Novel Techniques for Prevention and Management of Cancer Related Lymphedema

Transcript

• 00:00Good afternoon.
• 00:02Thank you everyone for being
• 00:04here. I'm Rachel Greenup. I'm
• 00:05the chief of breast surgery
• 00:07in the department of surgery
• 00:08here at Yale School of
• 00:09Medicine and co director of
• 00:11the breast program here at
• 00:12Smilo.
• 00:14And it's my honor to
• 00:15introduce my friend and colleague,
• 00:16Doctor. Subha Haykal, who's section
• 00:18chief of reconstructive
• 00:20oncology in the division of
• 00:22plastic and reconstructive
• 00:23surgery.
• 00:25Doctor. Haykal is a specialist
• 00:27in microsurgical reconstruction
• 00:29with research interests in breast
• 00:31reconstructive surgery and vascularized
• 00:33composite allotransplantation.
• 00:35She received her medical degree
• 00:37from the University of Ottawa,
• 00:39completed residency training in plastic
• 00:42and reconstructive surgery at the
• 00:43University of Toronto,
• 00:46did a microsurgery
• 00:48fellowship at the Albany Medical
• 00:50Center in New York, and
• 00:51during her residency, completed a
• 00:53PhD
• 00:54in tissue engineering and regenerative
• 00:56medicine.
• 00:58She worked at Toronto General
• 00:59Hospital University Health Network and
• 01:01Sinai Health in Toronto for
• 01:03several years prior to
• 01:05being recruited to Yale as
• 01:06an associate professor.
• 01:09She has received many awards,
• 01:11for her leadership, including the
• 01:13American Society for reconstructing
• 01:15reconstructive
• 01:16microsurgery,
• 01:18women in microsurgery
• 01:19travel scholarship, and the Hugh
• 01:21g Thompson
• 01:22humanitarian
• 01:23award. She's the author of
• 01:24over fifty peer reviewed publications
• 01:27focused on her research niche
• 01:29of breast reconstruction,
• 01:31cancer reconstruction,
• 01:33microsurgery,
• 01:34tissue engineering, and tissue repair.
• 01:36And I can say on
• 01:38a personal note, having both
• 01:40sat on the search committee
• 01:41as part of her recruitment
• 01:43and now having,
• 01:44gotten to know her both
• 01:46as a clinician and a
• 01:47colleague,
• 01:48she, is excellent in everything
• 01:50she does, and we are
• 01:51so lucky to have her
• 01:53here at Yale.
• 01:54Welcome.
• 02:01Thank you so much, Rachel,
• 02:03and thank you for having
• 02:04me today. It's an honor
• 02:05to be giving grand rounds
• 02:06today.
• 02:07So we'll be discussing a
• 02:09novel surgical management of cancer
• 02:11related lymphedema,
• 02:12and, specifically, I'll be talking
• 02:14about a few projects,
• 02:16that we're working on currently
• 02:18and we've worked on at
• 02:19my previous institution.
• 02:25So the objectives are to
• 02:26determine which patients are candidates
• 02:28for surgical management of lymphedema,
• 02:30to look at options for
• 02:31surgical and microsurgical management,
• 02:34to look at preoperative and
• 02:35postoperative
• 02:36rehabilitation
• 02:37protocol,
• 02:38to discuss future techniques such
• 02:40as prevention and in vivo
• 02:41models, to look at some
• 02:43of the qualitative
• 02:44studies, and to look at
• 02:46prediction models,
• 02:48specifically looking at some of
• 02:49the data here from the
• 02:50Smilow Cancer Center. My disclosure
• 02:52is that I am a
• 02:53consultant for Stryker.
• 02:56So acute lymphedema
• 02:58really presents with generalized protein
• 03:00and fluid accumulation,
• 03:02which leads to inflammation
• 03:04and dilation and fibrosis of
• 03:06the lymphatics.
• 03:07And chronic lymphedema
• 03:09is a sustained inflammatory
• 03:11response,
• 03:12increase in excessive adipose tissue,
• 03:15fibrosis,
• 03:16dilated vessels, and lymphangiogenesis.
• 03:20And there is a theory
• 03:21that we can potentially prevent
• 03:23chronic lymphedema
• 03:24if we can halt acute
• 03:26lymphedema.
• 03:28Obviously, the management of lymphedema
• 03:30is a multidisciplinary
• 03:31approach. So So it starts
• 03:33at the time of cancer
• 03:34diagnosis,
• 03:35and it runs through all
• 03:36the years of life.
• 03:38It really should focus on
• 03:40prevention and surveillance.
• 03:42So early assessment,
• 03:44referral for exercise and rehabilitative
• 03:47therapies,
• 03:48early physiotherapy
• 03:49is key, and, really, the
• 03:51treatment centers around that.
• 03:53Why is this necessary? We
• 03:54know that it reduces economic
• 03:56burden associated with intensive rehabilitation
• 03:59and hospitalization
• 04:00for infection.
• 04:02And second secondary,
• 04:04education,
• 04:05which is promotion of positive
• 04:07self efficacy strategies,
• 04:09really reinforces the survivor's ability
• 04:12to control lymphedema
• 04:13through early detection and early
• 04:16referral.
• 04:19So, really, the mainstay treatment
• 04:21is called combined or t
• 04:23con or complex decongestive therapy.
• 04:25So it involves
• 04:27two of multiple modalities. The
• 04:29first one being manual lymphatic
• 04:31drainage. So there are several
• 04:32different techniques.
• 04:34The VADER technique, the FOLDI
• 04:36method,
• 04:37the Leduc method.
• 04:38There's a plethora of articles
• 04:40that have been published on
• 04:41the effectiveness of these techniques,
• 04:43but there's really not a
• 04:45lot of data that really
• 04:46compares these these methods. And
• 04:48we know it really depends
• 04:49on the training of the
• 04:50therapist.
• 04:52And, also, compression. So compression
• 04:54allows to reduce that venous
• 04:56pressure and flow, which reduces
• 04:58the lymphatic load
• 05:00and encourages the lymphatics
• 05:02to take on,
• 05:03that tissue pressure. So that
• 05:05basically looks like bandages and
• 05:07then garments in later stages.
• 05:10So there are two phases
• 05:11to combine decongestive therapy. The
• 05:13first one is to reduce
• 05:15the size of the limb
• 05:16and to improve the skin.
• 05:18The second phase is ongoing.
• 05:20It's individualized.
• 05:21It's about self management
• 05:23to maintain all the
• 05:25gaze gains from phase one,
• 05:27and it's using those low
• 05:28stretch elastic stockings and sleeve
• 05:31compression
• 05:32and multilayer
• 05:33stockings. So the goals are
• 05:35to reduce the swelling, increase
• 05:37drainage, reduce the skin
• 05:40fibrosis, enhance the patient's functional
• 05:42status, relieve discomfort, and improve
• 05:45quality of life, and really
• 05:47also reduce the risk of
• 05:48cellulitis.
• 05:50So staging in lymphedema is
• 05:52actually key, and this really
• 05:55centers on whether or not
• 05:56these patients are candidates for
• 05:58surgery, which I'll further discuss.
• 06:00But there are several different,
• 06:02staging, systems. The one that
• 06:04we typically use is the
• 06:05one that was created in
• 06:06twenty thirteen
• 06:08by the International Society of
• 06:10Lymphology,
• 06:11which divides into stage zero,
• 06:13one, two, and three. So
• 06:14stage zero is subclinical.
• 06:16It's the absence of edema.
• 06:18So these are patients who
• 06:20will not actually see any
• 06:22volume changes,
• 06:23and
• 06:24whoever is examining them, whether
• 06:26it's their physician,
• 06:28or even their surgeons, they
• 06:29won't actually see any changes
• 06:31in volumes.
