BB&T Contributing Writer

ORLANDO — The 28th annual meeting of the American Society of Metabolic and Bariatric Surgeons (ASMBS; Gainesville, Florida) provided insight on a wealth of improvements on advanced products currently on the market, but little in regards to filling the gap with less invasive procedures that fall between medical therapy and surgery. With 68% of Americans being either overweight or obese, and the World Health Organization predicting that 700 million of the world's population will be obese by 2015, it is imperative that efforts are directed towards improved care and prevention for this life-threatening chronic disease. Unlike other subspecialties where interventional procedures are often employed once medical management fails and before surgery is required, there is little in that space for the obese patient. While many innovative devices have been in development to provide an intermediate step for patients unwilling, unable, or not quite ready to go under the knife, progress has been slower than expected in getting them to market. It appears as though many of the start-ups can't seem to get their pivotal trials through the FDA, meaning that there will be another 3 to 4 years before they hit the market.

“Many of the companies are calling it quits because of poor study results and because FDA is not setting realistic end points for clinical studies,“ an anonymous industry representative told BB&T.

This concept of filling the gap in care was demonstrated by Christopher Thompson, MD Director of Developmental and Bariatric Endoscopy, Brigham and Women's Hospital (Boston) in his presentation Emerging Endoluminal Bariatric Procedures: Gastroplasty, Balloons, Duodenal Sleeve, etc. Where he showed the chart above. (See Table 1)

Table 1

Continuum of Treatment Parameters for Surgical Specialties

Source: Christopher Thompson, MD at ASMBS

Endoluminal devices to treat obesity/diabetes

Many attempts to serve this gap in continuum of care have been made by various companies, both start-up and large corporations, but few are yet marketed. Thompson, who is an advisor to many companies in this arena, explained, “There are many endoscopic technologies in development that mimic surgical techniques.“ Thompson feels that most patients are not getting traditional bariatric surgery because it is expensive, requires good surgeon technical skill, and that patients are apprehensive about the surgery. “Since only 3%-5% of the obese patients who diet and exercise can maintain the weight loss at 5 years, and since patients are fearful of surgery, we need an interventional tool – much like other surgical specialties – that can address these concerns,“ he added. He then categorized and commented on the various endoluminal bariatric procedures, as shown in Table 2.

Table 2

Endoscopic Obesity Procedure Categories

Source: Christopher Thompson, ASMBS presentation

Thompson is a proponent of stratification of risk/reward benefits when evaluating these new devices; claiming that they cannot all be viewed as being the same. He also said in an editorial published last year in Gastrointestinal Endoscopy, “Endoscopic obesity procedures may offer a solution by providing improved effectiveness compared with medications, with a lower risk profile than traditional surgery. These emerging bariatric technologies could be of significant value in contending with the obesity epidemic. It is important to understand their potential roles and that regulatory agencies be flexible in the evaluation of these technologies. It is counterproductive to insist that all new devices be treated as primary obesity procedures when this may not be the intended application. These devices must be assessed in reference to how they can be most useful.“

It was rumored at this meeting that the FDA plans to meet with bariatric surgeons from Mass General Hospital (Boston) and Dartmouth Hitchcock Medical Center (Lebanon, New Hampshire) in October to discuss appropriate guidelines for evaluating novel devices that treat obesity.

In that same session on Innovations in Bariatric Surgery, Homera Rivas, MD Director of Innovative Surgery, Stanford University School of Medicine (Palo Alto, California) shared his opinion of what would be the most promising new technology for primary weight loss. “It needs to be quick (15 minutes), affordable ($1000), and can be repeatable every 2 years. Eventually, it can also be used as a preventative procedure.“ None of the products in development would meet those specifications but they are all headed in that direction, with those parameters as being the eventual goal.

When asked by an audience member specifically, “what is the most promising technology available today for reduction of the pouch and stoma?“ Rivas responded, “The use of sclerotherapy is excellent if the stoma is less than 2 cm. The second generation Apollo overstitch device can be used for either reducing the stoma, or the pouch, or both.“

Advanced minimally invasive bariatric surgery

While the companies with novel devices are busy dealing with the FDA, other companies are focused on enabling technologies to improve outcome and advance the art of being minimally invasive. Data-derived evidence of any benefit for single port surgery is still forthcoming, but in the interim, patients — especially women and adolescents — are requesting 'no scar' bariatric surgery. To meet this patient demand and still maintain a high safety profile, two companies exhibiting here were demonstrating their products for flexible laparoscopy that work well in single port or endoluminal surgery.

