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Speaker: Dr. Anderson is going to speak to us about an update on the evaluation and treatment of venous disease in the lower extremity. So please welcome Dr. Anderson.

Dr. Anderson: I appreciate those that have stayed this long day and we will try to make this quick and relevant. So some disclosures, I am speaker for KCI and Organogenesis, a consultant for KCI and part of the speaker bureau for Novadaq. A little bit of historical perspective. Venous leg ulcers have afflicted mankind since recorded history. Hippocrates theorized that venous leg ulcers were necessary to permit harmful humours to egress the body. Galen continued that thought process and stated that venous leg ulcers were the site to rid the body of bile entrapment that could lead to madness. Because of that, for a number of years if a venous leg ulcer was present and then closed, it was felt to be appropriate to reopen the venous leg ulcer so that people didn't go mad and that you got rid of the harmful humours. So obviously, we have increased in our knowledge and the goal is to heal venous leg ulcers. So a question is why should you as podiatric surgeons be interested in venous leg ulcers. I have had the opportunity to work very, very closely with some excellent podiatric surgeons. I have been involved in a limp preservation initiative for many years and it became obvious to us very early in the business that podiatric surgery and the marriage between podiatric surgery, vascular surgery and wound care was critical for limb preservation.

[02:15]

What I have noted in my interaction with podiatric surgeons and in my experience speaking to podiatric surgeons is that podiatric surgery as a specialty have stepped forward and taken the role in many institutions as the wound care doctors or at least they do that part time, perhaps more than any other specialty. Venous leg ulcers are the most common ulcers seen in many wound care clinics. The other factor is the era of pure ulcers is rapidly disappearing so that now when we have an ulcer, oftentimes it's a mixed ulcer. The patient may have edema or venous disease. They may also have arterial disease. They may be a diabetic. They may have some biomechanical changes in their foot. They may have neuropathy. So really to heal those ulcers takes somebody that understands the foot, understands the extremity and you as podiatric surgeons have that knowledge. An overview, venous leg ulcers number one, I will point out several times really a morbid condition. When we are talking about healing of venous leg ulcers, it really requires both a knowledge and treatment of the disease as well as knowledge of wound care and management of that wound. So you have to do both; manage the disease, manage the wound and continue to manage the disease in order to get these wounds healed and keep them healed. Venous leg ulcers are common. As I said many times, the most common ulcer we see in our wound care clinics. 2.5 million patients affected per year. As high as 70% to 90% of leg ulcers have a venous component. Doesn't mean they are pure venous ulcers.

[04:14]

Prevalence of venous leg ulcers increases with age, with little bit more common in females and the recurrence rate is very significant. So they are common increasing in incidents and tend to recur. I think what's underestimated or underemphasized is a better way to say it, it is the morbidity associated with these ulcers. All of you are very, very familiar with diabetic foot ulcers and you are familiar with a risk that diabetic foot ulcers have going on to amputation. Therefore, when you have a diabetic foot ulcer, you understand the importance of healing that diabetic foot ulcer so it does not lead to an amputation. Because venous leg ulcers rarely lead to amputation, I think they have been underemphasized. The impact of venous leg ulcers on the individual patient is very, very significant. There is a physiologic, physical or functional and social impact to these patients. 97% of patients reported functional restrictions. 66% reported that their mood was affected. Most felt that the ulcers never seem to heal. They became very, very discouraged. Some of the symptoms pain, exudate, itching, functional limitation, emotional, psychological. Many of these patients quit working. They end up divorced. They end up addicted to narcotics and oftentimes are given recurrent episodes or treatments with antibiotics which can contribute to chronic renal failure.

[06:05]

There is also a very, very significant economic impact of venous leg ulcers. The direct cost, medical care, therapeutics but there is an indirect cost and that as I have eluded to that the patients oftentimes don't work and it's estimated that six million days a year of work lost in the US due to chronic venous insufficiency. So when you look at that, the total cost, the direct cost, the indirect cost, an average of around $13,000 per venous leg ulcers and estimated 1.9 to 2.5 billion dollars per year. That's a lot of money. This is some additional information on the economic impact. The treatment cost is estimated to be around one billion, another number out there. And O'Donnell stated that venous leg ulcers account for 1% of the healthcare budget in some industrialized country. So how do we improve outcomes? How do we get these ulcers healed? How do we improve the quality of life in these patients with venous leg ulcers? Number one is you need to understand and address system issues and I will talk a little bit more about that. Understand and treat the disease. You can't just treat the wound. You have to understand and treat the disease as well as understanding and treating the wound and when appropriate, move on to advanced techniques, which can include surgical techniques as well as advanced wound care. We have the opportunity to work as a group and look at the care of venous leg ulcers in the VA and we discovered some things that I think are not unique to the VA.