• 06:32However,
• 06:33we know that those patients
• 06:35potentially have risk factors for
• 06:37developing lymphedema.
• 06:38And, ideally, as a surgeon
• 06:41who works with patients who
• 06:42have lymphedema, I would love
• 06:44to see them when they're
• 06:45at a stage zero. So
• 06:46we have to be able
• 06:47to identify these patients early
• 06:49on.
• 06:50In terms of stage one
• 06:52and stage two,
• 06:53there's different modalities for looking
• 06:55at how we determine whether
• 06:57or not there are these
• 06:58stages. So one is being
• 07:00physical examination
• 07:01looking for pitting edema.
• 07:03So if you speak to
• 07:04therapist, pitting edema is good.
• 07:06It's something that we can
• 07:08work with. It allows us
• 07:09to put compression on. It
• 07:11allows us to use elastic
• 07:12bandages. It allows us to
• 07:14actually allow for the flow.
• 07:16And, however, when there's no
• 07:17longer pitting edema, we start
• 07:19thinking that there's now progression
• 07:21of the lymphedema,
• 07:22and therefore, we have to
• 07:24think about other modalities.
• 07:26So typically for patients in
• 07:27stages one and two,
• 07:29we reserve physiologic
• 07:31techniques. So those are the
• 07:33microsurgical,
• 07:34supermicrosurgery
• 07:35techniques that I'll talk about.
• 07:37And at a later stage,
• 07:39the possible surgical techniques
• 07:41are things like liposuction
• 07:43and ablative techniques.
• 07:45So these are examples of
• 07:47what the what a patient
• 07:48could look like at the
• 07:49different stages.
• 07:51And we also start seeing
• 07:53skin changes that are gonna
• 07:54range from mild skin changes
• 07:56that could be reversible
• 07:58to moderate skin changes that
• 08:00are potentially start becoming irreversible
• 08:03with some hardening of tissue,
• 08:05some dry skin, some discoloration,
• 08:08where elevation
• 08:10is no longer helpful.
• 08:12And when we get to
• 08:13the severe stage of elephantiasis,
• 08:15it's extensive hardening,
• 08:18and very, very few things
• 08:20are actually,
• 08:21helpful at that stage.
• 08:24Now what happens when we
• 08:25look at the lymphatic vessels
• 08:26under the microscope at different
• 08:28stages?
• 08:29So typically a normal lymphatic
• 08:31vessel is thin,
• 08:33is translucent,
• 08:35and we can see flow
• 08:36when we cut into it.
• 08:37There's actually flow that comes
• 08:39out. The flow is slow,
• 08:41but it is there.
• 08:43Eventually with later stages, for
• 08:45example, as a stage one,
• 08:47we see what we call
• 08:48ectasia
• 08:50followed by contraction and then
• 08:52sclerosis.
• 08:53So at that point, the
• 08:54vessels actually look very different
• 08:56under the microscope.
• 08:57When you cut into them,
• 08:59there's very little flow,
• 09:01and, they're no longer,
• 09:03potentially,
• 09:05available for things such as
• 09:06a bypass.
• 09:08Now how do we determine
• 09:10what the most appropriate surgical
• 09:12technique is? It really depends
• 09:13on the things that we
• 09:14just talked about. So staging
• 09:16is key and imaging is
• 09:17key. The first thing that
• 09:19we want to know is,
• 09:21does the lymphatic system still
• 09:22work? Are there still any
• 09:24lymphatic vessels available,
• 09:26Most likely in the distal
• 09:28portion of the limb that
• 09:29are still flowing.
• 09:31So we look at we
• 09:31do clinical examination.
• 09:34We look at the different
• 09:35stages that we talked about,
• 09:37whether or not there's actually
• 09:38any edema.
• 09:39And another modality is lymphosyntography
• 09:42where a radioisotope
• 09:44is injected
• 09:45in the web spaces of
• 09:47the hand or the or
• 09:48the feet,
• 09:50and we look at whether
• 09:51or not there's actually any
• 09:53flow. And as you can
• 09:54see here I'm not sure
• 09:55if you can see my
• 09:56cursor.
• 09:58At stage zero, you'll still
• 10:00see some flow going into,
• 10:02the inguinal area.
• 10:04Here, there's some flow that
• 10:05is starting.
• 10:07Eventually, there's what we call
• 10:08dermal back flow, which I'll
• 10:10describe a little bit more,
• 10:11but we can still see
• 10:12that there's some flow in
• 10:13the inguinal area.
• 10:15Stage two, which is further
• 10:17progression,
• 10:18there's very very
• 10:19little, that is lining up
• 10:21in the inguinal area.
• 10:23And in this case, this
• 10:24is the other limb at
• 10:25stage three where there is
• 10:27no flow and complete obstruction.
• 10:30So another modality that we
• 10:32use that is a very
• 10:33helpful modality,
• 10:35that I feel is one
• 10:37of the things that most
• 10:38commonly we use and is
• 10:39very helpful at figuring out
• 10:41whether or not the lymphatic
• 10:43system works is indocyanin
• 10:44green.
• 10:45So that's a fluorescent dye
• 10:47that is injected in the
• 10:48same area.
• 10:50This can also be done
• 10:51in the clinic.
• 10:52And we've also been able
• 10:53to map out the progression
• 10:55of lymphedema
• 10:56depending on what the imaging
• 10:57looks like. So what we
• 10:59do is we use a
• 10:59near infrared
• 11:00spectroscopy.
• 11:02It's called the spy machine
• 11:04to take a look at
• 11:05the limb and to look
• 11:06at whether or not there's
• 11:07linear flow, which is normal
• 11:09flow.
• 11:11Then we start seeing different
• 11:12patterns. We start seeing a
• 11:14splash pattern,
• 11:15a stardust pattern, and a
• 11:17diffuse pattern as there's progression
• 11:19of lymphedema.
• 11:20So the interesting thing about
• 11:22doing this is that you
• 11:23can actually see it in
• 11:24real time.
• 11:25You can start seeing the
• 11:27flow, the movement of the
• 11:28lymphatics
• 11:29within the channels.
• 11:31And and you can also
• 11:32map that out, but also
• 11:34record it. So this an
• 11:36this is an example of
• 11:37one of my patients that
• 11:38I injected in the operating
• 11:40room where you can see
• 11:42there's,
• 11:43there's flow up to the
• 11:44level of the elbow.
• 11:46However, the flow changes. Initially,
• 11:48there's some linear flow
• 11:50followed by a splash pattern,
• 11:51a stardust pattern, and eventually
• 11:53a diffuse pattern with no
• 11:55further progression above the the
• 11:58elbow.
• 12:00So that allows us to
• 12:01figure out if, for example,
• 12:03this patient,
• 12:04we did lymphovenous bypasses on.
• 12:06I'll talk about I'll talk
• 12:08about it a little bit
• 12:09more in detail.
• 12:10But this,
• 12:11intraoperative
• 12:12ICG lymph angiography is key
• 12:14because I know in this
• 12:16area where there's a linear
• 12:17pattern
• 12:18and there's some flow,
• 12:20this is where I'm gonna
• 12:21do my bypasses.
• 12:23Because if I travel more
• 12:24proximally up the limb,
• 12:26then there won't be any,
• 12:28lymphatics that are flowing, and
• 12:30I won't be able to
• 12:31bypass them. This is an
• 12:32example under the microscope of
• 12:34a lymphatic that is stained
• 12:36in blue
• 12:37that is being anastomosed to
• 12:38a small venules that is
• 12:40of equal size.
• 12:41These vessels are typically less
• 12:43than one millimeter in size.
