Eric Rovner: Hi, Eric Rovner. Thanks to Neal and David and the committee for inviting me to talk. I'm going to hopefully not use up all 25 minutes. I certainly won't go over, Neal, I promise. I'm going to say some things that are probably a little bit less pithy than the prior panel and maybe a bit more disconcerting. Neal asked me to talk on incontinence options for women and men, specifically mesh and what's going on with mesh. That's how I'm going to spend the next 15 or 20 minutes talking about.

The first question is relevant to my title. Does any incontinence operation that we've ever done ever in men or women meet the definition of safe? If you look at the definition of safe out of the Miriam Webster dictionary, it's free from harm or risk or unhurt and secure from threat or danger, harm or loss. The answer is, does any of our incontinence operations meet that definition? No. None of them meet that definition. What is safe in surgery? For purposes of this talk, safe to me means reasonably free from harm and reasonably secure from the threat of danger, harm or loss.

Let's talk about men first because that's pretty easy. Is mesh safe in men with stress incontinence? The answer is probably yes. Although if you do an internet search, you can always find a few malcontents such as this website which talks about polypropylene mesh slings in men and possible problems. If you do a deep dig into the literature, you really won't find very many problems with this except perhaps some retention. This an article from last year looking at success rates and cure rates and complications in several studies of slings in men for post-prostatectomy incontinence. If you look all the way on the left, most of the studies are small numbers of patients less than a hundred and the cure rates are pretty fairly abysmal actually when you compare it to females, where the cure rates here are 15 to about 50 or 60%. The complications for male slings are pretty minimal. You get some perennial discomforts and paresthesias and some background urinary retention.

But the numbers are quite small in the studies that were published. We actually put together an abstract for the AUA this year. We did a multicenter study looking at almost 400 patients looking at the retention rate after the advanced sling for post-prostatectomy incontinence. Admittedly it's a retrospective study covered about 11 years, multiple institutions, and we define retention as a need for a Foley or CIC after the initial void trial. Basically what we found was the initial retention rate was 13%. It's probably not that different in females. The longterm retention rate was 1.5% at a mean follow-up of over 500 days, a year and a half. Which is also probably not that different from females also. Interestingly, we looked at urodynamics in this multicenter trial, and actually urodynamics did not predict for retention in males undergoing slings. If you're doing urodynamics to stratify for risk of retention, you probably don't need to do it, which is the reason I was doing urodynamics in these patients. So I actually did learn something from our study.

Is mesh safe in men with stress incontinence? Well, there's few lawsuits. I don't know if that's a barometer that you can actually go by. There's multiple types of male slings with small series and short follow-up. But what you can take from the data is the efficacy is probably less than female slings, but from a safety perspective, although variable, depending on this particular series, the safety's pretty comparable to what we do in females. None of the currently available products are any safer than any of the others based on the literature.

The much bigger question, is mesh safe for women? For women, really it's still a mesh. That's a joke. It's still a mesh. Mess. Okay. Anyway. How much of a mess depends on your perspective, and we'll talk a little bit about each of these perspectives. It's still very relevant and still timely. As most of you know, the FDA had a meeting back in February, which in April led to the withdrawal of all pelvic organ prolapse mesh that was at the time currently available. So this is a very timely topic.

How did we get to the withdrawal of all pelvic organ prolapse mesh from just a few years ago when it was so popular? Well, you're all familiar with the FDA initial regulatory actions on mesh from 2008 where they talked about mesh slings and pelvic organ prolapse mesh. Then in 2011 where the FDA gave a warning on pelvic organ prolapse mesh in and of itself. There were multiple subsequent FDA actions on mesh. In 2012 following the 2011 announcement is when the 522 plans were mandated requiring post-market surveillance studies for all pelvic organ prolapse mesh currently on the market at that time and all single incision mini slings. 2016, pelvic organ prolapse mesh was reclassified to Class III which required filing of a pre-market application. In 2017 even the mesh trocars and needles were reclassified from Class I to Class II. Finally, in 2019 as I showed you, POP mesh was removed from the US market.