[08:01]

And we labeled those as system issues within the VA, but again I think system issues in the management of venous leg ulcers nationally. No defined gatekeeper. Again, podiatric surgery has stepped forward for diabetic foot ulcers but who has really stepped forward for venous leg ulcers? I am a vascular surgeon, so I can talk about vascular surgeon. Vascular surgeons have not stepped forward and said, send us all your venous leg ulcers. So unlike limb preservation teams for diabetic foot ulcers, the management of venous leg ulcers usually lacks that integrated team approach, so there is fragmented care by various specialties. There has been a lack of guidelines that have been followed, oftentimes again treating the wound without treating the disease and a failure to really understand that in many of these patients, direct surgical intervention can help. So when we look at system issues, how can we improve the process, support a multidisciplinary approach? Just like we have for diabetic foot ulcers, define a team that's going to have a gatekeeper guidelines and pathways to other specialties that should get involved in the treatment of venous leg ulcer. So define referral guidelines to vascular surgeons and to other subspecialists, wound care specialist, and at times podiatric surgeon. To get people's attention, I think you need a banner. Certainly, with diabetic foot ulcers, the banner has been preventing the amputation. I think if you look for a banner with venous leg ulcers, it's functional restoration. It's getting these patients back to a functional life.

[10:00]

So integrate, develop or implement a functional program similar to the paid program in the VA, which again focuses on amputation, but in the venous leg ulcers, focus on functional restoration. Certainly, guidelines have become very common in the management of the diabetic foot. There are guidelines that have been proposed for venous leg ulcers but quite honestly have not been followed and we have some new guidelines that I am going to allude to in just a minute. There is some data that demonstrates that following guidelines in both diabetic foot ulcers and venous leg ulcers certainly improve outcomes. So this is brand new. This just came out in August of 2014. This is a consensus guidelines for venous ulcers. This is by the society for vascular surgery and the venous forum that got together and got an appropriate group together. You all recognize some very prominent names here and they came up with guidelines as I said that were just published. The management of venous leg ulcers, clinical practice guidelines of the society of vascular surgery and the American Venous Forum. So for the rest of the talk, I am going to allude to some of these guidelines, again that was just published. So first of all, it's important to understand the disease and define some terminology. You have to know what the disease is and how to treat it to really manage these patients. Venous insufficiency means that there is something insufficient about the venous system.

[12:02]

That insufficient can be either obstruction or valvular function. So either the venous system is obstructed or valves are incompetent or you can have both. You can have obstruction and valvular incompetence. It can involve both the deep venous system and superficial venous system or at times it can involve only the deep or only the superficial venous system. If you have to understand one physiologic principle in the management of venous disease, it would be ambulatory venous hypertension. If I have two individual standing side by side, one is normal and one has significant venous disease and they are of equal height and they are standing perfectly still and I put a needle in the foot of both patients or both individuals and I measure the pressure, it's the same. It's a column of blood. What happens in the patient with venous disease is as that patient exercises, the pressure will go down but it will come right back up just like squeezing a sponge. In the normal individual with exercise, the pressure goes down and it's stays down as long as that patient is exercising. So the ambulatory venous hypertension means that even when you have activated your muscle pump because of the obstruction incompetence [indecipherable] [00:13:38] that pressure remains high at the ankle level and that contributes to the venous hypertension that changes the skin and leads to venous leg ulcers. Venous ulcers are certainly a significant consequence of venous insufficiency, most commonly associated with deep venous and perforated insufficiency, although at times you will see when the patients have only superficial venous disease.

[14:09]

Important that we all speak the same language. The CEAP classification is a clinical classification used for the management of venous disease. You can see it C0 to C6 with C6 being an active venous ulcer. So diagnosis and treat the disease, confirm the diagnosis. Is it really a venous ulcer? Rule out arterial disease. Somewhere around 25% of venous leg ulcers have associated arterial disease. Consider Sickle cell, consider biopsy with atypical ulcers or ulcers that have been present for over four months. The venous Duplex scan is critical to diagnose venous disease. It can diagnose both obstruction and incompetence, so that's become the standard. Venography is rarely performed unless you are planning some specific surgical procedure on the deep venous system. So venous Duplex can has become the standard for the diagnosis of venous disease. We have done this study twice in our clinic. We have looked at patients referred to our clinic with a diagnosis of venous leg ulcers. In both series, approximately 40% of patients referred to our vascular surgery clinic with a diagnosis of venous leg ulcers had no evidence of venous disease. What they had was edema and they had an ulcer. Because they had edema and an ulcer, it was assumed that it was a venous ulcer. The majority of this 40% had congestive heart failure. They had a medical reason for their edema and their history is that every time they have an exacerbation of edema, they develop blistering.

