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FASXXX10.1177/1938640014557792Foot & Ankle SpecialistFoot & Ankle Specialist
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Dec 2014
Foot & Ankle Specialist
〈 Roundtable Discussion 〉 Osteochondritis Dissecans of the Talus
T
oday we will be talking about osteochondritis dissecans (OCD) of the talus. Let us start with some early stuff to get us started. We will assume for sake of discussion that conservative treatment has failed unless otherwise discussed.
Give me you best curbside consult of your algorithm for treating OCDs of the talus. Let us keep it straightforward and only address primary lesions, do not worry we will get to revision cases later. Raissi: I think the most important thing is to determine whether the X-rays or magnetic resonance imaging (MRI) finding is clinically relevant. I am sure we all gets multiple referrals with a positive finding and an MRI, but on further careful physical examination of the patient we realize that these findings are not relevant to their symptoms. So first things first, it is truly symptomatic. If there is any question, an intra-articular diagnostic injection can be of great benefit. If it is symptomatic, certain factors may determine the approach to treatment. These factors would include size, depth, location, and whether the articular surface is intact. In some cases a
computed tomography (CT) scan can be beneficial in further determining the quality of the lesion. If the articular surface is disrupted, then typically arthroscopy with debridement is my first step in surgical treatment. If I am convinced that the articular surface is intact, then we consent the patient for possible retrograde drilling. I will rarely resort to primary allograft or chondrocyte transplant procedure unless the lesion is massive.
Osteochondral lesions of the talus represent a perplexing challenge for many of us in the foot and ankle world. Despite significant publication and research on the disease, we seem to be limited with our ability to improve outcomes. Recently, a focus of identify specific characteristics about these lesions has been undertaken to improve outcomes. In addition, a tremendous amount of effort and money is being dedicated to understanding ways to manipulate the biology of this disease to increase success. In this roundtable, we have gathered 4 experts who have contributed significantly to understanding of the difficult issue to help guide us in our current treatment approach and give us a glimpse of what the future might hold.
DiDomenico: Initially, I would order 3 views of the foot and ankle. If these are negative and there is a history of an ankle sprain, a history of chronic or recurrent ankle sprains, I would obtain stress radiographs to the involved and uninvolved ankle looking for an underlining instability that may be causing the problem. If the plain or stress radiographs suggest a remote chance of an osteochondral defect, then I would order an MRI of the ankle. Based on the location and the stage of the lesion, my treatment will alter quite a bit. The treatment algorithm will range from diagnostic blocks consisting of a local anesthetic, to therapeutic injection therapy consisting of a local anesthetic and corticosteroid, immobilization, physical therapy, and finally surgery. Assuming the nonoperative care has failed and based on the location and the stage of the lesion, the surgical approach
DOI: 10.1177/1938640014557792. For reprints and permissions queries, please visit SAGE’s Web site at http://www.sagepub.com/journalsPermissions.nav. Copyright © 2014 The Author(s)
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CONTRIBUTORS Daniel Cuttica, DO The Orthopaedic Foot and Ankle Center of Washington DC Falls Church, VA Lawrence A. DiDomenico, DPM Section Chief, St Elizabeth Hospital Director Fellowship Training, Ankle and Foot Care Centers Youngstown, OH Adjunct Professor, Kent State College of Podiatric Medicine Independence, OH Teaching Faculty, Heritage Medical Center Beaver, PA Abdi Raissi, MD Desert Orthopaedic Center Las Vegas, NV Chris Reeves, DPM Orlando Foot and Ankle Clinic Faculty, Florida Hospital Orlando Podiatric Surgical Residency Program Orlando, FL ROUNDTABLE MODERATOR Stephen A. Brigido, DPM Director, Fellowship for Foot and Ankle Reconstruction Coordinated Health Bethlehem, PA SECTION EDITORS W. Bret Smith, DO, MS Director of Foot and Ankle Division Moore Center for Orthopedics Columbia, SC Stephen A. Brigido, DPM Director, Fellowship for Foot and Ankle Reconstruction Coordinated Health Bethlehem, PA
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would differ because of the stage and location of the lesion. Because of this unknown, it is a very difficult question to answer without specifics. In general, I would use an arthroscopic approach when possible. Ankle arthroscopy allows for minimal dissection and direct visualization of intra-articular structures without the need of an open arthrotomy or a malleolar osteotomy except in those cases in which the lesion stage and location dictate an arthrotomy and/or malleolar osteotomy. The arthroscopic procedure can range from diagnostic to therapeutic arthroscopy. Most of the cases will involve a synovectomy. The synovectomy can be of therapeutic benefit in those cases in which there is no articular pathology found. In cases where there is intra-articular pathology, again the treatment can range from a synovectomy followed by simple debridement to a more involved treatment of a lesion. The treatment can involve and range from curettage techniques to drilling (microfracture techniques) to cartilage replacement procedures. If the ankle were found to be unstable, I would employ an ankle stabilization procedure. In general, my experience has been arthroscopic procedures are typically very patient and physician friendly—especially in the postoperative course. Cuttica: I still perform microfracture via arthroscopy as first-line treatment for the majority of osteochondral lesions of the talus (OLT), as the literature shows this to provide good to excellent outcomes in 85% of patients. I will perform microfracture on any lesion less than 1.5 cm2, including shoulder lesions. Also, I prefer microfracture to drilling of the OLT, due to concerns of heat necrosis with drilling. In lesions larger than 1.5 cm2 or shoulder lesions, microfracture is still a good option. However, it is important to have a thorough discussion with the patient that there is a higher likelihood failure with microfracture in these lesions. As a result, in OLTs larger than 1.5 cm2, I will often utilize particulated juvenile cartilage allograft. In large shoulder lesions, I will use bulk allograft from fresh talus primarily. Finally, in large lesions with massive
Foot & Ankle Specialist
cystic defects, I will perform bulk allograft from fresh talus primarily. Reeves: The first thing I think that is important is to keep a high level of suspicion in patients that present with ankle pain. A thorough history is essential. Acute injuries are easy to keep in mind however sub acute or old injuries are even more important to keep this differential on the forefront. Mechanism is important especially knowing if the joint was “loaded” during the episode, but more so for identifying the location of the injury. Assessment of ankle instability is important as it is often concomitant with OLT’s and must be addressed if surgical treatment is necessary. Also of note is continued ankle pain following repair of ankle fractures. These are often the “forgotten” sequelae of an acute traumatic episode involving fractures about the ankle. I will usually start with a basic radiograph series. This can certainly rule in an OLT but not rule it out. Additionally in higher suspicial cases, I will often obtain an AP ankle radiograph with the foot plantar flexed. This helps indentify posterior lesions. From here, If I am still looking for diagnosis, I will move to advanced imaging which typically will entail an MRI. MRI is the best imaging modality for identifying the lesion and evaluating the integrity of the cartilage. If I am treating conservatively, I will often stop here. However, if I feel I have a known lesion I will often move to a CT scan.The bone marrow edema involved with MRI actually distorts the actual size of the lesion. A CT scan will give you a more representative picture of the lesion size, evaluate bone quality and help determine treatment course.
