BB&T Contributing Editor
SAN DIEGO — Nearly 16,000 physicians, researchers and academics from around the world gathered here in mid-May under brilliantly sunny skies and record-breaking warm temperatures to attend the 2008 Digestive Disease Week 2008, the largest conference of its kind.
Advances in micro-technology have expanded the options available for endoscopists to treat, in addition to diagnose, certain alimentary tract diseases in an even less-invasive manner than laparoscopy, a minimally invasive technique usually performed by surgeons.
Many innovative products were showcased here, from the latest advances in colon cancer surveillance and treatment to novel endoluminal techniques for obesity and GERD, all of which access the gastrointestinal tract through an endoscope.
Standard goals for new medical technologies are to provide for better patient care and/or reduce cost, both of which are captured with Confocal Laser Endomicroscopy (CLE). This new real-time microscopic technique may eventually lead to skipping the entire step of sending biopsies to pathology and could change the way gastrointestinal diseases are detected.
CLE, a technology currently FDA-cleared and marketed by Pentax Medical (Montvale, New Jersey) and Mauna Kea Technologies (Paris), places a tiny microscope at the tip of an endoscope that magnifies the image by 1000 times, helping endoscopists to determine on-the-spot whether a lesion is suspicious, or even cancerous, or not.
While the Pentax Medical system has the microscope incorporated into the endoscope, Mauna Kea's Cellvizio system — which has completed more than 1,000 procedures to date — allows its miniaturized microscope to be threaded through all endoscopes.
At that magnification, the resolution is almost as reliable as a pathologic sample, and may eliminate the need for biopsy to diagnose gastrointestinal conditions including reflux disease, colon cancer, and inflammatory bowel disease.
"Up until now, patients waited days or weeks for a diagnosis; further, it has been difficult to detect subtle precancerous lesions, often leading to time-consuming procedures as well as uncertainty about missing something important" said Pankaj Pasricha, MD, professor of medicine, gastroenterology and hepatology at Stanford University School of Medicine (Stanford, California). "New techniques such as CLE will change the way we diagnose patients, allowing us to treat them more accurately, quickly and appropriately."
Kerry Dunbar, MD, of the department of medicine-gastroenterology at the Johns Hopkins Medical Institutions in Nantes, France, has performed 2,102 CLE examinations and found that the overall accuracy rate for CLE was 91% in the upper GI tract and 93% in the lower tract. "This has the potential to help patients more quickly," said Dunbar, adding that given the rapid progression of cancers, earlier detection and treatment is critical.
In her study, she found that 20% to 30% of the cases would have had a changed diagnosis using CLE. At this point, biopsies are still taken and sent to the lab, but in the future with more experience with CLE, it will be possible to be able to immediately diagnose and treat, eliminating the weeklong trip the specimen takes to the pathology lab.
With that as the great promise for the future, today's advantage is that the number of biopsies taken per CLE examination are significantly reduced, offering a cost savings for pathology exams and a reduction in time the patient is under sedation — another savings in cost as well as providing better patient care.
In another collaborative study reported on by Dunbar, CLE was used to diagnose patients with Barrett's esophagus, a disease in which dysplasias are difficult to see with an endoscope. "We were able to take 60% fewer biopsies and still detect the same amount of cancers," she said. "We were able to better target our lesions and could take five biopsies instead of 20, realizing a tremendous cost and time saving without sacrificing accuracy."
Another CLE researcher who presented at DDW, Michael Wallace, MD, of the Mayo Clinic (Jacksonville, Florida), found that, "The probe-based confocal microendoscopy system allows immediate diagnosis of colorectal lesions with malignant potential and can distinguish them from non-neoplastic polyps with a high level of accuracy." He also noted that this method has the potential of obviating polypectomy of non-neoplastic polyps.
With these positive early reports and only two players, it is safe to assume that there will be new entries in this market in the near future.
Yet another interesting diagnostic technology is that of capsule endoscopy, introduced by Given Imaging (Yokneam, Israel) in 2001 and now boasting more than 730,000 PillCam video capsules having been sold.