[16:02]

That blistering goes on to develop large ulcers. These are the patients that have very large pretibial ulcers, oftentimes very, very exudative ulcers and very difficult ulcers to heal. The key is that they don't have any venous disease. So the management is wound care and management of the underlying medical condition leading to the edema. So it's important to understand that subset of patients and get the appropriate medical management of the edema. Venous ulcers on the other hand have underlying venous disease and as I will allude to in a minute, many times treatment of that disease either endovascularly or with open surgery can play a significant part in getting those venous leg ulcers healed or certainly preventing recurrence of those venous leg ulcers. So establish the diagnosis is it venous or edema? Treat the underlying etiology. Always compression, debridement, control of infection or colonization. Basic wound care with compression and then if failing to progress at four weeks, consider advanced wound care or surgical intervention. Compression therapy, first line treatment for venous leg ulcers. If you are treating the wound without compression, you are not treating the disease. As I mentioned, 15% to 25% of the patients with venous leg ulcers have arterial disease. One of the guidelines in these new guidelines recommend arterial pulse examination and measurement of ABIs in all patients with chronic venous leg ulcers. Compression therapy, not really known exactly how it works but several studies that again indicate the benefit. It's important to understand inelastic versus elastic compression therapy oftentimes confused.

[18:03]

Inelastic that works while the patient is exercising. So Unna boots for example are inelastic. You have a wrap and then as the patient exercises, you build up that compression. Elastic on the other hand whether one, two, three or four layers actually has an elastic component. So inelastic versus elastic. This is Cochrane database review, which again shows the benefit of compression therapy. There is still debate how many layers of compression therapy should be utilized. I would say in summary that looking at all of the data, there is certainty data that supports a multi-layer compression is better than a single layer compression, although at times again we sometimes just use Unna boots. There is a danger to compression. Again, realizing that somewhere around 25% of patients have arterial disease. If they have significant arterial disease with an ABI below 0.6 or certainly below 0.5, then putting on compression can actually lead to wounds. So another reason to certainly do a pulse exam and if any question, do an ABI. Infection control, I think antibiotics are overused in venous leg ulcers. If the ulcer is colonized as they all are, that is not an indication for antibiotics. Antibiotics are appropriate if there is associated cellulitis or rarely any kind of abscess formation. Once drained, if there is also existing cellulitis but most of the time, systemic antibiotics are not needed in venous leg ulcers.

[20:00]

The question of what kind of dressing to put on? Again, all of you like me have all kinds of people that come to your office selling lots of dressing. In this review, there were 42 randomized control studies and the type of dressing has not been shown to affect ulcer healing. So there is no significance between for example hydrocolloid dressing and a simple low adherent dressing when used underneath compression. So basically when you are looking at what kind of dressing, it's patient-dependent. Certainly, if you have highly exudative wound, then you are going to use something that's going to absorb that exudate so that you don't end up with a lot of maceration around the ulcer. So patient-dependent, a lot has to do with the drainage but no good data that one dressing is routinely better than another. A lot of debate about honey and you have seen some reviews and counter reviews, the latest Cochrane database review does not support honey dressing as an adjunct to compression. Those of you that read the wound care journals know this has been and continues to be debated. Systemic therapy, there is some literature that supports the use of Trental normally thought of as a drug used in small vessel arterial disease but there is data to support the benefit of Trental in venous leg ulcers. The operative and endovascular management of venous disease, when you look at these current guidelines and certainly you look at the trend in the vascular surgery literature, there is much more emphasis now on an active role of venous intervention for venous leg ulcers.

[22:02]

Maybe it's because we have too many vascular surgeons now and not enough arterial disease or maybe it's reimbursement, I am not sure, but there is renewed interest now in venous disease. Two potential benefits of operative intervention whether it's endovascular or open; one is to help those chronic ulcers heal but again always treat the disease and the wound and certainly there is very strong literature to support that treating the venous disease can help decrease the recurrence rate once the venous leg ulcer is healed. So candidates for venous surgery, patients with superficial venous disease or perforator disease are candidates for venous intervention. Direct intervention on the deep system is rarely done although there are some operations of deep venous bypass or valvular reconstruction, also some research on synthetic valve, but rarely used. Where deep venous disease is now evaluated and fairly commonly treated is in the iliac venous system. If you have iliac occlusion, then to recannalize that occluded iliac vein and stent that open has proven beneficial. So when we look at ablation, it can be surgical ligation plus or minus stripping, microphlebectomy perforator ligation. The trend has been like all of vascular surgery to endovascular or endovenous ablation utilizing either laser or radiofrequency and renewed interest now in sclerotherapy and foam therapy.

