Treatment of a Lower Leg Defect in the Course of Sarcoma with Microvascular Tissue

In this video, Dr. Dobke and his associate, Douglas Arm, share background and results from their case report, Treatment of a Lower Leg Defect in the Course of Sarcoma With Microvascular Tissue. Read the full article here.
 

Transcript:

Marek Dobke, MD: My name is Marek Dobke, and I am one of the surgeons embedded in the division of plastic surgery at University of California San Diego, and I am very privileged to be interviewed by the magazine that I read since in inception.

And during this session, I would like to share with you my experience with human microvascular tissue allograft product which we use for difficult wound with changing objectives that I will describe later on. I would like to introduce my, actually, research mentor, friend, Dr. Doug Arm who is with the company who supported me during the management of this particular patient as well as some other patients that we had fantastic experience with the product that was originally very new to me. So Doug work with the company that developed the product and maybe he should speak a little bit about the nature and biology of the product.

Douglas Arm: Thank you, Dr. Dobke. So my name is Doug Arm. I'm with a company called Microvascular Tissues, and we've developed a processed microvascular tissue, or PMVT, and it's a sterile, off-the-shelf, human microvascular structural tissue allograft. It's from a single human cadaver, and it consists of arterial, capillary and venule extracellular matrix. And you can see that in the upper left of the slide.

The product has been developed by MVT under the trade name of mVASC, and it's packaged as a lyophilized disc in a sealed glass vial for single patient use. It's intended to support the healing of full thickness skin wounds, and can be either topically applied in a dry form to the surface, or injected locally after reconstitution with sterile waters at the edges of the wound. PMVT has been shown to improve blood flow in ischemic tissues, as can be seen here in the mouse hind limb ischemia model with a laser doppler, and also in a randomized controlled clinical trial on diabetic foot ulcers. Its microvascular structure may serve as an extracellular matrix scaffold for revascularization, positioning it as an angioconductive option to address conditions of compromised vascularity. So with this foundational information, I'll turn it back to Dr. Dobke to go into some details about this interesting case.

Marek Dobke, MD: As I mentioned before, I have experience a few cases treated with the product, but this particular case is particularly interested. Actually, we were consulted a little bit by accident by orthopedic oncology. 29 years old, young, healthy male. They had skin lesions since his childhood as he remember, but lesions started to grow when he was 28, 29, and was originally handled by orthopedics and oncologists.

It turned to be poorly differentiated angiosarcoma with spindle cell sarcoma admixture. And surgical treatment was done by orthopedic colleagues. It was lesion in anterior distal lower leg. Lesion was excised, margins were negative. And the bottom of the defect was actually soft tissue, so orthopedics grafted with a split thickness skin graft that was lost. At the same time, I have to admit patient was under chemotherapy, soon to be followed by radiotherapy. They subsequently, to stabilize the wound, put amnion/chorion biologic dressing, hoping that they would stabilize the wound, and then they outreach to plastic surgery to consult and prepare for a flap-based reconstruction, practically free flap.

However, they ask us to maybe wait a little bit because of ongoing radiation. They wanted to complete radiation and have a duty chemotherapy. That was important because he was found to have actually metastatic lesion and distant lymph nodes. So we thought that in order to bridge the time that they will give us green light for reconstructive surgery, essentially to stabilize the wound, we decided to use the product. The reason for this was that they orthopedists lost not only split sickness skin graft, but also this biological dressing didn't work. Actually wound deteriorated forming five centimeters in diameter defect with exposed tibial wound. So in this situation with objective that we just want to stabilize the wound and stop deteriorating, stop enlargement of the wound, we started to put two discs of the microvascular tissue product to wound surroundings, hoping to increase his vascularity, hoping that it'll maybe granulate, but the goal was to arrest deterioration.

After five weeks, we noted that the depth of the defect and the appearance of its margins started to depth decreasing and margins started to improve by formation of epithelialized tissue overlying thin layer of granulation tissue. And in our article we show serial pictures how it was evolving.

Six weeks to 10 weeks after time of our original involvement, wound significantly decrease in size, form new epithelium. The size of exposed bone decreased from three centimeters in diameter to approximately two and a half. And when we reached week 12, there was great surprise awaiting for us during dressing change. The product and tissue wound was always covered with gauze. We relifted the gauze and bone sequester, came off and exposed vascularized granulation tissue like tissue covering tibial bone. Simply granulation tissue guided or stimulated by the product found its way under the necrotic sequester and a plate of this sequester. It was photographed and is shown in the article and then totally change the paradigm that what we were doing because we realized that as the patient continued chemotherapy, radiotherapy, objective that could be considered change from what we thought stabilization to perhaps healing.

