BB&T Contributing Writer

CHICAGO — If you do the math, there will not be enough gastroenterologists to perform the required amount of colonoscopies to meet the national goal of screening 60% of everyone over 50 years of age for colorectal cancer (CRC).

Several possible solutions to assist with this problem were presented here at the Digestive Disease Week (DDW) annual meeting in early June, along with a myriad of topics, all relevant to the alimentary tract.

DDW is a gathering of the four organizations that are exclusively focused on digestive diseases: the American Association for the Study of Liver Diseases (Alexandria, Virginia), the American Gastroenterological Association, (Bethesda, Maryland), the American Society for Gastrointestinal Endoscopy (Oak Brook, Illinois) and the Society for Surgery of the Alimentary Tract (Beverly, Massachusetts).

Some 12 million colonoscopies are performed annually in the U.S., 70% of which are for screening. To meet the goal of screening 60% of Americans over 50, about 21 million screening colonoscopies would need to be performed — more than the current resources available.

A recurring theme presented at this year's DDW gathering was that of using optical diagnosis during the colonoscopy to increase throughput by eliminating unnecessary polyp removals and reducing the number of repeat colonoscopies.

"Optical diagnosis" includes a variety of modalities — high-definition white light as offered by Olympus (Center Valley, Pennsylvania), narrow band imaging, chromoendoscopy, or the newest entity: confocal microscopy — all of which enhance the standard view seen through an endoscope

The question becomes: can the image be equivalent to, or used in lieu of, a histologic examination of the polyp?

Optical diagnosis of small polyps at colonoscopy could provide several advantages for both patients and practitioners. If the number of polypectomies performed were reduced, there could be an increased efficiency for the procedure, both in time and cost. Patients would have less risk of bleeding or perforations, two complications that are rare but can occur. In an ideal world, the optical diagnosis may even be more accurate than histopathology.

Ana Ignatovic, of St. Mark's Hospital (London), presented "Optical Biopsy at Colonoscopy: Are We Ready? DISCARD Study: Early Results," where her team studied a method that may be more effective at examining and identifying polyps that are precancerous, thereby eliminating the time and expense of sending biopsies to pathology.

In a study presented at last year's DDW meeting, researchers demonstrated that the majority of polyps 9 mm or less were typically benign; yet under the current endoscopy protocol the majority of polyps removed during the procedure are less than 10 mm and are sent for pathology examination, which takes about a week for results.

In the study at St. Mark's, four endoscopists with varying degrees of experience used one or a combination of optical modalities to attempt to predict the histopathology of each polyp seen during the colonoscopy. Each polyp was then removed and sent for formal histopathology examination.

The researchers found that of the 85 benign adenomas removed, 92% were correctly diagnosed; and of the 38 hyperplastic polyps, 97% were accurately identified from optical diagnosis. In total, among all four endoscopists, of the 355 polyps removed, 270 were correctly identified by optical diagnosis.

Ignatovic, an endoscopy research fellow, concluded, "Optical diagnosis allows us to predict accurately whether a polyp should be removed immediately during the colonoscopy. This not only spares the patient the risk involved in the unnecessary removal of non-precancerous polyps, but also eliminates the wait time and expense involved in the current protocol of sending biopsies to pathology.

Optical diagnosis in vivo is feasible, comparable, quicker and cheaper than conventional biopsy protocol."

Taking optical diagnosis one step further than simply enhancing the endoscopic image, Cellvizio (Fort Washington, Pennsylvania) actually adds a probe-based tiny microscope to any endoscope, providing confocal laser endomicroscopy to any portion of the digestive tract. The world's most miniaturized microscope brings the power of a microscope in real time directly inside the body to evaluate any suspicious tissue.

While other optical enhancements such as HD white light and chromoendoscopy can detect, or red flag, suspicious areas, confocal microendoscopy can actually characterize the tissue. The goal is that with ongoing studies, to be able to eventually confirm the status of a polyp without a biopsy.

The Cellvizio system was developed by venture-backed Mauna Kea Technologies (Paris) and has received a 510(k) clearance from the FDA. It can also be used in the lung.

Until recently, a potentially diseased esophagus has been one of the more difficult areas to examine and/or treat endoscopically, mainly because the suspected diseases found there, such as Barrett's esophagus and esophageal varices (varicose veins), are vulnerable to bleeding.