• 12:45In this case, this vessel
• 12:46is about zero point seven
• 12:47millimeters.
• 12:49So, for a lymphovenous bypass,
• 12:51we would typically perform multiple,
• 12:54different bypasses
• 12:55along the, the arm in
• 12:57the area where we'd expect,
• 12:59lymphatic flow or lymphatic vessels
• 13:02to still be present.
• 13:04So what is a lymphatico
• 13:05venous bypass, also referred to
• 13:07as an LVA or an
• 13:08LVB?
• 13:09So it's a microsurgical anastomosis
• 13:12of a lymphatic vessel to
• 13:13a small superficial
• 13:15vein
• 13:16to shunt that lymph fluid
• 13:18into the venous system.
• 13:20So the theory is that
• 13:21this,
• 13:22this lymphatico venous anastomosis
• 13:25will remain patent and open
• 13:26if the lymphatic pressure is
• 13:28higher than the venous system.
• 13:30So you can imagine if
• 13:32you open one of the
• 13:32venules and there's a lot
• 13:34of flow coming out of
• 13:35it, that is not a
• 13:36good recipient vein. Right? So
• 13:38you have to really find
• 13:40the appropriate venule to do
• 13:41that.
• 13:42So that is best ensured
• 13:44by do looking for a
• 13:45low pressure subdermal venule.
• 13:47And we think from looking
• 13:49at the, the studies is
• 13:50that patients could have a
• 13:52mean reduction
• 13:53of about thirty five percent
• 13:54of their volume at one
• 13:55year.
• 13:57And we also know from
• 13:58looking at studies that have
• 13:59been going on for quite
• 14:01some time is that after
• 14:02about two to three years,
• 14:03these patients potentially
• 14:05need more,
• 14:06lymphovenous bypasses.
• 14:09What's a lymph node transfer?
• 14:11So it's LNT or vascularized
• 14:13lymph node transfer.
• 14:15So this is typically reserved
• 14:16for stages two or more.
• 14:19So, basically, the recipient bed
• 14:21where there's a lymphedema
• 14:23is first prepared.
• 14:24So one of the most
• 14:25important things in that area
• 14:27is to excise all the
• 14:28scar because we think that
• 14:30removing the scar will actually
• 14:31help with the flow, and
• 14:33then you take a flap,
• 14:34basically, of tissue that has
• 14:36some lymph nodes in it.
• 14:38So the lymph nodes can
• 14:39be obtained from different sites,
• 14:41the omentum, the inguinal area,
• 14:43the thoracic area, or the
• 14:44cervical area. And, ideally, you
• 14:46wanna take them from areas
• 14:48where patients will not be
• 14:49developing lymphedema.
• 14:51So reverse mapping is key
• 14:53to determine which areas to
• 14:54take them from.
• 14:55So the theory behind this
• 14:57is that you're transferring healthy
• 14:59lymph nodes.
• 15:00They're gonna actually produce vascular
• 15:02endothelial growth factors that's gonna
• 15:04promote lymphangiogenesis
• 15:06and new connections between proximal
• 15:08distal lymphatics.
• 15:10The removal of the scar
• 15:12itself is also gonna enhance
• 15:13the immunological
• 15:14function
• 15:16and reduce the development of
• 15:17infection,
• 15:19but there's no data that
• 15:20actually suggests that lymphatic vessels
• 15:22actually regenerate from those nodes.
• 15:25So all those nodes, the
• 15:26only thing they're doing is
• 15:28producing the growth factors
• 15:30required to allow the lymphatic
• 15:32vessels that are there to
• 15:34actually reform.
• 15:36So preventative techniques are also
• 15:38important. So one preventative technique
• 15:42used to be called the
• 15:43lymphatic microsurgical
• 15:44prevent preventing healing approach,
• 15:47lympha.
• 15:48We now call it immediate
• 15:49lymphatic reconstruction.
• 15:51So this is used for
• 15:53primary prevention
• 15:54of arm lymphedema, for example,
• 15:56in breast cancer, but it
• 15:57can also be used from
• 15:58melanoma in the trunk.
• 16:00It's a lymphovenous
• 16:01bypass similar to what we
• 16:03just described,
• 16:04but they're done in a
• 16:05patient who does not have
• 16:06lymphedema.
• 16:07So they're done as a
• 16:09possibly preventative method
• 16:11to hopefully decrease their risk
• 16:13of lymphedema,
• 16:14and they don't require any
• 16:15lymph nodes. They don't require
• 16:17any, lymph vessel harvesting.
• 16:20So our algorithm algorithm for
• 16:22treatment is in the phase
• 16:23one, when I see a
• 16:24patient that has lymphedema, I
• 16:26wanna make sure they're well
• 16:27optimized for their CPT or
• 16:29their CDT. So they have
• 16:30therapists on board. They've done
• 16:32their combined econjestive therapy. They've
• 16:34been very rigorous,
• 16:36for six to twelve months.
• 16:38You'll see that,
• 16:39most of the patients that
• 16:40we do end up seeing,
• 16:41and we'll talk about barriers
• 16:43of care in this area
• 16:44as well,
• 16:45are patients who are actually
• 16:47very good at their lymphedema
• 16:49care.
• 16:50And then the second phase
• 16:51would be microsurgery,
• 16:53and then the postoperative phase
• 16:54is just as important, which
• 16:56is involves a lot of
• 16:56rehabilitation and a
• 16:58rehabilitation
• 16:59and a lot of follow-up.
• 17:00So in terms of what
• 17:02do we do, so for
• 17:03prevention,
• 17:04we try to avoid lymphatic
• 17:06injury as best as possible
• 17:08by performing good dissections,
• 17:10and we try to do
• 17:11immediate lymphatic reconstruction.
• 17:13And for treatment,
• 17:15early on at an early
• 17:16stage, we would do multiple
• 17:17lymphovenous bypasses
• 17:19and later on maybe liposuction
• 17:22once we're at a stage
• 17:23where there's more of a
• 17:24fatty component
• 17:26to the lymphedema, which happens
• 17:28in the chronic lymphedema phase.
• 17:30The postoperative
• 17:31protocols are very key.
• 17:33At my previous institution,
• 17:35we had a very big
• 17:36group,
• 17:38involving physiotherapists,
• 17:39manual lymphatic therapists,
• 17:41and we came up with
• 17:43different ways,
• 17:44to
• 17:45follow them postoperatively.
• 17:46It really depends on whether
• 17:47or not they're having a
• 17:48lymphovenous bypass or a lymph
• 17:50node transplant.
• 17:52It involves six weeks of
• 17:53compression.
• 17:54It involves a change in
• 17:56the manual lymphatic regimen. So
• 17:57we talked about a low
• 17:59flow to low flow system
• 18:00where typically patients who have
• 18:02lymphedema
• 18:03massage up towards the axilla,
• 18:05for example.
• 18:06In this case, you wanna
• 18:08keep the anastomosis
• 18:09open so you actually start
• 18:11massaging towards the anastomosis
• 18:13as well.
• 18:14And the goal is to
• 18:16for them to decrease the
• 18:17amount of compression and time
• 18:19they actually spend on their
• 18:20lymphedema
• 18:21care.
• 18:22We also, we started a
• 18:24prospective study. So we wanted
• 18:26to see, do these things
• 18:27actually work?
• 18:28Does surgery actually work?
• 18:31So, we teamed up with,
• 18:33doctor Fifi Liu and her
• 18:34lab at Princess Margaret Hospital
• 18:35at my previous institution where
• 18:37we operated on patients who
• 18:39had lymphedema, and we followed
• 18:40them with time.
• 18:42Interestingly,
• 18:43they were really interested in
• 18:44looking at potentially any biomarkers
• 18:46or any transcriptome
• 18:48profiling for patients with lymphedema.