At first, we didn't know whether we were going to be able to heal it or not given negative experience with let's say skin graft that came on seemingly vascularized soft tissue. Anyway, this granulation tissue thickened and ultimately we didn't even skin graft because tissue was getting more vascular. There was more bleeding during each dressing change, defect shrink. So we didn't even proceed with a skin graft. Ultimately, it healed by secondary intention forming new epidermis over few millimeters thick granulation tissue. That was outcome that was exceeded our wildest expectation and this early outcome really obviated need for a free flap. Plastic surgeons know that thin epithelium over tibia doesn't mean that it is the end of the game, but one year later the tissue overlying this exposed bone became even more robust.

Douglas Arm: One of the reasons that in discussing the potential for the PMVT product and its ability to potentially help this patient with Dr. Dobke was some of the other work that was ongoing and Doctors Gould, Zelen, Armstrong and others were involved in a randomized control trial evaluating PMVT. This was a prospective multi-center trial, 100 subjects for diabetic patients with non-healing Neuropathic Wagner one and two foot ulcers. In their publication, the weekly application of PMVT significantly increased complete wound closure 12 weeks after the start of treatment or within 12 weeks of treatment. And the percent wound area reduction was also increased. There was decreased time to healing and improved local neuropathy compared to the control arm. And interestingly, in this randomized control trial, some exploratory results with fluorescent angiography indicated that there was an increased wound site perfusion that accompanied PMVT accelerated wound resolution. So with this as a background, in addition to some other experience that Dr. Dobke had had, which I'll let him tell you about, I think we agreed that the PMVT allograft made sense for this particular tibial exposed wound.

Marek Dobke, MD: My experience with PMVT, and I am not sponsored by the company, I actually I am just university practitioner, was because of incidental use and sort desperado situation. The most remarkable surprise was when we dealt once with 30 years old men who had 30 surgeries for his very large originally cleft palate. And he, after many surgeries that started when he was a baby, had this final few millimeters in diameter not healing oral nasal fistula and he was prepared for another flap surgery prior to securing him obturator, but we were really not counting on success. In order to improve the recipient side of this fistula tract, we decided to inject this several times with the product and pictures showing the sequence of changes were published in Journal of Dental and Maxillofacial Surgery, actually under my name and my associate with oral maxillofacial surgeon, Dr. Joel Berger.

To our surprise, the defect healed and the patient didn't have his 31st surgery. Just like we were surprised by healing of this lower leg defect. And actually I used this in some other cases that it was never product that was used as a first line of treatment. It was always that everything failed and we then outreach to the company if they would let us use the product. And like another case, also sarcoma with a patient who had heart sarcoma surgeries, radiation and develop persistent pericardial cutaneous fistula that drained. We used the product, very similar injections pattern like for oral nasal fistula and it healed sealing the defect, which is, cases of these fistulas are particularly important because there is one issue to heal defect that doesn't produce constant fluid and another to heal a pipe essentially. And it shows power of the product that we are able to do that. All results were surprising to me because our objective were changing. It was hopeless situation. In almost all cases, the intent was to stabilize the wound or improve the wound biology, but we never expected healing.

Douglas Arm: There's a lot of areas where we can look to expand the potential use of the PMVT product. First is the question of within the wound field, what might make sense? And so the company is looking to do additional research in not just diabetic foot ulcers, but in other cases and other series of challenging wounds such as the compromised vascular situations that Dr. Dobke has done a few cases in. We're looking at Mohs wounds after Mohs surgery. Some of those can be quite challenging to heal as well. So an array of different, both surface wounds and internal wounds as it were.

Marek Dobke, MD: I am personally involved in research on exosomes and stem cell and other forms of regenerative medicine and surgery. So at certain point was I became so impressed by mVASC. I thought that logistics of mVASC delivery injection, external application can be merit with exosomes and robustness of this delivery can be enhanced by delivering in such form to the tissue that it is almost immediately intracellular.

Douglas Arm: Yeah, there's many different technologies out there in development, but I think one thing the company and I know Dr. Dobke feels strongly about is the need to provide robust clinical evidence. And that's whatever technologies or combination of technologies are ultimately developed. They need to, in this healthcare environment, be cost-effective and clinically practical as well.