SAN DIEGO, CA (May 19, 2008) – New developments in polyp detection, colonoscopy preparation and sedation techniques that will increase the effectiveness of colonoscopy and ease patient concerns about the procedure will be presented today at Digestive Disease Week® 2008 (DDW®). Research advances in sedation include computer-assisted sedation systems and the new evidence supporting the administration of propofol by gastroenterologists. DDW is the largest international gathering of physicians and researchers in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.
“A significant percent of the population is not undergoing colorectal cancer screening, despite the fact that it has been proven to save lives,” according to Sidney J. Winawer, MD, FASGE, AGAF, Paul Sherlock Chair, gastroenterology and nutrition service, Memorial Sloan-Kettering Cancer Center. “We hope that new research, such as that presented today, will encourage patients to get screened and to work with their doctors to discuss which screening methods may be best for them.”
Colorectal cancer is the second leading cause of cancer deaths in the U.S. – more than 24,000 men and nearly 26,000 women die of the disease each year. However, colorectal cancer is curable when detected early. Screening rates for colorectal cancer in the U.S. lag far behind those for other cancers despite research showing that high mortality rates are lowered by detecting colorectal cancer at an early stage.
“The most common neoplastic outcome of colorectal cancer screening is the identification of polyps which require follow-up. Colorectal cancer is curable and preventable when polyps are found and removed early,” said Dr. Winawer. “If physicians followed recommended screening guidelines, there would be more appropriate surveillance which would help shift resources to screening.”
A Computer-Assisted Personalized Sedation System to Administer Propofol Versus Standard of Care Sedation for Colonoscopy and EGD: A 1000 Subject Randomized, Controlled, Multi-Center Pivotal Trial (Late Breaking Abstract)
During endoscopic procedures, patients are placed under moderate sedation, which allows them to undergo these procedures comfortably. Traditional sedation agents, such as midazolam, meperidine and fentanyl, are often administered by the endoscopy team during the procedure. Propofol is an alternative medication which takes effect quickly and allows for a quicker recovery period, but may place the patient under a deeper sedation. Currently, propofol is administered by anesthesiologists or nurse anaesthetists.
The SEDASYS™ System is a computer-assisted personalized sedation (CAPS) monitor that allows an endoscopist and nurse team to administer on-label, propofol sedation during colonoscopy and endoscopy procedures. The system delivers propofol to the patient following the endoscopist’s instructions and closely monitors the patient to help assure that the level of sedation is appropriate — even more closely than a human. This 1,000 subject controlled, randomized, multi-center trial sought to test the safety and efficacy of this sedation method, as well as the benefits to both physicians and patients.
“A computer-assisted system of this type allows for sedation to be completely personalized to the patient, giving the physician greater, more precise control with improved safety,” said Robert Hardi, MD, clinical faculty at George Washington University Hospital in Washington, DC. “The machine, which may have beneficial cost implications, also allows for a shorter recovery time.”
The study found that physician and nurse teams were able to safely and effectively administer propofol sedation using the SEDASYS System during both colonoscopy and endoscopy procedures. In fact, patients who experienced SEDASYS sedation had significantly lower measure of cumulative oxygen desaturation (17.8 percent per second) compared to those who underwent traditional sedation (98.8 percent per second). Additionally, both patients and physicians were surveyed using a list of measures to determine the quality of their experience with their sedation and the procedure overall. Both the subjects treated with the SEDASYS System and particularly the physicians administering the procedure reported higher satisfaction with the sedation achieved with the SEDASYS System.
American College of Radiology (ACR) Recommendations for CT Colonography (CTC) Interpretation: Implications for Resection of High Risk Adenoma Findings (Abstract # 878)
The American College of Radiology (ACR) has released guidelines recommending that polyps < 5 mm in size not be reported on computed tomographic colonography (CTC) studies. As a result, investigators set out to determine the effect of the ACR guidelines by applying them to an endoscopic database that collected information about polyps that have been removed and processed.
The database results included information for 10,780 polyps that were removed from 5,079 patients (among 10,034 colonoscopies) over a five-year interval. These patients were then broken into two groups, those with low risk – whose findings included no more than one to two tubular adenomas (benign tumors) and who were recommended to go five to 10 years before receiving a follow-up colonoscopy – and those with high risk – whose findings include advanced adenoma or three or more adenomas of any size.
“Our findings suggest that because of the ACR’s de-emphasis of small polyps, CTC may not identify enough patients with important polyp findings,” said Douglas Rex, MD, Chancellors professor of medicine, Indiana University School of Medicine and director of endoscopy at Indiana University Hospital. “The full implications and impact of these findings on cancer prevention is not yet known, because the natural history of small adenomas is still not understood.”
Researchers sought to determine how many patients would have been identified as high risk according to the post-polypectomy surveillance guidelines if they had undergone CTC as their initial diagnostic test instead of colonoscopy. In all, 5,079 patients (51 percent) had at least one polyp and 2,907 (29 percent) had at least one adenoma. More than 1,000 (10 percent) had high risk findings, including 421 patients (4.1 percent) with one adenoma that was >1 cm in size. Two hundred and ninety-three patients had > three adenomas <5 mm in size or an advanced adenoma <5 mm and no polyp of any histology >5 mm in size. One hundred and eighty-four patients (18 percent of those with high risk findings) had either three or more adenomas <9 mm in size or an advanced adenoma <9 mm in size, or both (and no polyp >1 cm in size).
