Name: ultrasonographic evaluation of breast cancer-related lymphedema
Uploaded: 2017-01-12T13:00:00.000+00:00
Duration: 5 min 44 s
Description: Watch this Scientific Journal Video about Ultrasonographic Evaluation of Breast Cancer-related Lymphedema at JoVE.com

The authors have nothing to acknowledge.

All of the procedures were reviewed and approved by the Institutional Review Board of Chungnam National University Hospital.
1. Measurement with Ultrasonography
<ol>
	<li>Set the posture of the patient.
	<ol>
		<li>Lay the patient&#39;s arm in a supine position, with both arms on the bed.</li>
	</ol>
	</li>
	<li>Determine the measurement sites on the patient&#39;s upper limb.
	<ol>
		<li>Mark in the mid-point of the wrist crease, the mid-point between the medial and lateral epicondyles at the level of the elbow, and the bicipital groove by a pen.</li>
		<li>Using a pen directly connect these three points by a ruler. Mark the two target areas on the upper arm and forearm (Figure 1).
		<ol>
			<li>Mark the proximal part, 10 cm proximal to the elbow point along the line between the elbow and bicipital groove.</li>
			<li>Mark the distal part, 10 cm distal to the elbow point along the line between the elbow and wrist.</li>
		</ol>
		</li>
	</ol>
	</li>
	<li>Measure the thickness of the subcutaneous tissue and muscle of the upper limb. The procedure should be performed by a skilled sonographer.
	<ol>
		<li>Switch on the ultrasound system. Enter 2D mode of soft tissue via the keyboard. Set the depth to 5 cm.
		<ol>
			<li>Choose the 14L5 linear array transducer.</li>
			<li>Apply sufficient gel to the ultrasound transducer. Focus on the subcutaneous tissue.</li>
		</ol>
		</li>
		<li>Place the ultrasound transducer perpendicularly to the upper limb ventral axis. Use the short-axis view. Capture the image where the thickness of the gel is at least 1 cm and the soft tissue contour is not distorted.</li>
		<li>Measure the thicknesses of the muscle and subcutaneous tissue.
		<ol>
			<li>Draws a line by selecting the calibrator in the software via the keyboard of the ultrasound system</li>
			<li>Measure the thickness of the muscle, defined as the distance from the highest point on the boundary of the bone to the highest point on the boundary portion of the fascia (Figure 2).</li>
			<li>Measure the thickness of the subcutaneous tissue, defined as the distance from the skin to the fascia.</li>
		</ol>
		</li>
	</ol>
	</li>
</ol>
2. Clinical Application of Ultrasonography to BCRL
<ol>
	<li>Measure the thickness of the subcutaneous tissue and muscle of the upper limb at baseline.
	<ol>
		<li>Perform the baseline measurements in the order shown in Step 1.</li>
	</ol>
	</li>
	<li>Instruct the patient to perform a series of PREs using a 0.5 kg dumbbell14.
	<ol>
		<li>Give the patient a compression stocking or a multilayer bandage to wear. Choose a 0.5 kg dumbbell.</li>
		<li>Instruct the patient to perform the PREs in the following order: (1) dumbbell fly, (2) triceps extension, (3) one arm bent-over row, (4) biceps curl, (5) dumbbell side raise, and (6) lifting the arms forward (Figure 3).
		<ol>
			<li>Instruct the patient to complete the 6 exercises twice a day, according to the following schedule: 5 times each during the 1st week, 10 times each during the 2nd week, 15 times each during the 3rd week, 20 times each during the 4th week, and 25&#160;times each during 5th-8th weeks (Figure 4).</li>
		</ol>
		</li>
	</ol>
	</li>
	<li>Use ultrasonography to identify the therapeutic effects of PRE compared to conventional therapy.
	<ol>
		<li>Measure the thickness of the subcutaneous tissue and muscle of the upper limb at 4 and 8 weeks. Perform the measurements in the order shown in Step 1.</li>
	</ol>
	</li>
	<li>Calculate the thickness of the subcutaneous tissue and muscle at baseline, 4 weeks, and 8 weeks.</li>
	<li>Analyze the data.
	<ol>
		<li>Compare the difference between both arms using a paired t-test. Compare the changes in subcutaneous tissue and muscle thickness using a repeated-measures ANOVA.</li>
	</ol>
	</li>
</ol>