[24:00]

This is the endovenous obliteration, ultrasound identification of the vein, wire placed in the vein and then either a laser or radiofrequency catheter placed at length of that vein, slowly withdrawn and that seals the vein. When we look at chronic venous leg ulcers, unfortunately even if you are doing things right, there are number of those ulcers that go on to become chronic ulcers. And the question is what can we do in the subset that becomes chronic venous leg ulcers? Or another question can we identify those patients that are on that track to becoming chronic venous leg ulcers? This is where the four-week reassessment becomes very important. It's certainly become part of our standard now for the management of diabetic foot ulcers, popularized by the late Dr. Sheehan but also very, very important in venous leg ulcers. So looking at the progress that has been made at four weeks and if there is a lack of appropriate progress, then consider advanced modalities. These are some of the references again supporting the four-week reassessment. So doing the standard of care, infection control, debridement, moist wound care, compression, reassess at four weeks and if less than a 40% improvement at four weeks, then consider advanced therapy. That advanced therapy can either be advanced wound care, i.e., human cellular and tissue based products or consider direct venous intervention or both.

[26:00]

So when we think of the cellular and tissue-based products, again, an area that we could spend all afternoon. Lots and lots of emphasis, a rapid evolving field but somewhat confusing field oftentimes led by marketing versus science. It's still important in my opinion to understand the difference between acellular products and cellular products. Acellular products or matrix tissue nonviable cells, tissue base that can be human or animal, cellular viable human cells, non-cultured intact tissue, cultured in-vitro or cultured in-vitro and placed on a synthetic substrate. So when you look at cellular products then as a subgroup, you have autologous, some of you may be familiar with new technology. The cellular tome, which is an epithelial graft that can be placed on wounds, allogenic human foreskin leading to Apligraf or Dermagraft. Placenta, leading to Grafix, which is different than the other placental tissues and that it's cryo-preserved living tissue. Spray delivery of cells in final research studies about to come to market and stem-cell derived wound care. To quote the guideline, we suggest the use of cultured allogenic bi-layered skin replacement with both epidermal and dermal layers to increase the chance of healing in patients with difficult venous leg ulcers in addition to compressive therapy. Apligraf is the only PMA bilayered product approved for venous leg ulcers. This is the study -- the large randomized control study that led to the approval of Apligraf for venous leg ulcers, again showing improvement and complete closure rate over time and 85 days faster wound closure.

[28:14]

You can say 85 days. I can tell you if you are a patient out of work for 85 days, that's a big deal. Acellular matrices, large number of products increasing number of products. Acellular matrix products differ mainly in the source of tissue material and the methods used or in manufacture. They act as a scaffold to support cell ingrowth and granulation tissue formation, have receptors that permits fibroblast to attach to the scaffold. They can stimulate angiogenesis, they can act as a chemoattractant for endothelial cells and they may contain or protect growth factors. So what is the role in venous leg ulcers, again you can see the number of products, increasing number of products. 20 RCTs were identified, five showed significant improvement for wound healing. This is again from the guidelines only porcine small intestine, intestinal mucosa, i.e., Oasis as perspective randomized control data support and its use to accelerate venous leg ulcers. That's from the guidelines that were just published a week ago. So maintenance therapy, the key is that when you have a patient with venous leg ulcer, even if you have that ulcer healed, the patient still has the disease. Therefore, continuing compression and consideration for surgical intervention can play a role in helping prevent recurrence.

[30:00]

So in summary, venous leg ulcers, what works and what is on the horizon? What works has been shown to work in diabetic foot ulcers and to a lesser extent in venous leg ulcers is a coordinated approach, treating the disease as well as treating the wound and using appropriate guidelines. What's on the horizon? I think with the current guidelines that have just been published, I think what we will see hopefully is more centers adapting not only that integrated approach but following those guidelines. With a better use of guidelines, I think we will see an increased use of intervention, direct intervention on the venous system and appropriate use of biologics with further definition of what biologics really work in the venous system. So in conclusion, improved outcomes may require system changes. Improved outcomes require a knowledge of venous disease, institution of guidelines, assessment and treating of the venous disease as well as treating the wound and understanding the select role of direct intervention and advanced wound care products. Thank you for the privilege of the podium.

[Applause]


TAPE ENDS - [31:29]