While the prevalence of Barrett's esophagus is only 2% to 5% among the general adult population, it is between 5% and 10% for those with gastroesophageal reflux disease (GERD), the third-most-prevalent disease in the US.

Esophageal varices is found in about 50% of the 10 million Americans with cirrhosis, but standard endoscopy in these patients can become a prescription for disaster, with a great potential for bleeding. Both confocal microendoscopy and wireless camera endoscopy are less-invasive alternatives to standard endoscopy with biopsy.

The Pillcam ESO 2 by Given Imaging (Yokneam, Israel) is a small ingestible capsule the size of a large vitamin and is equipped with a miniature video camera and its own light source to visualize the esophagus. Data is transmitted to a recorder and the physician later reviews the compiled video data to make a diagnosis.

In a poster presentation by Neil Sharma, MD, of the division of digestive disease and nutrition at the University of South Florida (Tampa), he compared capsule endoscopy using Pillcam to standard upper endoscopy and concluded: "Detecting and monitoring varices is critical in this patient population. Requiring no sedation, esophageal capsule endoscopy provides a less-invasive but equally effective option for the screening of esophageal varices."

Although Given was the first to market with capsule endoscopy, other companies involved with the development of capsule endoscopes include Pentax (Montvale, New Jersey), Fujinon (Wayne, New Jersey), Olympus, Royal Philips Electronics (Best, the Netherlands), and Siemens (Malvern, Pennsylvania), and Innurvation (Columbia. Maryland).

The number of companies entering this space confirms the advantages and benefits of capsule endoscopy.

Researchers at Northwestern University (Evanston, Illinois) have pioneered a new method to screen for colon cancer through a minimally intrusive optical diagnostic test.

Herman Roy, MD, presented "Spectroscopic and Optical Signatures for Colorectal Cancer Screening," where he described the technology as a novel non-invasive optical light that shines inside the colon and analyzes how the reflected light interacts with the lining of the colon.

American BioOptics (also Evanston), a privately held company, has been formed around this technology to commercialize the company's, which can be highly accurate, office-based, require no bowel prep, and be inexpensive.

Roy said, "There are 90 million Americans over the age of 50 who should be screened for CRC, but most won't do it. We want to address those patients."

Simple solutions for patient compliance issues

Some 40 million Americans have arthritis, and 100 million have low back pain. Another 100 NSAID (non-steroidal anti-inflammatory drug) prescriptions are written each year for pain; 30% of which are for ibuprofen. Some 30% of patients taking NSAIDs will develop an ulcer; 100,000 of them will be hospitalized, and 20,000 of them will die.

So how is the pain managed without ulcers sneaking into the digestive tract? One way would be to have the patient take a gastro-protective agent along with the NSAID. The problem is that only 30% of the prescriptions written for NSAIDS are accompanied with a prescription for a gastro-protective drug.

The bigger problem is that patients don't comply even if given the prescription for the gastro-protective agent. Patients readily take their NSAID because should they forget to do so, the pain will remind them. But ulcers develop painlessly and without symptoms until the ulcer has progressed to the point of bleeding.

So it is only human nature to forget to take the drug that will prevent ulcers when there are no reminders until it is too late. If deaths from the gastrointestinal effects of NSAIDS were tabulated separately in the National Vital Statistics reports, these effects would equate to the 15th most common cause of death in the U.S.

The first thing you notice (well, can't miss) when entering the enormous lakeside McCormick Place convention hall complex for the DDW conference are end-to-end, tall banners draped alongside both halls promoting "Connect To Protect," an education program to educate physicians on risks associated with NSAID use.

Co-sponsored by the the American Gastroenterological Association (AGA; Bethesda, Maryland) and Horizon Therapeutics (Northbrook, Illinois), "Connect to Protect" was designed to increase awareness about the gastrointestinal (GI) risks associated with the use of NSAIDs such as ibuprofen, and to highlight the connection between NSAID use and GI risks.

The goal was to encourage patients and physicians to connect more often about ways to avoid NSAID-induced ulcers, including but not limited to GI protective co-therapy.