• 18:51We looked at PPARs,
• 18:52which are our paroxysone
• 18:54proliferator activated receptors.
• 18:57We found interestingly that the
• 18:59dermal fibrosis staining in lymphedema
• 19:01is increased.
• 19:02We also looked at,
• 19:04RNA sequencing, and we looked
• 19:06at heat maps to look
• 19:07at what is downregulated,
• 19:09and we noticed that these
• 19:10PPARs
• 19:11were actually downregulated
• 19:12in patients with lymphedema. So
• 19:14these are from biopsies from
• 19:15their skin.
• 19:17And more importantly,
• 19:18we looked at IL seventeen
• 19:20signaling using immunohistochemistry,
• 19:22and we found that there
• 19:23was an upregulation
• 19:24of IL seventeen. So what
• 19:26does this mean?
• 19:27So these PPARs
• 19:29are fatty acid sensors. They're
• 19:31involved in transcription. They're involved
• 19:31in transcription. They're involved in
• 19:33adipogenesis,
• 19:34lipid metabolism,
• 19:36insulin sensitivity,
• 19:38and maintenance of metabolic homeostasis.
• 19:41Their reduced expression really suggests
• 19:43that there's a metabolic shift
• 19:44that could contribute to this
• 19:46inflammatory
• 19:47stage, and the RNA sequencing
• 19:50of these tissues really demonstrated
• 19:52that there's a down regulation
• 19:53of these
• 19:54and including different targets.
• 19:57So really this highlights,
• 19:59the role of particular
• 20:02genes in this,
• 20:03most specifically PPAR
• 20:05gamma and other related FAO
• 20:08genes.
• 20:09They were really interested in
• 20:10looking at, can we have
• 20:11target therapeutics for patients who
• 20:13currently have lymphedema?
• 20:15So we know from these
• 20:17observations that lymphedema is linked
• 20:19to obesity,
• 20:20but also metabolic syndrome.
• 20:23And the goal from this
• 20:24was to really investigate these
• 20:26metabolic alterations at the time
• 20:28of cancer surgery.
• 20:30Our goal is to identify
• 20:32the early markers of lymphedema
• 20:34risk, to evaluate
• 20:35baseline inflammatory
• 20:37markers and cytokines in patients
• 20:39who are undergoing
• 20:40lymph node,
• 20:41dissection,
• 20:42to understand the roles of
• 20:44PPAR gamma and FAO pathways.
• 20:47It could really, help in
• 20:48predicting
• 20:49a framework for assessing lymphedema
• 20:51risk and to really bridge
• 20:53the gap between inflammatory
• 20:55states and later metabolic
• 20:57dysfunction in these patients.
• 20:59And, ultimately, the goal is
• 21:00to identify a buy biomarker
• 21:02that predicts who will develop
• 21:04lymphedema.
• 21:06So with these patients as
• 21:07well, we did a prospective
• 21:09study looking at the impact
• 21:10of lymphovenous
• 21:12bypass,
• 21:13and lymphovenous anastomosis
• 21:14as a treatment for upper
• 21:16and lower limb lymphedema.
• 21:18And Catherine Bowman, who's currently
• 21:19doing her PhD at Stanford,
• 21:22worked on this,
• 21:23with our cohort, our patients
• 21:25from Toronto.
• 21:26She is going back to
• 21:28do her, medical school in
• 21:30Calgary after she's done her
• 21:31PhD, but this was one
• 21:33of hers, the studies that
• 21:34she worked on.
• 21:36So I wanna first thank,
• 21:37all the members
• 21:39involved in this study. We
• 21:40had a lot of patient
• 21:41advisers for the study who
• 21:43had invaluable
• 21:44contributions.
• 21:45We had a we did
• 21:46a lot of interviews with
• 21:47these patients, and we had
• 21:49a lot of study
• 21:51participants. So we wanted to
• 21:53look at whether or not,
• 21:55prospectively, we can are we
• 21:57decreasing volume? But more importantly,
• 21:59can we look at quality
• 22:00of life for these patients?
• 22:03So what we used is
• 22:04we had initial consult with
• 22:06the with our patients with
• 22:07lymphedema. They had a clinical
• 22:09appointment.
• 22:10We used ICG Green to
• 22:11map them in the clinic.
• 22:13We identified
• 22:14them as possible candidate for
• 22:16lymphovenous
• 22:17bypass surgery.
• 22:18They under they had already
• 22:20been doing CDT, but they
• 22:22underwent
• 22:23a two week bandaging regimen,
• 22:24which is a three layer
• 22:26compression.
• 22:27They then underwent a preoperative
• 22:29assessment
• 22:30of limb measures, questionnaires,
• 22:33interviews.
• 22:34They underwent their lymphovenous anastomosis
• 22:36intraoperatively
• 22:38and then underwent six weeks
• 22:39of bandaging regimen after, and
• 22:41we followed them post postoperatively
• 22:43where we performed limb measurements
• 22:45again,
• 22:46questionnaires,
• 22:47interviews,
• 22:48and I wanna show some
• 22:49of the results from this.
• 22:51So the primary outcome that
• 22:53we looked at was limb
• 22:55volume changed based upon circumferential
• 22:57measurements, and we did find
• 22:59that there was a significant
• 23:00decrease in their in their
• 23:02volume measurements. But what was
• 23:03important for us was to
• 23:04look at the secondary
• 23:06quantity quali quant qualitative outcomes.
• 23:09So we perform semi structured
• 23:11interviews that really focus on
• 23:12quality of life,
• 23:14psychosocial
• 23:15well-being,
• 23:16symptomology,
• 23:17function,
• 23:18and surgical experience.
• 23:20So these are our results.
• 23:22So our findings in terms
• 23:24of demographics
• 23:25are most reflective of the
• 23:26published literature. So the majority
• 23:28of patients were female.
• 23:30They had stage two lymphedema
• 23:32and a history of cancer.
• 23:35And when we looked at,
• 23:37at some scores, some quality
• 23:39of life scores that were
• 23:40not,
• 23:41for lymphedema in particular, there
• 23:43was no significant in decrease,
• 23:45increase or decrease.
• 23:47There was just no significance.
• 23:49But when we looked at
• 23:50quality of life score, so
• 23:52lymph quality of life score,
• 23:53we noticed that preoperatively
• 23:55compared to postoperatively, there was
• 23:57an increase in their quality
• 23:59of life score.
• 24:00So let's look at some
• 24:01of the preoperative qualitative findings.
• 24:04So
• 24:05in terms of functional impacts
• 24:07of lymphedema on their activities
• 24:09of daily living, their mobility,
• 24:11and their activity limits, ninety
• 24:13three percent of these patients
• 24:15had an it had an
• 24:16impact on their activities of
• 24:18daily living.
• 24:19Eighty seven percent of them
• 24:20had limited activity.
• 24:23Seventy nine percent, it affected
• 24:25their mobility,
• 24:26and seventy three percent, it
• 24:28impacted
• 24:28on exercise.
• 24:30So a patient said I
• 24:32cannot lift things.
• 24:33It would have been easy
• 24:34to lift them before. There
• 24:36are times where I need
• 24:37actual help to get dressed.
• 24:39There are just things that
• 24:40I can't do anymore.
• 24:42In terms of physical symptoms,
• 24:45ninety one percent reported swelling
• 24:47and sixty percent reported pain.
• 24:49We often don't consider pain
• 24:51as something associated with lymphedema,
• 24:53but it can be.
• 24:55The pain is debilitating,
• 24:56and the pain causes me
• 24:58stress, which is very hard
• 25:00on my mental health.
• 25:02In terms of psychosocial impact,
• 25:04so on anxiety,
• 25:05low mood, and chronic disease
• 25:07coping,
• 25:08seventy seven percent of patients
• 25:10had an impact on low
• 25:12mood.
• 25:13Fifty five percent talked about
• 25:15anxiety.
• 25:16Eighteen percent had anxiety with
• 25:18their upcoming surgery.
• 25:19Thirty six percent had anxiety
• 25:21related to their disease progression.
• 25:24I'm strong minded, so when
• 25:25I talk to somebody one
• 25:27on one like this, I
• 25:28get emotional.
• 25:29But in front of my
• 25:30family, I put on a
• 25:31very, very brave face, and
• 25:33I try to push it
• 25:34through, or I can pretend
• 25:35that I'm okay so they
• 25:37don't worry.
• 25:38In terms of cellulitis,
• 25:40forty one percent of our
• 25:41patients experienced cellulitis.
• 25:43With more than one episode,
• 25:45they reported fear and distress
• 25:47related to cellulitis, and twenty
• 25:49four percent of them were
• 25:50hospitalized.
• 25:51I'm always concerned that the
• 25:53antibiotics will stop working,
• 25:55that I'll have a raging
• 25:56uncontrolled infection,
• 25:58and there's also a potential
• 26:00for death.
• 26:02In terms of treatment modalities,
• 26:04these patients have pretty much
• 26:05tried it all. Obviously, compression
• 26:07and manual lymphatic drainage,
• 26:10exercise,
• 26:11nomadic pump, skin care. There's
• 26:13always some sort of new
• 26:14device.
• 26:15And there's a lot of
• 26:16treatment challenges
• 26:18related to discomfort,
• 26:20improper fitting,
• 26:21financially,
• 26:22as well as mobility restriction.
• 26:25I hate compression garments. I
• 26:27don't think anyone likes wearing
• 26:28them. It's like wearing a
• 26:30scuba suit. It's difficult to
• 26:32walk.
• 26:32I get shortness of breath
• 26:34walking up a hill because
• 26:35there's, like, this added resistance.
• 26:39Now let's look at our
• 26:40postoperative
• 26:41qualitative findings.
• 26:43In terms of limb volume,
• 26:45discomfort,
• 26:46pain, heaviness, tightness, and tingling,
• 26:48eighty eight percent of patients
• 26:50reported reduction in heaviness.
• 26:52So heaviness is one of
• 26:54these things that I feel
• 26:55we don't ask about enough.
• 26:58It's the patients that come
• 26:59with stage zero disease,
• 27:02and, you know, we do
• 27:03this we do different measurements,
• 27:05and we don't see a
• 27:06difference at all, but, really,
• 27:07they're feeling heavy. So those
• 27:09are the patients we need
• 27:10to see early.
• 27:11Eighty three percent of them
• 27:12reported pain reduction,
• 27:14seventy eight percent of them
• 27:15reported volume reduction,
• 27:17and sixty seven percent reported
• 27:19reduction in discomfort.
• 27:21It's been almost two years
• 27:23since I've had this, the
• 27:24surgery,
• 27:26and I was dealing with
• 27:27constant pain and swelling. And
• 27:29after the surgery, I've noticed
• 27:30a huge improvement.
• 27:32In terms of functional impacts
• 27:34of LVA,
• 27:35I'm moving heavier things. I'm
• 27:37lifting heavier loads, so it
• 27:39could be anything from groceries
• 27:41to furniture.
• 27:42I'm participating
• 27:43more in moving those types
• 27:45of things before I and
• 27:46I wouldn't before.
• 27:48More rigorous cleaning,
• 27:49some more sustained activity where
• 27:51I have where usually I
• 27:53would take more time to
• 27:54rest.
• 27:55In terms of appearance,
• 27:57anxiety, depression, fears, and worries,
• 28:00seventy five percent had a
• 28:01positive change in appearance.
• 28:03Fifty percent of them had
• 28:05a fear that lymphedema would
• 28:06return, and fifty percent had
• 28:08move mood improvement.
• 28:10I can see my wrist
• 28:11bone, and I could never
• 28:12see it before.
• 28:13I might be able to
• 28:14get my wedding ring on
• 28:16soon, so that's pretty impressive.
• 28:19So the postoperative bandage reg
• 28:21regimen,
• 28:22it's not a mystery that
• 28:23they were not happy with
• 28:24it.
• 28:25So the only time I
• 28:26remove the bandaging is in
• 28:27the middle of the night.
• 28:28I try to change it
• 28:29at two o'clock. It starts
• 28:31bugging my feet. My feet
• 28:32start feeling weird like pain,
• 28:35and I feel needles, and
• 28:36then I feel numb, and
• 28:37then I have to remove
• 28:39the bandages. So there continues
• 28:40to be challenges.
• 28:42What were their reasons for
• 28:43seeking out surgery?
• 28:45Eighty percent of them were
• 28:46looking for symptom control.
• 28:49Forty percent had exhausted all
• 28:51other therapies, and thirty percent
• 28:53had a physiotherapy referral.
• 28:55It felt out of control.
• 28:57I went to lots and
• 28:58lots of appointments with therapists,
• 29:00and we weren't able to
• 29:01contain it.
• 29:02I was so worried that
• 29:04I would swell and swell,
• 29:05and one day I'd have
• 29:06an infection and I would
• 29:07lose my arm. I was
• 29:08so worried about it. I
• 29:10already lost body parts. I
• 29:12just need a break. I
• 29:13just want to focus on
• 29:14normal things like normal people.
• 29:17The meaning of surgery. They
• 29:19expressed things like gratitude, hope,
• 29:21and symptom control. Seventy percent
• 29:23had symptom and situational improvement.
• 29:26Sixty percent felt hope. Forty
• 29:28percent felt gratitude.
• 29:30Tears are coming to my
• 29:31eyes. It's hard to put
• 29:33into words. My best attempt
• 29:34is a fresh start,
• 29:36hopefulness, and care. I really
• 29:38feel cared for and so
• 29:40grateful
• 29:41for the help with this.
• 29:42Yes. It's surprising me too
• 29:43how different I feel now
• 29:45after having surgery.
• 29:47I always felt like there's
• 29:48a point I'm devoting so
• 29:50much time to this, but
• 29:51I can actually now see
• 29:52the results of my management
• 29:54clearly,
• 29:55and I'm more motivated
• 29:56in doing this. I do
• 29:58feel like it's made a
• 29:59difference
• 30:00in terms
• 30:01of stopping the progression at
• 30:03the speed at which the
• 30:04disease progresses.
• 30:05I feel like I've gained
• 30:07some time. I'm not as
• 30:08worried about things going badly
• 30:10in five years. I'm now
• 30:12thinking, okay. Maybe this is
• 30:13a relatively good quality of
• 30:15life for the next ten
• 30:16to twenty years in terms
• 30:17of my leg alone.
• 30:19I'm not as worried about
• 30:20it. I feel relief.
• 30:22So in terms of synthesizing
• 30:24this data, we've come up
• 30:25with models of care.
• 30:27The fundamentals of surgical lymphedema
• 30:30care will center on patient
• 30:31screening and eligibility,
• 30:34comprehensive perioperative
• 30:35education,
• 30:37postoperative functional rehabilitation,
• 30:39psychosocial
• 30:40support for anxieties,
• 30:42fears, and worries that they
• 30:43all express,
• 30:44and outcomes assessment, really looking
• 30:46at the timelines, frequency, and
• 30:48tools for these outcomes.
• 30:51So a second project that
• 30:52I wanna talk about is
• 30:54one that,
• 30:55Alex Matia has taken the
• 30:57lead on. She's a medical
• 30:58student in Florida working with
• 30:59us for a year as
• 31:00a research fellow.
