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HPV-Related Oral Cancer Incidence Spikes Sharply
CHICAGO – Human papillomavirus infection was firmly linked to the recent rise in oropharyngeal cancers in the United States, based on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program.
If current trends continue, the incidence of HPV-related oral cancers will soon surpass that of cervical cancers, senior author Dr. Maura Gillison reported at the annual meeting of the American Society of Clinical Oncology.
The incidence of HPV-positive oropharyngeal cancers increased 225% – from 0.8 per 100,000 to 2.8 per 100,000 – between 1988 and 2004, the researchers found. At the same time, the incidence rate for HPV-negative oropharyngeal cancers, which are strongly related to tobacco and alcohol use, declined by 50% – from 2.0 per 100,000 to 1.0 per 100,000.
Consequently, the overall incidence of oropharyngeal cancers increased 28%.
Even by the conservative estimate that 70% of oropharyngeal cancers in 2020 will be HPV positive, the annual number of HPV-positive oral squamous cell carcinomas (8,653 cases) is expected to surpass cervical cancers (7,726 cases). Further, the majority will occur among men (7,426 cases), said Dr. Gillison, a medical oncologist and the Jeg Coughlin Chair in Cancer Research at Ohio State University Comprehensive Cancer Center in Columbus.
Changes in sexual behavior among recent birth cohorts and increased oral HPV exposure probably influenced the increases in incidence and prevalence, Dr. Gillison speculated. Having a high lifetime number of sexual partners is a known risk factor for HPV infection.
Although the rise in oral cancers in the United States has been attributed to HPV infection, the empirical evidence to back the contention was uncovered prior to the SEER study. A previous study by Dr. Gillison and her colleagues helped to establish that HPV infection causes an epidemiologically and clinically different form of oral cancer. Their findings documented a major increase in the incidence of HPV-related oral cancers in the United States, particularly among young, white men, and that survival rates are significantly higher in patients with HPV-related oral cancers than in those with HPV-negative cancers (J. Clin. Oncol. 2008;26:612-9).
The evidence surrounding HPV-related oral cancers has been mounting, "but I don’t think there is a lot of awareness in the general medical community," Dr. Gillison said in an interview. Most of her head-and-neck cancer patients who are nonsmokers were referred to her after undergoing months of antibiotic therapy for presumed tonsillitis.
Screening the sexual partners of oropharyngeal cancer patients has been discussed, but there is no evidence to support the practice. The risk for oral cancer is fourfold higher in HPV-positive patients’ partners, but the absolute risk is low, Dr. Gillison said. Alternatively, there are now three or four case reports of husband-wife couples with HPV16-positive tonsillar cancer.
"Probably 80% of people have HPV exposures in their life and 99.1% clear the infections without consequence," she said. "So, whatever [stable sexual partners] have swapped in terms of infection, they’ve already swapped. Just because they suddenly found that one of them got cancer from it doesn’t mean the other one will."
The researchers called for more studies to evaluate the efficacy of HPV vaccines in preventing oral HPV infections.
Dr. Gillison worked for 3 years with Merck & Co., the maker of the HPV vaccine Gardasil, and commented that Merck will not likely pursue this indication. Merck was interested in studying the vaccine in prevention of oral cancers but saw the endeavor as too much of an uphill battle in part because oral cancers are not readily accessible visibly or through biopsy. Merck instead successfully opted to seek approval for the prevention of anal cancers, an indication that was approved in December 2010 for male and females 9-26 years old.
It was already approved in the same age groups for the prevention of cervical, vulvar, and vaginal cancer and of genital warts caused by HPV types 6, 11, 16, and 18 in females and for the prevention of genital warts caused by HPV types 6 and 11 in males.
Invited discussant Dr. Lisa Licitra of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, said that oral cancers are on the rise in Europe in both men and women and that a vaccine should be pursued. Data on oropharyngeal cancer from her institute did not find a greater contribution from men.
"A preventive vaccine is worth considering," she said. "In particular, when we consider the European data, I think that in this direction, action should be taken."
In their study, Dr. Gillison and her colleagues used four different assays to determine the HPV status for 271 oropharyngeal cancer cases collected from 1984 to 2004 by three population-based cancer registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results program in Hawaii, Iowa, and Los Angeles. Trends in HPV prevalence across four calendar periods were estimated using logistic regression.
The HPV prevalence in oropharyngeal cancer significantly increased across the time period, regardless of the assay used, and remained statistically significant, even after correcting for potential loss in assay sensitivity, Dr. Gillison reported. Genotyping with the Inno-LiPA assay appeared to be the most precise, detecting more than a fourfold increase in HPV prevalence from 16.3% in 1984-1989 to 72.7% in 2000-2004.
Median survival was significantly better for patients with HPV-positive cancer at 131 months vs. 20 months for HPV-negative patients (log rank P value less than .001). HPV-positive cases on all assays had a significant reduction in hazard of death compared with HPV-negative cases after adjustment for age, sex, race, registry, calendar period, stage, surgery, chemotherapy, and radiotherapy.
Survival of HPV-positive cases increased over the study period but remained unchanged for HPV-negative cases. Consequently, survival of all oropharyngeal cancer cases improved over time, according to the results of the study, which was led by Dr. Amil Chaturvedi, an investigator with the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.
Dr. Gillison and Dr. Chaturvedi reported no conflicts of interest. A coauthor disclosed consultancy, research funding, and honoraria from Merck.