The initial clinical interest in Apollo Endosurgery's (Austin, Texas) flexible endoscopic instruments was that they could be used for NOTES (Natural Orifice Transluminal Endoscopic Surgery). Currently, they are more focused on their endoscopic suturing system (Overstitch) and endoscopic scissor (Flexshears) that serve well for post-operative repairs of complications in bariatric and other procedures such as repairing leaks and closing fistulas. FDA cleared in 2008, they have deliberately managed a slow introduction in 15 US centers that has allowed them to identify improvements incorporated into their second-generation device. They intend to launch the smaller, lighter, more user friendly and cost effective ($599) device at the American College of Surgeons meeting this fall. Even though they do not yet address any primary therapies, as a first time exhibitor at this meeting they enjoyed endorsements from the podium as well as a buzz at the exhibit booth. Apollo is a venture-backed private company serving a 50-50 mix of gastroenterologists and surgeons who perform gastrointestinal procedures.

TransEnterix (Durham, North Carolina) was also initially thought of as a NOTES-type platform, but has successfully re-grouped to meet current market needs and was demonstrating their SPIDER system, a disposable platform for facilitating less invasive (especially single port) surgery. The SPIDER system employs single site triangulation with true left and true right control and advanced steerability. TransEnterix was launching their second-generation system here that boasts increased strength and fine motor control, along with better ergonomics. TransEnterix is a privately held, well-funded start-up company employing direct sales reps. They received their CE mark March 2011 and are planning to commercialize in Europe by the end of 2011. The disposable platform device with instruments costs from $800-$1000 and so far hospitals using the system absorb the cost in the DRG with margin to spare.

Robert Marema, MD, bariatric surgeon at Flager Hospital (St. Augustine, Florida) has performed over 40 sleeve gastrectomies using the SPIDER system. In his experience, he feels that patients view sleeve gastrectomy as middle of the road: more invasive than a lap-band, less risky than gastric bypass. “Patients seem more willing to accept the risk/reward benefit of the sleeve over the band or bypass. Sleeve gastrectomy may serve as a solution that addresses a broader population,“ Marema said. “The Excess Weight Loss (EWL) with a sleeve is more than that experienced with a band but less than that with a gastric bypass and has similar co-morbidity resolution,“ opined Marema. He found that the SPIDER was especially enabling for performing a single incision sleeve gastrectomy. In those 40 plus patients there has been an average of 40% EWL at 3 months and he expects to see 65% EWL at 6 months.

Sleeve gastrectomy expanding number of procedures

There is great hope among bariatric surgeons that the newest surgical procedure to treat obesity, sleeve gastrectomy, can capture additional patients into the surgical equation and in some ways be the less invasive procedure that patients are seeking. More or less stalled out at about 250,000 procedures annually in the U.S., any new tools to attract the other 22 million qualified patients into surgery would be most welcomed.

Audience interactive sessions

Similar to the way Hollywood TV has made a dramatic switch away from scripted programs and towards reality shows, many of the sessions at this meeting were audience interactive with questions and answers, or with case presentations, as opposed to prepared presentations based on (scripted) research.

In a session titled “The Great Debate,“ a panel of surgeons presented their viewpoint on a specific topic, then an audience vote was taken via text messaging, both before and after their presentations. The speaker who converted the most audience members (measured by percent converts according to text votes) was declared “the winner.“ The first question posed was “Single Port Surgery versus Conventional Laparoscopic Surgery versus Robotic

Surgery for Sleeve Gastrectomy: Which is Best?“ Raul Rosenthal, MD, of the Cleveland Clinic (Weston, Florida) presented the reasons why surgeons should continue to perform conventional laparoscopic surgery while Julio Teixeira, MD, Chief of Single Port Surgery, Associate Clinical Professor of Surgery at Columbia University College (New York) presented reasons to perform single port, and Erik Wilson, MD, Associate Professor of Surgery, University of Texas Medical School (Houston) debated the value of robotic surgery. (See table 3)

Table 3

Benefits of Conventional, Single Port, and

Robotic Surgery for Sleeve Gastrectomy

Reasons to Perform Single Port Sleeve Gastrectomy

• Patients want it

• Will attract more patients into getting the surgery

• Virtually no scar

• Less pain

• Nominal increase in cost ($40)

Reasons to Utilize Robot

• More comfortable for surgeon

• Vision is superior to either of other modalities

• Improves technical skill

• Will enable surgeons who are unable to perform single port surgery (although not yet FDA cleared)

Reasons to Perform Conventional Laparoscopic Sleeve

Gastrectomy

• Safety profile good with long term data

• No confusion of right versus left

• No clashing of instruments

• Patients are going to get abdominoplasty anyway so who cares about cosmesis?