• 31:02Looking at disparities in breast
• 31:04cancer related lymphedema, we did
• 31:06a systematic review of inequities
• 31:08and barriers in care.
• 31:11So we know that this
• 31:12is a chronic condition.
• 31:14We know that patients of
• 31:15diverse and disadvantaged patient populations
• 31:18continue to be understudied
• 31:19in the area of breast
• 31:21cancer survivorship.
• 31:22So we wanted to summarize
• 31:24the evidence for disparities and
• 31:26barriers surrounding breast cancer related
• 31:28lymphedema care, particularly in diagnosis
• 31:31and education
• 31:32and accessibility
• 31:33to treatment.
• 31:35So we did, we followed
• 31:36the PRISMA guidelines.
• 31:38We did a a search
• 31:39of, multiple,
• 31:41different web web bases.
• 31:43We followed the Joanna Briggs
• 31:45Institute critical appraisal tool. We
• 31:48included
• 31:48different types of studies
• 31:50and multiple articles.
• 31:53We yielded ten fifty nine
• 31:54articles. Thirty nine of them
• 31:56met the inclusion criteria.
• 31:58We looked particularly
• 31:59at racial and ethnic disparities,
• 32:02increased risks with certain socio
• 32:04demographic
• 32:06factors.
• 32:07We looked at inadequate provider
• 32:09and patient knowledge.
• 32:11We looked at,
• 32:12low patient education and burden.
• 32:15We looked at barrier and
• 32:16receipt of health care provider
• 32:18diagnosis,
• 32:19and the subthemes that we
• 32:21looked at are cost burden,
• 32:23psychosocial barriers, and the role
• 32:25of patient self efficacy. So
• 32:26this is what we found.
• 32:28So younger non caucasian
• 32:31patients
• 32:32located in rural geographic regions
• 32:34with low income and education
• 32:36levels appear to be at
• 32:38greatest risk of for self
• 32:40reported
• 32:41breast cancer related lymphedema
• 32:43rather than physician diagnosed.
• 32:46The patients of diverse racial
• 32:48and ethnic backgrounds and low
• 32:49socioeconomic
• 32:50status were at increased risk
• 32:52for inadequate
• 32:54self care,
• 32:56practice education,
• 32:57insufficient breast cancer survivorship,
• 33:00support, and low accessibility to
• 33:02treatment resources.
• 33:04And even though the mechanism
• 33:05driving the increased risk amongst
• 33:07minority patient populations is unknown,
• 33:11Active prevention and multisperity interventions
• 33:14are really imperative to lower
• 33:15breast cancer,
• 33:16related lymphedema rates in this
• 33:18group, and we wanna empower
• 33:20our breast cancer survivors, and
• 33:21we wanna strengthen their self
• 33:23efficacy.
• 33:25So one of the final
• 33:26projects I wanna discuss today
• 33:28is,
• 33:29is a project from,
• 33:31the cohort here at the
• 33:32Yale Cancer Center.
• 33:34So Stav Brown is a,
• 33:37is our research associate,
• 33:39this year, and Alina Chen
• 33:41is a medical student at
• 33:42Yale that worked on this.
• 33:43We wanted to look at
• 33:44whether or not we could
• 33:45predict cancer related lymphedema.
• 33:48And interestingly,
• 33:49we have a huge cohort
• 33:51lymphedema patients here. We have
• 33:53about fifteen thousand six hundred
• 33:55and sixty six cases of
• 33:57axillary lymph node dissection here.
• 33:59So we wanted to look
• 34:00at outcomes.
• 34:02So we know that lymphedema
• 34:03is irreversible and incurable.
• 34:06There are over
• 34:07thirty eight prediction models available
• 34:10out there. So that's a
• 34:12lot of models.
• 34:14So what is wrong with
• 34:15them and why don't they
• 34:16work? How can we not
• 34:17predict who's gonna have lymphedema?
• 34:19The limitations
• 34:20of the current, prediction models
• 34:23as are that they don't
• 34:24predict the time of diagnosis.
• 34:27They're based on small cohorts,
• 34:29and there's therefore lack of
• 34:30sufficient statistical power.
• 34:33Patients are followed for a
• 34:35very short period of time.
• 34:36They don't account for race
• 34:38and ethnicity.
• 34:39They don't even address important
• 34:40comorbidities.
• 34:42They don't include
• 34:43laboratory based predictive markers, and
• 34:46they don't
• 34:47really,
• 34:48give you the information that
• 34:49you need. That information is
• 34:51not readily available.
• 34:53So our aims were to
• 34:54look at the risk of,
• 34:56were to look at the
• 34:57risk of lymphedema.
• 35:00Most specifically, can we predict
• 35:01lymphedema,
• 35:02but can we predict the
• 35:03time of lymphedema as well?
• 35:05So we wanted to look
• 35:06at the impact of demographic
• 35:08and clinic variables
• 35:10clinical variables,
• 35:12following axillary lymph node dissection,
• 35:14And we wanted to explore
• 35:15the effects of laboratory based
• 35:17markers on the risk of
• 35:19developing cancer related lymphedema
• 35:21following axillary lymph node dissection.
• 35:23And similarly for the time
• 35:25of lymphedema,
• 35:26explore demographic and clinical variables
• 35:29and see whether or not
• 35:31laboratory based markers,
• 35:33can have an effect on,
• 35:35on lymphedema diagnosis.
• 35:37So this was a retrospective
• 35:39cohort. So we looked at
• 35:40all the patients who had
• 35:41undergone
• 35:42axillary lymph node dissection at
• 35:44Yale Cancer Center between twenty
• 35:46thirteen and twenty twenty four.
• 35:48We collected
• 35:49age, BMI,
• 35:51gender, race,
• 35:52chemotherapy,
• 35:53radiation, diabetes,
• 35:55hemoglobin a one c,
• 35:57lymph and then looked at
• 35:58outcomes such as lymphedema development
• 36:00and also time from axial
• 36:02lymph node
• 36:04to lymphedema development.
• 36:06We did a two multivariate
• 36:08regression
• 36:09models
• 36:10were developed to evaluate this
• 36:11these risk factors
• 36:13specifically and at the time
• 36:15of first diagnosis following accident
• 36:17lymph node dissection.
• 36:19We did a multivariate logistic
• 36:20regression for the risk of
• 36:21lymphedema and a multilinear
• 36:23and Cox proportional hazard regression
• 36:26for time to first diagnosis.
• 36:28So as mentioned, these were
• 36:30fifteen thousand six hundred and
• 36:32sixty six cases. So we
• 36:34we look at other tertiary
• 36:35cancer centers.
• 36:37This is about two to
• 36:38three times the volume in
• 36:40only about a decade.
• 36:42So there's about twenty three,
• 36:44forty five patients, so about
• 36:45fifteen percent of patients that
• 36:47develop cancer related lymphedema post
• 36:49axial lymph node dissection, and
• 36:50that fits well with the
• 36:51literature.
• 36:53Patients develop lymphedema with an
• 36:55average onset of twenty and
• 36:56a half months post axillary
• 36:58lymph node dissection.
• 37:01When we look to add
• 37:02to the risk of lymphedema
• 37:04and particularly
• 37:05risk factors,
• 37:06so the risk factors
• 37:08that are associated
• 37:10are BMI of over thirty,
• 37:13chemotherapy,
• 37:14which is not seen in
• 37:15other,
• 37:16other literature,
• 37:17diabetes,
• 37:20race,
• 37:21black African American, as well
• 37:23as radiation. So those have
• 37:25all presented
• 37:27as, risk factors
• 37:28in our clinical model.