The study demonstrates the massive increase taking place in the United States in HPV-related oropharyngeal cancer, and that this really will be the major form of head and neck cancer in the next decade.
The findings also support previous work from Sweden, although the two studies are not mirror images.
These are the kind of data that we need to inform the National Cancer Institute and the Centers for Disease Control and Prevention that more research support is needed to identify risks for this disease, to develop therapeutic vaccines, and to understand the immunity and carcinogenesis of this disease.
This disease really deserves research funding, because it is curable today with tools that are available and have not been effectively applied.
Dr. Marshall Posner is director of head and neck medical oncology and the office of cancer clinical trials at the Tisch Cancer Institute, Mount Sinai School of Medicine, New York. He made these comments in an interview and has no relevant financial conflicts of interest.
The study demonstrates the massive increase taking place in the United States in HPV-related oropharyngeal cancer, and that this really will be the major form of head and neck cancer in the next decade.
The findings also support previous work from Sweden, although the two studies are not mirror images.
These are the kind of data that we need to inform the National Cancer Institute and the Centers for Disease Control and Prevention that more research support is needed to identify risks for this disease, to develop therapeutic vaccines, and to understand the immunity and carcinogenesis of this disease.
This disease really deserves research funding, because it is curable today with tools that are available and have not been effectively applied.
Dr. Marshall Posner is director of head and neck medical oncology and the office of cancer clinical trials at the Tisch Cancer Institute, Mount Sinai School of Medicine, New York. He made these comments in an interview and has no relevant financial conflicts of interest.
The study demonstrates the massive increase taking place in the United States in HPV-related oropharyngeal cancer, and that this really will be the major form of head and neck cancer in the next decade.
The findings also support previous work from Sweden, although the two studies are not mirror images.
These are the kind of data that we need to inform the National Cancer Institute and the Centers for Disease Control and Prevention that more research support is needed to identify risks for this disease, to develop therapeutic vaccines, and to understand the immunity and carcinogenesis of this disease.
This disease really deserves research funding, because it is curable today with tools that are available and have not been effectively applied.
Dr. Marshall Posner is director of head and neck medical oncology and the office of cancer clinical trials at the Tisch Cancer Institute, Mount Sinai School of Medicine, New York. He made these comments in an interview and has no relevant financial conflicts of interest.
CHICAGO – Human papillomavirus infection was firmly linked to the recent rise in oropharyngeal cancers in the United States, based on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program.
If current trends continue, the incidence of HPV-related oral cancers will soon surpass that of cervical cancers, senior author Dr. Maura Gillison reported at the annual meeting of the American Society of Clinical Oncology.
The incidence of HPV-positive oropharyngeal cancers increased 225% – from 0.8 per 100,000 to 2.8 per 100,000 – between 1988 and 2004, the researchers found. At the same time, the incidence rate for HPV-negative oropharyngeal cancers, which are strongly related to tobacco and alcohol use, declined by 50% – from 2.0 per 100,000 to 1.0 per 100,000.
Consequently, the overall incidence of oropharyngeal cancers increased 28%.
Even by the conservative estimate that 70% of oropharyngeal cancers in 2020 will be HPV positive, the annual number of HPV-positive oral squamous cell carcinomas (8,653 cases) is expected to surpass cervical cancers (7,726 cases). Further, the majority will occur among men (7,426 cases), said Dr. Gillison, a medical oncologist and the Jeg Coughlin Chair in Cancer Research at Ohio State University Comprehensive Cancer Center in Columbus.
Changes in sexual behavior among recent birth cohorts and increased oral HPV exposure probably influenced the increases in incidence and prevalence, Dr. Gillison speculated. Having a high lifetime number of sexual partners is a known risk factor for HPV infection.
Although the rise in oral cancers in the United States has been attributed to HPV infection, the empirical evidence to back the contention was uncovered prior to the SEER study. A previous study by Dr. Gillison and her colleagues helped to establish that HPV infection causes an epidemiologically and clinically different form of oral cancer. Their findings documented a major increase in the incidence of HPV-related oral cancers in the United States, particularly among young, white men, and that survival rates are significantly higher in patients with HPV-related oral cancers than in those with HPV-negative cancers (J. Clin. Oncol. 2008;26:612-9).
The evidence surrounding HPV-related oral cancers has been mounting, "but I don’t think there is a lot of awareness in the general medical community," Dr. Gillison said in an interview. Most of her head-and-neck cancer patients who are nonsmokers were referred to her after undergoing months of antibiotic therapy for presumed tonsillitis.
Screening the sexual partners of oropharyngeal cancer patients has been discussed, but there is no evidence to support the practice. The risk for oral cancer is fourfold higher in HPV-positive patients’ partners, but the absolute risk is low, Dr. Gillison said. Alternatively, there are now three or four case reports of husband-wife couples with HPV16-positive tonsillar cancer.
"Probably 80% of people have HPV exposures in their life and 99.1% clear the infections without consequence," she said. "So, whatever [stable sexual partners] have swapped in terms of infection, they’ve already swapped. Just because they suddenly found that one of them got cancer from it doesn’t mean the other one will."
The researchers called for more studies to evaluate the efficacy of HPV vaccines in preventing oral HPV infections.
Dr. Gillison worked for 3 years with Merck & Co., the maker of the HPV vaccine Gardasil, and commented that Merck will not likely pursue this indication. Merck was interested in studying the vaccine in prevention of oral cancers but saw the endeavor as too much of an uphill battle in part because oral cancers are not readily accessible visibly or through biopsy. Merck instead successfully opted to seek approval for the prevention of anal cancers, an indication that was approved in December 2010 for male and females 9-26 years old.