• Shortest OR time

• Most cost effective

Source: Presentations by authors listed in text above at ASMBS

The audience submitted their vote for which type of surgery they believed was most beneficial via text message both before and after the presentations. (See Table 4)

Table 4

Most Beneficial Technique for Sleeve Gastrectomy

According to Audience Vote

Teixiera's presentation on single port was declared the winner by virtue of highest conversion rate.

Not present but accounted for

Unlike prior meetings, the emphasis at this one was improved advanced surgical technique, such as single port and sleeve gastrectomy, rather than novel endoscopic approaches. Because they cannot sell their devices yet, the innovative start-ups were not exhibiting at the meeting, but an update of their status (as best as we know) is in Table 5.

Table 5

Select Companies with Technologies in

Development for Endoluminal Bariatric Procedures

* on market now

Source: BB&T, Industry sources

Few new start-ups identified

Although two companies that utilized plication techniques for gastric restriction are now taking a new direction, a new start up also based on restriction is in the early stages of development. InTailor Surgical (Marietta, Georgia) has a device that endoscopically creates a gastric pouch with a restricted outlet. The device produces a substantial plication of the entire perimeter of the stomach by utilizing two rings, or hoops, which invaginate a circumferential pleat of tissue that is then anchored by sutures. The created stoma has hoop strength, much like the bands on wooden barrels of wine, that is supposed to have a higher potential for durability since the hoop forces pull on the hoop itself rather than on the tissue. Another key advantage of their system is that the augmented tissue is fixed together on the outside, or serosal side of the stomach. The serosal side of the stomach has been shown to fuse together, unlike the inside, or mucosal side of the stomach. Suspended just beneath the newly created orifice is an impeding ball that slows down the movement of food as it passes through the opening. The ball can be easily removed endoscopically and replaced with a smaller or larger ball, making the product adjustable; and in times when increased nutritional support is needed, such as pregnancy or disease, the ball can be removed altogether. The company's gastric restriction technology may also be used in conjunction with other surgical procedures or devices, such as endolumenal bypass. The InTailor procedure is performed transorally, is adjustable, and has so far demonstrated that it is safe and feasible in a small animal study. InTailor has 4 patents issued with several more pending and is seeking $5 million in series A funding to take them through a 12 patient human pilot study.

Aspire Bariatrics (Philadelphia) has developed what can be considered a reverse PEG tube where once the tube is implanted, food is sucked out of the patient's stomach shortly after injestion. The company just completed its U.S. pilot trial with success and expects to launch the product outside the United States in 2011 and within the U.S. in early 2014. The BariAssist is designed to help the patient to achieve portion control, reduce caloric intake, and lose weight utilizing an endoscopically placed tube called the G-shunt.

Updates on other endoluminal devices

GI Dynamics (Lexington, Massachusetts) appears to be the clear frontrunner for managing their way through the FDA process, although they have yet to be cleared for marketing. “We continue to have productive and ongoing discussions with the FDA,“ said Stu Randle, CEO. “In addition, we have the CE mark for both Type 2 diabetes and obesity with our strategy in Europe to transition a small number of Centers of Excellence from clinical use to commercial use. Currently, we have eight centers in Europe and one in South America up and running,“ Randle elaborated. GI Dynamics has implanted more than 500 patients worldwide with their Endobarrier and has recently established a registry to follow patients after their implant. After their first pilot trial where diabetic patients showed an immediate decrease in the intensity of their disease, GI Dynamics made a conscious and strategic shift to focus on diabetes first and weight loss second, driving an entirely different data set to prove results and maximize reimbursement potential.

GI Dynamcs is conducting studies now to determine optimum timing for implant of a second Endobarrier following the 12 months initial implant duration. Happily, in anecdotal observations, both the weight re-gain and HbA1c levels have rebounded much more slowly than expected. However, if there is a need for a second round of treatment, GI Dynamics wants to know with certainty what time would be optimum for re-implantation.

Valentx (Carpinteria, California) is the only other direct competitor to GI Dynamics, other than bypass or switch surgery, that addresses diabetes remission as well as weight loss. Different than the Endobarrier, Valentx has an additional restrictive component to their intestinal sleeve and it is estimated that they have implanted about 40 devices in humans.

Another company, Safestitch Medical (Miami), has successfully tested their first investigational intraluminal gastroplasty device for obesity in 5 patients in Hungary. Given FDA go ahead with their clinical trial protocol, they anticipate starting human clinical trials in the U.S. first half of 2012; and are preparing the documentation for European clinical trials to be submitted by year end.

The dirty little secret: revision surgery

Intuitively, as each year accumulates another 250,000 post-bariatric patients, the number of revision surgeries has been climbing. A documented 12-50% of all post-bariatric surgery patients regain a significant amount of weight – enough to qualify for a revision procedure. The scary thing is that although the primary bariatric surgical procedure carries a low risk, revision surgery has a 5 times greater morbidity and mortality rate. Dean Mikami, MD, Assistant Professor of Surgery, Ohio State University (Columbus, Ohio) likened obesity to cancer. “Fat cells are like cancer cells growing out of control. As with cancer, patients need constant surveillance following treatment.“ The difference is that cancer patients come in routinely for check ups while bariatric patients who are not losing as much weight as they think they should fail to come in. They tend to look at themselves as a failure or they blame the surgery as a failure. There are common patterns to weight re-gain that can be addressed if the patients stay on their weight management program. (See Table 6)

Table 6

Common Patterns That Lead to Weight Regain

• No surveillance

• Grazing

• Lack of exercise

• No support

• Insufficient monitoring

• Not using food log

Bariatric surgeons recognize that lifestyle changes are the culprit — not a failed surgery — but are at a quandary as to how to get the “failed“ patients back into a structured program when they do not keep their appointments. Very rarely does weight re-gain happen to a patient who followed the program. When patients who have re-gained weight do come back, they come back hoping it was a failed surgery, not them. About one-third of failed patients can get back to where they were (weight-wise) if they re-enter the weight management program,“ according to Meghan Ariagno, RD, Tufts Medical Center (Boston, Massachusetts) who was a panel member at an industry sponsored symposium. Other panel members said that they add three months of phenteramine to the weight management program of a newly returned patient if the patient is otherwise medically healthy in order to give them a jump-start and get their momentum back.

According to Kelvin Higa, MD, Professor of Surgery, University of California, San Francisco “Surgical operations have longevity – it's just that there is no algorithm of which patients do best with which operation. Since we don't know the pathophysiology of the disease we don't know if we chose the right procedure in the first place. Since obesity is a chronic disease, there will be some failures.“ He also said that he felt revision surgery is a sub specialty of bariatric surgery and not all bariatric surgeons should be performing revisions. He added, “If the revision is for a medical reason, a 95% success rate can be expected; if it is for a social reason, or non-compliance, there will probably be little success with the revision surgery.“

Reinforcement of suture line

With the renewed interest in performing sleeve gastrectomies, comes a new choice for surgeons to make: to buttress the seam line or not. This is not a concern for Lap Bands as there is no suture line, and for gastric bypass the suture line is shorter. But sleeve gastrectomy creates a fairly substantial suture line and leaks, although rare (1%-2%), are a number one concern. About half of bariatric surgical procedures, with the exception of bands, utilize some form of buttress, or reinforcement of the suture line. Three companies offer staple line reinforcement: Synovis Surgcal Innovations (St. Paul, Minnesota), who has about 30% market share in bariatrics, provides the only buttress made purely of a biomaterial, Peri-strips; W.L.Gore & Associates (Newark, Delaware) manufactures Seamguard, a bioabsorbable material; and Covidien (North Haven, Connecticut) recently launched their Duet system where the synthetic buttress material comes supplied with their stapler. The aim of all these companies is to prevent having a “do-over“ for the bariatric patient.

Hopefully, the FDA will produce guidelines that will allow future interventional technologies to address this huge and growing market.