• 37:30When we look at,
• 37:32time to lymphedema,
• 37:34so,
• 37:35race such as, black African
• 37:37American,
• 37:39Asians, and radiation are early
• 37:40predictors,
• 37:42in terms of timing, so
• 37:44more likely
• 37:45early for them to present.
• 37:47And diabetes
• 37:48is a late predictor of
• 37:50lymphedema.
• 37:52When we looked at laboratory
• 37:54based,
• 37:56features and the our model,
• 37:58so BMI,
• 38:00chemotherapy,
• 38:01and hemoglobin a one c
• 38:02at the time of axillary
• 38:04lymph node dissection. So this
• 38:05is also in patients who
• 38:06don't necessarily have diabetes, but
• 38:08it's rather that laboratory value.
• 38:12They were shown to be
• 38:13risk factors for lymphedema.
• 38:16And when we looked at
• 38:17timing,
• 38:18BMI of over thirty and
• 38:20hemoglobin
• 38:21a one c were predictors
• 38:23of developing
• 38:24late lymphedema.
• 38:27So the conclusions from this
• 38:28part of the study, this
• 38:29is a larger single center
• 38:31study. So there's,
• 38:33there's no one else who
• 38:34had this has this much
• 38:36data.
• 38:36We're actually surprised at the
• 38:38amount of data that we've,
• 38:40you know, we have here,
• 38:41which is great because this
• 38:42allows
• 38:43us to develop this tool.
• 38:46So it can we can
• 38:48basically
• 38:49potentially predict, and we can
• 38:50develop algorithms
• 38:51for individualized
• 38:53risk and time to diagnosis.
• 38:55This is the first study
• 38:56to highlight hemoglobin a one
• 38:58c as a novel independent
• 39:00predictive
• 39:01marker.
• 39:02These findings really offer,
• 39:05a foundation
• 39:06to create these individualized screening
• 39:08tools and early preventive measurements
• 39:11in high risk patients.
• 39:13And if you look here
• 39:14in terms of future studies,
• 39:16our goal is to really
• 39:17improve
• 39:18multidisciplinary
• 39:19approach to treatment,
• 39:21to enhance early diagnosis,
• 39:23to prevent barriers and disparities
• 39:25in care, to identify novel
• 39:28biomarkers,
• 39:29to establish predictive techniques as
• 39:31standard of care,
• 39:32and to create individualized predictive
• 39:34models. And each of these
• 39:36can be its own massive
• 39:37projects and have multiple sub,
• 39:39subthemes.
• 39:41And I also wanna put
• 39:42a pitch in there as
• 39:43Kate asked me to do
• 39:44that we do currently have
• 39:46a pathway as well for
• 39:48a breast cancer related lymphedema
• 39:49in terms of how do
• 39:51we,
• 39:52how do we assess these
• 39:53patients. So I wanna thank
• 39:54you all,
• 39:55for listening, and I'm open
• 39:57to any questions.
• 40:08I'm looking at the chat.
• 40:10Okay. Here we go.
• 40:17Yes. Sorry. Go ahead.
• 40:21It's it's it's
• 40:24it's it's it's it's it's
• 40:24it's it's it's it's it's
• 40:24it's it's it's it's it's
• 40:24it's it's it's it's it's
• 40:24it's it's it's it's it's
• 40:24it's it's it's it's it's
• 40:24it's it's it's it's it's
• 40:24it's it's it's it's it's
• 40:24it's it's
• 40:32it
• 40:35we don't we don't think
• 40:36it's related to,
• 40:39to gender.
• 40:41And when we looked at
• 40:42our clinical model, we did
• 40:43not identify that. However, having
• 40:45said that, if we look
• 40:47at our cohort, it's mainly
• 40:48breast cancer related lymphedema, so
• 40:50you could understand that there's
• 40:51a bias towards female. And
• 40:53when we looked when we
• 40:54did our prospective studies, about
• 40:55eighty percent of our women
• 40:57are of our patients were
• 40:58female as well.
• 40:59But currently, there's no predilection,
• 41:02or anything that would imply
• 41:04that women are more likely
• 41:05to develop lymphedema.
• 41:10Again, with age, we didn't
• 41:12find that there was a
• 41:13particular age, but we know
• 41:14that the earlier you're diagnosed,
• 41:16the more likely you're gonna
• 41:17have a worse progression. So
• 41:19there's obviously some patients who
• 41:21are born with primary lymphedema.
• 41:23So whether they develop it
• 41:24when they're born versus as
• 41:25an adolescent or later on
• 41:27in life. And we know
• 41:28the longer that they have
• 41:29lymphedema,
• 41:30the more their lymphedema progresses.
• 41:33But,
• 41:34for secondary lymphedema,
• 41:36it's not known to be
• 41:37associated with a particular age.
• 41:40Yes.
• 41:42Thank you.
• 41:44Yesterday, I asked this question.
• 41:46She
• 41:50had about a year and
• 41:51a half out, doing really
• 41:52well, has no signs of
• 41:54edema.
• 41:54She said, am I unclear?
• 41:57And I said no, but
• 41:59I didn't have a great
• 42:00response to her
• 42:01as well. Yeah. Kind of
• 42:02what Yeah. I think her
• 42:04her next step. So I
• 42:06think her next step is
• 42:07for her to continue to
• 42:08follow. So, interestingly, I feel
• 42:10that right now, we do
• 42:11immediate lymphatic reconstruction, but we
• 42:13don't necessarily follow them long
• 42:15term.
• 42:15And we know if you
• 42:16look at when do patients
• 42:18develop lymphedema, the average is
• 42:20about twenty and a half
• 42:21months after the axillary lymph
• 42:23node dissection. So she's really
• 42:24not necessarily in the clear.
• 42:27But regardless of that, we
• 42:28have to continue to follow
• 42:29them because we talked about
• 42:31things like
• 42:32not even
• 42:34signs, but rather, like, symptoms.
• 42:36Right? They're they're feel if
• 42:37she's starting to feel any
• 42:38progression
• 42:39or any heaviness,
• 42:41she's someone that I would
• 42:42consider really maybe even putting
• 42:44in a garment
• 42:45and having her use other
• 42:47tools,
• 42:47to further decrease her risk,
• 42:49but she's definitely not in
• 42:51the clear.
• 42:56With
• 42:57alerts even if they've had
• 42:58essential Yes. Disease.
• 43:00Yeah.
• 43:01Meaning no IVs, no blood
• 43:02pressure cocks. You know, these
• 43:03poor women get stuck over
• 43:05and over again in their
• 43:05arm that has not had
• 43:06any accessory surgery. What are
• 43:08your thoughts on
• 43:09stethal lymphoblastibrosis and
• 43:12the ability to use that
• 43:13arm? Yeah.
• 43:15So I think even for
• 43:16both,
• 43:17we we know that a
• 43:18blood pressure cuff we actually
• 43:19have studies. A blood pressure
• 43:21cuff and IV, it shouldn't
• 43:22increase the risk of lymphedema.
• 43:24However, if you look at
• 43:25the lymphedema modality and care,
• 43:27a big one centers on
• 43:29skin care.
• 43:30So if, for example, the
• 43:31IV
• 43:33is likely to cause you
• 43:34an infection or likely to
• 43:36cause you skin irritation,
• 43:38that makes you more at
• 43:39higher risk of either an
• 43:41cellulitis or infection or even
• 43:42progression of your lymphedema, similar
• 43:44with a blood pressure cuff.
• 43:46I don't know if you
• 43:46noticed, but sometimes in the
• 43:47operating room, we have blood
• 43:48pressure cuffs on patients and
• 43:49their arm kinda changes colors
• 43:51a little bit, and you're
• 43:52like, what's going on? So,
• 43:53actually, there's been a lot
• 43:54of studies that show that
• 43:56that blood pressure cuff doesn't
• 43:58increase your risk of lymphedema,
• 43:59but it's the fact that
• 44:00it could cause some irritation,
• 44:02some skin changes,
• 44:04and therefore,
• 44:06potentially cause them, cellulitis.