What happens over those past 10 years that led eventually to the POP mesh being removed? Was it removed for safety reasons and specifically valid safety reasons? Well, you can look at it from the perspective of industry or patients or physicians or the judiciary legal system or even the government. Let's look at all of those perspectives. It was really a nuclear explosion in our world of female pelvic medicine and reconstructive urology. If you think back 10 years, which is not a long time, mesh was everywhere. There were 33 manufacturers of transvaginal mesh for pelvic organ prolapse and stress incontinence. There were more than 50 products on the market. You see all the vendors there. There are a bunch more vendors that I didn't put on this slide. Mesh was so good back in the early 2000s or late 2000s, it was so good. I was sitting at dinner in New York City with Vic Nitti and Roger Dmochowski. I get up to go to the bathroom, and I see this wine bottle named Mesh. Mesh was so good they named wine after it, it was so good. Okay.

Following the FDA announcement, there was a mesh recession specifically with respect to industry. Bard discontinued all their POP mesh products. J&J discontinued all their POP products and multiple single incision products. Cook discontinued all of their POP products and as you know, Endo/AMS, American Medical Systems basically sold off part of their business and then eventually reorganized and it eventually went out of business.

Back to that FDA meeting in 2019, the purpose of this meeting was actually to figure out how FDA should evaluate the risks of POP mesh and specifically how to put together a PMA process for these Class III devices. That was the goal of the meeting. The goal of the meeting wasn't to take POP mesh off the market. There were multiple presentations at that meeting; The FDA, industry, organized medicine, physicians, patients, lots of people presented. The 36-month data from all of the 522 studies was actually not yet peer-reviewed or published, so we didn't know the outcome of the post-market surveillance studies at the time of this meeting. Nevertheless, the advisory panel recommendations were to remove all of the mesh used for pelvic organ prolapse that were still on the market in the US, which consisted really of only two companies at the time, Coloplast and Boston Scientific. That was despite having essentially no data. Notably, the FDA at that time and up to this date did not affect mesh for mid-urethral slings or abdominal sacral colpopexy mesh.

Where does that leave industry? Well, with respect to mid-urethral slings, retropubic slings and transobturator slings, they're still available. There is no FDA action currently taken against mid-urethral slings. However, only a few manufacturers remain in the United States. POP mesh is no longer available in the United States. The 522 studies for single incision slings have not yet been reported to my knowledge. They've been presented in abstract form, but they have not been published nor presented in a public forum.

The bigger question, and this goes to the title of the talk, is safety of mesh. Why do some patients have complications with mesh? Why? Is it the mesh? Is mesh the problem? Is polypropylene inherently a problem? Is it the surgeon? Are we terrible at these operations? Or is it the patient? Are we implanting these in the wrong patients? Because clearly there are complications.

Let's talk about the mesh first. Is polypropylene bad? Should we not put polypropylene in humans? Multiple claims against polypropylene mesh, including autoimmunity, there's papers on carcinogenesis. There's papers on degradation. There's papers on inherent infection in microbiomes of mesh as you implant it in the vagina. I had the honor of being the chair of the Surgery for Stress Incontinence Committee at the last ICI, the last International Consultation on Incontinence. We actually devoted part of the chapter to mesh specifically. We looked at all the available literature up to 2016 regarding these particular claims against mesh. The conclusion was that all of those claims as of 2016 were basically unproven. So it's not the mesh.

The next question is, is it the surgeon? Are we the surgeons to blame? Of course, we are never to blame for anything, right? My fellow from last year started a project, which I'm actually pretty proud of. They looked at all of the mesh revisions that myself and my partners have done over the last six years. My fellow this year finished the project. Over five years we had almost 300 cases of mesh explants, reconstructions, a variety of things involving mesh. Yes, four of the cases were from our own institution, four of the 289. So we do air our own dirty laundry. We looked specifically at why did this patient have a complication? Was there something from the original surgery or something found at subsequent surgery that could have led to this complication? This is the indication for re-exploration. This is just going back through my records, my fellow going back through my records. Basically 65% were re-operated on for obstruction, and you'll see a variety of other things. Pain, erosion into the urinary tract, recurrent UTIs, et cetera.