OK, so we have a bit of an idea about how you might organize your thoughts, we can move onto a case example and dig in a bit more. The case is of a 28-year-old male. He is a healthy active weekend warrior, with a
remote history of ankle sprains. No recent injury of note. Complains of pain with certain sports activities and feels that he “doesn’t quite trust his ankle.” Based on you own protocols, walk me through your workup protocol to help with your diagnosis. We can assume that everyone will have taken a standard 3-view radiograph of the ankle. Raissi: First things first, examine the patient thoroughly. Determine whether there are symptoms originating from the ankle joint either medial or lateral. Also determine whether there is any gross instability and pain over the anterior talo-fibular ligament itself. If there is any question of the joint being the origin of the symptoms, again, an intra-articular injection can be quite helpful in this regard. Ultimately, this patient typically will go on to have an MRI should they wish to pursue further treatment. If there is a significant cystic quality to the lesion then a CT or single-photon emission computed tomography (SPECT) scan would also be of significant benefit. Although conservative options such as nonsteroidal anti-inflammatory drugs and immobilization should be discussed with the patient, there are occasions where we know based on our experience that conservative treatment may only delay the patient’s healing process, and we should be upfront about the occasional limited benefit or futile outcome of conservative treatment of many lesions. These decisions would depend on, again, size, location stability of the lesion, and duration of symptoms. DiDomenico: Based on the understanding that the 3-view radiographs of the ankle were taken and were read as negative. Conservative care has previously failed along with the patient continuing to experience pain and symptoms as described above. Because he is a relatively young, active male and there is a history of ankle sprains, “a lack of trust” with his ankle, along with ankle pain, I am always suspicious of ankle instability as being a causative factor. Therefore, I would obtain stress radiographic of the affected and nonaffected ankle for comparison. If
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the affected side is positive (demonstrating pathologic findings with either the anterior drawer and/or the talar tilt), I would suggest ordering an MRI of the ankle. Clearly, this will assist in the diagnosis of instability, specifically with the capsular tissue as well as which ligaments are involved. Should there be pathologic findings such as an osteochondral injury, this will assist with the extent of the injury, the staging, as well as other soft tissue injuries such as peroneal tendon pathologies. If the anterior drawer and/or talar tilt is negative (not demonstrating pathologic findings), I would still order an MRI, as this will provide additional information as stated above. Cuttica: Any workup should start with a thorough history and physical. Important information includes any prior episodes injury, as there is often a history of inversion injury or other trauma to the ankle. It is also important to ask about mechanical symptoms such as locking or catching at the ankle, giving way episodes, or recurrent swelling. Physical exam should include assessment for any effusion, areas of point tenderness especially along the joint line, and range of motion. I will perform anterior drawer and talar tilt tests as well. Finally, it is also important to assess the peroneal tendons in these cases, as they are a secondary stabilizer of the ankle and can be a source of chronic pain. Weightbearing X-rays are essential, and if there is a high suspicion for ankle instability, I will perform stress X-rays. Finally, if there is high suspicion for OLT, I will utilize MRI as my primary diagnostic modality. Reeves: I would want a bit more detail from him as to what elicits his symptoms and are they medial or lateral ankle symptoms. Does it bother him walking down stairs? Is there instability? Additionally, I regularly perform diagnostic blocks and evaluate the patient both non-weight-bearing and weight-bearing following the block. True intra-articular ankle pain will improve following the block. From here, I will move to advanced imaging. Though MRI has been the
accepted go to modality to evaluate OLTs, I typically obtain a CT scan (specifically helical CT scans if available). Recent literature appears to support this idea. The bone marrow edema involved with MRI actually distorts the actual size of the lesion. CT scans do a better job of establishing the true extent of the lesion and sclerotic margins to allow for better surgical planning. I typically reserve MRI when I need to evaluate adjacent soft tissue pathology or if I have a high suspicion for an OLT in the face of a negative CT scan.
So we find out that our person in the last example got advanced imaging (ie, CT scan, MRI, SPECT, etc) of your choice. To keep it simple, the MRI comes back and reads as a 10 mm × 8 mm OCD on the lateral portion of the talus, associated edema, minimal cystic changes, no significant displacement, and fluid signal under the cap. What is you treatment of choice for this patient? Raissi: Again, I would offer the patient conservative options such as immobilization, but given our experience and knowledge with these lesions, they tend not to respond to these treatment options. Typically, if these lesions are symptomatic they require surgical intervention. Given the size and location of this lesion, I feel this patient is an appropriate candidate for debridement and microfracture/ drilling of the lesion. Also, a lateral ligament reconstruction may be required as well depending on the instability of this patient. DiDomenico: In cases such as described above, it is difficult to provide a specific answer as the lesion and the environment of the surrounding lesion are sometimes very different intraoperatively in comparison from the reports/films of MRI, CT, and so on. With this type of the lesion, I believe the
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treatment/consent needs to be open to a certain degree, as the surgeon does not know exactly what he/she may see during the time of surgery. For example, how much fluid is under the cap, how stable or unstable is the cap, the degree of cystic involvement, and the quality of the subchondral bone? Certainly the cap needs to be addressed from a salvage technique to a complete excision of the cap. Obviously, if the cap appears to be healthy, has a decent thickness to it, remains partially attached, and the cystic bone has been repaired, attempting a salvage of the cap would seem prudent. The cystic changes need to be addressed. In my experience, even if the cystic bone is minimal, in most cases by the time one curettes this area, and possibly drills the area, I have found the need to autogenous cancellous bone graft packed tightly provides a nice environment for a reparative process. Cuttica: Nonoperative treatment is typically successful in 45% of cases, based on Tol’s meta-analysis. In cases without OLT displacement or free fragment, I will typically consider a trial of nonoperative treatment, but it is important to educate the patient that nonoperative treatment is successful only 45% of the time. In this particular case, I would recommend a course of immobilization in a weight-bearing cast or walking boot for approximately 4 to 6 weeks, followed by a course of formal physical therapy. Should he fail nonoperative treatment, I would proceed with an arthroscopy and microfracture of the OLT. If there were evidence of lateral ankle instability, I would also add a Brostrom-Gould lateral ligament procedure. This is because if the instability is not treated there will be a higher likelihood of failure of microfracture alone. Reeves: Since we are assuming all conservative measures have failed, this is a patient I will move forward with arthroscopy. I will evaluate for any loose or dislodged debris and remove. If we end up with any exposed subchondral bone then microfracture techniques will
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be employed; however, I would not expect this in the given situation. Additionally, subchondral drilling can be employed in a retrograde fashion under fluoroscopic guidance and packed with autogenous bone graft. Wouldn’t you know it but our former patient has a sister who also has a history of ankle issue. She is a 35-year-old active female who enjoys running, swimming, and yoga. About 7 years ago, she had been having ankle pain and was diagnosed with an OCD on her lateral talus. She was treated out of town, but remembers they “looked in her ankle with a camera and drilled into her bone.” Her pain is back, but even worse than before. She complains of swelling and catching with certain activities. Her MRI shows lateral talar OCD that is 15 mm × 15 mm with significant surrounding edema, cystic formation, and involving the shoulder region. Appears unstable per the radiologist’s report. Where do you go with this one? Raissi: If possible, I would like to review the patient’s operative report and intraoperative images prior to proceeding. Oftentimes, patients are told that adequate debridement and microfracture was performed, but it has been my experience that in the general orthopedic community proper treatment had been lacking. Having said that, given the size and location of this lesion, one would have to consider alternative options such as OATS, structural allograft, or chondrocyte transplant with or without bone graft. Depending on the location of the lesion, an extensile open incision may be required with or without fibular osteotomy. DiDomenico: It appears that this patient previously underwent an arthroscopy and a procedure consistent with a microfracture or a drilled technique. It appears that she may have responded well for several years; however, now she presents with a pretty good size lesion with surrounding bony issues involving the shoulder region. Based on the above report, the lesion is in the shoulder region and can make this repair difficult and less predictable in
Foot & Ankle Specialist
terms of outcome. The lesion appears unstable, and it is necessary to find out the extent of the instability. The surgeon must identify this tissue and remove it. Due to the significant surrounding edema along with the cystic formation, it appears as if this is the type of lesion, once debrided, will need bone grafting and packing the defect tightly coupled with an OATS, ACI, or DeNovo type of procedure. Again, the shoulder located lesions makes the treatment more difficult. Cuttica: The patient has mechanical symptoms and an unstable OCD with displacement. The other important fact is that she has failed prior marrow stimulation surgery. Due to the large size of the lesion, cystic nature, and involvement of the shoulder of the talus, I would treat this with bulk allograft from a fresh talus. This would require lateral malleolar osteotomy, as it would require perpendicular access to the lesion. Reeves: As in the previous scenario, I would start with an ankle arthroscopy with debridement and microfracture/ drilling. She had good overall success previously. The addition of an “cartilage technique” of choice in this scenario offers good adjunctive options prior to a more invasive osseous procedure (OATS). If the area demonstrates a large area of bone deficiency, autogenous grafting can be employed and fibrin glue overlaid.
Let us change course for a bit and start talking biology. How important do you feel the component of associated osseous edema with relation to the OCD lesion factors into your treatment plan? Raissi: I find osseous edema on MRI to be somewhat nonspecific. However, if a large portion of the medial or lateral talus is involved, this tends to be an ominous sign for poor long-term results for primary debridement. DiDomenico: I believe the amount of osseous edema is an important factor
in the diagnostics of osteochondral lesions. I believe it is in fact indicative of the bodies’ response to the extent of the injury, it provides the extent of the deformity, and it can also assist with the time frame of the injury when one is following up with a series of MRIs. Cuttica: This certainly is important in decision-making process. Larger volume and intensity of edema on MRI has been shown to have a negative correlation with clinical outcome in the treatment of osteochondral lesions. I also view a decreased edema response as an early sign of OLT healing. Therefore, if there is a large volume or intensity of edema on MRI, I may be more likely to treat the lesion operatively rather than nonoperatively. Reeves: I think more important is the overall quality of the underlying bone versus the amount of edema. Is this edema an area of necrosis, fibrosis, or other abnormality?
Let us head a bit further down this rabbit hole. Does anyone incorporate any additional biologic supplements (ie, BMA, PRP, bone graft, etc) during a primary arthroscopic debridement with marrow stimulating technique? Raissi: As an “old school surgeon” for primary procedures, I have not routinely incorporated much additional biologic supplements. There is limited data currently to support the adjunct of these treatments, not to mention additional associated costs at ASCs. However, as more data are available with time I would be open to supplementation as long as there is definitive proof that they may prevent recurrence and further procedures. DiDomenico: Yes, in cases that represent a lesion with a deep cavity or subchondral bone defect, bone in the cavity that does not feel firm or cystic in
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nature, I will typically use autogenous bone graft. Prior to bone grafting, I will debride and curettage the area very aggressively until I come in contact with much more “firm” healthier bone. Next, I will direct my attention to the ipsilateral calcaneus, or the distal tibia, and harvest autogenous cancellous bone graft to replace the “diseased” cancellous bone. I will pack the autogenous bone graft very tight using a tamp and a mallet. If the lesion is large, then I may consider one of the cartilage graft techniques such as OATS, ACI, or DeNovo. At this time, I am not convinced that the other costly products have proven to be more effective? Other than the conditions outlined above, I do not typically incorporate additional biological supplements during a primary arthroscopy. Currently, microfracture is the preferred primary treatment for small lesions and primary arthroscopy, whereas autologous osteochondral transplantation may be considered for larger or cystic lesions. To the best of my knowledge, the biologic supplements seem promising; however, there is no evidence-based studies that can substantiate the cost for primary arthroscopy. Cuttica: I will occasionally utilize bone marrow aspiration concentrate. I believe this is a nice adjunct to marrow stimulation. But this certainly does not replace sound surgical technique. Reeves: The simple answer is “it depends.” How much exposed subchondral bone is present and what is its quality? How deep is the lesion? However, in larger lesion (approximately 1.5 cm or greater) or with inadequate subchondral support, I will employ varying arrays of biologic adjunctive therapies.
If you are using a biologic adjunct (this can be any case primary or revision), what are your feelings as to the rationale for choosing one option over another? Raissi: Hopefully data and not a consulting agreement should serve as your rationale for picking one biologic
agent over another. Given the limited data available, I find that discussing the experience of your trusted colleagues also serves as an important source of information with new agents. DiDomenico: I reserve these types of cases for revision surgery. I believe if good surgical technique is used, most lesions will improve to some extent on primary cases. For those that do not, I rationalize the use of advanced biologics to assist with the improvement of the lesion. Most of the advanced biologic adjunctive treatment is very costly and should be reserved for the cases that have not responded favorably. That being said, if the lesion is large, I think the OATS procedure has a decent track record for this type of condition. In scenarios where the lesions are not large, I do not believe there are any studies that compare the effects of ACI, MACI, DeNovo, or PRP demonstrating one product more beneficial over the other. At this point I do not have enough experience with any one of the aforementioned products to provide a rationale for using one product over another. Cuttica: Bone marrow aspiration concentration contains mesenchymal stem cells that promote a healing environment with chondrogenic potential, more so than PRP or bone grafting. Bone grafting is rarely necessary, as there is rarely a large bone void that requires bone grafting. If there is a large bone defect or cyst, I will utilize a bulk allograft from a fresh talus.
Are you currently using any cartilage replacing products (ie, ACI/MACI, DeNovo, Biocartilage, etc)? Give me an example of when you would incorporate that type of technique if you use it, and how does it affect your postoperative course? Raissi: Unfortunately, many of these products are cost prohibitive. I have started using a DeNovo. I will incorporate this product mostly on a revision case as
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long as the lesions are well contained and limited in size and depth and do not involve a significant portion of the shoulder. If not cost prohibitive, I feel it be reasonable to use in adjunct biologic in high-performance athlete or performer. Postoperative protocol non-weightbearing status would typically be extended to 6 weeks as opposed to 2 weeks with simple microfracture. DiDomenico: Yes, I reserve this type product for those patients who have been previously operated on by myself and have not responded to previous treatment of arthroscopy and microfracture technique, and so on. If the patient had been treated elsewhere, I will suggest an ankle arthroscopic procedure and a more standard approach with the possibility of employment of a cartilage-replacing product if necessary. Due to the significant cost of these products, I would like to see the ankle joint and lesion with an attempt of a more standard treatment prior to embarking on a more expensive product with treatment. My postoperative course will be non-weight-bearing and immobilization for 4 weeks and then an aggressive course of physical therapy and weight-bearing in a CAM boot for another 4 weeks. Cuttica: I will utilize particulated juvenile cartilage allograft in cases of failed microfracture. However, it must be a contained lesion, as this should be avoided in shoulder lesions. I will also consider utilizing it in OLTs larger than 1.5 cm2 primarily. Postoperatively, I will keep these patients non-weight-bearing × 6 weeks. However, I will start AROM exercises beginning 2 weeks postoperative, as early motion is important for cartilage healing. Formal physical therapy will start at 6 weeks postoperative. Reeves: Typically in the patient who has already failed arthroscopy, microfracture is a good candidate. I typically increase my non-weight-bearing time to 6 weeks; however, range of motion activity will follow the protocols for arthroscopic recovery.
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Give me your best example of a patient that you would employ an OATS-type procedure or other bulk allograft/autograft technique? I want to see this patient through your eyes and how you connect the dots. Raissi: I feel that lesions that involve a large portion of the talus or the shoulder talus or have a significant subchondral cystic component should be treated with structural allograft. I have shied away from an OATS procedure due to donor site morbidity. Also, large lesions that have failed primary arthroscopy would be appropriate candidates for the aforementioned technique. DiDomenico: I would suggest using an OATS procedure for a lesion that measures large in size. I would also consider an OATS procedure for a lesion that has not responded to a primary treatment. I would use a bulk allograft/ autograft technique for those lesions that are deep and large with a notable bone void following debridement. Cuttica: I will generally use an OATS or bulk allograft in revision scenarios. The ideal patient is one with a larger lesion that involves the shoulder and has failed a prior microfracture. I will also employ an OATS in patients with a contained lesion, but have failed prior attempts at microfracture and particulated juvenile cartilage allograft.
Foot & Ankle Specialist
Finally, patients with an OLT and massive cystic defect generally require a bulk allograft. I favor the use of a fresh talus allograft. Certainly in all these cases this must be an isolated OLT with no degenerative changes present at the ankle joint. Reeves: Greater than 1.5 cm lesion with failed arthroscopic debridement and microfracture technique. Have failed or are not a candidate for “cartilage techniques.”
To leave us on a high note lets move into the future. Give me your best ideas as to where we need to go with treatment of OCDs of the talus in the next 5 to 10 years. Bonus points will be given for creativity! Raissi: I would like to see a greater shift toward biologics in the future. Ideally, even larger lesions hopefully can be treated arthroscopically without the need for medial or lateral malleolar osteotomies. Perhaps BMP and plateletderived growth factor can play greater role in filling the bony defects in the future with limited exposure. Hopefully, some day autologous cartilage (perhaps with the aid of stem cells) can be regenerated at minimal cost in a speedy fashion. However, we should be careful what we wish for as we could all be out of a job if this is able to occur.
DiDomenico: We need to move forward with prospective doubleblinded studies. Currently, we have a lot of “recipes” from multiple surgeons’ anecdotal reports of treatment regimens. There are no specifics with respect to treatment algorithms. Basic scientific evidence for biological augmentation is promising; however, well-designed clinical trials are needed to extrapolate findings to the clinical setting and specific lesion type. Due to the specifics of the anatomic locations, size, and depth of these lesions, it would be nice to have the assistance of robotics and computerassisted devices for more precise reparative/replacement of these challenging defects. Cuttica: The future in treatment is exciting. The treatment of OLTs has progressed significantly over the past several decades, and I believe that treatment options for these lesions will improve as our understanding of OLTs continues to evolve. Many of these options will likely involve biologic adjuncts and tissue engineering technologies that focus more on cellular-based therapies rather than mechanical treatments. Reeves: The wave of the future will continue to be in the arena of biologics with improved and more economical cartilage replacement techniques. I think the stem cell arena and the stem cell with adipose tissue poses good optimism as we move forward.
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FASXXX10.1177/1938640014557792Foot & Ankle SpecialistFoot & Ankle Specialist
478
Dec 2014
Foot & Ankle Specialist
〈 Roundtable Discussion 〉 Osteochondritis Dissecans of the Talus
T
oday we will be talking about osteochondritis dissecans (OCD) of the talus. Let us start with some early stuff to get us started. We will assume for sake of discussion that conservative treatment has failed unless otherwise discussed.
Give me you best curbside consult of your algorithm for treating OCDs of the talus. Let us keep it straightforward and only address primary lesions, do not worry we will get to revision cases later. Raissi: I think the most important thing is to determine whether the X-rays or magnetic resonance imaging (MRI) finding is clinically relevant. I am sure we all gets multiple referrals with a positive finding and an MRI, but on further careful physical examination of the patient we realize that these findings are not relevant to their symptoms. So first things first, it is truly symptomatic. If there is any question, an intra-articular diagnostic injection can be of great benefit. If it is symptomatic, certain factors may determine the approach to treatment. These factors would include size, depth, location, and whether the articular surface is intact. In some cases a
computed tomography (CT) scan can be beneficial in further determining the quality of the lesion. If the articular surface is disrupted, then typically arthroscopy with debridement is my first step in surgical treatment. If I am convinced that the articular surface is intact, then we consent the patient for possible retrograde drilling. I will rarely resort to primary allograft or chondrocyte transplant procedure unless the lesion is massive.
Osteochondral lesions of the talus represent a perplexing challenge for many of us in the foot and ankle world. Despite significant publication and research on the disease, we seem to be limited with our ability to improve outcomes. Recently, a focus of identify specific characteristics about these lesions has been undertaken to improve outcomes. In addition, a tremendous amount of effort and money is being dedicated to understanding ways to manipulate the biology of this disease to increase success. In this roundtable, we have gathered 4 experts who have contributed significantly to understanding of the difficult issue to help guide us in our current treatment approach and give us a glimpse of what the future might hold.
DiDomenico: Initially, I would order 3 views of the foot and ankle. If these are negative and there is a history of an ankle sprain, a history of chronic or recurrent ankle sprains, I would obtain stress radiographs to the involved and uninvolved ankle looking for an underlining instability that may be causing the problem. If the plain or stress radiographs suggest a remote chance of an osteochondral defect, then I would order an MRI of the ankle. Based on the location and the stage of the lesion, my treatment will alter quite a bit. The treatment algorithm will range from diagnostic blocks consisting of a local anesthetic, to therapeutic injection therapy consisting of a local anesthetic and corticosteroid, immobilization, physical therapy, and finally surgery. Assuming the nonoperative care has failed and based on the location and the stage of the lesion, the surgical approach
DOI: 10.1177/1938640014557792. For reprints and permissions queries, please visit SAGE’s Web site at http://www.sagepub.com/journalsPermissions.nav. Copyright © 2014 The Author(s)
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CONTRIBUTORS Daniel Cuttica, DO The Orthopaedic Foot and Ankle Center of Washington DC Falls Church, VA Lawrence A. DiDomenico, DPM Section Chief, St Elizabeth Hospital Director Fellowship Training, Ankle and Foot Care Centers Youngstown, OH Adjunct Professor, Kent State College of Podiatric Medicine Independence, OH Teaching Faculty, Heritage Medical Center Beaver, PA Abdi Raissi, MD Desert Orthopaedic Center Las Vegas, NV Chris Reeves, DPM Orlando Foot and Ankle Clinic Faculty, Florida Hospital Orlando Podiatric Surgical Residency Program Orlando, FL ROUNDTABLE MODERATOR Stephen A. Brigido, DPM Director, Fellowship for Foot and Ankle Reconstruction Coordinated Health Bethlehem, PA SECTION EDITORS W. Bret Smith, DO, MS Director of Foot and Ankle Division Moore Center for Orthopedics Columbia, SC Stephen A. Brigido, DPM Director, Fellowship for Foot and Ankle Reconstruction Coordinated Health Bethlehem, PA
vol. 7 / no. 6
would differ because of the stage and location of the lesion. Because of this unknown, it is a very difficult question to answer without specifics. In general, I would use an arthroscopic approach when possible. Ankle arthroscopy allows for minimal dissection and direct visualization of intra-articular structures without the need of an open arthrotomy or a malleolar osteotomy except in those cases in which the lesion stage and location dictate an arthrotomy and/or malleolar osteotomy. The arthroscopic procedure can range from diagnostic to therapeutic arthroscopy. Most of the cases will involve a synovectomy. The synovectomy can be of therapeutic benefit in those cases in which there is no articular pathology found. In cases where there is intra-articular pathology, again the treatment can range from a synovectomy followed by simple debridement to a more involved treatment of a lesion. The treatment can involve and range from curettage techniques to drilling (microfracture techniques) to cartilage replacement procedures. If the ankle were found to be unstable, I would employ an ankle stabilization procedure. In general, my experience has been arthroscopic procedures are typically very patient and physician friendly—especially in the postoperative course. Cuttica: I still perform microfracture via arthroscopy as first-line treatment for the majority of osteochondral lesions of the talus (OLT), as the literature shows this to provide good to excellent outcomes in 85% of patients. I will perform microfracture on any lesion less than 1.5 cm2, including shoulder lesions. Also, I prefer microfracture to drilling of the OLT, due to concerns of heat necrosis with drilling. In lesions larger than 1.5 cm2 or shoulder lesions, microfracture is still a good option. However, it is important to have a thorough discussion with the patient that there is a higher likelihood failure with microfracture in these lesions. As a result, in OLTs larger than 1.5 cm2, I will often utilize particulated juvenile cartilage allograft. In large shoulder lesions, I will use bulk allograft from fresh talus primarily. Finally, in large lesions with massive
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cystic defects, I will perform bulk allograft from fresh talus primarily. Reeves: The first thing I think that is important is to keep a high level of suspicion in patients that present with ankle pain. A thorough history is essential. Acute injuries are easy to keep in mind however sub acute or old injuries are even more important to keep this differential on the forefront. Mechanism is important especially knowing if the joint was “loaded” during the episode, but more so for identifying the location of the injury. Assessment of ankle instability is important as it is often concomitant with OLT’s and must be addressed if surgical treatment is necessary. Also of note is continued ankle pain following repair of ankle fractures. These are often the “forgotten” sequelae of an acute traumatic episode involving fractures about the ankle. I will usually start with a basic radiograph series. This can certainly rule in an OLT but not rule it out. Additionally in higher suspicial cases, I will often obtain an AP ankle radiograph with the foot plantar flexed. This helps indentify posterior lesions. From here, If I am still looking for diagnosis, I will move to advanced imaging which typically will entail an MRI. MRI is the best imaging modality for identifying the lesion and evaluating the integrity of the cartilage. If I am treating conservatively, I will often stop here. However, if I feel I have a known lesion I will often move to a CT scan.The bone marrow edema involved with MRI actually distorts the actual size of the lesion. A CT scan will give you a more representative picture of the lesion size, evaluate bone quality and help determine treatment course.
OK, so we have a bit of an idea about how you might organize your thoughts, we can move onto a case example and dig in a bit more. The case is of a 28-year-old male. He is a healthy active weekend warrior, with a
remote history of ankle sprains. No recent injury of note. Complains of pain with certain sports activities and feels that he “doesn’t quite trust his ankle.” Based on you own protocols, walk me through your workup protocol to help with your diagnosis. We can assume that everyone will have taken a standard 3-view radiograph of the ankle. Raissi: First things first, examine the patient thoroughly. Determine whether there are symptoms originating from the ankle joint either medial or lateral. Also determine whether there is any gross instability and pain over the anterior talo-fibular ligament itself. If there is any question of the joint being the origin of the symptoms, again, an intra-articular injection can be quite helpful in this regard. Ultimately, this patient typically will go on to have an MRI should they wish to pursue further treatment. If there is a significant cystic quality to the lesion then a CT or single-photon emission computed tomography (SPECT) scan would also be of significant benefit. Although conservative options such as nonsteroidal anti-inflammatory drugs and immobilization should be discussed with the patient, there are occasions where we know based on our experience that conservative treatment may only delay the patient’s healing process, and we should be upfront about the occasional limited benefit or futile outcome of conservative treatment of many lesions. These decisions would depend on, again, size, location stability of the lesion, and duration of symptoms. DiDomenico: Based on the understanding that the 3-view radiographs of the ankle were taken and were read as negative. Conservative care has previously failed along with the patient continuing to experience pain and symptoms as described above. Because he is a relatively young, active male and there is a history of ankle sprains, “a lack of trust” with his ankle, along with ankle pain, I am always suspicious of ankle instability as being a causative factor. Therefore, I would obtain stress radiographic of the affected and nonaffected ankle for comparison. If
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the affected side is positive (demonstrating pathologic findings with either the anterior drawer and/or the talar tilt), I would suggest ordering an MRI of the ankle. Clearly, this will assist in the diagnosis of instability, specifically with the capsular tissue as well as which ligaments are involved. Should there be pathologic findings such as an osteochondral injury, this will assist with the extent of the injury, the staging, as well as other soft tissue injuries such as peroneal tendon pathologies. If the anterior drawer and/or talar tilt is negative (not demonstrating pathologic findings), I would still order an MRI, as this will provide additional information as stated above. Cuttica: Any workup should start with a thorough history and physical. Important information includes any prior episodes injury, as there is often a history of inversion injury or other trauma to the ankle. It is also important to ask about mechanical symptoms such as locking or catching at the ankle, giving way episodes, or recurrent swelling. Physical exam should include assessment for any effusion, areas of point tenderness especially along the joint line, and range of motion. I will perform anterior drawer and talar tilt tests as well. Finally, it is also important to assess the peroneal tendons in these cases, as they are a secondary stabilizer of the ankle and can be a source of chronic pain. Weightbearing X-rays are essential, and if there is a high suspicion for ankle instability, I will perform stress X-rays. Finally, if there is high suspicion for OLT, I will utilize MRI as my primary diagnostic modality. Reeves: I would want a bit more detail from him as to what elicits his symptoms and are they medial or lateral ankle symptoms. Does it bother him walking down stairs? Is there instability? Additionally, I regularly perform diagnostic blocks and evaluate the patient both non-weight-bearing and weight-bearing following the block. True intra-articular ankle pain will improve following the block. From here, I will move to advanced imaging. Though MRI has been the
accepted go to modality to evaluate OLTs, I typically obtain a CT scan (specifically helical CT scans if available). Recent literature appears to support this idea. The bone marrow edema involved with MRI actually distorts the actual size of the lesion. CT scans do a better job of establishing the true extent of the lesion and sclerotic margins to allow for better surgical planning. I typically reserve MRI when I need to evaluate adjacent soft tissue pathology or if I have a high suspicion for an OLT in the face of a negative CT scan.
So we find out that our person in the last example got advanced imaging (ie, CT scan, MRI, SPECT, etc) of your choice. To keep it simple, the MRI comes back and reads as a 10 mm × 8 mm OCD on the lateral portion of the talus, associated edema, minimal cystic changes, no significant displacement, and fluid signal under the cap. What is you treatment of choice for this patient? Raissi: Again, I would offer the patient conservative options such as immobilization, but given our experience and knowledge with these lesions, they tend not to respond to these treatment options. Typically, if these lesions are symptomatic they require surgical intervention. Given the size and location of this lesion, I feel this patient is an appropriate candidate for debridement and microfracture/ drilling of the lesion. Also, a lateral ligament reconstruction may be required as well depending on the instability of this patient. DiDomenico: In cases such as described above, it is difficult to provide a specific answer as the lesion and the environment of the surrounding lesion are sometimes very different intraoperatively in comparison from the reports/films of MRI, CT, and so on. With this type of the lesion, I believe the
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treatment/consent needs to be open to a certain degree, as the surgeon does not know exactly what he/she may see during the time of surgery. For example, how much fluid is under the cap, how stable or unstable is the cap, the degree of cystic involvement, and the quality of the subchondral bone? Certainly the cap needs to be addressed from a salvage technique to a complete excision of the cap. Obviously, if the cap appears to be healthy, has a decent thickness to it, remains partially attached, and the cystic bone has been repaired, attempting a salvage of the cap would seem prudent. The cystic changes need to be addressed. In my experience, even if the cystic bone is minimal, in most cases by the time one curettes this area, and possibly drills the area, I have found the need to autogenous cancellous bone graft packed tightly provides a nice environment for a reparative process. Cuttica: Nonoperative treatment is typically successful in 45% of cases, based on Tol’s meta-analysis. In cases without OLT displacement or free fragment, I will typically consider a trial of nonoperative treatment, but it is important to educate the patient that nonoperative treatment is successful only 45% of the time. In this particular case, I would recommend a course of immobilization in a weight-bearing cast or walking boot for approximately 4 to 6 weeks, followed by a course of formal physical therapy. Should he fail nonoperative treatment, I would proceed with an arthroscopy and microfracture of the OLT. If there were evidence of lateral ankle instability, I would also add a Brostrom-Gould lateral ligament procedure. This is because if the instability is not treated there will be a higher likelihood of failure of microfracture alone. Reeves: Since we are assuming all conservative measures have failed, this is a patient I will move forward with arthroscopy. I will evaluate for any loose or dislodged debris and remove. If we end up with any exposed subchondral bone then microfracture techniques will
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be employed; however, I would not expect this in the given situation. Additionally, subchondral drilling can be employed in a retrograde fashion under fluoroscopic guidance and packed with autogenous bone graft. Wouldn’t you know it but our former patient has a sister who also has a history of ankle issue. She is a 35-year-old active female who enjoys running, swimming, and yoga. About 7 years ago, she had been having ankle pain and was diagnosed with an OCD on her lateral talus. She was treated out of town, but remembers they “looked in her ankle with a camera and drilled into her bone.” Her pain is back, but even worse than before. She complains of swelling and catching with certain activities. Her MRI shows lateral talar OCD that is 15 mm × 15 mm with significant surrounding edema, cystic formation, and involving the shoulder region. Appears unstable per the radiologist’s report. Where do you go with this one? Raissi: If possible, I would like to review the patient’s operative report and intraoperative images prior to proceeding. Oftentimes, patients are told that adequate debridement and microfracture was performed, but it has been my experience that in the general orthopedic community proper treatment had been lacking. Having said that, given the size and location of this lesion, one would have to consider alternative options such as OATS, structural allograft, or chondrocyte transplant with or without bone graft. Depending on the location of the lesion, an extensile open incision may be required with or without fibular osteotomy. DiDomenico: It appears that this patient previously underwent an arthroscopy and a procedure consistent with a microfracture or a drilled technique. It appears that she may have responded well for several years; however, now she presents with a pretty good size lesion with surrounding bony issues involving the shoulder region. Based on the above report, the lesion is in the shoulder region and can make this repair difficult and less predictable in
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terms of outcome. The lesion appears unstable, and it is necessary to find out the extent of the instability. The surgeon must identify this tissue and remove it. Due to the significant surrounding edema along with the cystic formation, it appears as if this is the type of lesion, once debrided, will need bone grafting and packing the defect tightly coupled with an OATS, ACI, or DeNovo type of procedure. Again, the shoulder located lesions makes the treatment more difficult. Cuttica: The patient has mechanical symptoms and an unstable OCD with displacement. The other important fact is that she has failed prior marrow stimulation surgery. Due to the large size of the lesion, cystic nature, and involvement of the shoulder of the talus, I would treat this with bulk allograft from a fresh talus. This would require lateral malleolar osteotomy, as it would require perpendicular access to the lesion. Reeves: As in the previous scenario, I would start with an ankle arthroscopy with debridement and microfracture/ drilling. She had good overall success previously. The addition of an “cartilage technique” of choice in this scenario offers good adjunctive options prior to a more invasive osseous procedure (OATS). If the area demonstrates a large area of bone deficiency, autogenous grafting can be employed and fibrin glue overlaid.
Let us change course for a bit and start talking biology. How important do you feel the component of associated osseous edema with relation to the OCD lesion factors into your treatment plan? Raissi: I find osseous edema on MRI to be somewhat nonspecific. However, if a large portion of the medial or lateral talus is involved, this tends to be an ominous sign for poor long-term results for primary debridement. DiDomenico: I believe the amount of osseous edema is an important factor
in the diagnostics of osteochondral lesions. I believe it is in fact indicative of the bodies’ response to the extent of the injury, it provides the extent of the deformity, and it can also assist with the time frame of the injury when one is following up with a series of MRIs. Cuttica: This certainly is important in decision-making process. Larger volume and intensity of edema on MRI has been shown to have a negative correlation with clinical outcome in the treatment of osteochondral lesions. I also view a decreased edema response as an early sign of OLT healing. Therefore, if there is a large volume or intensity of edema on MRI, I may be more likely to treat the lesion operatively rather than nonoperatively. Reeves: I think more important is the overall quality of the underlying bone versus the amount of edema. Is this edema an area of necrosis, fibrosis, or other abnormality?
Let us head a bit further down this rabbit hole. Does anyone incorporate any additional biologic supplements (ie, BMA, PRP, bone graft, etc) during a primary arthroscopic debridement with marrow stimulating technique? Raissi: As an “old school surgeon” for primary procedures, I have not routinely incorporated much additional biologic supplements. There is limited data currently to support the adjunct of these treatments, not to mention additional associated costs at ASCs. However, as more data are available with time I would be open to supplementation as long as there is definitive proof that they may prevent recurrence and further procedures. DiDomenico: Yes, in cases that represent a lesion with a deep cavity or subchondral bone defect, bone in the cavity that does not feel firm or cystic in
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nature, I will typically use autogenous bone graft. Prior to bone grafting, I will debride and curettage the area very aggressively until I come in contact with much more “firm” healthier bone. Next, I will direct my attention to the ipsilateral calcaneus, or the distal tibia, and harvest autogenous cancellous bone graft to replace the “diseased” cancellous bone. I will pack the autogenous bone graft very tight using a tamp and a mallet. If the lesion is large, then I may consider one of the cartilage graft techniques such as OATS, ACI, or DeNovo. At this time, I am not convinced that the other costly products have proven to be more effective? Other than the conditions outlined above, I do not typically incorporate additional biological supplements during a primary arthroscopy. Currently, microfracture is the preferred primary treatment for small lesions and primary arthroscopy, whereas autologous osteochondral transplantation may be considered for larger or cystic lesions. To the best of my knowledge, the biologic supplements seem promising; however, there is no evidence-based studies that can substantiate the cost for primary arthroscopy. Cuttica: I will occasionally utilize bone marrow aspiration concentrate. I believe this is a nice adjunct to marrow stimulation. But this certainly does not replace sound surgical technique. Reeves: The simple answer is “it depends.” How much exposed subchondral bone is present and what is its quality? How deep is the lesion? However, in larger lesion (approximately 1.5 cm or greater) or with inadequate subchondral support, I will employ varying arrays of biologic adjunctive therapies.
If you are using a biologic adjunct (this can be any case primary or revision), what are your feelings as to the rationale for choosing one option over another? Raissi: Hopefully data and not a consulting agreement should serve as your rationale for picking one biologic
agent over another. Given the limited data available, I find that discussing the experience of your trusted colleagues also serves as an important source of information with new agents. DiDomenico: I reserve these types of cases for revision surgery. I believe if good surgical technique is used, most lesions will improve to some extent on primary cases. For those that do not, I rationalize the use of advanced biologics to assist with the improvement of the lesion. Most of the advanced biologic adjunctive treatment is very costly and should be reserved for the cases that have not responded favorably. That being said, if the lesion is large, I think the OATS procedure has a decent track record for this type of condition. In scenarios where the lesions are not large, I do not believe there are any studies that compare the effects of ACI, MACI, DeNovo, or PRP demonstrating one product more beneficial over the other. At this point I do not have enough experience with any one of the aforementioned products to provide a rationale for using one product over another. Cuttica: Bone marrow aspiration concentration contains mesenchymal stem cells that promote a healing environment with chondrogenic potential, more so than PRP or bone grafting. Bone grafting is rarely necessary, as there is rarely a large bone void that requires bone grafting. If there is a large bone defect or cyst, I will utilize a bulk allograft from a fresh talus.
Are you currently using any cartilage replacing products (ie, ACI/MACI, DeNovo, Biocartilage, etc)? Give me an example of when you would incorporate that type of technique if you use it, and how does it affect your postoperative course? Raissi: Unfortunately, many of these products are cost prohibitive. I have started using a DeNovo. I will incorporate this product mostly on a revision case as
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long as the lesions are well contained and limited in size and depth and do not involve a significant portion of the shoulder. If not cost prohibitive, I feel it be reasonable to use in adjunct biologic in high-performance athlete or performer. Postoperative protocol non-weightbearing status would typically be extended to 6 weeks as opposed to 2 weeks with simple microfracture. DiDomenico: Yes, I reserve this type product for those patients who have been previously operated on by myself and have not responded to previous treatment of arthroscopy and microfracture technique, and so on. If the patient had been treated elsewhere, I will suggest an ankle arthroscopic procedure and a more standard approach with the possibility of employment of a cartilage-replacing product if necessary. Due to the significant cost of these products, I would like to see the ankle joint and lesion with an attempt of a more standard treatment prior to embarking on a more expensive product with treatment. My postoperative course will be non-weight-bearing and immobilization for 4 weeks and then an aggressive course of physical therapy and weight-bearing in a CAM boot for another 4 weeks. Cuttica: I will utilize particulated juvenile cartilage allograft in cases of failed microfracture. However, it must be a contained lesion, as this should be avoided in shoulder lesions. I will also consider utilizing it in OLTs larger than 1.5 cm2 primarily. Postoperatively, I will keep these patients non-weight-bearing × 6 weeks. However, I will start AROM exercises beginning 2 weeks postoperative, as early motion is important for cartilage healing. Formal physical therapy will start at 6 weeks postoperative. Reeves: Typically in the patient who has already failed arthroscopy, microfracture is a good candidate. I typically increase my non-weight-bearing time to 6 weeks; however, range of motion activity will follow the protocols for arthroscopic recovery.
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Give me your best example of a patient that you would employ an OATS-type procedure or other bulk allograft/autograft technique? I want to see this patient through your eyes and how you connect the dots. Raissi: I feel that lesions that involve a large portion of the talus or the shoulder talus or have a significant subchondral cystic component should be treated with structural allograft. I have shied away from an OATS procedure due to donor site morbidity. Also, large lesions that have failed primary arthroscopy would be appropriate candidates for the aforementioned technique. DiDomenico: I would suggest using an OATS procedure for a lesion that measures large in size. I would also consider an OATS procedure for a lesion that has not responded to a primary treatment. I would use a bulk allograft/ autograft technique for those lesions that are deep and large with a notable bone void following debridement. Cuttica: I will generally use an OATS or bulk allograft in revision scenarios. The ideal patient is one with a larger lesion that involves the shoulder and has failed a prior microfracture. I will also employ an OATS in patients with a contained lesion, but have failed prior attempts at microfracture and particulated juvenile cartilage allograft.
Foot & Ankle Specialist
Finally, patients with an OLT and massive cystic defect generally require a bulk allograft. I favor the use of a fresh talus allograft. Certainly in all these cases this must be an isolated OLT with no degenerative changes present at the ankle joint. Reeves: Greater than 1.5 cm lesion with failed arthroscopic debridement and microfracture technique. Have failed or are not a candidate for “cartilage techniques.”
To leave us on a high note lets move into the future. Give me your best ideas as to where we need to go with treatment of OCDs of the talus in the next 5 to 10 years. Bonus points will be given for creativity! Raissi: I would like to see a greater shift toward biologics in the future. Ideally, even larger lesions hopefully can be treated arthroscopically without the need for medial or lateral malleolar osteotomies. Perhaps BMP and plateletderived growth factor can play greater role in filling the bony defects in the future with limited exposure. Hopefully, some day autologous cartilage (perhaps with the aid of stem cells) can be regenerated at minimal cost in a speedy fashion. However, we should be careful what we wish for as we could all be out of a job if this is able to occur.
DiDomenico: We need to move forward with prospective doubleblinded studies. Currently, we have a lot of “recipes” from multiple surgeons’ anecdotal reports of treatment regimens. There are no specifics with respect to treatment algorithms. Basic scientific evidence for biological augmentation is promising; however, well-designed clinical trials are needed to extrapolate findings to the clinical setting and specific lesion type. Due to the specifics of the anatomic locations, size, and depth of these lesions, it would be nice to have the assistance of robotics and computerassisted devices for more precise reparative/replacement of these challenging defects. Cuttica: The future in treatment is exciting. The treatment of OLTs has progressed significantly over the past several decades, and I believe that treatment options for these lesions will improve as our understanding of OLTs continues to evolve. Many of these options will likely involve biologic adjuncts and tissue engineering technologies that focus more on cellular-based therapies rather than mechanical treatments. Reeves: The wave of the future will continue to be in the arena of biologics with improved and more economical cartilage replacement techniques. I think the stem cell arena and the stem cell with adipose tissue poses good optimism as we move forward.
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