• 44:09Yeah. It could be a
• 44:10trigger.
• 44:22Three d?
• 44:23That would be amazing.
• 44:26So lymphosendicography
• 44:27I use to use quite
• 44:28a lot. I actually don't
• 44:29use it here.
• 44:30One, because,
• 44:32I actually really haven't found,
• 44:34anyone who could really do
• 44:35it for me. So I
• 44:36do our our own ICG
• 44:37ICG lymphangiography
• 44:38in the clinic and in
• 44:39the operating room.
• 44:41But to take a look
• 44:42at it three d would
• 44:43be super interesting because what
• 44:44we currently do is
• 44:46it's actually quite extensive, is
• 44:48we try to map patients.
• 44:49Let's say we're doing an
• 44:51upper extremity. We try to
• 44:52map,
• 44:53we try to map this
• 44:54way and then this way
• 44:55and then rotate and take
• 44:57different pictures and record them,
• 44:59when ideally, what you wanna
• 45:01see is what do all
• 45:02the channels look like. So
• 45:03if we can translate
• 45:04all those images that we're
• 45:06taking into something three d,
• 45:08that would be amazing.
• 45:09And I if you're interested
• 45:10in that, I would love
• 45:11to work on that with
• 45:13you.
• 45:14Yeah.
• 45:15Yes.
• 45:17Wonderful. Thank you. Thank you.
• 45:20Your thoughts around chemotherapy
• 45:22as an independent
• 45:25effect.
• 45:27Considering either in the acute
• 45:29phase,
• 45:30it being a proxy for
• 45:32steroid use Yes.
• 45:34Symptoms. And if the
• 45:36survivorship
• 45:37phase, it being a reflection
• 45:38of potential sarcopenia.
• 45:41Mhmm.
• 45:42What's your
• 45:44Yeah.
• 45:45I so one, we were
• 45:46surprised to see that because
• 45:48that's not known in the
• 45:49literature either. So, typically, we
• 45:51know that radiation
• 45:52therapy is a risk factor
• 45:54is an independent risk factor,
• 45:55but we found that chemotherapy
• 45:56was,
• 45:58which, was interesting.
• 46:00I agree that we have
• 46:00to separate it from the
• 46:02steroid use, but also the
• 46:03steroid use could also have
• 46:04an effect on hemoglobin a
• 46:06one c, the sugar levels,
• 46:08etcetera.
• 46:09So we're still gonna delve
• 46:10into that data a little
• 46:12bit more,
• 46:13to see to see as
• 46:14to why.
• 46:16But,
• 46:17it's really interesting what we
• 46:19are saying about the late
• 46:20effect of the sarcopenia. We
• 46:22haven't really looked at that.
• 46:25Hi.
• 46:32Yes.
• 46:34Yes.
• 46:41Mhmm.
• 46:42Right. So,
• 46:44breast lymphedema is actually very
• 46:45difficult to diagnose.
• 46:48One of my so when
• 46:50they present with a red
• 46:52breast or a breast that
• 46:53kinda swells or a breast
• 46:55that continues and progresses,
• 46:58I really try to sort
• 46:59of get to,
• 47:01to be honest, it it
• 47:02takes me I get a
• 47:03lot of the information from
• 47:04the history
• 47:06and with how they're presenting
• 47:07because I do think it's
• 47:08a rare diagnosis.
• 47:10So first things that I
• 47:12I try to make sure
• 47:13that it's not as recurrence,
• 47:15and sometimes we often forget
• 47:17that that is a reason
• 47:19for swelling and for them
• 47:20to look different.
• 47:22Also, you know, we talk
• 47:22about inflammatory
• 47:24breast cancer, which can also
• 47:26present that way.
• 47:29However, having,
• 47:31having sort of seen a
• 47:33few patients,
• 47:34I've realized that most the
• 47:36the reason why it's so
• 47:37difficult to diagnose is because
• 47:38it's hard to image as
• 47:39well.
• 47:40So we've currently developed,
• 47:43a few ways to image
• 47:45it in the clinic,
• 47:46by injecting
• 47:47very similar to you know,
• 47:49you can use ICG by
• 47:50injecting around the nipple areolar
• 47:52complex
• 47:53to take a look at
• 47:54what drains the breast into
• 47:55the XLL. Right? That's one
• 47:57of the ways to find
• 47:58your lymph node, for example,
• 47:59your central lymph node. So
• 48:01I started using that and
• 48:02as well as injecting
• 48:04some of the, the quadrants.
• 48:07I noticed that there it's
• 48:09also hard to differentiate
• 48:10from radiation
• 48:12induced edema.
• 48:14Right?
• 48:15So I think
• 48:16those are that's why it's
• 48:17such a difficult diagnosis.
• 48:19If they haven't had radiation,
• 48:21but they're still presenting with
• 48:23a heavy breast, with a
• 48:24lot of edema,
• 48:25edema that doesn't get better,
• 48:27when they do a lot
• 48:28of massaging, it gets better,
• 48:30I think that's breast related,
• 48:32lymphedema, breast cancer lymph breast
• 48:34cancer lymph
• 48:35but if they're if they've
• 48:36had radiation
• 48:37and they're very early following
• 48:39their course,
• 48:41I don't think we can
• 48:42diagnosis that diagnose it as
• 48:44breast lymphedema.
• 48:45So it's a I think
• 48:46it's a very rare diagnosis,
• 48:48and there's only a couple
• 48:49of other places where we're
• 48:51kinda looking at how do
• 48:52we map it. Is it
• 48:53an actual diagnosis?
• 48:56So, yeah, it's a bit
• 48:57it's very tricky.
• 48:59Yeah. I think it's a
• 48:59diagnosis of exclusion. That's sort
• 49:01of how I would define
• 49:02it right now.
• 49:10Any other questions?
• 49:13Let me see if there's
• 49:14something here.
• 49:17There's a question here. Is
• 49:18it feasible to collect lymphatic
• 49:20fluid at the time of
• 49:21surgery? If it is feasible,
• 49:22what is the range of
• 49:23volumes that can be collected?
• 49:25That's a thank you for
• 49:26that question. So when we
• 49:28did that prospective trial where
• 49:29we looked at skin biopsies,
• 49:31looking at RNA sequencing,
• 49:34and immunohistochemistry,
• 49:35we try we collected skin,
• 49:38we collected fat, and we
• 49:40tried to collect,
• 49:41lymphatic fluid.
• 49:43Collecting lymphatic fluid is actually
• 49:45excessively
• 49:46difficult.
• 49:48We tried to, you know,
• 49:50use different pipettes,
• 49:51and it was actually very
• 49:52difficult. The range of volumes
• 49:54that are collected are very
• 49:55minimal.
• 49:56Maybe
• 49:58one ml would be the
• 49:59max, and I'm not sure
• 50:00that that's enough to do
• 50:01any sort of,
• 50:03sort of studies with that.
• 50:05The other way to potentially
• 50:07collect it, and this is
• 50:09in patients who,
• 50:11are undergoing liposuction,
• 50:14is to collect it in
• 50:15the lipoaspirate,
• 50:16but then you'd have to
• 50:17be able to find a
• 50:19way to sort of divide
• 50:20it divide the, light lipid
• 50:22portion of it to the
• 50:24lymphedema
• 50:24to the lymphatic fluid portion
• 50:26of it, and I think
• 50:27that can also be very
• 50:28difficult. But that's potentially another
• 50:30way to do it.