Horizon Therapeutics is a late-stage, privately held biopharmaceutical company that has developed an innovative proprietary combination drug of the most prescribed NSAID, ibuprofen, and the most potent H2 antagonist, famotidine, commonly referred to as Pepcid. By combining the two drugs, patients cannot take their ibuprofen without its accompanying gastro-protective agent; insuring patient compliance.

Two poster presentations on this drug and one oral presentation were made here, each demonstrating pain reduction with gastric acid suppression. Loren Laine, MD, of the University of Southern California (Los Angeles) Keck School of Medicine, presented "Does High-Dose Famotidine Reduce Gastric and Duodenal Ulcers in NSAID Users?"

The oral presentation included data from more than 1,300 patients who participated in the REDUCE 1 or REDUCE 2 study, whose primary objective was to compare patients treated with ibuprofen alone to patients treated with the combination drug to see if there was a difference in the development of ulcers over the course of the 24 week study.

Both groups had endoscopies at weeks 1, 8, 16 and 24. The single tablet combination ibuprofen-famotidine cohort developed significantly fewer endoscopically diagnosed gastric and/or duodenal ulcers than the group treated with ibuprofen alone.

"NSAIDS, such as ibuprofen, are among the most widely used drugs in the world," said Laine. "[They] are effective at treating pain, but they also increase the risk of developing ulcers in the stomach or intestines and the risk of developing ulcer complications, such as bleeding. Patients at increased risk of gastrointestinal ulcers may benefit from protective co-therapy, although many such patients do not receive or adhere to this co-therapy."

Now that the trials have been completed, Horizon will be submitting its data to the FDA and European Medicines Agency, with hopes of being on the market in late 2010 to early 2011. Who would have thought by combining a pain med with a gastro-protective agent there are hopes of eliminating 20,000 deaths a year?

Another life-threatening problem that depends on patient compliance is that of pediatric patients who have had a liver transplant and must take their meds religiously in order to avoid a rejection. Tamir Miloh, MD, assistant professor in pediatric hepatology and surgery, Mount Sinai Hospital (New York), took a look at the effectiveness of sending text messages to his patients in order to improve adherence and reduce organ rejection events.

Missing medication is especially dangerous since their bodies can reject the transplanted liver after only two missed doses of medication; and delayed timing of taking their meds causes wide fluctuations in the level of the medication in their bloodstream. Because young people are generally technologically savvy, Miloh sought to determine if sending text messages would result in improved compliance.

Forty-one young people with an average age of 15 were sent text messages at predetermined times reminding them to take their med and were given 30 minutes to respond back that they had in fact taken the medication. If not, their caregiver was sent a text message.

To determine the effectiveness, he compared the number of rejections the year prior to the study with the number during the year of the study. In the prior year, there were 12 out of 41 patients who experienced a rejection event that required hospitalization due to improper medication dosage.

One year into this study, only two of the 41 patients have experienced a rejection event. "The implications for this study are vast because this practice could be used for any other chronic disease," said Miloh, who is currently conducting another randomized study with more patients.

Patient compliance not only saves lives, but also provides significant cost savings by avoiding unnecessary hospitalizations and expensive treatments to correct an avoidable problem. Cell phones are a lot less expensive than a liver transplant.

Trial: Positive Barrett's esophagus treatment

Clinical trial results presented at the DDW meeting revealed that endoscopic radio frequency ablation performed in a community practice setting is safe and effective for eradicating a pre-cancerous esophageal condition known as Barrett's esophagus.

The study, titled "Radiofrequency Ablation of Barrett Esophagus: Outcomes of 429 Patients from a Multi-center Community Practice Registry," was presented by Ronald Pruitt, MD, of Nashville Clinical Research (Nashville, Tennessee), at a scientific session sponsored by the American Society for Gastrointestinal Endoscopy (Oak Brook, Illinois).

Pruitt reported on 429 patients with Barrett's esophagus, with and without advanced dysplasia (cellular signs of advanced progression towards cancer), who were treated with radiofrequency ablation using the HALO ablation system from Barrx Medical (Sunnyvale, California) over the last four years.

He added that the adverse event rate was favorable, with a low stricture risk (about 1%) and no serious adverse events. After an average of two ablation procedures and 20-month follow-up, 77% of patients were cured of their Barrett's disease. For those patients that had baseline evidence of dysplasia, 100% had complete eradication of all signs of dysplasia.