It was already approved in the same age groups for the prevention of cervical, vulvar, and vaginal cancer and of genital warts caused by HPV types 6, 11, 16, and 18 in females and for the prevention of genital warts caused by HPV types 6 and 11 in males.
Invited discussant Dr. Lisa Licitra of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, said that oral cancers are on the rise in Europe in both men and women and that a vaccine should be pursued. Data on oropharyngeal cancer from her institute did not find a greater contribution from men.
"A preventive vaccine is worth considering," she said. "In particular, when we consider the European data, I think that in this direction, action should be taken."
In their study, Dr. Gillison and her colleagues used four different assays to determine the HPV status for 271 oropharyngeal cancer cases collected from 1984 to 2004 by three population-based cancer registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results program in Hawaii, Iowa, and Los Angeles. Trends in HPV prevalence across four calendar periods were estimated using logistic regression.
The HPV prevalence in oropharyngeal cancer significantly increased across the time period, regardless of the assay used, and remained statistically significant, even after correcting for potential loss in assay sensitivity, Dr. Gillison reported. Genotyping with the Inno-LiPA assay appeared to be the most precise, detecting more than a fourfold increase in HPV prevalence from 16.3% in 1984-1989 to 72.7% in 2000-2004.
Median survival was significantly better for patients with HPV-positive cancer at 131 months vs. 20 months for HPV-negative patients (log rank P value less than .001). HPV-positive cases on all assays had a significant reduction in hazard of death compared with HPV-negative cases after adjustment for age, sex, race, registry, calendar period, stage, surgery, chemotherapy, and radiotherapy.
Survival of HPV-positive cases increased over the study period but remained unchanged for HPV-negative cases. Consequently, survival of all oropharyngeal cancer cases improved over time, according to the results of the study, which was led by Dr. Amil Chaturvedi, an investigator with the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.
Dr. Gillison and Dr. Chaturvedi reported no conflicts of interest. A coauthor disclosed consultancy, research funding, and honoraria from Merck.
CHICAGO – Human papillomavirus infection was firmly linked to the recent rise in oropharyngeal cancers in the United States, based on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program.
If current trends continue, the incidence of HPV-related oral cancers will soon surpass that of cervical cancers, senior author Dr. Maura Gillison reported at the annual meeting of the American Society of Clinical Oncology.
The incidence of HPV-positive oropharyngeal cancers increased 225% – from 0.8 per 100,000 to 2.8 per 100,000 – between 1988 and 2004, the researchers found. At the same time, the incidence rate for HPV-negative oropharyngeal cancers, which are strongly related to tobacco and alcohol use, declined by 50% – from 2.0 per 100,000 to 1.0 per 100,000.
Consequently, the overall incidence of oropharyngeal cancers increased 28%.
Even by the conservative estimate that 70% of oropharyngeal cancers in 2020 will be HPV positive, the annual number of HPV-positive oral squamous cell carcinomas (8,653 cases) is expected to surpass cervical cancers (7,726 cases). Further, the majority will occur among men (7,426 cases), said Dr. Gillison, a medical oncologist and the Jeg Coughlin Chair in Cancer Research at Ohio State University Comprehensive Cancer Center in Columbus.
Changes in sexual behavior among recent birth cohorts and increased oral HPV exposure probably influenced the increases in incidence and prevalence, Dr. Gillison speculated. Having a high lifetime number of sexual partners is a known risk factor for HPV infection.
Although the rise in oral cancers in the United States has been attributed to HPV infection, the empirical evidence to back the contention was uncovered prior to the SEER study. A previous study by Dr. Gillison and her colleagues helped to establish that HPV infection causes an epidemiologically and clinically different form of oral cancer. Their findings documented a major increase in the incidence of HPV-related oral cancers in the United States, particularly among young, white men, and that survival rates are significantly higher in patients with HPV-related oral cancers than in those with HPV-negative cancers (J. Clin. Oncol. 2008;26:612-9).
The evidence surrounding HPV-related oral cancers has been mounting, "but I don’t think there is a lot of awareness in the general medical community," Dr. Gillison said in an interview. Most of her head-and-neck cancer patients who are nonsmokers were referred to her after undergoing months of antibiotic therapy for presumed tonsillitis.
Screening the sexual partners of oropharyngeal cancer patients has been discussed, but there is no evidence to support the practice. The risk for oral cancer is fourfold higher in HPV-positive patients’ partners, but the absolute risk is low, Dr. Gillison said. Alternatively, there are now three or four case reports of husband-wife couples with HPV16-positive tonsillar cancer.
"Probably 80% of people have HPV exposures in their life and 99.1% clear the infections without consequence," she said. "So, whatever [stable sexual partners] have swapped in terms of infection, they’ve already swapped. Just because they suddenly found that one of them got cancer from it doesn’t mean the other one will."
The researchers called for more studies to evaluate the efficacy of HPV vaccines in preventing oral HPV infections.
Dr. Gillison worked for 3 years with Merck & Co., the maker of the HPV vaccine Gardasil, and commented that Merck will not likely pursue this indication. Merck was interested in studying the vaccine in prevention of oral cancers but saw the endeavor as too much of an uphill battle in part because oral cancers are not readily accessible visibly or through biopsy. Merck instead successfully opted to seek approval for the prevention of anal cancers, an indication that was approved in December 2010 for male and females 9-26 years old.
It was already approved in the same age groups for the prevention of cervical, vulvar, and vaginal cancer and of genital warts caused by HPV types 6, 11, 16, and 18 in females and for the prevention of genital warts caused by HPV types 6 and 11 in males.
Invited discussant Dr. Lisa Licitra of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, said that oral cancers are on the rise in Europe in both men and women and that a vaccine should be pursued. Data on oropharyngeal cancer from her institute did not find a greater contribution from men.
"A preventive vaccine is worth considering," she said. "In particular, when we consider the European data, I think that in this direction, action should be taken."
In their study, Dr. Gillison and her colleagues used four different assays to determine the HPV status for 271 oropharyngeal cancer cases collected from 1984 to 2004 by three population-based cancer registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results program in Hawaii, Iowa, and Los Angeles. Trends in HPV prevalence across four calendar periods were estimated using logistic regression.
The HPV prevalence in oropharyngeal cancer significantly increased across the time period, regardless of the assay used, and remained statistically significant, even after correcting for potential loss in assay sensitivity, Dr. Gillison reported. Genotyping with the Inno-LiPA assay appeared to be the most precise, detecting more than a fourfold increase in HPV prevalence from 16.3% in 1984-1989 to 72.7% in 2000-2004.
Median survival was significantly better for patients with HPV-positive cancer at 131 months vs. 20 months for HPV-negative patients (log rank P value less than .001). HPV-positive cases on all assays had a significant reduction in hazard of death compared with HPV-negative cases after adjustment for age, sex, race, registry, calendar period, stage, surgery, chemotherapy, and radiotherapy.
Survival of HPV-positive cases increased over the study period but remained unchanged for HPV-negative cases. Consequently, survival of all oropharyngeal cancer cases improved over time, according to the results of the study, which was led by Dr. Amil Chaturvedi, an investigator with the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.
Dr. Gillison and Dr. Chaturvedi reported no conflicts of interest. A coauthor disclosed consultancy, research funding, and honoraria from Merck.
FROM THE ANNUAL MEETING OF THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major Finding: Between 1988 and 2004, the incidence of HPV-positive oropharyngeal cancers increased 225%. Genotyping indicated more than a fourfold increase in HPV prevalence from 16.3% in 1984-1989 to 72.7% in 2000-2004.
Data Source: Analysis of 271 oropharyngeal cancer cases in the Surveillance, Epidemiology, and End Results (SEER) program in Hawaii, Iowa, and Los Angeles.
Disclosures: Dr. Gillison and Dr. Chaturvedi reported no conflicts of interest. A coauthor disclosed consultancy, research funding, and honoraria from Merck.
Financial Incentives Discourage Bundling of Endoscopic Procedures
CHICAGO – Same-day bundling of endoscopic procedures offers several important advantages, yet bundling was not used for 37% of procedures in a national sample of Medicare patients who had both colonoscopy and upper endoscopy within 180 days.
Moreover, the two procedures were separated from each other by a median of only 26 days, and nearly 30% of procedures that were not performed on the same day were separated by just 4 days or less.
"The lack of bundling was unlikely to be explained by clinical necessity," lead investigator Dr. Hashem B. El-Serag said at the annual Digestive Disease Week. "The financial implications to the health care system and the increased adverse events in patients are likely to be large," he stated.
Although bundling is convenient for patients, efficient for providers, and offers cost savings to the health care system, there is a financial disincentive for physicians to embrace this approach.
Reimbursement by Medicare for bundled procedures occurs at a rate that is less than the sum of the two procedures when they are charged separately. For example, reimbursement for a diagnostic upper endoscopy, or esophagogastroduodenoscopy (EGD) is just $75 when bundled and $150 when not bundled, while an upper GI endoscopic biopsy is $88 bundled vs. $177 when not bundled, explained Dr. El-Serag, professor of medicine and chief of gastroenterology and hepatology at Baylor College of Medicine in Houston.
The researchers examined 2007 outpatient Medicare claims from a 5% random sample of patients who lived in one of the Surveillance, Epidemiology and End Results (SEER) database regions. They then identified 12,905 Medicare beneficiaries who underwent both a colonoscopy and EGD within 180 days of each other. Patients who were not enrolled in Medicare parts A and B or were members of an HMO were excluded.
Based on ICD-9 codes, potential clinical indications for colonoscopy included evidence of GI bleeding such as anemia, heme-positive stool, hemorrhage of the rectum and anus, and iron deficiency; colon symptoms such as abdominal mass, distention, pain or mass, anorexia, bowel obstruction, change in bowel habits, constipation, diarrhea, fecal incontinence, weight loss, and nausea and vomiting; and colon surveillance in the presence of Crohn’s disease or a personal history of colorectal cancer, colon polyps, or ulcerative colitis.
Indications for EGD included signs of GI bleeding and upper GI symptoms. The median age of the patients was 75 years, 63% were female, and 79% were white.
In all, 8,100 procedures (63%) were bundled on the same day, 2,624 (20%) were performed within 30 days of each other, and 2,181 (17%) were performed within 31-180 days of each other, Dr. El-Serag said.
Nearly 30% of the 4,805 procedures that were not bundled were performed within 4 days of each other, with another 10% performed within 12 days of each other and 5% or less performed 44 or more days apart.
"Most procedures that were not bundled were performed reasonably close to each other," he said.
There were no significant differences between the three groups of patients – those who had bundled procedures, those who had them within 30 days, and those who had them within 31-180 days – with regard to gender or age. Patients who had bundled procedures, however, were less likely to be black (7.3% for bundled vs. 10.7% within 1-30 days vs. 7.5% within 31-180 days) or to live in a metropolitan area (82% vs. 87% vs. 87%, respectively).
An indication of GI bleeding was more likely in patients who had bundling, Dr. El-Serag said. Also, patients with bundled procedures were less likely to have screening as an indication, compared with patients whose procedures were not bundled.
Limitations of the study include possible inaccuracies in coding for some of the determinants, residual confounding by uncollectible factors such as patient preference or doctor’s advice, and generalizability. Strengths of the study are its population-based design that reflects a wide array of practices, its large sample size, and its complete capture of procedures in a non-HMO population, he said.
During a discussion of the study, an attendee asked how the researchers could be certain that an upper endoscopy performed 3 weeks after a colonoscopy was done for an indication known at the time of the first procedure. Dr. El-Serag replied that, while they couldn’t be absolutely certain when the additional indication popped into the chart, the 30-day window reduced the possibility of an emergent diagnosis requiring an additional procedure in the majority of cases.
"So you can be quite safe that for anything done within 30 days of each other, there was nothing new," he said.
Another attendee asked whether physician factors such as years in practice or type of facility may have influenced the use of bundling. Dr. El-Serag said that he and his associates have not done such an analysis and are limited by the nature of the database. It was noted during the discussion, however, that some ambulatory care centers have almost a standing policy against bundling, and that large institutions have been known to get around the thorny issue of reimbursement by having two providers at the same institution bill for procedures performed on the same day.
Session cochair Dr. James M. Scheiman, professor of internal medicine at the University of Michigan Health System in Ann Arbor, said, "I was surprised it [non-bundling] was only a third, I expected it to be much higher."
Dr. El-Serag said in an interview after the presentation that he too was surprised by the results, but he expected more physicians to bundle the two procedures because patients with suspected GI disorders often need both colonoscopy and upper endoscopy.
"It begs the question that the indication was the same one and that it was just a matter of convenience, patient request, or financial disincentive," he said. "Removing the financial disincentive for physicians to bundle procedures is likely to reduce the overall costs to the health care system by saving the facility fees, anesthesia, and work days lost."
Dr. El-Serag disclosed research support and other financial relationships with Astra-Zeneca and Onyx Pharmaceuticals and consulting for Vertex Pharmaceuticals. Coauthor Dr. Gregory S. Cooper reported consulting for and serving on advisory committees/review panels for Medtronic.
CHICAGO – Same-day bundling of endoscopic procedures offers several important advantages, yet bundling was not used for 37% of procedures in a national sample of Medicare patients who had both colonoscopy and upper endoscopy within 180 days.
Moreover, the two procedures were separated from each other by a median of only 26 days, and nearly 30% of procedures that were not performed on the same day were separated by just 4 days or less.
"The lack of bundling was unlikely to be explained by clinical necessity," lead investigator Dr. Hashem B. El-Serag said at the annual Digestive Disease Week. "The financial implications to the health care system and the increased adverse events in patients are likely to be large," he stated.
Although bundling is convenient for patients, efficient for providers, and offers cost savings to the health care system, there is a financial disincentive for physicians to embrace this approach.
Reimbursement by Medicare for bundled procedures occurs at a rate that is less than the sum of the two procedures when they are charged separately. For example, reimbursement for a diagnostic upper endoscopy, or esophagogastroduodenoscopy (EGD) is just $75 when bundled and $150 when not bundled, while an upper GI endoscopic biopsy is $88 bundled vs. $177 when not bundled, explained Dr. El-Serag, professor of medicine and chief of gastroenterology and hepatology at Baylor College of Medicine in Houston.
The researchers examined 2007 outpatient Medicare claims from a 5% random sample of patients who lived in one of the Surveillance, Epidemiology and End Results (SEER) database regions. They then identified 12,905 Medicare beneficiaries who underwent both a colonoscopy and EGD within 180 days of each other. Patients who were not enrolled in Medicare parts A and B or were members of an HMO were excluded.
Based on ICD-9 codes, potential clinical indications for colonoscopy included evidence of GI bleeding such as anemia, heme-positive stool, hemorrhage of the rectum and anus, and iron deficiency; colon symptoms such as abdominal mass, distention, pain or mass, anorexia, bowel obstruction, change in bowel habits, constipation, diarrhea, fecal incontinence, weight loss, and nausea and vomiting; and colon surveillance in the presence of Crohn’s disease or a personal history of colorectal cancer, colon polyps, or ulcerative colitis.
Indications for EGD included signs of GI bleeding and upper GI symptoms. The median age of the patients was 75 years, 63% were female, and 79% were white.
In all, 8,100 procedures (63%) were bundled on the same day, 2,624 (20%) were performed within 30 days of each other, and 2,181 (17%) were performed within 31-180 days of each other, Dr. El-Serag said.
Nearly 30% of the 4,805 procedures that were not bundled were performed within 4 days of each other, with another 10% performed within 12 days of each other and 5% or less performed 44 or more days apart.
"Most procedures that were not bundled were performed reasonably close to each other," he said.
There were no significant differences between the three groups of patients – those who had bundled procedures, those who had them within 30 days, and those who had them within 31-180 days – with regard to gender or age. Patients who had bundled procedures, however, were less likely to be black (7.3% for bundled vs. 10.7% within 1-30 days vs. 7.5% within 31-180 days) or to live in a metropolitan area (82% vs. 87% vs. 87%, respectively).
An indication of GI bleeding was more likely in patients who had bundling, Dr. El-Serag said. Also, patients with bundled procedures were less likely to have screening as an indication, compared with patients whose procedures were not bundled.
Limitations of the study include possible inaccuracies in coding for some of the determinants, residual confounding by uncollectible factors such as patient preference or doctor’s advice, and generalizability. Strengths of the study are its population-based design that reflects a wide array of practices, its large sample size, and its complete capture of procedures in a non-HMO population, he said.
During a discussion of the study, an attendee asked how the researchers could be certain that an upper endoscopy performed 3 weeks after a colonoscopy was done for an indication known at the time of the first procedure. Dr. El-Serag replied that, while they couldn’t be absolutely certain when the additional indication popped into the chart, the 30-day window reduced the possibility of an emergent diagnosis requiring an additional procedure in the majority of cases.
"So you can be quite safe that for anything done within 30 days of each other, there was nothing new," he said.
Another attendee asked whether physician factors such as years in practice or type of facility may have influenced the use of bundling. Dr. El-Serag said that he and his associates have not done such an analysis and are limited by the nature of the database. It was noted during the discussion, however, that some ambulatory care centers have almost a standing policy against bundling, and that large institutions have been known to get around the thorny issue of reimbursement by having two providers at the same institution bill for procedures performed on the same day.
Session cochair Dr. James M. Scheiman, professor of internal medicine at the University of Michigan Health System in Ann Arbor, said, "I was surprised it [non-bundling] was only a third, I expected it to be much higher."
Dr. El-Serag said in an interview after the presentation that he too was surprised by the results, but he expected more physicians to bundle the two procedures because patients with suspected GI disorders often need both colonoscopy and upper endoscopy.
"It begs the question that the indication was the same one and that it was just a matter of convenience, patient request, or financial disincentive," he said. "Removing the financial disincentive for physicians to bundle procedures is likely to reduce the overall costs to the health care system by saving the facility fees, anesthesia, and work days lost."
Dr. El-Serag disclosed research support and other financial relationships with Astra-Zeneca and Onyx Pharmaceuticals and consulting for Vertex Pharmaceuticals. Coauthor Dr. Gregory S. Cooper reported consulting for and serving on advisory committees/review panels for Medtronic.
CHICAGO – Same-day bundling of endoscopic procedures offers several important advantages, yet bundling was not used for 37% of procedures in a national sample of Medicare patients who had both colonoscopy and upper endoscopy within 180 days.
Moreover, the two procedures were separated from each other by a median of only 26 days, and nearly 30% of procedures that were not performed on the same day were separated by just 4 days or less.
"The lack of bundling was unlikely to be explained by clinical necessity," lead investigator Dr. Hashem B. El-Serag said at the annual Digestive Disease Week. "The financial implications to the health care system and the increased adverse events in patients are likely to be large," he stated.
Although bundling is convenient for patients, efficient for providers, and offers cost savings to the health care system, there is a financial disincentive for physicians to embrace this approach.
Reimbursement by Medicare for bundled procedures occurs at a rate that is less than the sum of the two procedures when they are charged separately. For example, reimbursement for a diagnostic upper endoscopy, or esophagogastroduodenoscopy (EGD) is just $75 when bundled and $150 when not bundled, while an upper GI endoscopic biopsy is $88 bundled vs. $177 when not bundled, explained Dr. El-Serag, professor of medicine and chief of gastroenterology and hepatology at Baylor College of Medicine in Houston.
The researchers examined 2007 outpatient Medicare claims from a 5% random sample of patients who lived in one of the Surveillance, Epidemiology and End Results (SEER) database regions. They then identified 12,905 Medicare beneficiaries who underwent both a colonoscopy and EGD within 180 days of each other. Patients who were not enrolled in Medicare parts A and B or were members of an HMO were excluded.
Based on ICD-9 codes, potential clinical indications for colonoscopy included evidence of GI bleeding such as anemia, heme-positive stool, hemorrhage of the rectum and anus, and iron deficiency; colon symptoms such as abdominal mass, distention, pain or mass, anorexia, bowel obstruction, change in bowel habits, constipation, diarrhea, fecal incontinence, weight loss, and nausea and vomiting; and colon surveillance in the presence of Crohn’s disease or a personal history of colorectal cancer, colon polyps, or ulcerative colitis.
Indications for EGD included signs of GI bleeding and upper GI symptoms. The median age of the patients was 75 years, 63% were female, and 79% were white.
In all, 8,100 procedures (63%) were bundled on the same day, 2,624 (20%) were performed within 30 days of each other, and 2,181 (17%) were performed within 31-180 days of each other, Dr. El-Serag said.
Nearly 30% of the 4,805 procedures that were not bundled were performed within 4 days of each other, with another 10% performed within 12 days of each other and 5% or less performed 44 or more days apart.
"Most procedures that were not bundled were performed reasonably close to each other," he said.
There were no significant differences between the three groups of patients – those who had bundled procedures, those who had them within 30 days, and those who had them within 31-180 days – with regard to gender or age. Patients who had bundled procedures, however, were less likely to be black (7.3% for bundled vs. 10.7% within 1-30 days vs. 7.5% within 31-180 days) or to live in a metropolitan area (82% vs. 87% vs. 87%, respectively).
An indication of GI bleeding was more likely in patients who had bundling, Dr. El-Serag said. Also, patients with bundled procedures were less likely to have screening as an indication, compared with patients whose procedures were not bundled.
Limitations of the study include possible inaccuracies in coding for some of the determinants, residual confounding by uncollectible factors such as patient preference or doctor’s advice, and generalizability. Strengths of the study are its population-based design that reflects a wide array of practices, its large sample size, and its complete capture of procedures in a non-HMO population, he said.
During a discussion of the study, an attendee asked how the researchers could be certain that an upper endoscopy performed 3 weeks after a colonoscopy was done for an indication known at the time of the first procedure. Dr. El-Serag replied that, while they couldn’t be absolutely certain when the additional indication popped into the chart, the 30-day window reduced the possibility of an emergent diagnosis requiring an additional procedure in the majority of cases.
"So you can be quite safe that for anything done within 30 days of each other, there was nothing new," he said.
Another attendee asked whether physician factors such as years in practice or type of facility may have influenced the use of bundling. Dr. El-Serag said that he and his associates have not done such an analysis and are limited by the nature of the database. It was noted during the discussion, however, that some ambulatory care centers have almost a standing policy against bundling, and that large institutions have been known to get around the thorny issue of reimbursement by having two providers at the same institution bill for procedures performed on the same day.
Session cochair Dr. James M. Scheiman, professor of internal medicine at the University of Michigan Health System in Ann Arbor, said, "I was surprised it [non-bundling] was only a third, I expected it to be much higher."
Dr. El-Serag said in an interview after the presentation that he too was surprised by the results, but he expected more physicians to bundle the two procedures because patients with suspected GI disorders often need both colonoscopy and upper endoscopy.
"It begs the question that the indication was the same one and that it was just a matter of convenience, patient request, or financial disincentive," he said. "Removing the financial disincentive for physicians to bundle procedures is likely to reduce the overall costs to the health care system by saving the facility fees, anesthesia, and work days lost."
Dr. El-Serag disclosed research support and other financial relationships with Astra-Zeneca and Onyx Pharmaceuticals and consulting for Vertex Pharmaceuticals. Coauthor Dr. Gregory S. Cooper reported consulting for and serving on advisory committees/review panels for Medtronic.
FROM THE ANNUAL DIGESTIVE DISEASE WEEK
Major Finding: In patients who underwent both colonoscopy and upper endoscopy within 180 days of each other, 37% of procedures were not bundled – instead, they were performed separately on different days.
Data Source: Population-based analysis of 12,905 Medicare beneficiaries.
Disclosures: Dr. El-Serag disclosed grant/research support from Astra-Zeneca and Onyx Pharmaceuticals and disclosed consulting for Vertex Pharmaceuticals. Coauthor Dr. Gregory S. Cooper reported serving on advisory committees/review panels for Medtronic.
Etiology Unknown in Most XY Disorder Patients
Major Finding: An etiologic diagnosis was made in 87.5% of patients with an XX disorder, but only 29% of those with an XY disorder.
Data Source: Ten-year retrospective analysis of 199 patients with disorders of sexual development.
Disclosures: The authors said they had no relevant financial disclosures.
CHICAGO – Etiology remains elusive in many patients with disorders of sexual development, according to data from one of the largest cohorts reported to date.
The analysis found that most patients with an XX disorder of sexual development (DSD) have an etiologic diagnosis, but that more than two-thirds of those with an XY disorder have only an anatomical diagnosis.
“We as clinicians should be aiming for an etiological diagnosis rather than an anatomical diagnosis in such patients to provide better care,” Dr. Karamdeep Bhullar said.
Recent consensus guidelines stress the importance of early diagnosis and coined the term DSD to describe any congenital condition in which the development of chromosomal, gonadal, or anatomical sex is atypical (Arch. Dis. Child. 2006;91:554-63). Although most cases of DSD are identified in infancy, individuals with normal male or female genitalia and discordant internal anatomy are often not identified until adulthood. A girl might present with primary amenorrhea in the case of vaginal agenesis or present with inguinal hernia that is actually testes in cases of complete androgen insensitivity syndrome, said Dr. Bhullar of the department of pediatrics at the University of Melbourne.
She presented an analysis of 199 patients, born between 1999 and 2008 and managed at the Royal Children's Hospital in Melbourne, one of the world leaders in DSD research. In all, 107 (54%) presented with XY DSD, 64 (32%) with XX DSD, and 28 (14%) as sex chromosome aneuploidy DSD. A definitive diagnosis was made in only 57% of the cohort, Dr. Bhullar said.
An etiologic diagnosis was made in 87.5% of patients with XX DSD, but only 29% of those with XY DSD.
Of the XY children, 92% were raised as males and 8% as females, while only one (2%) XX DSD child was raised as a male. Of the chromosome aneuploidy DSD children, 68%were assigned female sex and 32%, male sex.
The consensus guidelines stress that all children with DSD should receive a sex assignment, and that evaluation and long-term management should be carried out at a center with an experienced multidisciplinary team. Senior author Dr. Garry Warne, director of Royal Children's Hospital International, Melbourne, said that early assignment of sex is thought to be the best way to prevent psychosocial harm to the child. In addition, there is a significant risk of gonadal malignancy in 46, XY DSD and sex chromosome aneuploidy DSD when there is a Y chromosome. In two conditions – partial androgen insensitivity syndrome and Y chromosome–positive gonadal dysgenesis – the risk of cancer is around 50% if the gonad is intraabdominal.