The PillCam video capsule is a disposable, miniature video camera contained in a capsule that can be easily ingested by the patient and whose images are then captured and stored in a belt worn around the patient's waist for eight hours.
The capsule transmits high-quality color images of the gastrointestinal (GI) tract, enabling physicians to visualize distinct portions of the tract.
Given's first product, cleared by the FDA in 2001, captured images of the small intestine, followed by the clearance of the esophageal PillCam in 2004, and the PillCam Colon that already has its CE-mark will be FDA-cleared for use in the U.S. next.
Swallowing a pill is much easier for many patients who cannot or will not have an endoscope placed in their GI tract, or who cannot undergo the sedation required for endoscopic procedures.
In addition to ease of use for the patient, the PillCam also is the only non-invasive device able to visualize the entire small bowel mucosa, previously visible only by surgery.
The results of an eight-center European study presented here by Jacques Deviere, MD, of Erasme Hospital (Brussels, Belgium), demonstrated encouraging results for detecting colo-rectal polyps compared to colonoscopy.
"The promise of PillCam Colon is increasing the number of colo-rectal screenings, which remain disappointingly low in Europe," he said. "This patient-friendly alternative could become a key tool in the effort to reduce the more than 212,000 colo-rectal cancer deaths annually in Europe."
Deviere added, "Patients who can't or are unwilling to undergo a colonoscopy have a new way to be screened in a very easy, painless way. If polyps or cancerous lesions are found, then the physician can perform a subsequent procedure to remove the lesions."
He said the initial data on PillCam Colon is "extremely promising, and we look forward to additional clinical information to determine how best to use this valuable diagnostic tool."
Taking NOTES on a surgical option
No gastrointestinal meeting would be complete without a session on NOTES, or Natural Orifice Trans-lumenal Endoscopic Surgery, a marriage between flexible endoscopy and laparoscopic surgery that was designed to be scarless, and now is found to also be almost painless, and with shorter recovery times than laparoscopic surgery.
DDW featured Anthony Kalloo, MD, professor of medicine and gastroenterology at Johns Hopkins University School of Medicine (Baltimore) and a pioneer of NOTES in the U.S. Discussing "Breakthroughs in Endoscopic Techniques and NOTES," Kalloo had the attitude of "If you can imagine it, it can happen."
Expounding on the very latest experiments that have been done using the NOTES procedure, he pointed out that the initial goals of NOTES were to be able to practice fundamental surgical principles, such as those listed in Table 5, while operating through a flexible endoscope.
Kalloo described early glimpses into research that have the opportunity to change the way medicine is practiced today.
1) The opportunity to perform surgery outside of the operating room. Early studies have shown that a sterile environment such as the OR may not be required for NOTES procedures nor anesthesia in many procedures, alleviating the need for the costly OR.
2) Acute trauma may be able to start treatment onsite. Paramedics may be able to begin treatment of an acute trauma at the site of the injury using NOTES techniques, such as applying cellulose to stop intra-peritoneal hemorrhage.
3) Previously non-accessible areas of the spine could be treated. There has never been access to the anterior spinal column, but with NOTES, this could present a big opportunity for spinal repairs such as disc replacements, and other interventions that have been considered inaccessible.
4) Mobile robots may be able to treat from a distance. Mobile robots may be able to be passed down the scope, make incisions, and have a surgeon perform the actual surgery from a remote place. These are all possibilities for this new technology and are being investigated worldwide.
5) Intrauterine fetal procedures. Another new frontier that is being tested is the use of NOTES in pregnancy. Kalloo cited research presented here by Samuel Giday, MD, of the department of medicine and gastroenterology at Johns Hopkins, titled "Successful Diagnostic and Therapeutic Intrauterine Fetal Interventions by NOTES."
"An intrauterine fetal intervention is an area where morbidity and mortality using standard laparoscopic techniques is substantial," said Kalloo. Current transabdominal laparoscopic fetoscopy is less invasive, but limited by rigid instruments that only allow anterior access to fetal parts.
