Well, good morning. It is a pleasure to introduce the Ulf Olmsen Memorial Lectureship in our tenth annual iteration. Ulf Olmsen, as many of you may know, was a Swedish urogynecologist professor at Uppsala University where he was the chairman of the OBGYN department. He preceded many of us in being very active in Ayuga with Secretary Treasurer, but is probably best known as the developer of the TBT procedure. Upon his early demise, we established a lectureship. This lectureship was funded by a donation from Gynecare. And the purpose of this lectureship is to promote and recognize innovation in urogynecologic surgery. And it is the honor for the Ayuga president to be able to select the speaker on a yearly basis. The list of speakers is extremely distinguished. Many of the names in front of you, you will recognize. And many of you have sat in on these lectures and have shared with me and many others the stimulating nature of these lectures and the purpose of really bringing about innovation in urogynecology. So now we're in 2014 and we really want to focus on innovation. Being the tenth anniversary of this lecture, I thought it would be very appropriate to talk about TBT and how TBT came to being, starting as a concept and leading to a product that many of us use and many of us may consider, in fact, to be the gold standard. So I thought it would be a very interesting exercise to go through the history of how TBT came to being and what we can learn from this process in this time when, arguably, innovation is a bit stifled by the problems we're having in urogynecology. So I asked two of the people who were most intimately involved in the development of TBT to share their experiences with us. First, Dr. Peter Petros from Perth, Australia, who developed the concept behind TBT, and I've asked him to share with us some of the early experiments and experiences which led to bringing this product to market. And our Scandinavian colleagues, in particular Dr. Carl Gustaf Nielsen, were the ones who developed the clinical studies, the clinical protocols, the training necessary in order for this product to reach the position in our armamentarium that it currently has. So what I've asked him to do is share with us, over the next half an hour or so, the history of TBT. The whole purpose of this lectureship is to stimulate young minds, to stimulate innovation, and to demonstrate how we can take a concept, bring it to market, and bring it to market in a very fruitful way. So I'd like to introduce Dr. Peter Petros as our first speaker, and then Peter will give us a bit of the history on the concept. Thank you for being here, Peter. Thank you, Dr. Davila. Ladies and gentlemen, it's a pleasure to take you through some of the scientific discoveries leading to the TBT. However, the main point of this lecture is to encourage innovative thought processes among our younger members. Therefore, the context of this lecture is within Thomas Kuhn's classical work, The Structure of Scientific Revolutions. Kuhn made two main points in his book. It is crisis which leads to innovation. It is anomaly which leads to discovery of new paradigms. The discovery pathway leading to the TBT fits Kuhn's description of a scientific revolution. It began with two observations. The first was that urine loss on coughing can be controlled by midurethral support. Here a haemostat is placed immediately behind the symphysis, and with gentle pressure upwards, you will see that it perfectly controls urine loss. The second observation was that an implanted Teflon tape caused a collagenous tissue reaction around it. This led to two hypotheses, that a loose pubourithral ligament causes stress incontinence, and a tape in midurethra would create a collagenous neoligament to cure the incontinence. On the left, you will see the prototype tunneller. On the right, during cadaveric testing, you will see that application of the tunneller immediately behind the symphysis is exactly along the track of the pubourithral ligament. So the idea was to use the tunneller to insert a tape to create collagen, to reinforce the pubourithral ligament, and thereby cure the incontinence. We operated on 13 dogs. Radioactive gallium studies showed a low inflammatory reaction. We tested the wound, serum reactions. We tested the tape intensively, bacteriologically. The tape was in the vagina of the dog for 6 to 12 weeks. Nevertheless, there were no pathogenic bacteria grown, only mixed organisms. The dogs were afebrile and well at all times, and they had a normal white cell count. We tested for collagen type. Collagen 3 in the blue began to transform to collagen 1 by 4 to 6 weeks. We did extensive gross anatomy and histology studies. In this specimen, 2 weeks after the tape was taken out, where the white arrows are indicates the creation of a very significant collagenous neoligament. We tested the neoligament for strength. It pulled out of the grips of the instron tensiometer at 92 pounds per square inch. Then we applied it to 30 humans. The tape was inserted at mid urethra and removed at 6 weeks. This is a schematic view of the operation. The red horizontal line, this is a coronal view, the red horizontal line represents the rectus sheath. A mersaline tape was placed around it, with 2 ends going into a rubber tube in the vagina, and both ends exiting at the inferior part of the tube. There were holes in the tube, in the tape, and these were secured by interrupted sutures. So the idea was, if there was obstructed micturition, we would cut the sutures one by one to lower the sling and relieve the obstruction. And indeed, by the time the sling was lowered towards C or D, all patients were urinating normally and all were continent. This experiment proves that the mechanism of continents with TVT is not obstructive. In the first 30 patients, 25 also had urgency, what we call mixed incontinence. With the tape in situ, all patients were cured of their stress and their urge. However, when the tape was removed, there was a 50% recurrence not only of the stress but also of the urgency. Immediately we had 2 anomalies. The first anomaly was that stress and urge were cured and recurred simultaneously. Did they have the same etiology? The second anomaly was that urge had been cured surgically. This was supposed to be impossible. We did x-ray studies before and after. We found that all patients were cured without any bladder neck elevation whatsoever. On the top right hand you will see a foley catheter balloon descending below the symphysis on straining at exactly the same pattern after the patient was cured. Clearly these findings invalidated the pressure transmission theory. Where the red arrow is, the tape was grasped with a haemostat and the patient was asked to strain. Immediately 3 directional vectors became evident. Backwards and downwards behind the tape and forwards in front of the tape. A small diversion to the younger members, these directional forces are the key to the function of not only the bladder but the anorectum. Let's move on. These 4 anomalies could not be explained by existing concepts. Kuhn stated that it is anomaly which leads to discovery of new paradigms. We chased up these anomalies with further experiments. A new theory, a new paradigm began to evolve. That competent ligaments were required for normal bladder function. This of course is the integral theory as published in Acta Scandinavica in 1990. You can get a copy of it on the integral theory website. In 1989 I presented the results of the first 30 cases at the Royal Women's Hospital in Melbourne. There I met Ulf Holmsten for the first time. He was quite intrigued at this work. We had long discussions. The following year he visited me in Perth for a week. He reviewed 80 patients. We did 3 operating lists. At the end of the week he said, I think your theory is correct. However, it needs some more work. Our collaboration commenced. Over the next 3 years we revisited 80 patients and realised that we needed a permanent sling to get good longer term results. We tested various tapes. We had problems with erosions. However, by 1996 it was clear that polypropylene had solved the erosion problem. Thank you Peter. So that's the early history. Some of the animal experiments and some of the histologic studies. This led to a product which was then ready to be tested in humans. Professor Nielsen will give us a historical review of how this was tested in humans once it passed the initial experimentation. So dear Willie, thank you for your nice introduction. Ladies and gentlemen, dear colleagues, I would like to thank the organisers of this excellent congress and especially Willie Davila for inviting me to be part of this Ulf Ulmsteen Memorial Lecture. I feel very privileged and very honoured to stand here today. I was asked by the organisers 3 questions on the early development of the TBT procedure for treatment of female stress urinary incontinence. The issues of these questions were which were the early groups of patients we tested, what were the safety and efficacy concerns and how was training to perform the procedure decided on. I will try to answer these questions. Before I go to my presentation on these issues, I would like you to realise that I am putting up the follow-up time and the year of publication of all the articles I am going to refer to in my talk. I want you to also realise that the results of the clinical trials were available for us mostly even a year before these were published in international peer-reviewed journals. The TBT procedure was first launched in the Nordic countries and in Europe at the end of 1997 and a year later in the United States. The first question asked was what patient groups were selected for the early experience with the TBT. Very naturally the first group to be tested was primary uncomplicated cases. The first publication on these patients appeared in 1996 and it was already a two-year study, a two-year follow-up. It was a one-centre study from Sweden in Uppsala and the results were extraordinarily good and very encouraging. The next step was to bring the whole procedure out in normal clinical settings, so that was a multi-centre study in both Sweden and Finland. It was published in 1998 and the follow-up was one year and the results were as good as the primary trial. There were other studies showing the same way. The next step was to look at the more complicated cases, the recurrent cases that had been operated upon before because of incontinence. Here I show you the first four-year follow-up published already in 2001, showing once again excellent results. There were other studies confirming this, as you can see from the slide. The next was to look at the mixed continence group and once again a four-year follow-up published in 2001 with excellent results. And finally, the intrinsic sphincter dysfunction patients, which always have been thought to be the most problematic group of patients to treat by surgery. And as I'm going to show you in a while, the results were not as good as in the other groups, but still rather good. From the very beginning, Professor Ulf Ulmsten thought that we should have the same protocol in all these trials. And I'm not going through the protocols in detail, but you can see that at least these evaluations were done both pre- and post-operatively, with the only exception that later on we skipped the post-operative urodynamics. At that time, there weren't very many quality-of-life questionnaires available, and we still wanted to have an element of subjective evaluation, so we used a visual analog scale with a scale from 0 to 100, where 0 represented no urinary problems whatsoever, and 100 unbearable such. We also wanted to define the criteria for cure and as well improvement, and you can see what was demanded to be regarded cured, and what was the criteria for improvement. Now, this is the result of the first study from Uppsala in 1996. There were 75 women with primary uncomplicated incontinence, and after two years, the cure rate, according to the criteria I just showed you, was as good as 84 percent. Eight percent were improved and eight percent were failures. Then the group of women with mixed incontinence, a four-year follow-up, 85 percent were cured, 11 percent were failed. And then those with intrinsic sphincter dysfunction, the tricky ones, the cure rate was a little bit lower, 73 percent, but it compares well to the results we have seen with the traditional incontinence operations. And then in Finland, we unfortunately had a very long waiting list for incontinence surgery, and that gave us the opportunity to offer the TBT procedure to an unselected patient group, and some of them consented on having a TBT, and of these, 28 percent were recurrent cases, 37 percent were mixed incontinence cases, and 11 percent had a low-pressure urethra. And we were very excited to see how it worked in such a population. And once again, we got very good results, 87 percent being totally cured, completely dry, according to the same criteria I just showed you in the beginning, and only five percent were failures. And there's another study on recurrent cases. Once again, very good results, as you can see from the blue figures. The second question asked was, what were the early concerns regarding TBT safety and efficacy? And I think that's a very, very relevant question, because we know that we have many patients with many procedures out there, some already taken off the market that had many safety problems. Efficacy, of course, was the prime interest at that moment, and already in 1999, there were two separate series of patients that had been followed up for three years and showing good results. And then in 2001, we were able to publish the five-year results with the TBT procedure. What comes to safety, we think that in single series of patients, between 50 and 100 patients, might pick up some complications, but certainly not all the complications that might occur during surgery. So we started a registry on all these operations done in Finland. Finland is a small country. Everybody knows almost each other, and it was easy to start a registry. I'll speak about that in a moment. And then, of course, training was very crucial. As a part of the training, the 12 gold medals and points were created to guide everybody that was performing the procedure. And here you see the five-year follow-up published in 2001. 85 percent, again, according to the same criteria I showed you, were completely dry and cured, and 11 percent were significantly improved. Now this is the registry, and it's special in the way that these are the first almost 1,500 patients ever operated in Finland in a total of 35 hospitals. And all the operating doctors had gone through the training program, which I'm going to show you in a while, at the clinic in Helsinki. And as you can see, even if these figures include the learning curve of every single doctor, the rates of complications are very low, emphasizing how important training is. We are far from the era when see one, do one, teach one. We have to do it in another way. Now, the 12 golden points, I won't go through them. They are there. And the third question was how was required training decided upon. Now, there was an overall alignment between the inventors and the Geinecke of Johnson & Johnson that the launch of the TVT in the Nordic countries and actually in the rest of Europe had to be supported by strong training and professional education. And we were able to do it in a very systematic way in Finland and combined it with the registry that I just mentioned, and this has been published in 2002. During the training, it was emphasized that the TVT procedure is a minimally invasive procedure. It is done in local anesthesia, and there are special features to pay attention to. From the very beginning, it was the idea of Professor Ulf Sundsten that we should standardize the performance of the procedure as good as we ever could so it could be taught and performed in the same way all over the world. And the mid-urethra theory calls for a very careful placement of the tape at the mid-urethra. As you all know, the functional length of the female urethra is very short, and the tape is 11 millimeters wide, and the functional length usually is 2 1⁄2 to 3 1⁄2 centimeters. In Finland, at least, training and certification was required before you were allowed to perform the procedure by your own, and we had an agreement with Johnson & Johnson that they wouldn't sell the kits to these hospitals unless they had a certified doctor. The procedure was kept minimally invasive, for example, by doing it in local anesthesia. It didn't allow you to do anything else at the same time, and special measures were made to avoid intraoperative complications. I'm not going into that now. Now the training consisted of a theoretical training, actual lectures describing the theory and even the procedure, and then surgical training and a follow-up program including involvement into the registry. And the surgical training, all those trained were specialists in gynecology and usually the ones responsible for incontinence surgery at their hospitals. And depending upon their level of experience, they had to attend between two and eight TBT procedures, then assist at between two and four procedures, and then perform two to three ones under supervision. And I didn't put it in the slide, but then they went home to their own hospitals, and I was the teacher. I went there to see that they worked within the team as they had been taught. And then it was decided upon how to manage the patients and their information post-operatively. So we don't get anything new that could work without a theory, without a hypothesis, but a theory without proof is fantasy. A theory translated into successful clinical practice is reality. And I think that, as in the title is spoken about the new gold standard, that the TBT procedure has been studied and developed in a way that I think it deserves to be the new gold standard. I'd like to thank Professor Ulf Ulfsten for what he's done, and I thank you for your attention. Thank you very much. Thank you, Professor Nielsen. So that brings us to where we are today. And for those of you who are taking notes, you had a cookbook on how to innovate, how to come from a concept and bring this to a reality, and a validated reality that has scientific rigor. So I thought in the next few minutes, since we have a few minutes left, we would talk about where the future takes us. We have TBT in front of us, and we've been using it. So where are we going? Where are we going to go? So I asked Peter to give us some insight as to what his concept, his theory, takes us next, and then asked Carl to comment on that as well. So, Peter? Thanks, Willy. Okay. Well, Carl has shown you very comprehensively what we can do with the puborethral ligament. But where are we today? We've got more crises. We've got the FDA mesh problems. Native tissue repair has high failure rates. And we have what are called incurable symptoms, such as urgency, nocturia, chronic pelvic pain. It's important that we address these, because patients come to you with symptoms. Kuhn, again, it is crisis which leads to innovation. So we have applied the neoligament principle to repair of the four other ligaments in the body. There is the utero-sacral, USL, on the left, cardinal, CL, arcus tendineus, perineal body. All of these structures play a role in prolapse and symptom causation. We have applied, practically, the neoligament principle to systocele repair. You will see a sling on the top which reinforces the distal vagina, and one along the cervix, the cardinal ligament, for repair of systocele. We have applied it to apical repair, a sling at cardinal ligament and utero-sacral. Importantly, we have noted, and I say we because there are several publications now, improvement or cure in symptoms such as nocturia, chronic pelvic pain, urgency, abnormal bladder and emptying, and cases of non-sphincteric fecal incontinence. We have applied the principle to rectocele repair, reinforcing the posterior vaginal wall. Up the top with the utero-sacral ligament sling, and down the bottom with the perineal body sling. We have been able to cure obstructive defecation, and importantly, descending perineal syndrome, which apparently is said to be incurable. So let's wrap it up. Without new paradigms, there are no RCTs, there are no meta-analyses, there's no Cochrane, there's no science. To the younger members, I urge you to read Kuhn's book. It will open up a wonderful vista of discovery, not just, it doesn't mention medicine very much, but discovery is discovery. I urge the younger members to examine the relationship between the symptoms and ligaments. The cure of symptoms is the next paradigm. And take care to check out those three directional movements, which are the key to the function and dysfunction of the bladder and anorectum. Do not dismiss anomalies. Follow them up. Anomalies are the pathway to discovery. Challenge everything. Don't accept something just because an expert committee tells you. Look at the anatomy of it. Work it out. Why does this happen? Innovation is born from challenge, not conformity. Persist, even if you meet resistance. And you will surely meet resistance. Thank you, ladies and gentlemen. A little Peter Petraeus philosophy and passion for knowledge. Well, we asked Carl to come in and give us his thoughts now. Now we have a shift in the paradigm. We have an expansion of the theory. Carl, come give us your thoughts. I have no slides to show you, but we have seen a great shift in paradigm from the bladder neck concept to the mediorita concept. And I don't think that we in the near future will see the same kind of a shift. What we are going to see that we in more detail get to understand how the mediorita theory really works. That's one part of the future. The other part of the future, I think, is at least at the moment much more relevant. And that is that I think we are going to have very much stricter rules for how to launch new surgical procedures. There are going to be ethical and moral rules. And we'll be close to what we see with medication today. And I think it's crucial we should not anymore jump on any procedure that is presented to us that has no documentation whatsoever. That is a waste of resources, and it's very unfair to the patients. Thank you very much, Professor Nielsen. Well, I think we would all agree that Ulf Homsen would be very proud of today's lecture. Hopefully it's met its mission of stimulating thought process and innovation, especially in our young attendees, young urogynecologists. So I'd like to share my gratitude to Professor Petros and Professor Nielsen for their brilliant presentations. I'd like to present them with two plaques. And hopefully you'll share with me a round of applause for them. Thank you very much. Thank you.

Ulf Olmsen Memorial Lectureship

TBT procedure

scientific discoveries

patient groups

safety and efficacy concerns

training program

neoligament principle