Overall, the study determined that if CTC rather than colonoscopy had been used in this population, and assuming 100 percent sensitivity of CTC for polyps >5 mm, then according post-polypectomy surveillance guidelines 29 percent of all patients and 30 percent of patients over age 50 with high risk adenomas would have been categorized as normal. An additional 18 percent would have had polypectomy delayed for at least three years.
Non-Anesthesiologist Administered Propofol Sedation for Endoscopic Procedures: A Worldwide Safety Review (Abstract #883)
For endoscopy, the administration of propofol sedation by an anesthesiologist is expensive. The alternative, propofol administration provided by a non-anesthesiologist (NAP), however, is considered controversial due to safety concerns. As a result, researchers sought to investigate actual data on NAP to determine if the safety concerns are in fact warranted.
“Our findings show that non-anesthesiologist administered propofol sedation is safe,” said Douglas Rex, MD, Chancellors professor of medicine, Indiana University School of Medicine, director of endoscopy at Indiana University Hospital. “The data shows that NAP has a track record superior to gastroenterologist administered opioids and benzodiazepines and equal to or better than anesthesiologists administering general anesthesia.”
A total of 456,918 NAP procedures from around the world (213,527 published and 243,391 unpublished) were collected by the researchers and assembled into a database. The database information was searched and reviewed to assess the number of adverse events and safety problems that occurred in these procedures. In all, the researchers found that three deaths, four endotracheal intubations and one neurologic injury (a seizure) occurred in all of the procedures reviewed. Each of the three deaths occurred during upper endoscopy in patients with advanced ASA classes. Additionally, the overall number of cases requiring mask ventilation was 322 out of 400,769 cases with available data.
Dr. Rex adds that “the findings of this study also have cost implications; on average the use of an anesthesiologist for endoscopic procedures costs approximately $286 per case. We found that use of an anesthesiologist to administer sedation to all these patients, if completely effective in preventing all injury, would have cost about $4.4 million per quality adjust life year saved, which would not be a cost-effective practice.”
Cost Savings of Removing Diminutive Polyps Without Histologic Assessment (Abstract #877)
When colonoscopy is performed, polyps are removed, even those that are very small. The polyps are collected and sent to a lab to determine their histology. Approximately 80 percent of all polyps are diminutive - less than 6 mm in size - and these polyps are rarely cancerous. Despite this, current practice is to send all polyps to a lab for testing, incurring costs that may be unnecessary.
Real-time endoscopic assessment of histology has become increasingly accurate and shows great promise in the ability to determine if a polyp is cancerous during the procedure. If assessment is done in real time, a cost savings will incur in the avoidance of pathology fees.
Researchers reviewed data from 10,060 colonoscopies, during which 4,474 procedures removed at least one diminutive polyp. In these 4,474 colonoscopies, there were 10,400 total polyps removed and 9,042 were diminutive. Investigators compared real-time endoscopy histology followed by polyp removal and discard to removal and lab submission.
“These findings present an opportunity for colonoscopy to become even more cost effective,” said Douglas Rex, MD, Chancellors professor of medicine, Indiana University School of Medicine, director of endoscopy at Indiana University Hospital. “With continued improvement in our ability to assess pathology in real-time, the rationale for submitting diminutive polyps for histologic assessment will decline.”
The study found that the cost to perform histologic tests on small polyps is very large compared to the potential benefit of the procedure. The study model predicted that 40 percent of 1.6 million annual colonoscopies remove at least one polyp under 6 mm. The potential savings of not submitting diminutive polyps to pathology exceeds $95 million.
The Continued Follow up Study of the Polyp Prevention Trial: A Prospective Study of Utilization and Yield of Surveillance Colonoscopy (Abstract #794 )
New research shows that doctors are performing colonoscopy on many patients who have low risk of cancer, while not conducting enough procedures on patients at higher risk of developing cancer. This study found that doctors were performing colonoscopy in low risk patients earlier than recommended by practice guidelines.
“We conducted this study because of the realization that we have limited resources, so we need to prioritize more effectively,” said Adeyinka O. Laiyemo, MD, a cancer prevention fellow at the National Cancer Institute. “We wanted to know whether there was a discrepancy between what the guidelines recommend and what doctors were doing.”
Investigators studied participants in the Polyp Prevention Trial (PPT) after the trial ended. The PPT was a four-year, randomized controlled trial in which some patients adopted a low fat, high fiber, fruit and vegetable diet to determine if the diet would prevent polyp recurrence. Of 2,079 enrolled, 1,905 (92 percent) completed the trial, undergoing a mean of 3.1 colonoscopies. When the trial ended, 1,297 subjects agreed to additional, passive follow-up by providing their subsequent colonoscopy records.