"We believe that the results of our trial are unique and relevant to the scientific knowledge-base, as this is the largest patient experience reported to date and the first multi-center trial conducted at community practice centers for using radio frequency ablation to eradicate Barrett's esophagus," said Pruitt. "Most importantly, we found that the safety and efficacy outcomes garnered in this clinical setting comport with those from reported trials conducted as predominantly academic tertiary referral centers."

Study centers were comprised of large community practices with expertise in therapeutic endoscopy and the management of Barrett's esophagus. Radio frequency ablation was applied with a balloon-based circumferential device and an endoscope mounted focal device.

Patients underwent biopsy sampling of tissue from the esophagus at regular intervals to determine if all Barrett's disease had been eradicated. To be considered a "complete responder," all biopsy samples had to be normal.

"This study is highly relevant and represents an important contribution to the science related to Barrett's esophagus therapy," said David Utley, MD, chief medical officer at Barrx Medical. "The study's strengths lie in its large number of studied patients, relatively long follow-up and objective histology endpoints."

He added, "This evidence suggests that ablative therapy can be delivered by the expert endoscopist in the community setting, with an expectation for comparable results as seen in prospective trials from tertiary referral centers."

Results from several other studies were presented during DDW, revealing new outcomes data related to use of the HALO ablation system for eradicating Barrett's esophagus.

Among them, reports included durability outcomes from a randomized sham-controlled trial, safety and efficacy outcomes from a U.S. registry of 429 patients, a randomized trial comparing ablation to endoscopic resection, and the largest European series to date in patients with high-grade dysplasia and early cancer.

As the DDW meeting commenced, the New England Journal of Medicine published a paper titled, "Radiofrequency Ablation for Barrett's Esophagus Containing Dysplasia." This is a U.S. randomized sham-controlled trial demonstrating high rates of complete eradication of Barrett's and dysplasia in the ablation group as compared to control, as well as a significant reduction in cancer progression.

At DDW, researchers presented new data from this now published trial, showing that the ablation effect achieved at one-year follow-up was highly durable at the two-year follow-up.

In the largest patient series to date, "Radiofrequency Ablation of Barrett's Esophagus: Outcomes of 429 Patients from a Multi-center Community Practice Registry," U.S. investigators reported a low stricture risk (about 1%) and no serious adverse events. After an average of two ablation procedures using the HALO ablation system and 20-month follow-up, 77% of patients were cured of their Barrett's disease.

A European multi-center randomized trial included 47 patients with Barrett's containing dysplasia and early cancer that were randomized to receive either endoscopic resection or radiofrequency ablation with the HALO ablation system. While both interventions had very high complete eradication rates (95% to 100%), endoscopic resection was associated with a significantly higher risk of complications.

In the largest European series reported to date, "Radiofrequency Ablation for Eradication of Barrett's Esophagus Containing High-Grade Dysplasia or Early Cancer: A Prospective Series of 73 Patients," researchers combined a baseline focal endoscopic resection for disease staging, and then applied serial RFA with the HALO ablation system.

A complete response was achieved in 95% of patients without occurrence of serious adverse events.

Both HALO systems are cleared by the FDA for use in the U.S. and both have the CE mark for use in Europe. More than 30,000 procedures have been performed in some 280 hospitals around the world.

In other DDW news:

Ethicon Endo-Surgery (Cincinnati) said that multiple studies demonstrate that the company's investigational Toolbox enables natural orifice translumenal endoscopic surgery (NOTES) procedures without laparoscopic support in porcine models.

One of the studies concluded that a new adaptable, minimally invasive surgical platform for NOTES and single-site laparoscopy (SSL) was successfully used to complete a variety of key surgical activities critical to pure natural orifice surgery and SSL.

The seven studies, which involved porcine models and a variety of NOTES procedures, follows 15 studies involving Ethicon Endo-Surgery devices presented at the Society of American Gastrointestinal and Endoscopic Surgeons annual meeting in April.

Ethicon said that in the coming months, the Toolbox for natural orifice surgery will be evaluated in a human clinical trial under an investigational device exemption from the FDA.

"To date, most NOTES procedures performed in humans have been with laparoscopic support. In our study, we found several of the devices in the Ethicon Endo-Surgery Toolbox could successfully be used to address some of the critical visibility and access obstacles present with a pure NOTES approach, warranting further investigation," said Klaus Thaler, MD, of the department of surgery, University of Missouri Health System.

Investigators of the study titled, "The Development and Testing of an Adaptable Minimally-Invasive Surgical Platform — The Hydra," found that this surgical platform addressed several challenges with NOTES, including visibility, platform stability and adaptability to be used in multiple interventions and procedures.

The surgical platform was used both transgastrically and transvaginally completing multiple key surgical activities that included dissection, ligation, and specimen retrieval. The study, presented as a poster at DDW, involved porcine models and was conducted by investigators from Sahlgrenska University Hospital (Gothenburg, Sweden) and Imperial College (London).

"With the introduction of this adaptable minimally-invasive surgical platform, we believe we will be able to further address many of the issues experienced when NOTES or SSL procedures are performed with conventional surgical equipment designed for standard endoscopic or laparoscopic use," said Kenneth Sumner, PhD, vice president, clinical and regulatory affairs at Ethicon Endo-Surgery.

"We plan to continue our research to investigate the existing contents of the Ethicon Endo-Surgery Toolbox for natural orifice surgery, as well as develop additional products for inclusion in it that may help fulfill the promise of this approach to minimally invasive surgery," he said.

Another poster presentation titled "Hybrid Transgastric NOTES Cholecystectomy in a Porcine Model Using a Magnetically Anchored Cautery and Novel Instrumentation," conducted by the University of Texas Southwestern Medical Center demonstrated preliminary feasibility for a particularly difficult NOTES procedure, transgastric cholecystectomy.

Several devices specifically designed for natural orifice surgery were utilized in the study, including a live video manipulation (LVM) system and magnetically anchoring and guidance system (MAGS). Study investigators specifically cited the retraction abilities of the grasper and improved visibility of the provided by LVM, the latter which greatly reduced the workload on the surgical team.

The content of the Ethicon Endo-Surgery Toolbox includes Tissue Apposition System, Steerable Flex Trocar with Rotary Access Needle, Flexible Bipolar Hemostasis Forceps, Flexible Maryland Dissector, Articulating Hook Knife, Articulating Snare, Articulating Needle Knife, Articulating Graspers and Articulating Biopsy Forceps.

Those devices listed will be used within the IDE trial. The Adaptable Minimally-Invasive Surgical Platform and MAGS are limited to non-clinical applications at this time.

Ethicon Endo-Surgery is a Johnson & Johnson (New Brunswick, New Jersey) company.

GI Dynamics (Lexington, Massachusetts), a developer of non-surgical, endoscopic approaches for the treatment of Type 2 diabetes and obesity, said that its EndoBarrier Gastrointestinal Liner was highlighted by leading experts in metabolic disorders and endoscopy at DDW.

"This is proving to be a very successful year for GI Dynamics and our development efforts in support of the EndoBarrier," said CEO Stuart Randle. "Based on the data we have seen to date, we believe EndoBarrier, as part of a multidisciplinary approach, has the potential to dramatically change the treatment paradigm for Type 2 diabetes and weight problems due to its unique profile as a non-surgical and non-pharmaceutical treatment option.

"Notably," he said, "EndoBarrier may provide the benefits of gastric bypass surgery without the complications and risks associated with a highly invasive procedure, and unlike traditional pharmaceutical approaches, our implantable device removes the burden of dose regimen compliance from the patient."

The EndoBarrier Gastrointestinal Liner is placed in the GI tract endoscopically (via the mouth) to create a barrier between food and the wall of the intestine. The company said physicians believe that preventing food from coming into contact with the intestinal wall may alter the activation of hormonal signals that originate in the intestine, thus mimicking the effects of a Roux-en-Y gastric bypass procedure without surgery.

It said a "growing body of pre-clinical and clinical evidence supports the potential for EndoBarrier Gastrointestinal Liner to dramatically change the treatment landscape for people living with Type 2 diabetes, obese people at risk for Type 2 diabetes, and people with severe weight problems."

The company also is developing the EndoBarrier Flow Restrictor, which is designed to further enhance the effectiveness of the liner by doubling the amount of weight-loss that can be achieved using the liner alone.