Advances in Endoscopy

Update on the Use of NOTES Procedures

Christopher J Gostout

G&H Could you discuss the changes and advancements of natural orifice translumenal endoscopic surgery that have occurred over the past few years?

CG In natural orifice translumenal endoscopic surgery (NOTES) procedures, the peritoneal cavity, or the abdominal cavity, is entered through the gastrointestinal tract using a natural orifice. The past two years, in particular, have been extraordinary in terms of the progression of NOTES in a significant fashion, both from the experimental and clinical aspects of conceptualization and acceptance.

On the experimental side, the animal research that is being performed—from the standpoint of developing procedures, studying new instrumentation, and examining the physiology of NOTES-performed surgery—has become much more sophisticated. Prior to, say, two years ago, a fair amount of the laboratory work involved merely trying to obtain a basic sense of what was possible and what was not and examining the entire field of surgery from the perspective of a flexible instrument. Now, NOTES has matured; target applications have been identified (eg, cholecystectomy), and the physical, mechanical, and instrumental means to perform a targeted procedure are now well along the way. A variety of instruments have been created over the past several years to specifically facilitate pure NOTES procedures.

In terms of clinical applications, NOTES procedures are being performed more or less in a hybrid fashion using some elements of laparoscopy and some elements of flexible endoscopy. The creation of instrument sets designed specifically to be used during NOTES has been a huge advancement in the last two years. However, commercial instrument sets are relatively unavailable as of yet, and this lack of availability is impeding NOTES from reaching its full potential in early pure NOTES clinical applications.

From a physiologic perspective, more work is being completed examining the responses of the body to operative trauma in response to a NOTES procedure. We are learning that these responses suggest significantly less trauma compared to other types of minimally invasive surgeries. Thus, we have a good overall impression of NOTES and its potential benefits for patients.

G&H Could you expand on specific applications of NOTES that have been used thus far?

CG In data that are being accumulated in the animal laboratory (including in our own developmental endoscopy unit at the Mayo Clinic), we are working on specific targeted NOTES applications that we think would be ideal for both gastroenterologists and surgeons to perform. We are also busy creating animal models that can be used to teach NOTES procedures in a reproducible and consistent fashion. This has been a significant gain over the last few years.

One example of a specific application is a project currently underway that is designed to create benign lymphadenopathy in a pig model. It is difficult to induce lymphadenopathy in animals unless they are radically ill. This effort would create a model for both gastroenterologists and surgeons to develop NOTES procedures specifically directed at cancer staging. Currently, cancer staging is done using a variety of radiologic methods (eg, computed tomography, magnetic resonance imaging, positron emission tomography scans) as well as endoscopic ultrasound. There may be circumstances, for example, with targeted malignant disease, in which there is uncertainty or a technological disadvantage using the older methods, which would make a NOTES staging procedure useful. I am fairly convinced that there can be a significant rebirth of staging peritoneoscopy using NOTES-style transgastric, transvaginal, or even transrectal approaches; however, good lymphadenopathy models are needed for physicians to practice these techniques and learn the necessary skills to identify lymph nodes as well as remove them safely and successfully.

Another NOTES application that we at the Mayo Clinic feel strongly about is the Heller myotomy for treating achalasia. We have developed a unique method called the SEMF (submucosal endoscopy with mucosal flap) method, which creates a working space or tunnel between the inner lining of the gut and the muscular layer. By creating this working space, we can develop an offset entry point. For example, we could enter the submucosal space at point X, place an endoscope into the space, advance it to point Y (typically a distance greater than 5 cm), and then have an exit point where we could enter into any abdominal cavity. We have demonstrated this method to work well for accessing the mediastinum. We are now in the process of establishing the methodology and outcomes of this technique in a standardized fashion in the pig model, to confirm whether it can be applied to humans, which I believe is possible. In fact, the SEMF method has already been used with success in Venezuela and Japan.

