a widely available single–detector row helical CT unit because of the relatively prolonged lymphatic enhancement with iopamidol.

The mammary gland is, in a sense, a single biologic unit with the skin because of its embryologic origin from ectoderm, and lymphatic drainage from almost the entire mammary gland and from the overlying skin usually share a common centrifugal lymphatic pathway toward the same axillary nodes (2,4,16,24,25). This explains the joining of the drainage lymphatic vessels from the periareolar and peritumoral areas and the subsequent drainage into a single common axillary SLN in the majority of the present patients. However, as seen in the present exceptional case and as was occasionally encountered in previous scintigraphic studies, medially located breast tumors may drain into the parasternal internal mammary chains (2,4,7,8,21).

Although the exact mechanisms of iopamidol uptake and transport in the lymphatic system are unknown, this agent appears to penetrate easily into the lymphatic vessels through the clefts in the terminal lymphangioles of the interstitial space, similar to other water-soluble low-molecular-weight solutes (25–28). This agent relies passively on prevailing fluid dynamics to produce a flow of lymph that is visible with x rays. Its distribution in the lymphatic pathways may depend on the complex interaction of the volume administered; flow restriction of contrast media; and the number, size, and integrity of associated peripheral lymphatic vessels and nodes (28–30). The relatively long duration of nodal enhancement may be related to slow transission and sequestration of iopamidol in the nodal sinusoids (28–30). The excellent enhancement of the SLN may be related to greater compartmentalization in this node caused by direct flow restriction of iopamidol. Gentle massage of the injection sites facilitates migration and nodal accumulation of iopamidol, and this procedure is advantageous for shortening the examination time (4,8,11,15). Although iopamidol may partly drain into the venous system, the volume appears to be negligible in the breast, because no noticeable venous enhancement was visually observed in the present study. The reason for this selective enhancement of lymphatic drainage is unknown, but it is greatly beneficial for obtaining a good-quality CT lymphographic scan.

Indirect CT lymphography is possible by using iodinated lymphotropic nanoparticles, such as perflubron or chylomicron remnant–like emulsion or nanocrystalline suspensions of the ethylester of diatrizoic acid (31–35). However, the majority of these contrast media with lymphotropic properties associated with phagocytosis activity of macrophages show slow maximum nodal enhancement between 4 and 24 hours after administration. In addition, they are not trapped selectively in the primary SLN (31–35). Furthermore, these agents are not yet commercially available, and the safety profile remains unknown. In contrast, iopamidol appears to offer a favorable safety potential, as local inflammation and swelling were reported to be minimal and temporary when the volume of extravasated contrast medium was less than 20 mL in a clinical setting (36,37). Rapid disappearance of swelling in the injection sites may be related to rapid spread of this agent into the interstitial space and transfer to the lymphatic system, and this activity may prevent tissue injury caused by persistent mechanical compression. However, a further survey of side effects such as inflammatory reaction and necrosis in subcutaneous tissues of the injection sites is needed in a further study of a large number of subjects.

In conclusion, indirect CT lymphography with iopamidol appears to be clinically applicable for breast SLN mapping. Its excellent depiction of the direct connection between SLN and its afferent lymphatic vessels with detailed cross-sectional anatomy may address the potential disadvantages of the scintigraphic and blue dye–staining methods. It is beneficial for clinical practice that quick CT lymphography can be simultaneously performed with routine contrast-enhanced abdominal and/or thoracic CT to evaluate distant metastases. However, the multiplicity of SLNs and other distant nodes per patient, the histologic and functional status of the breast, age, and hormone replacement therapy experience may have an effect on lymphatic enhancement and on outcome. There may be interaction between lymph nodes. Further studies are warranted to clarify these issues. Further studies are also required to determine the clinical effectiveness of CT lymphography, compared with scintigraphic and/or blue dye–staining methods.


   FOOTNOTES
 
Abbreviations: SLN = sentinel lymph node, 3D = three-dimensional

Author contributions: Guarantor of integrity of entire study, K.S.; study concepts and design, K.S., A.T.; literature research, Y.Y.; clinical studies, K.S., A.T., M. Oka, S.Y.; data acquisition, K.S., A.T., Y.Y.; data analysis/interpretation, M. Okada, A.T., K.S., Y.Y.; statistical analysis, M. Okada; manuscript preparation, editing, and final version approval, K.S.; manuscript definition of intellectual content and revision/review, N.M.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 

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