What did we find? Again, 92% of the original operative notes from the original implanting surgeon were available. Why? Because I tell my patients, "Before I operate on you, I want to see the original operative note." I've always done that. 8.3% of the time there was unambiguous descriptions by the surgeon in the operative note that was poor technique, and I'll show you some examples in just a second. There were 10 cases where the urethra was injured at the time of the sling insertion and the sling was put in anyway. 10 times out of 289 cases. What did I say? What do I mean by unambiguous descriptions? Well, here's one. The sling was tightened and the outer sheath was removed, or the mesh was snugged underneath the urethra, or the sling was pulled up snugly, or there was good backing in the area of the bladder neck.

The point is these are tension-free slings. You all know these are tension free slings. You're not supposed to make tension. You're not supposed to make it snug. That leads to problems. That's an operative problem in the original description of the operative note. Not to mention the 10 times that somebody bungled into the urethra and then put the sling in anyway. 67% of the time on the operative findings in my operative findings were problems with the sling, either it was placed too proximal, too distal, too deep. It was over tensioned. In essence, over 70% of the time in my experience in re-operative surgery, these mid-urethral sling complications were directly attributable to surgical factors of the original implantation. That is remediable. That is something that can be fixed with education and proper training on how to put these devices in. That's surgeon factors and mesh factors with regard to safety.

What about, what's the government doing? Well, the Attorney Generals in several states have initiated legal action against mesh manufacturers. Some of you are probably familiar with this. If you live in say, Washington, or California, or Kentucky, or Mississippi, the state Attorney Generals are now suing the manufacturers. Globally, there are mesh bans in Scotland, in Australia, in New Zealand, and currently in all of the UK until the Baroness decides whether or not mesh is okay for females again.

What about medico-legally? Where are we in 2019? How big is the medico-legal fallout for mesh? It's the largest medical plaintiff litigation ever across all fields. It's larger than breast implants. It's larger than the Dalkon Shield. Those were only $3 billion and $4 billion. It's larger than Phen-Fen. That was only $3.75 billion. There are thousands of individual cases across the United States and class action lawsuits in several states and multidistrict litigation going on. What is multidistrict litigation? That is not a class-action suit. What it is is a type of litigation where cases are lumped together in order to facilitate the process in the courts. Once the patterns are discerned, cases are settled in the numbers of hundreds of cases at the same time. That's the strategy of getting most of these lawsuits settled.

What's going on currently? The current transvaginal mesh MDL has been going on since 2013 in West Virginia. There were more than 70,000 cases initially. There are still 40,000 cases pending. Of those cases, you can see this is the latest data I can find from about a year ago. 20,000 cases still pending against J&J, 15,000 against Boston Scientific, and you can read the rest of the list yourself. It's still a tremendous amount. How much money has transferred hands? Endo/AMS, or what's left of them as a legal entity, $830 million to settle 20,000 cases. You can read the rest of those. It's a humongous amount of money. There was an article in the New York Times in February suggesting that the legal fees are now entering near $8 billion from transvaginal mesh.

You'd say, "Well, this is all POP mesh. This is all pelvic organ prolapse mesh. That's off the market. It's all fixed." No, not really. This is a paper from Karen Eilber at Cedar Sinai where she looked at the mesh litigation over a decade. Actually the majority of the current lawsuits in 2017 were actually from mid-urethral slings, not from pelvic organ prolapse, from both transobturator slings and retropubic slings. So it's not all pelvic organ prolapse mesh.

Where are we with organized medicine? AUA, SUFU, AUGS, ICS, SGS all still support the use of mid-urethral slings for stress urinary incontinence in the uncomplicated patient. Moving forward, mesh for pelvic organ prolapse in the US is gone. Mesh for stress incontinence and abdominal sacral colpopexy is still here for now. There's more data coming from the 522. There's more litigation coming. There's more regulation coming probably from FDA.

Let's answer the first question I asked. What's safe in surgery? Well, it's reasonably free from harm and risk and reasonably secure from the threat of danger and I would say, are slings safe? Well, when they're done well for the correct indication, they are reasonably free from harm and risk. So yes. Thank you.

David Chaikin: Have a seat. Thanks, Dr. Rovner. Great presentation. I think that everybody in the room is really sort of saying, "Okay, what do we do?". So we have a couple of cases to present quickly, garden variety cases that all of us face. Obviously the POP, the prolapse surgery is ... The idea of using mesh is not around anymore, but I think everybody is very intrigued on what to do for an index stress incontinence patient. The first female case.

Tamra Lewis: Okay. I put up just a case study, kind of an index patient here. I can read through it, but is this somebody that you would still offer a mesh sling to?

David Chaikin: I think what we have here is just a garden variety stress incontinent patient. The question to Dr. Rovner is, what are you going to do?

Eric Rovner: Mid-urethral slings, primarily retropubic injuries. Well, slings still make up the majority of my stress incontinence practice. I suspect it still makes up the majority of most of the individuals in this room, stress and urinary incontinence practice in an uncomplicated female without prior surgery, without any urgency symptoms. It's still the best operation we have. It's the best operation I've ever done for stress incontinence. It's quick. It's easy when done in the right circumstances. It works well and the patients are happy when done well. I would still do a retropubic mid-urethral sling in this individual.

David Chaikin: I would say the same thing. I agree. I do mesh slings in everybody pretty much in the beginning, although we offer autologous slings as well.

Tamra Lewis: Great. I agree with that too. I put up a couple of what-ifs here. On the first case, the patient had some hypermobility. What if the patient did not have hypermobility? What if she had mixed incontinence? What if she was a smoker, higher BMI, older age? There's a lot of different what-ifs here. Can you pick some of those as maybe who would you pick something other than a mesh sling for?

Scott MacDiarmid: Great job. No hypermobility. I would do a sling, and I'd lower the success rate by 10%. So if you normally say 90, I'd drop it to 80 because you're not going to have maybe as much backboard effect or they're not descending. Mixed incontinence, no matter how bad this stress is, I treat OAB first. Then I warn that in about a third, it can persist, and in a small percent it can worsen once you do the sling. Two packs a day smoking, I ignore. Obesity's only an issue with the pannus is so enlarged. I do a retropubic kind of spark-like sling. I will switch maybe to a TOT if I thought the obesity was too much of a safety issue. 82-year-olds, I tend to lean slings versus injectable. I actually think about injectables in the ederly. 32-year-old women who want to have a child, I try to see one of our physical therapists and really not do surgery but ultimately I'm not going to do an injectable and I'll do a mesh sling. Prior sling with persistent stress, I repeat the sling, I ignore the other one. I don't look for it but I lower the success by 10%. She doesn't want mesh, I send them to Rovner.

David Chaikin: Okay. Why don't we try to get the second case study done because we don't want to ignore the male question. I think everybody here is very interested in how you would proceed with the male slings. I'll turn that back to Scott. He likes the microphone.

Scott MacDiarmid: Yeah. I mean if you've had, let's say in this case, an advanced sling that failed, we'll go right to it and we'll just sort of go down the panel. I put it in a sphincter. Some good friends of mine, I believe the data probably is there, I haven't read it personally, that you can repeat the male sling. I just kind of been nervous to do that quite frankly. So I just go put a sphincter in distally and I don't think there's ever been a good role to justify urethral injectables in male incontinence.

David Chaikin: I agree with Scott. I must say that doing another sling when a sling has failed, especially if you think the original sling was done correctly, it seems folly to me. And a sphincter is a great option.

Neal Shore: Great presentation. There's a tremendous amount of male incontinence that just doesn't get treated. Just gross under penetration of putting in sphincters. Now we have concerns that you've clearly demonstrated that it's a technical problem with your review of the data. So Eric, what's the solution to improving technical training both for female repair and for male insertion?

Eric Rovner: That's an age-old question, and that's a question that organizations like the RRC or the board need to figure out how we can better train surgeons. As we as a specialty became more medically oriented and now we're this pendulum swinging back towards surgery, I think the training starts in residency, principles of surgery, surgical technique. Then the desire to want to continue to learn how to do these new procedures. Urologists have been innovative for a hundred years. We have managed to take on new technology, flexible ureteroscopy and lithotripsy and all the things that we do. Yet we've had so much trouble with mesh for reasons that are not clear. Part of it may be related to initial training where up to 40% of residencies don't have a female pelvic medicine specialist. Maybe these people were taking on cases that they'd never seen before and operating on patients they'd never seen before. But I don't know the answer to that, Neal.