The median follow-up time was 6.2 years; a total of 774 subjects had a repeat colonoscopy. Among 431 subjects with a baseline low risk adenoma and no adenoma recurrence at the end of the PPT trial, which was the lowest-risk category, 30 percent underwent early repeat colonoscopy within four years, and had a low yield of significant polyp recurrence. In contrast, among 55 subjects who were at high risk for a polyp recurrence, only 41 percent had a repeat colonoscopy within the recommended three years and 64 percent had an exam within five years.
“People who are categorized as high-risk deserve to get in the door earlier than people at low-risk,” said Dr. Laiyemo. He continued to say that the discrepancy between risk and colonoscopy follow-up may be even more skewed in the general population. PPT subjects already had three colonoscopies as part of the trial, and as a result their utilization may be even less than that of the majority of individuals in the U.S.
Duration of the Interval Between Completion of the Bowel Preparation and Start of the Colonoscopy as a Better Predictor of Bowel Preparation Quality than Colonoscopy Start Time Alone (Abstract #237)
The shorter the wait between completing a bowel preparation regimen and the start of a colonoscopy may ultimately mean a higher quality colonoscopy according to researchers. Effective bowel preparation is key to conducting a successful colonoscopy by reducing the number of missed lesions and incomplete examinations.
Previous research suggested that the time of day the colonoscopy is conducted has a significant influence on the quality of the procedure, with morning examinations being more successful than those performed in the afternoon. “Our study found that it’s not the time of day, but the time interval that matters most in performing a quality colonoscopy,” said Kenneth Yang, MD, clinical gastroenterology fellow at the Dallas VA Medical Center and the University of Texas Southwestern Medical Center.
Flat polyps have been shown to have higher rates than elevated polyps of becoming cancerous, and require a “good or excellent” bowel prep to be detected during a colonoscopy. Typical bowel preparation regimen prior to colonoscopy involves having patients on a clear liquid diet 24 hours prior to the procedure and taking laxatives the night before. This study, involving 378 VA outpatients, began the bowel prep two days prior to the colonoscopy which included a low-residual diet, commencement of a clear liquid diet at dinner, followed by a dose of laxatives. One day prior to the procedure, patients continued the clear liquid diet and further doses of laxatives.
Medical histories, demographics, compliance with the bowel preparation and dietary restrictions, and the time since the last dose of the bowel prep agent were recorded for each patient prior to the colonoscopy. Endoscopists and endoscopy nurses independently graded the quality of the bowel preparation using a standardized “preparation quality” scale with good interobserver agreement.
The study found that in patients whose preparations were scored as excellent/good, the interval between the last dose of bowel prep agent and the start time of the colonoscopy was significantly shorter than in those whose preparations were scored fair/poor/inadequate. Further, the study found no significant difference in the bowel prep quality between morning and afternoon colonoscopies.
“These findings indirectly advocate for the less commonly used ‘split prep’ regimen prior to colonoscopy,” said Dr. Yang. “Because this type of bowel prep involves administering the last dose of bowel prep agent the morning of the procedure, the time interval between the bowel prep and the start of the colonoscopy can be shortened, leading to a higher quality procedure.”
Limitations of the study include having used a more intensive bowel preparation than is typically used for colonoscopies. Further, the study used only VA patients, which included a primarily male and slightly older population.
Water Infusion In Lieu Of Air Insufflation Enhanced Performance Of Up-Front Scheduled Unsedated Colonoscopy In United States (US) Veterans. (Abstract #W1420)
A new method of colonoscopy using water instead of air could improve patient experience without sedation. The findings could be significant because they may encourage more patients to undergo colonoscopy to detect colon cancer at its early stages when it is most treatable.
A colonoscopy is performed on a healthy person to look for silent/early colon cancers. To help them relax during the procedure, patients are often given a sedative which carries the possibility of a very small risk of complication such as irregular heartbeat, drop in blood pressure, decline in blood oxygen and, in extremely rare cases, death. “These risks are completely avoided when sedation is not used,” said Felix Leung, MD, a UCLA professor of medicine at VA Sepulveda Ambulatory Care Center in California.
Without sedation, the exam can be uncomfortable due to stretching caused by air pumped into the colon. Investigators have developed a simple, inexpensive method in which air is replaced with water to more comfortably open the colon and more easily insert the colonoscope.
When compared to the air method, water infusion significantly improved the success rate (97 percent vs. 87 percent) of completing the colonoscopy examination. The study also found that a significantly greater proportion of patients would be willing to repeat the examination without medication in the future (92 percent vs. 78 percent).
Dr. Leung reports that the water method provides doctors with a more complete look at the colon because water is suctioned out, along with any residual fecal matter that can block a clear view of the colon. This result was incidental, however, since the water was not used to clean the colon but to see it more clearly, which significantly improved the quality of the exam.
This method also gives more control to patients. “If a patient is not sedated, they can tell us if anything is bothering them, they can ask questions, and they can be involved in their care, which they seem to appreciate,” said Dr. Leung.
While the water method is often longer in duration, Leung said that as long as the procedure is performed correctly, the method will not delay or hamper the exam considerably, if at all.
Digestive Disease Week® 2008 (DDW®) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW takes place May 17-22, 2008 in San Diego, Calif. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology.