BB&T Contributing Writer
PHILADELPHIA — A sunny day in the "Brotherly Love" city was the setting for the annual spring meeting of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES; Los Angeles), where topics ranging from advances in col-onoscopy to pancreatic cancer treatments are discussed, debated and research presented on these topics shared.
The most controversial topic, Natural Orifice Translumenal Endoscopic Surgery (or NOTES), once considered a laboratory/research-only procedure, once again attracted a ballroom of standing-room-only attendees.
NOTES has been coined as an "invisible surgery" because there is no external visible scars as a result. NOTES entails any surgical or diagnostic procedure that uses a flexible scope which passes through a natural orifice (oral, vaginal, urethral, or rectal), then transects through that lumen into the open peritoneum where the actual surgery is performed.
An entire half-day session was dedicated to this topic, one that continues to attract larger crowds each year, a testament that this new procedure is not going to be confined to the laboratory but will thrive until otherwise shown not to be valid or to have no market uptake — the latter of these being especially unlikely.
In order to proceed with NOTES research in a controlled, ethical, regulated manner, an initiative named Natural Orifice Surgery Consortium for Assessment and Registry (NOSCAR) has been established to provide a virtual community to police and monitor the progress of all NOTES procedures (www.noscar.org).
Under the auspices of both the American Society for Gastrointestinal Endoscopy (ASGE; Oakbrook, Illliinois) and SAGES, NOSCAR is comprised of six members from each group. One of its goals is to provide a network to foster research, maintain a registry and bring together interested parties.
NOSCAR receives research support from industry sources as well as $3 million from CIMIT/TATRC, a division of the Department of Defense, its largest single supporter. With an additional $2.7 million supplied by Ethicon Endo-Surgery (Cincinnati) Olympus (Center Valley, Pennsylvania), Covidien (Mansfield, Massachusetts) and Karl Storz America (Culver City, California). NOSCAR is now accepting grant proposals for human trials from interested institutions and individuals that will be supported by the fund.
Getting in, getting out — then closing
The primary areas for improvement in these procedures — and the focus of ongoing research — were discussed at the SAGES meeting, the first issue being how to enter and exit the entry lumen space safely and then closing of the surgical field, with several companies evaluating this strategies.
"Without a safe entry and secure closure, there is no NOTES procedures," said Richard Rothstein, MD, of Dartmouth-Hitchcock Medical Center (Lebanon. New Hampshire).
"Each orifice of entry poses its own advantages and disadvantages," he said. "The advantage of using the stomach as an organ of entry is that it requires no bowel preparation, the acid is anti-bacterial, and patients prefer it. The disadvantages are that it means a blind entry into the peritoneum, the instrument size is limited by the LES, and there are no instruments currently available for this specific purpose."
To that end, several companies and surgeon groups have scrambled to address this issue. Ethicon Endo Surgery has developed a flexible access trocar kit for this purpose that includes a veress needle, balloon, and overtube for gastric entry.
Another company (the name not disclosed by Rothstein) is developing an echo-endoscope that will guide the blind entry, he said. And two different surgical teams have developed techniques that make a gastric entry safe and closable.
Choosing the right orifice
The specific surgical or diagnostic procedure will dictate which orifice should be used. For instance, rectal entry provides easy access to the gall bladder and upper abdominal structures and is simpler than a gastric entry; however it requires colon cleansing and has an increased infection risk and the concept is,for obvious reasons, not to the liking of patients.
Vaginal entry into the abdomen is not new, except that with NOTES techniques appendectomies, cholecsystectomies and sleeve gastrectomies are now being performed through the vagina, which is a new strategy for the procedure. One problem with vaginal access is that it requires a blind insertion into the peritoneum.
Access through the bladder is sterile and allows for use of familiar rigid instruments, but limits the size of instruments that can be used and most patients would choose another orifice. The most exciting as-pect of bladder entry is for transvesicular assistance for transoral procedures, or the use of two orifices for one procedure, where one orifice is used for viewing while the other is used for operating. And dual-access NOTES procedures add appeal and safety for many who have adopted the NOTES strategy.
Another area of great interest but not yet heavily investigated, is that of making a pericardial window through the esophagus. This could open up a whole arena for new cardiovascular procedures if a safe entry and exit can be developed.
"Secure closure appears to be one of the biggest challenges at this juncture," said Rothstein, "We now know that surgical clips don't work because a full thickness plication is required. The gProx system developed by USGI [San Clemente, California] for GERD works, as did the NDO Plicator also developed for GERD but is no longer available."
Thus, the opportunity to design a closure device specifically for gastric entry NOTES procedures has several companies all jockeying for position in a market that only exists in its very earliest stages. (See Table 5). "There are many options for closure and access. It all depends on where you want to go and why," Rothstein said.
Following safe entry and secure closure, the next frontier for NOTES procedures is infection control.
Jeffry Marks, MD, associate professor at Case Western Reserve University School of Medicine (Cleveland), addressed this topic in his presentation, "Infectious Issues and NOTES: Laboratory Studies To Date, Sterile Conduits-Necessary or Not?"
"There is a full library list of organisms in the stomach," he said. "Laboratory studies have shown that although 50% of all the foreign bodies left after a gastric NOTES procedure grew bacteria, all of the animals survived, which begs the question: Is there a physiological effect in the presence of bacteria? The peritoneal cavity appears to tolerate a lot of bacterial presence."
In another lab experiment, Marks found that gastric washing with antibiotics was unnecessary because it did not affect the infection rate. What he did find was a high correlation between oral contamination (not gastric) and infection, suggesting the need for a transgastric conduit that protects the instrumentation from oral contaminants.
Apollo Endosurgery (Austin, Texas) is developing a gastric peritoneal access system that employs a balloon on either side of the gastric wall to prevent infection by sealing off any potential oral contaminants from entering the peritoneum.
Marks also found that PPI inhibition causes bacterial overgrowth, leading to the conclusion that for infection control in gastric NOTES procedures, a transgastric conduit that bypasses oral contaminants and stopping PPIs are required. Since NOTES procedures do not enter the abdomen the same as laparoscopic procedures, a "trocar-less" armamentarium of instruments needs to be designed.
An intriguing concept is that of using magnets as retractors, a strategy discussed by Daniel Scott, MD, associate professor at the University of Texas Southwestern, (Dallas). The beauty of using a magnetic anchoring and guidance system (MAGS) is that it overcomes the in-strument limitations of NOTES procedures while complementing flexible endoscopes.
Transabdominal magnetic an-choring and guidance systems deploy multiple instruments through a single 15-mm transabdominal trocar. These instruments are positioned in the peritoneal cavity and are controlled by externally placed magnets to reduce the need for multiple transabdominal trocars. (Table 6 identifies some of the locations and procedures using MAGS systems.) Although MAGS systems overcome instrument limitations in NOTES procedures, the strategy isn't feasible until the problems of instrument clumping and tether management are solved.
NOTES too patient-driven?
At this point in time, NOSCAR requires that all NOTES procedures must be performed under an investigational research board protocol, and that laboratory rehearsal using NOTES procedures and techniques first are practiced on cadavers. This is partly to avoid a rush to technology that may be overly patient-driven and therefore not yet proven and potentially too risky, paralleling the first laparoscopic cholecsystectomies in the 80's.
The potential demand for NOTES was demonstrated at the SAGES meeting in a patient survey conducted by Lee Swanstrom, MD, program director of Good Samaritan Hospital (Portland, Oregon). In the survey 192 patients were informed concerning the risks and benefits of a cholecsystectomy performed by either NOTES or laparoscopy.
Of these 192, more than half (56%) opted for NOTES, despite the warning of potentially a higher rate of complications. This may be because the potential risks are outweighed by the reported benefits — the absence of an external scar, and reports, according to clinicians who have performed NOTES, that the procedures are virtually pain-free.
In a prospective study reported by Ricardo Zorron, MD, of the University Hospital Teresopolis HCTCO-FESO (Rio de Janeiro, Brazil) two identical groups of 15 patients each received a cholecsystectomy, one group by transvaginal NOTES and the other group, standard laparoscopy. Both groups had similar results and complications, with the exception of the NOTES group which had longer operative times.
The most significant difference between the groups was the lack of post-op pain in the NOTES group, with half of the patients taking no post-op meds at all.
However, NOTES is still considered investigational, precluding any reimbursement. And this may be the major barrier in NOTES development and market uptake.
There is one group of patients, however, where NOTES has a distinct clinical advantage: the bariatric patient. Laparoscopic instruments have had to be elongated specifically for the bariatric patients.
Even in this case, however, the distance from the surgeon to the actual operative field offers the primary difficulty. In addition, wounds in the abdomens of those who are obese often do not heal well.
But transvaginal sleeve gastrectomies and pouch reductions in bariatric patients have been performed successfully, providing promise for future advancements in bariatric procedures. Coupled with this excitement is the fact that most bariatric patients actually have a vagina.
Expect turf battles?
The age-old question of who will be performing these procedures is one being asked among many subspecialties these days. One must conclude that with recent technology advances, there has been an associated blurring of the lines between specialists. Radiologists work hand-in-hand with surgeons for minimally invasive breast cancer treatments, interventional radiologists likewise work with cardiologists, and cardiologists often perform hybrid procedures with cardiovascular surgeons. What once was considered grounds for turf battles now have cooperation among subspecialists, driven by technological advancements.
The same is true for NOTES. NOTES represents the intersection of laparoscopy and endoscopy: the trademark of two different specialists, the surgeon and the endoscopist. Brian Dunkin, MD, of The Methodist Institute for Technology, Innovation and Education (Houston, Texas), in his presentation, "Training and Credentialing for NOTES," compared a surgeon's training to a gastroenterologist's training and found skills from each group play vital roles in NOTES (See Table 7). Dunkin concluded "Surgeries have been replaced by procedures. We need to work together."
To which Anthony Kallo, MD, associate professor of nedicine, Division of Gastroenterology at Johns Hopkins Hospital (Baltimore) — often referred to as the father of NOTES — added: "While endoscopy has evolved into being more therapeutic and beyond the gastrointestinal lumen, the endoscope has not traditionally been used to dissect and resect lesions. NOTES is clearly a hybrid of specialties with only slightly more surgeons doing the work today."
The most provocative concept in the NOTES session was presented by G.V. Rao, MD, of the University of Maryland Medical Center (Baltimore), discussing "The Future of NOTES in the 3rd World."
He said, "The limitations of the first world will move NOTES procedures into the strengths of the third world." He pointed out that historically there has been a "brain drain" from the first world into the third world; that we have always seen technology move from the U.S. into third-world countries with time.
And he said that the restrictions now of regulation and reimbursement in the U.S. have created a "reverse brain drain" where the research continues to flow from the west but the human experience is being done in third-world countries.
"This is what has caused the movement towards medical tourism, which is predicted to be $2 billion by 2012 and where medical procedures cost one-10th of what they cost in the U.S.," Rao said.
Human procedures using NOTES was begun in India, and there have been reports of 116 cases in Brazil, 158 cases in South America, and many cases in France, Germany, Spain, Italy, Ukraine, but all told only about 200 total human cases in the U.S.
Don't confuse NOTES with NOTUS
Another newly coined term, NOTUS, for Natural Orifice Transabdominal Umbilicus Surgery, should not be confused with NOTES. NOTUS is a laparoscopic procedure that performed either through a single port in the umbilicus or in conjunction with a NOTES procedure. NOTUS involves the use of a trocar or trocars, with entry to the peritoneum through the umbilicus, hiding any scar in the belly button.
Novare Surgical Systems (Cupertino, California) entertained a throng of interested clinicians at its exhibit booth, showcasing its single-port surgeries that use the company's line of Real Hand instrumentation. Novare says that its RealHand HD instruments are the very first full range of motion hand-held laparoscopic instruments designed to mirror the surgeon's hand direction and offer tactile feedback.
Unlike standard laparoscopic instrumentation, RealHand offers complete 7 of freedom of movement in a hand-held instrument and with no need for additional hardware, according to Novare.
Over 15 types of surgeries and more than 150 cases have been completed in general surgery, gynecology and urology, using up to three trocars in the umbilicus through a single port and leaving no other scar behind. We have clearly moved minimally invasive surgery into its next destination: invisible surgery.