This technique is regarded as safe because of its offset entry and exit and can be used in the chest cavity to gain access to the heart. It has not yet been used for much more than merely confirming that the heart can be reached via a transesophageal approach, but it may offer a new spectrum of NOTES-type operations. Other groups such as a working group in France at the Institut de Recherche contre les Cancers de l’Appareil Digestif (IRCAD) and a group at Harvard Medical School are also interested in this method. We have been working hard to try to develop new techniques and models, with the hope that others will run with them and develop new applications for NOTES.

G&H How widespread has the adoption of NOTES been thus far?

CG Over the past few years, hundreds of NOTES operations have been performed across the world. NOTES has particularly caught on in Latin America, where I would estimate that close to 400 NOTES operations have been performed. The vast majority of NOTES operations have been cholecystectomies, mainly using transvaginal access points. The transvaginal route has become the most common approach, at least during the early phase of NOTES surgery, because of its history as an established operative entry point. Until satisfactory NOTES toolsets are universally available on the clinical side, the transvaginal approach is preferred; however, it obviously has limitations as a gender-specific approach.

In the United States, we are approaching the completion of 75–100 NOTES cholecystectomies. The institution in this country that currently has the most experience in clinical NOTES operations is the University of California at San Diego, which is becoming the leader of developing NOTES surgery, not only with transvaginal approaches but with transgastric approaches as well. Other centers in the country, most located in major cities, are joining in on more and more of these procedures. At the present time, surgeons are focusing on cholecystectomy because it is a very common operation, which makes it easy to compare how NOTES stacks up relative to minimally invasive laparoscopic cholecystectomy.

I think that the surgical community has grown to accept NOTES as a potential surgical option. At this point, community surgeons are curious about NOTES, and academic surgeons are already actively thinking about how to incorporate NOTES into the grand scheme of all surgeries, including general surgery, gastrointestinal-specific surgery, thoracic surgery, urologic surgery, and even transplant surgery and gynecology-oncology surgery.

Some physicians think that NOTES has lost momentum, but I do not agree. NOTES has gained acceptance, which has created a different mindset now. The thrill and the excitement of NOTES has now shifted and matured into more practical matters such as exploring which specific applications can be used for NOTES.

G&H Could you discuss any limitations currently associated with NOTES procedures?

CG It has become increasingly obvious that trying to perform an operation exclusively through a flexible endoscope is challenging due to two major limitations. The first limitation is the difficulty of working in a tight or small visual field. When surgeons perform minimally invasive laparoscopic surgery, they often use multiple ports in the abdominal cavity, for example, and can use additional cameras to view not only the operative field that they are working in but the surrounding structures as well. In contrast, with an endoscope, the closer the endoscopist moves toward the working point, the less they see of the surrounding anatomy. Missing out on some of the surrounding anatomy can potentially be problematic. We are now recognizing these limitations with NOTES and are trying to determine whether they need to be overcome or whether endoscopists need to do a better job working in the given microenvironment.

This leads to the second limitation, having at most two working channels to place instruments through when using flexible endoscopes. These instruments work in parallel, and it is very difficult to manipulate tissues and structures when using two instruments in parallel. In contrast, laparoscopic surgeons, for example, can triangulate and enter from different access points with their instruments, making their work and manipulation of structures much easier. Thus, recognizing that the demands on instrumentation are steadily increasing, instruments will be needed that can be deflected or perhaps endoscope channels will be increased in number with additional movable devices that can be placed through the channels to try to duplicate the triangulation that laparoscopic surgeons currently have. At the present time, most physicians performing NOTES procedures are still putting a single port into the abdominal cavity to facilitate organ manipulation or retraction, both of which are basic functions that cannot be accomplished in this microenvironment. Not having complete NOTES toolsets available for clinicians limits NOTES approaches from other access points, particularly the stomach. When the concept of NOTES procedures was first proposed by the Apollo group and Dr. Anthony Kalloo at the Johns Hopkins School of Medicine in 1998, NOTES was intended to be a transgastric procedure. In fact, many physicians view the transgastric approach as a more preferable access point for NOTES operations.