<ol>
	<li>Lasinski, B. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Complete+decongestive+therapy+for+treatment+of+lymphedema.">Complete decongestive therapy for treatment of lymphedema.</a> Seminars in Oncology Nursing. 29 (1), 20-27 (2013).</li><li>Clark, B., Sitzia, J., Harlow, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Incidence+and+risk+of+arm+oedema+following+treatment+for+breast+cancer:+a+three-year+follow-up+study.">Incidence and risk of arm oedema following treatment for breast cancer: a three-year follow-up study.</a> Q J Med. 98 (5), 343-348 (2005).</li><li>Hayes, S. C., Speck, R. M., Reimet, E., Stark, A., Schmitz, K. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Does+the+effect+of+weight+lifting+on+lymphedema+following+breast+cancer+differ+by+diagnostic+method:+results+from+a+randomized+controlled+trial.">Does the effect of weight lifting on lymphedema following breast cancer differ by diagnostic method: results from a randomized controlled trial.</a> Breast Cancer Res Treat. 130 (1), 227-234 (2011).</li><li>Fu, M. R., Ridner, S. H., Armer, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Post-breast+cancer+lymphedema:+part+1.">Post-breast cancer lymphedema: part 1.</a> Am J Nurs. 109 (7), 48-54 (2009).</li><li>Rockson, S. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasonography+in+the+Evaluation+of+Breast+Cancer-Related+Lymphedema.">Ultrasonography in the Evaluation of Breast Cancer-Related Lymphedema.</a> Lymphatic Research and Biology. 14 (1), 1 (2016).</li><li>Suehiro, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Significance+of+Ultrasound+Examination+of+Skin+and+Subcutaneous+Tissue+in+Secondary+Lower+Extremity+Lymphedema.">Significance of Ultrasound Examination of Skin and Subcutaneous Tissue in Secondary Lower Extremity Lymphedema.</a> Ann Vasc Dis. 6 (2), 180-188 (2013).</li><li>Lee, J. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasonographic+Evaluation+of+Therapeutic+Effects+of+Complex+Decongestive+Therapy+in+Breast+Cancer-Related+Lymphedema.">Ultrasonographic Evaluation of Therapeutic Effects of Complex Decongestive Therapy in Breast Cancer-Related Lymphedema.</a> Ann Rehabil Med. 37 (5), 683-689 (2013).</li><li>DiSipio, T., Rye, S., Newman, B., Hayes, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Incidence+of+unilateral+arm+lymphoedema+after+breast.">Incidence of unilateral arm lymphoedema after breast.</a> Lancet Oncol. 14 (6), 500-515 (2013).</li><li>Stanton, A. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lymphatic+drainage+in+the+muscle+and+subcutis+of+the+arm+after+breast+cancer+treatment.">Lymphatic drainage in the muscle and subcutis of the arm after breast cancer treatment.</a> Breast Cancer Res Treat. 117 (3), 549-557 (2008).</li><li>Godoy, M. F. G., Pereira, M. R., Oliani, A. H., Godoy, J. M. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synergic+Effect+of+Compression+Therapy+and+Controlled+Active+Exercises+Using+a+Facilitating+Device+in+the+Treatment+of+Arm+Lymphedema.">Synergic Effect of Compression Therapy and Controlled Active Exercises Using a Facilitating Device in the Treatment of Arm Lymphedema.</a> Int J Med Sci. 9 (4), 280-284 (2012).</li><li>Cormie, P., Pumpa, K., Galv&#227;o, D. A., Turner, E., Spry, N., Saunders, C., Zissiadis, Y., Newton, R. U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Is+it+safe+and+efficacious+for+women+with+lymphedema+secondary+to+breast+cancer+to+lift+heavy+weights+during+exercise:+a+randomised+controlled+trial.">Is it safe and efficacious for women with lymphedema secondary to breast cancer to lift heavy weights during exercise: a randomised controlled trial.</a> J Cancer Surviv. 7 (3), 413-424 (2013).</li><li>Bok, S. K., Jeon, Y., Hwang, P. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasonographic+evaluation+of+the+effects+of+progressive+resistive+exercise+in+breast+cancer-related+lymphedema.">Ultrasonographic evaluation of the effects of progressive resistive exercise in breast cancer-related lymphedema.</a> Lymphatic Research and Biology. 14 (1), 18-24 (2016).</li><li>Milne, H. M., Wallman, K. E., Gordon, S., Courneya, K. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+a+combined+aerobic+and+resistance+exercise+program+in+breast+cancer+survivors:+a+randomized+controlled+trial.">Effects of a combined aerobic and resistance exercise program in breast cancer survivors: a randomized controlled trial.</a> Breast Cancer Res Treat. 108 (2), 279-288 (2008).</li><li>Schmitz, K. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Weight+lifting+for+women+at+risk+for+breast-cancer-related+lymphedema.">Weight lifting for women at risk for breast-cancer-related lymphedema.</a> JAMA. 304 (24), 2699-2705 (2010).</li><li>Kiel, K. D., Rademacker, A. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Early-stage+breast+cancer:+Arm+edema+after+wide+excision+and+breast+irradiation.">Early-stage breast cancer: Arm edema after wide excision and breast irradiation.</a> Radiology. (1), 279-283 (1996).</li></ol>

The authors have nothing to disclose.

Evaluations of BCRL can be conducted through various techniques, including arm circumferences tape measurement, water displacement measurement, bioimpedance spectroscopy, perometry (optoelectronic volumeter), lymphoscintigraphy, clinician diagnosis, or swelling self-reports by the patient. However, there are no standards for the measurement of BCRL; the diagnosis and duration of treatment can be determined empirically in a number of ways, depending upon the clinic.
Clinically, measuring arm circumference by tape measure is the most popular and convenient method. However, this method cannot evaluate structural changes in the subcutaneous tissue, and errors can be caused by excessive tape measure pressure on the skin, inaccurately marked points, and an improper measurement angle in relation to the long axis of the limb. Furthermore, tape measurement may be less accurate than water displacement or perometry in estimating the volume of lymphedema.
Volumetry using water or an infrared light beam are excellent procedures that can give the volume of the upper limb automatically. However, volumetry cannot check the structural changes in the subcutaneous tissue and is not suitable for the proximal part of the limb and trunk. Other weaknesses are that the water displacement method is time-consuming and inconvenient, while the perometry method is very expensive.
Bioimpedance spectroscopy has been shown to be sensitive to early extracellular fluid changes, which are reliable, reproducible, and easy to manage. However, there is no standardized reference, and it has not been used in bilateral lymphedema. It also has limitations in detecting non-pitting edema at later stages, where the interstitial fluids have been replaced by deposition of adipose tissue and/or fibrotic tissue.
Ultrasonography is a clinically convenient tool; the examiner can evaluate the status of soft tissues in the office setting. The thickness of the cutaneous, epifascial, and subfascial tissue can be measured by ultrasonography, which can elucidate the fluid collection and fibrosis. In contrast to CT or MRI, ultrasonography is readily available in many clinics and is also noninvasive and inexpensive.
Ultrasonography is a relatively subjective technique whose findings can be affected by the examiner&#39;s skill. Ultrasonic measurements are operator-dependent, and technical differences in pressure application may affect the results of subcutaneous volume and compliance. However, if practitioners perform the procedure at the correct site, and if the technique can be mastered precisely, it is possible to overcome this weakness of ultrasonography.
The critical steps during ultrasonic evaluation are keeping the contour of soft tissue constant and defining the muscle thickness. The soft tissue is likely to be distorted by pressure from the examiner, so the practitioner should put sufficient gel on the transducer and maintain constant pressure to keep the subcutaneous tissue even. The thickness of the muscle is defined as the distance from the highest point on the boundary of the bone to the highest point on the boundary portion of the fascia; it is important to determine the highest point on the boundary of the bone.
This study showed that the muscle thickness in the affected arm significantly decreased more than in the unaffected side, as measured by ultrasonography. The primary causes may be the direct damage of muscles by surgery or the influence of radiation therapy or chemotherapy on the tissue. Another cause is the tendency to avoid using the affected arm. Many patients have a considerable fear that the swelling of the arm occurs due to resistive exercise. They only perform stretching and low-level aerobic exercises such as walking, so a reduction of muscle mass appears to occur. However, in the previous studies, PRE does not induce deterioration in cases of lymphedema11,13,14.
The present study found that the thickness of subcutaneous tissue was more decreased in the PRE group than in the non-PRE. Also, the PRE group had a greater increase in muscular thickness than the non-PRE group. These changes are easily measured by ultrasonography, which can more accurately distinguish between muscular and edematous areas than other tools. Ultrasonography is widely used in many clinics because of its easy accessibility, safety, and inexpensiveness3,4. Therefore, if the techniques of ultrasonography are skillfully acquired, ultrasonography may become the first-choice method of diagnosing and determining treatment efficacy on BCRL.
The main limitation of the current study relates to the subjectivity of ultrasound. However, ultrasound has been widely used in many medical fields despite this weakness. If the examiners learn the precise techniques, ultrasonography will become a valid method for measuring lymphedema. Diagnosis of lymphedema using ultrasound will be further generalized, because of its ease to measure the change of lymphedema in the clinics. Efforts will have to be made to reduce the variability of each test, such as increasing the sensitivity of the machine or finding the standard landmark.

Lymphedema is defined as a condition of localized protein-rich fluid retention and tissue swelling caused by a compromised lymphatic system1,2. As lymphedema progresses, fibrocytes and/or adipocytes proliferate in the affected areas, leading to changes in the texture of the skin and subcutaneous tissue and an increased vulnerability to bacterial and fungal infections3,4. The observation of these changes in various parts of the extremities may further elucidate the severity and extent of lymphedema. The subfascial lymphatic system contributes to the severity of lymphedema more than the epifascial lymphatic system.
Recent research has mainly focused on the use of ultrasonography in the diagnosis of lymphedema5,6. Ultrasonography is a relatively inexpensive method to observe soft-tissue characteristics. A previous study reported that lymphedema can be reliably diagnosed with ultrasonography by comparing the thickness of the skin and subcutaneous tissue and also by evaluating the compliance of the subcutaneous tissue in a clinical setting7,8. In addition, ultrasonography is widely used in the clinic because of its easy accessibility, safety from radiation exposure, and inexpensiveness5,6. In spite of these benefits, studies on ultrasonography for lymphedema have only been focused on diagnosis, not on evaluation of therapeutic intervention.
Therefore, the current study aimed to determine not only the usefulness of ultrasonography in elucidating the effects of PRE&#160;on BCRL, but also whether ultrasonography has a clinical significance as a follow-up test in confirming treatment efficacy. This study was conducted to establish the protocol for ultrasounds performed to examine lymphedema.

<table><tbody><tr><td>ACUSON S2000</td><td>Siemens</td><td>10041461</td><td></td></tr><tr><td>Eco Gel 99</td><td>Seung Won Medical Corp.</td><td></td><td></td></tr></tbody></table>

ultrasonographic evaluation of breast cancer-related lymphedema

Lymphedema is one of the most common complications after breast cancer surgery. There are many diagnostic tools for lymphedema, but no standard method yet exists. Progressive Resistance Exercise (PRE) is expected to improve lymphedema without additional swelling. This study showed the therapeutic effects of PRE on lymphedema by using ultrasonography to measure the change in thickness of the muscle and subcutaneous tissue. The thickness of subcutaneous tissue decreased more in the PRE group than in the non-PRE group. Ultrasonography is widely used in many clinics because of its easy accessibility, safety, and inexpensiveness. Ultrasound is one of the best tools for diagnosing and determining treatment efficacy on breast cancer-related lymphedema (BCRL).

This study included 32 patients diagnosed with BCRL. The thickness of muscle and subcutaneous tissue and the circumferences of proximal and distal upper limbs were measured at baseline, 4 weeks, and 8 weeks after PRE. Examiners measured the circumference of upper limbs with a tape measure, and then the thickness of the muscle and subcutaneous tissue were measured by ultrasonography. Patients were randomly divided into a PRE group and a non-PRE group. Participants were reminded to not reveal their group assignment before measurement and evaluation sessions.
At baseline, the initial muscle thickness (cm) of all participants measured by ultrasonography was significantly lower in the lymphedematous arm compared to the unaffected arm (Table 1). The subcutaneous tissue in the arm affected with lymphedema was significantly thicker compared to the unaffected arm (Table 1).
According to the tape measurement, arm circumference did not significantly change in the PRE group after 4 weeks of exercises; however, both distal and proximal arm circumferences showed a significant reduction after 8 weeks. These circumferences did not significantly change in the control group (Figure 5).
As measured by ultrasonography in the PRE group, the thickness of muscle in the distal part showed significant increases at 4 weeks and 8 weeks, and the proximal part demonstrated a significant increase in thickness at 8 weeks (Figure 6). Statistical analyses were performed using SPSS 12.0. Statistical significance for the differences between both arms was tested using a paired t-test. Changes in the subcutaneous tissue and muscle thickness, and upper limb circumference were analyzed using repeated-measures ANOVA. Statistical significance level was set at the p-value of 0.05 or less.
In the PRE group, the thickness of subcutaneous tissue in the affected upper limb significantly decreased after 8 weeks. No significant difference in these parameters was observed in the non-PRE group (Figure 7).
<img alt="Figure 1" src="/files/ftp_upload/54996/54996fig1.jpg" /> 
Figure 1. A Photograph Illustrating the Measurement Sites on a Patient&#39;s Upper Limb. The mid-point of the wrist crease, the mid-point between the medial and lateral epicondyles at the level of the elbow, and the bicipital groove were marked. These three points were connected linearly, and the 3 measuring sites were marked: (A) the midpoint at the elbow (elbow), (B) 10 cm above the mid-point at the elbow (proximal), and (C) 10 cm below the mid-point at the elbow (distal).
<img alt="Figure 2" src="/files/ftp_upload/54996/54996fig2.jpg" /> 
Figure 2. Measurements of the Thickness of Muscle and Subcutaneous Tissue on the Upper Limbs. Ultrasound was used to measure the thickness of the muscle and subcutaneous tissue at the determined points. S.C., the thickness of subcutaneous tissue; M., the thickness of muscle. Reprinted with permission from12.
<img alt="Figure 2" src="/files/ftp_upload/54996/54996fig3.jpg" /> 
Figure 3. The PRE Protocol. The prescribed exercises include: 1) dumbbell fly, 2) triceps extension, 3) one arm bent-over row, 4) biceps curl, 5) dumbbell side raise, and 6) lifting the arms forward. Reprinted with permission from12.
<img alt="Figure 2" src="/files/ftp_upload/54996/54996fig4.jpg" /> 
Figure 4. PRE Evaluation. Patients were evaluated at baseline and after 4 and 8 weeks. Reprinted with permission from 12.
<img alt="Figure 5" src="/files/ftp_upload/54996/54996fig5.jpg" /> 
Figure 5. Tape Measurements of the Circumferences of the Affected and Unaffected Limb. The change in upper limb circumferences. *p &#60;0.05, according to repeated measurements by ANOVA. Reprinted with permission from 12.
<img alt="Figure 6" src="/files/ftp_upload/54996/54996fig6.jpg" /> 
Figure 6. Ultrasonography Measurements of the Thickness of Muscle on the Affected and Unaffected Limb. The change in muscle thickness. *p &#60;0.05, according to repeated-measurements by ANOVA. Reprinted with permission from 12.
<img alt="Figure 2" src="/files/ftp_upload/54996/54996fig7.jpg" /> 
Figure 7. Ultrasonography Measurements of the Thickness of Subcutaneous Tissue on the Affected and Unaffected Limb. The change in the thickness of subcutaneous tissue. *p &#60;0.05, according to repeated-measurements by ANOVA. Reprinted with permission from 12.
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td colspan="2">Thickness</td>
			<td>Affected arm</td>
			<td>Unaffected arm</td>
			<td>P-value</td>
		</tr>
		<tr>
			<td rowspan="2">Muscle</td>
			<td>Proximal</td>
			<td>2.01 (0.63)</td>
			<td>2.12 (0.55)</td>
			<td>0.025*</td>
		</tr>
		<tr>
			<td>Distal</td>
			<td>0.92 (0.37)</td>
			<td>1.04 (0.35)</td>
			<td>0.037*</td>
		</tr>
		<tr>
			<td rowspan="2">Subcutaneous tissue</td>
			<td>Proximal</td>
			<td>0.87 (0.37)</td>
			<td>0.54 (0.49)</td>
			<td>0.016*</td>
		</tr>
		<tr>
			<td>Distal</td>
			<td>0.67 (0.22)</td>
			<td>0.49 (0.42)</td>
			<td>0.02*</td>
		</tr>
	</tbody>
</table>