Giday introduced transgastric and/or transvaginal flexible endoscopes fitted with high-resolution ultrasound into the peritoneal cavity and allowed for full viewing of the fetus with visualization that was equivalent or superior to transabdominal ultrasound. He also was able to perform transuterine intracardiac injections with no immediate complications or evidence of induction of preterm labor following the procedures. "Although far away from clinical applications, NOTES has potential for intrauterine diagnostic and therapeutic fetal procedures," Kalloo said.
After mentioning that several new products were developed quickly by industry in order to enable the physician to practice these fundamentals, he stated that even further futuristic research is continuing in NOTES, as listed in Table 6.
New roles for endoscopists
Endoscopic procedures were first introduced as a diagnostic tool that allowed the physician visualization of the alimentary tract and resulted in well over 2 million scope procedures being performed in the U.S. annually. The next step to be able to treat through the endoscope required advanced enabling technology, an example of which are polypectomies, which occur in 20% of all colonoscopies, where the polyps are removed with the same scope and at the same time as the screening procedure.
Advanced technologies allow for new clinical applications to rapidly spring up. Such is the case with flexible therapeutic endoscopy which now also includes NOTES procedures, as well as new methods to treat Barrett's disease, GERD and obesity, to name a few. Endoscopists, initially thought of as diagnosticians, are assuming more treatments, using the latest advances in their primary tool: the endoscope. Now there are a myriad of procedures from treatment for GERD and Barrett's esophagus to novel bariatric procedures that can be performed through a flexible endoscope, with the numbers of new advances and applications for these new technologies growing almost daily.
"Bariatric surgery is one of the most common surgical procedures in the U.S., with more than 240,000 surgeries performed annually and the prediction of laparoscopic gastric bypass becoming the most commonly performed surgical procedure in the US during this decade," said Adam Slivka, MD, associate chief of gastroenterology, hepatology and nutrition at the University of Pittsburgh Medical Center.
"A new role for endoscopists is that of managing the complications of bariatric surgery where the endoscopist is playing an increasing role in post-op care," said Lawrence Friedman, MD, professor of medicine at Harvard University and Tufts University School of Medicine (both Boston). Bariatric surgery patients are, by definition, a high-risk population and as they age will continue to present with late stage surgery-specific issues, most of which can be handled endoscopically.
In addition to endoscopic repairs for bariatric procedures post-op, several new technologies are addressing other novel approaches to performing once-surgical procedures through an endoscope.
Charles Filipi, MD, of Creighton University School of Medicine (Omaha, Nebraska), presented a new transoral gastroplasty device for GERD and obesity, which is expected to be available for human trials later this year.
The noninvasive gastroplasty device can treat two separate disorders: GERD and morbid obesity, both of which "are particularly serious health issues in the western hemisphere and major contributors to the escalating cost of health care in the U.S.," Filipi said.
He added, "We believe that this device will result in much more effective treatments for both conditions, fewer complications and less patient expense, while permitting each procedure to be performed on an outpatient basis."
Conventional treatments for GERD and obesity are performed surgically, requiring hospitalization and the potential for complications. GERD is the third-most-prevalent disease in the U.S., with more than 19 million people suffering from it weekly and 61 million Americans reporting heartburn monthly.
The device, a flexible tube with a metal capsule at the tip, is introduced through the mouth and esophagus, suctions two sides of the specified juncture in position for suturing, removes the mucosal lining, then stitches the two sides back together. The theory being that by suturing mucosa-to-mucosa, a stronger bond is formed and the resulting durability allows it to last longer, distinguishing this procedure from other noninvasive methods that have been developed.
Safestitch Medical (Miami) has developed the device with licensed intellectual property from Creighton University.
Also competing in this space is Endogastric Solutions (Redmond, Washington), which recently reported that 85% of patients remain symptom-free and off daily GERD medication at one year after transoral incisionless fundoplication surgery using the company's EsophyX device.
The EsophyX device also enables surgeons and advanced interventional gastroenterologists to offer their patients substantive anatomical repair without incisions for gastroesophageal reflux disease (GERD).
Earlier entries in the area of endoluminal procedures for GERD were C.R. Bard's (Murray Hill, New Jersey) Endostitch and NDO Surgical's (Mansfield, Massachusetts) Plicator.