There are some frustrations with adapting pure NOTES procedures in clinical practice, but most physicians believe that this can be easily overcome by technological advances; I do not think that anyone has given up on any potential applications as of yet. With technological advances, it is hopeful that the applications will be successful in the future. It is unclear when exactly these advances will come, but it is likely that within the next 5 years, there will be a significant increase in NOTES operations across the country.

G&H How has the Natural Orifice Surgery Consortium for Assessment and Research influenced the development of NOTES procedures over the last few years?

CG The major change over the past few years is that the Natural Orifice Surgery Consortium for Assessment and Research (NOSCAR) has matured its focus from basic animal studies to clinical trials, and I wholeheartedly agree with this change. Over the past several years, NOSCAR has been instrumental in funding basic NOTES animal-based research and has poured a phenomenal amount of money ($3.5–4.5 million) into research for NOTES. The consortium is now moving toward a policy in which the majority of research dollars derived from its program will be designated for clinical studies. There is an effort currently underway by NOSCAR to create a multicenter US trial comparing NOTES cholecystectomy to laparoscopic cholecystectomy. This will be a key clinical prospective study that will challenge NOTES in its current form. Many physicians are already anxiously awaiting the outcome of this trial, the details of which will likely be announced at this year’s annual NOSCAR meeting in July.

The other achievement of NOSCAR is its use as a role model across the world for similar groups to organize in different countries. EURO-NOTES, for example, is modeled exactly after NOSCAR in terms of function, activities, research, and support. Similarly, a Latin American NOTES group and a Japanese NOTES group have been formed and modeled after NOSCAR.

G&H Could you discuss the NOTES/NOSCAR outcomes registry that was established last year and its role in gathering outcomes data and guiding future developments?

CG One of the main missions of NOSCAR has been to enable NOTES to develop, either successfully or unsuccessfully. NOSCAR intended to make sure that there would be no rogue NOTES operations being conducted unchecked, unsupervised, or unmonitored that could halt the momentum of this new concept. The NOTES/ NOSCAR outcomes registry was created to encourage physicians to conduct all of their clinical cases under a very specific research protocol guideline and then to input that data into the NOSCAR registry. This is a noble and valuable mission that NOSCAR has initiated, and the registry has been successful in the sense that physicians are including their cases to compile clinical information as to what is happening and where it is happening. I do not know whether there have been enough cases in certain areas to look at the data and analyze it yet. We are anticipating a status update of the database at the July NOSCAR meeting.

G&H How is the issue of training being dealt with for NOTES? Will NOTES be performed primarily by gastroenterologists or surgeons?

CG When I travel around the world to talk about NOTES, the most frequent question I am asked is how physicians are going to be trained to perform NOTES procedures. We at the Mayo Clinic have spent a good deal of time thinking carefully about this, as have others such as Dr. Richard Rothstein at Dartmouth Medical School and Dr. David Ratner at Harvard Medical School. In my opinion, and I think that there is a consensus on this, NOTES will be performed predominantly by surgeons. There is little doubt regarding this point because NOTES is a form of surgery, which places inherent training limitations with its use. There are certainly opportunities for gastroenterologists; Dr. Anthony Kalloo is absolutely convinced that there is no reason why NOTES cannot be as well-embraced by gastroenterologists as by surgeons. The dividing line in the issue is background training. Gastroenterologists, by and large, do not receive any formal training in surgery. If gastroenterologists are going to perform NOTES operations, they will need to know basic surgical landmark anatomy to function safely and efficiently. It is possible to argue that this can be condensed into specific operations, anatomies, and features, but, by and large, gastroenterologists do not have any surgical training and are not boarded in surgery, making this problematic.

The one application that is wide open for gastroenterologists to embrace and to resume using is cancer staging. Gastroenterologists previously performed this procedure on a regular basis laparoscopically—I trained and performed it for years—but then it was relinquished to surgeons because they moved it into laparoscopic surgery and more conveniently and efficiently took over that aspect of cancer staging. I think that this procedure can fall back into the gastroenterologist’s lap, as it is a safe environment for gastroenterologists to become involved in NOTES using transgastric, transrectal, and transvaginal approaches, provided that they have the right tool set. They can perform these procedures by passing their endoscopes through and closing their access points safely and efficiently. This procedure will likely not be a problem, particularly in terms of credentialing and privileging because it was done by gastroenterologists in the past and did not require formal surgical training.

However, for a gastroenterologist, performing a cholecystectomy or appendectomy would be a huge roadblock. For example, I have discussed this issue within my institution and we have decided that in order to become a NOTES surgeon, 1–2 years of surgical residency would be required of me to become internally credentialed. However, as I am not willing to drop everything to become a resident again, I will never become an independent NOTES surgeon. I can certainly participate and assist in these procedures, though, which is thrill enough for me.

For surgeons, retraining would likely be less extensive. Surgeons have a mixed experience in endoscopy; some surgeons are very active with flexible endoscopy, but, by and large, the truly complex flexible endoscopic procedures are performed by gastroenterologists. The surgeon community has a bit of an issue insofar as having a strong background in complex flexible endoscopy, but this is something that can be easily overcome. It is probably an easier hurtle for a surgeon to become involved in NOTES without obtaining extra training through an advanced endoscopy fellowship.

G&H What will NOTES training look like for fellows?

CG Fellows in the pipeline are a different story. In our program at the Mayo Clinic, on the medical side, if a fellow wants to become a hybrid NOTES interventionist (note the specific title), that individual would be expected to do 3 years of general gastrointestinal fellowship, 1 year of advanced endoscopy fellowship, and 2 years of minimally invasive surgical residency. The surgical residency is not exclusively minimally invasive, but it is weighed toward that. This individual would essentially be shunted back into the general surgery program, on a separate track. Each institution would have to decide what that track should be.

This is in contrast to the requirements for surgical fellows who want to come at NOTES from a pure surgery background. Surgical residents would be expected to do standard general surgery residency, which is typically 5 years. Afterwards, we would recommend 1–2 years of advanced endoscopy fellowship, depending upon the flexible endoscopy experience that the individual has had, and then, most likely, a minimally invasive surgery fellowship, which is 1–2 years as well. These are long roads, from the training standpoint, at the present time.

From the gastrointestinal side, the fellow would finish as a board-certified gastroenterologist but not a surgeon; they would only have a certificate of training in surgery. The surgeon, on the other hand, would finish as a boarded general surgeon with endoscopic privileges and may have subsequent added certifications in a subspecialty surgical area such as minimally invasive surgery, thoracic surgery, or pediatric surgery.

G&H Will there be training classes to offer some exposure to physicians who do not necessarily want to go back and become credentialed?

CG I serve as Director of the American Society for Gastrointestinal Endoscopy (ASGE) Institute for Training and Technology (IT&T) and am actively engaged in creating programs to develop advanced endoscopic skill sets. We, as a professional society, have recognized that there will be a current training deficit of both gastroenterologists and surgeons, and are thus constructing hands-on training programs to obtain very intensive training on specific techniques and applications. For example, last November, we held the first NOTES hands-on human cadaver–based course. This course was not directed toward cholecystec-tomy-targeted operations; it was simply exposure for surgeons and gastroenterologists, to familiarize themselves with passing flexible endoscopes into abdominal cavities and experiencing the associated limits and advantages. It was very interesting because the majority of participants in the course were gastroenterologists; I had expected the opposite to be true. From the ASGE and IT&T perspective, we are very actively sorting this issue out and we have monthly conference calls to discuss how to move progressively and successfully into this arena.

G&H What are the next steps for research and development in NOTES?

CG The next steps will be a shift into prospective human trials to standardize operations and techniques and recognize the real needs in a human environment. This will be the biggest step forward. The other step will be in establishing instrument needs beyond those currently in the pipeline, recognizing future instrument needs, and testing new platforms such as robotic-style platforms. In addition, a subset of research will hopefully involve physicians exploring and conceiving of brand-new, out-of-the-box NOTES applications. We all have some of our own ideas as to the next evolution of NOTES applications, but they are being kept under wraps thus far.