Values are presented as mean (standard deviation)
*p&#60;0.05, according to paired t-test.
Table 1. Ultrasonography Measurements of the Initial Difference in Thickness between Both Upper Limbs of All Participants. The initial muscle thickness (cm) of all participants measured by ultrasonography significantly decreased in the affected arm compared to the unaffected arm at baseline measurement. Values are presented as mean (standard deviation). *p &#60;0.05, according to paired t-test. Reprinted with permission from 12.

Watch this Scientific Journal Video about Ultrasonographic Evaluation of Breast Cancer-related Lymphedema at JoVE.com

Ultrasonographic Evaluation of Breast Cancer-related Lymphedema

This study utilized ultrasonography for diagnosis and follow-up tests to confirm treatment efficacy of Progressive Resistance Exercise (PRE) in breast cancer-related lymphedema (BCRL). Ultrasonography can be applied effectively to ensure diagnosis and treatment of lymphedema.

Lymphedema is one of the most common complications after breast cancer surgery. There are many diagnostic tools for lymphedema, but no standard method yet ...

ultrasonographic-evaluation-of-breast-cancer-related-lymphedema

Nanyang Technological University

Research

JoVE Journal

Cancer Research

9.2K Views.  Chungnam National University Hospital (CNUH).  Deze studie gebruikt echografie voor diagnose en follow-up tests om werkzaamheid van de behandeling van Progressive Resistance Exercise (PRE) te bevestigen bij borstkanker in verband met lymfoedeem (BCRL). Echografie kan effectief worden toegepast voor diagnose en behandeling van lymfoedeem waarborgen. 

Video: Ultrasonographic Evaluation of Breast Cancer-related Lymphedema

Non-invasive Optical Imaging of the Lymphatic Vasculature of a Mouse

The lymphatic vascular system is an important component of the circulatory system that maintains fluid homeostasis, provides immune surveillance, and mediates fat absorption in the gut. Yet despite its critical function, there is comparatively little understanding of how the lymphatic system adapts to serve these functions in health and disease1. Recently, we have demonstrated the ability to dynamically image lymphatic architecture and lymph "pumping" action in normal human subjects as well as in persons suffering lymphatic dysfunction using trace administration of a near-infrared fluorescent (NIRF) dye and a custom, Gen III-intensified imaging system2-4. NIRF imaging showed dramatic changes in lymphatic architecture and function with human disease. It remains unclear how these changes occur and new animal models are being developed to elucidate their genetic and molecular basis. In this protocol, we present NIRF lymphatic, small animal imaging5,6 using indocyanine green (ICG), a dye that has been used for 50 years in humans7, and a NIRF dye-labeled cyclic albumin binding domain (cABD-IRDye800) peptide that preferentially binds mouse and human albumin8. Approximately 5.5 times brighter than ICG, cABD-IRDye800 has a similar lymphatic clearance profile and can be injected in smaller doses than ICG to achieve sufficient NIRF signals for imaging8. Because both cABD-IRDye800 and ICG bind to albumin in the interstitial space8, they both may depict active protein transport into and within the lymphatics. Intradermal (ID) injections (5-50 &mu;l) of ICG (645 &mu;M) or cABD-IRDye800 (200 &mu;M) in saline are administered to the dorsal aspect of each hind paw and/or the left and right side of the base of the tail of an isoflurane-anesthetized mouse. The resulting dye concentration in the animal is 83-1,250 &mu;g/kg for ICG or 113-1,700 &mu;g/kg for cABD-IRDye800. Immediately following injections, functional lymphatic imaging is conducted for up to 1 hr using a customized, small animal NIRF imaging system. Whole animal spatial resolution can depict fluorescent lymphatic vessels of 100 microns or less, and images of structures up to 3 cm in depth can be acquired9. Images are acquired using V++ software and analyzed using ImageJ or MATLAB software. During analysis, consecutive regions of interest (ROIs) encompassing the entire vessel diameter are drawn along a given lymph vessel. The dimensions for each ROI are kept constant for a given vessel and NIRF intensity is measured for each ROI to quantitatively assess "packets" of lymph moving through vessels.

Recently developed imaging techniques using near-infrared fluorescence (NIRF) may help elucidate the role the lymphatic system plays in cancer metastasis, immune response, wound repair, and other lymphatic-associated diseases.

The lymphatic  vascular system is an important component of the circulatory system that  maintains fluid homeostasis, provides immune surveillance, and ...

Immunology and Infection

Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma

Tyr::CreER+,BrafCA/+,Ptenlox/lox&#160;genetically engineered mice (Braf/Pten mice) are widely used as an in vivo model of metastatic melanoma. Once a primary tumor has been induced by tamoxifen treatment, an increase in metastatic burden is observed within 4-6 weeks after induction. This paper shows how Ultra-High-Frequency UltraSound (UHFUS) imaging can be exploited to monitor the increase in metastatic involvement of the inguinal lymph nodes by measuring the increase in their volume.
The UHFUS system is used to scan anesthetized mice with a UHFUS linear probe (22-55 MHz, axial resolution 40 &#181;m). B-mode images from the inguinal lymph nodes (both left and right sides) are acquired in a short-axis view, positioning the animals in dorsal recumbency. Ultrasound records are acquired using a 44 &#181;m step size on a motorized mechanical arm. Afterward, two-dimensional (2D) B-mode acquisitions are imported into the software platform for ultrasound image post-processing, and inguinal lymph nodes are identified and segmented semi-automatically in the acquired cross-sectional 2D images. Finally, a total reconstruction of the three-dimensional (3D) volume is automatically obtained along with the rendering of the lymph node volume, which is also expressed as an absolute measurement.
This non-invasive in vivo technique is very well tolerated and allows the scheduling of multiple imaging sessions on the same experimental animal over 2 weeks. It is, therefore, ideal to assess the impact of pharmacological treatment on metastatic disease.

Melanoma is a very aggressive disease that quickly spreads to other organs. This protocol describes the application of ultra-high-frequency ultrasound imaging, coupled with 3D rendering, to monitor the volume of the inguinal lymph nodes in the Braf/Pten mouse model of metastatic melanoma.

Tyr::CreER+,BrafCA/+,Ptenlox/lox&#160;genetically engineered mice (Braf/Pten mice) are widely used as an in vivo model of metastatic melanoma. Once a ...

Tracking the Mammary Architectural Features and Detecting Breast Cancer with Magnetic Resonance Diffusion Tensor Imaging

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of life and survival of breast cancer patients. In this paper a new approach for the detection of breast cancer is described, based on tracking the mammary architectural elements using diffusion tensor imaging (DTI). 
The paper focuses on the scanning protocols and image processing algorithms and software that were designed to fit the diffusion properties of the mammary fibroglandular tissue and its changes during malignant transformation. The final output yields pixel by pixel vector maps that track the architecture of the entire mammary ductal glandular trees and parametric maps of the diffusion tensor coefficients and anisotropy indices. 
The efficiency of the method to detect breast cancer was tested by scanning women volunteers including 68 patients with breast cancer confirmed by histopathology findings. Regions with cancer cells exhibited a marked reduction in the diffusion coefficients and in the maximal anisotropy index as compared to the normal breast tissue, providing an intrinsic contrast for delineating the boundaries of malignant growth. Overall, the sensitivity of the DTI parameters to detect breast cancer was found to be high, particularly in dense breasts, and comparable to the current standard breast MRI method that requires injection of a contrast agent. Thus, this method offers a completely non-invasive, safe and sensitive tool for breast cancer detection.

We describe how to obtain parametric and vector maps of the diffusion tensor of the breast using magnetic resonance imaging. The protocol and final output following imaging processing are tailored for tracking breast architectural features and detecting breast malignancy.

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of ...

Medicine

High-frequency Ultrasound Imaging of Mouse Cervical Lymph Nodes

High-frequency ultrasound (HFUS) is widely employed as a non-invasive method for imaging internal anatomic structures in experimental small animal systems. HFUS has the ability to detect structures as small as 30 &#181;m, a property that has been utilized for visualizing superficial lymph nodes in rodents in brightness (B)-mode. Combining power Doppler with B-mode imaging allows for measuring circulatory blood flow within lymph nodes and other organs. While HFUS has been utilized for lymph node imaging in a number of mouse&#160; model systems, a detailed protocol describing HFUS imaging and characterization of the cervical lymph nodes in mice has not been reported. Here, we show that HFUS can be adapted to detect and characterize cervical lymph nodes in mice. Combined B-mode and power Doppler imaging can be used to detect increases in blood flow in immunologically-enlarged cervical nodes. We also describe the use of B-mode imaging to conduct fine needle biopsies of cervical lymph nodes to retrieve lymph tissue for histological&#160; analysis. Finally, software-aided steps are described to calculate changes in lymph node volume and to visualize changes in lymph node morphology following image reconstruction. The ability to visually monitor changes in cervical lymph node biology over time provides a simple and powerful technique for the non-invasive monitoring of cervical lymph node alterations in preclinical mouse models of oral cavity disease.

This protocol describes the application of high-frequency ultrasound (HFUS) for imaging mouse cervical lymph nodes. This technique optimizes visualization and quantification of cervical lymph node morphology, volume and blood flow. Image-guided biopsy of cervical lymph nodes and processing of lymph tissue for histological evaluation is also demonstrated.

High-frequency ultrasound (HFUS) is widely employed as a non-invasive method for imaging internal anatomic structures in experimental small animal ...

Integrating Augmented Reality Tools in Breast Cancer Related Lymphedema Prognostication and Diagnosis

Breast cancer related lymphedema (BCRL) is a detrimental condition characterized by fluid accumulation in the upper limb in breast cancer patients subjected to axillary surgery and/or radiations. Its etiology is multifactorial and include also tumor-specific pathological features, such as lymphovascular invasion (LVI) and extranodal extension (ENE). To date, no widely employed guidelines for the early diagnosis of BCRL are available. Here, we illustrate a protocol for a digitally assisted BCRL assessment using a 3D laser scanner (3DLS) and a tablet computer. It has been specifically optimized in a discovery cohort of high-risk breast cancer patients. This study provides a proof-of-principle that augmented reality tools, such as 3DLS, can be incorporated into the clinical workup of BCRL to allow for a precise, reproducible, reliable, and cheap diagnosis.

Breast cancer related lymphedema is frequent in breast cancer survivors, but there are not widely employed guidelines for its diagnosis and quantification. Here, we introduce a reliable and cost-effective protocol to define, quantify, and compare upper limb volume in breast cancer patients.

Breast cancer related lymphedema (BCRL) is a detrimental condition characterized by fluid accumulation in the upper limb in breast cancer patients ...

A Revised Method for Inducing Secondary Lymphedema in the Hindlimb of Mice

Animal models are of paramount importance in the research of lymphedema in order to understand the pathophysiology of the disease but also to explore potential treatment options. This mouse model allows researchers to induce significant lymphedema lasting at least 8 weeks. Lymphedema is induced using a combination of fractioned radiotherapy and surgical ablation of lymphatics. This model requires that the mice get a dose of 10 Gray (Gy) radiation before and after surgery. The surgical part of the model involves ligation of three lymph vessels and extraction of two lymph nodes from the mouse hindlimb. Having access to microsurgical tools and a microscope is essential, due to the small anatomical structures of mice. The advantage of this model is that it results in statistically significant lymphedema, which provides a good basis for evaluating different treatment options. It is also a great and easily available option for microsurgical training. The limitation of this model is that the procedure can be time consuming, especially if not practiced in advance. The model results in objectively quantifiable lymphedema in mice, without causing severe morbidity and has been tested in three separate projects.

This animal model enables researchers to induce statistically significant secondary lymphedema in the hindlimb of mice, lasting at least 8 weeks. The model can be used to study the pathophysiology of lymphedema and to investigate novel treatment options.

Animal models are of paramount importance in the research of lymphedema in order to understand the pathophysiology of the disease but also to explore ...

A Murine Tail Lymphedema Model

Lymphedema is extremity swelling caused by lymphatic dysfunction. The affected limb enlarges because of accumulation of fluid, adipose, and fibrosis. There is no cure for this disease. A mouse tail model that uses a focal full thickness skin excision near the base of the tail, resulting in tail swelling, has been used to study lymphedema. However, this model may result in vascular comprise and consequent tail necrosis and early tail swelling resolution, limiting its clinical translatability. The chronic murine tail lymphedema model induces sustained lymphedema over 15 weeks and a reliable perfusion to the tail. Enhancements of the traditional murine tail lymphedema model include 1) precise full thickness excision and lymphatic clipping using a surgical microscope, 2) confirmation of post-operative arterial and venous perfusion using high resolution laser speckle, and 3) functional assessment using indocyanine green near infrared laser lymphangiography. We also use tissue nanotransfection technology (TNT) for novel non-viral, transcutaneous, focal delivery of genetic cargo to the mouse tail vasculature.

Lymphedema is extremity swelling caused by lymphatic dysfunction. We describe a chronic murine tail model of lymphedema and the novel use of tissue nanotransfection technology (TNT) for genetic cargo delivery to the tail.

Lymphedema is extremity swelling caused by lymphatic dysfunction. The affected limb enlarges because of accumulation of fluid, adipose, and fibrosis. ...

Technique for Salivary Gland Ultrasound Examination of Sjogren's Syndrome

Ultrasonographic Evaluation of Salivary Glands for Sjogren's Syndrome: Diagnostic and Monitoring Insights

Sjogren's syndrome (SS) is a chronic autoimmune condition commonly affecting the exocrine glands, causing oral or ocular dryness and extraglandular manifestations including arthralgia, cytopenia, and lymphoma. The presence of autoantibodies against SSA/Ro, labial salivary gland biopsy, ocular staining, Schirmer's test, or salivary flow assessment are included in the current classification criteria of SS. However, the availability and invasiveness of these procedures limit their widespread use in clinical settings. Salivary gland ultrasonography (SGUS) is a non-invasive imaging modality for the evaluation of the salivary gland parenchyma and is increasingly utilized to aid diagnosis and monitoring in SS. 
This article presents the protocol of SGUS for image acquisition at the parotid and submandibular glands. The objective is to present a standardized, reproducible, and practical approach to diagnostic SGUS for SS in daily clinical settings. Major salivary glands are scanned in a stepwise approach, beginning at the angle of the mandible for the superficial lobe of the parotid gland, followed by the deep lobe below the ramus of the mandible. Submandibular areas are then scanned for the submandibular glands. The steps in obtaining salivary gland images at each anatomical site are explained in the accompanying video. The echogenicity and echotexture at the thyroid gland are taken as a reference. The homogeneity, the presence and distribution of hypoechoic areas within the glands, and the border of the salivary glands are examined. The sizes and features of intra-/peri-glandular lymph nodes are recorded. The most distinctive sonographic feature in SS is glandular heterogeneity with the presence of hypoechoic/hyperechoic areas within the glands. 
In summary, while SGUS cannot diagnose SS on its own, it can supplement the current classification criteria of SS and guide the clinical decision for salivary gland biopsy to support the diagnosis of SS in patients with sicca syndrome or suspicious systemic features, combined with autoantibody testing.

Author Spotlight: A Focus on Standardized Salivary Gland Ultrasound Protocol in Connective Tissue Disease Research

Salivary gland ultrasonography is a promising tool for the diagnosis and evaluation of disease activity and complications in Sjogren's syndrome (SS). The scanning technique for salivary gland ultrasound examination relevant to SS is described in the article.

Sjogren's syndrome (SS) is a chronic autoimmune condition commonly affecting the exocrine glands, causing oral or ocular dryness and extraglandular ...

Endoscopic Bilateral Nipple-sparing Mastectomy via a Single Axillary Incision with Immediate Pre-pectoral Implant-based Breast Reconstruction

Oncoplastic breast surgery, with its focus on improving cosmetic outcomes while maintaining oncological safety, has fundamentally transformed the landscape of breast cancer surgical treatment, giving rise to an array of techniques for breast reconstruction. Nipple-sparing mastectomy (NSM) with immediate implant-based breast reconstruction (IBBR) has emerged as a cornerstone in managing early breast cancer. Aligned with the principles of minimally invasive surgery, recent years have witnessed the widespread integration of endoscopic approaches in breast surgery, encompassing procedures like endoscopic breast-conserving surgery (E-BCS) and endoscopic nipple-sparing mastectomy (E-NSM), among others. Capitalizing on the advantages of inconspicuous and shorter incisions, improved visibility, and the avoidance of radiation therapy, the popularity of E-NSM with IBBR is on the rise. However, conventional E-NSM with IBBR often requires two or more incisions, which can result in suboptimal cosmetic outcomes and even prosthesis loss.This paper presents a comprehensive account of the intricate surgical procedures involved in endoscopic bilateral nipple-sparing mastectomy with immediate pre-pectoral implant-based breast reconstruction. The insights shared are drawn from the collective experience of our institution. Notable benefits associated with the described surgical approach encompass enhanced cosmetic outcomes, improved postoperative quality of life, and enhanced physiological functions attributable to the application of pre-pectoral implant-based breast reconstruction through a single incision.

Here, we present detailed surgical procedures for endoscopic bilateral nipple-sparing mastectomy via a single axillary incision with immediate pre-pectoral implant-based breast reconstruction. This procedure is a secure and viable method for breast cancer patients.

Oncoplastic breast surgery, with its focus on improving cosmetic outcomes while maintaining oncological safety, has fundamentally transformed the ...

Comprehensive Breast Exam

Source: 
Alexandra Duncan, GTA, Praxis Clinical, New Haven, CT 
Tiffany Cook, GTA, Praxis Clinical, New Haven, CT 
Jaideep S. Talwalkar, MD, Internal Medicine and Pediatrics, Yale School of Medicine, New Haven, CT
Breast exams are a key part of an annual gynecological exam and are important for all patients, no matter their sex or gender expression. One out of every 8 women will be diagnosed with breast cancer; male breast cancer, though less common, has a lifetime incidence of 1 in 1000.
Breast exams can feel invasive to patients, so it is important to do everything possible to make the patients feel comfortable and empowered, rather than vulnerable. Examiners should be aware of what they are communicating, both verbally and non-verbally, and give their patients control wherever possible (for instance, always allowing them to remove their own gowns). Examiners may choose to utilize chaperones for the patients&#39; (as well as their own) comfort. Some institutions require the use of chaperones.
While it is always important to avoid overly clinical language, certain colloquial words can cross the line from caring to overly intimate in this exam. It is helpful to avoid the words &#34;touch&#34; and &#34;feel&#34; in this exam, as this language can feel sexualized. Instead, use words like &#34;assess,&#34; &#34;check,&#34; or &#34;examine.&#34;
Additionally, the best practice dictates avoiding assumptions about patients&#39; gender, as patients with female anatomy may identify as another gender (e.g., transgender, genderqueer, etc.). This video depicts the approach to patients whose history has revealed no specific complaints or risk factors related to breast health.
In order to avoid missing potential findings, the breast exam should be performed in a systematic approach and consist of three main components: visual inspection of the breast tissue, palpation of the lymph nodes, and palpation of breast tissue.
The breast tissue extends from directly under the clavicle to around the fifth rib (or bra line). Laterally, it extends from the midaxillary line to the sternal border. The breast is viewed in four quadrants; the upper outer quadrant has the most tissue and is the location of many lymph nodes, and the tail of Spence (or axillary tail) extends to the edge of the axilla, where it attaches to the chest wall (Figure 1).
<img alt="Figure 1" src="/files/ftp_upload/10118/10118fig1.jpg" /> 
Figure 1. Breast anatomical landmarks.

Ultrasonographic Evaluation of Breast Cancer-related Lymphedema

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