“If the decision is made to retain a gonad in such circumstances, it is essential that a risk-management strategy be prepared and clearly communicated to the patient,” Dr. Warne said in an interview. “This is done to prevent physical harm to the patient.”
In the current analysis, the spectrum of diagnoses among children raised as males included cloacal and bladder exstrophy (17%), partial/mixed gonadal dysgenesis (6%), Klinefelter syndrome and its variants (4%), ovotesticular DSD (2%), testicular regression syndrome (2%), and partial androgen insensitivity syndrome (1%). An anatomical diagnosis without a definitive etiology was made in 68% of these patients, Dr. Bhullar said.
The most common diagnosis among children raised as females was congenital adrenal hyperplasia (CAH) (47%), followed by Turner syndrome and its variants (18%), cloacal and bladder exstrophy (12%), and ovotesticular DSD (6%). Other less common diagnoses included complete androgen insensitivity (CAIS) (4%), complete gonadal dysgenesis (1%), and partial/mixed gonadal dysgenesis (1%). About 11% of those raised as females had an anatomical diagnosis without any etiology established, she said.
Except for certain conditions such as CAH and CAIS, a female sex rearing is strongly preferred based on long-term outcomes, Dr. Warne said. For most other conditions, there are either insufficient long-term outcomes data or the diagnosis is so uncertain that it is impossible to be sure how things will turn out.
During a discussion of the analysis, an audience member said the data provide a good starting point for research aimed at better classifying these disorders, but pointed out that contention still exists regarding the consensus guidelines and the inclusion of isolated hypospadias with palpable gonads and the placement of coital entropies in the labial adhesion category.
Dr. Warne said it is important for guidelines to be evidence based as far as possible, and acknowledged that mistakes have been made in the past, resulting in postoperative gender dysphoria that is extremely difficult to treat and leaves many patients, understandably, feeling deeply aggrieved.
“There are movements dedicated to opposing what is perceived to be current medical practice,” he said. “Having said that, the medical profession accepts that practices need to change, and is trying very hard to develop protocols that better protect the best interests of patients.”
The researchers published a set of ethical principles for the management of infants with DSD (Horm. Res. Paediatr. 2010;74:412-8) that were endorsed by the Fifth World Congress on Family Law and Children's Rights, and are looking to test the principles in Australia and other cultural settings. They also are studying new methods of molecular diagnosis using Next-Gen Sequencing and gene chip technology that may provide swift and accurate diagnoses, he said.
Major Finding: An etiologic diagnosis was made in 87.5% of patients with an XX disorder, but only 29% of those with an XY disorder.
Data Source: Ten-year retrospective analysis of 199 patients with disorders of sexual development.
Disclosures: The authors said they had no relevant financial disclosures.
CHICAGO – Etiology remains elusive in many patients with disorders of sexual development, according to data from one of the largest cohorts reported to date.
The analysis found that most patients with an XX disorder of sexual development (DSD) have an etiologic diagnosis, but that more than two-thirds of those with an XY disorder have only an anatomical diagnosis.
“We as clinicians should be aiming for an etiological diagnosis rather than an anatomical diagnosis in such patients to provide better care,” Dr. Karamdeep Bhullar said.
Recent consensus guidelines stress the importance of early diagnosis and coined the term DSD to describe any congenital condition in which the development of chromosomal, gonadal, or anatomical sex is atypical (Arch. Dis. Child. 2006;91:554-63). Although most cases of DSD are identified in infancy, individuals with normal male or female genitalia and discordant internal anatomy are often not identified until adulthood. A girl might present with primary amenorrhea in the case of vaginal agenesis or present with inguinal hernia that is actually testes in cases of complete androgen insensitivity syndrome, said Dr. Bhullar of the department of pediatrics at the University of Melbourne.
She presented an analysis of 199 patients, born between 1999 and 2008 and managed at the Royal Children's Hospital in Melbourne, one of the world leaders in DSD research. In all, 107 (54%) presented with XY DSD, 64 (32%) with XX DSD, and 28 (14%) as sex chromosome aneuploidy DSD. A definitive diagnosis was made in only 57% of the cohort, Dr. Bhullar said.
An etiologic diagnosis was made in 87.5% of patients with XX DSD, but only 29% of those with XY DSD.
Of the XY children, 92% were raised as males and 8% as females, while only one (2%) XX DSD child was raised as a male. Of the chromosome aneuploidy DSD children, 68%were assigned female sex and 32%, male sex.
The consensus guidelines stress that all children with DSD should receive a sex assignment, and that evaluation and long-term management should be carried out at a center with an experienced multidisciplinary team. Senior author Dr. Garry Warne, director of Royal Children's Hospital International, Melbourne, said that early assignment of sex is thought to be the best way to prevent psychosocial harm to the child. In addition, there is a significant risk of gonadal malignancy in 46, XY DSD and sex chromosome aneuploidy DSD when there is a Y chromosome. In two conditions – partial androgen insensitivity syndrome and Y chromosome–positive gonadal dysgenesis – the risk of cancer is around 50% if the gonad is intraabdominal.
“If the decision is made to retain a gonad in such circumstances, it is essential that a risk-management strategy be prepared and clearly communicated to the patient,” Dr. Warne said in an interview. “This is done to prevent physical harm to the patient.”
In the current analysis, the spectrum of diagnoses among children raised as males included cloacal and bladder exstrophy (17%), partial/mixed gonadal dysgenesis (6%), Klinefelter syndrome and its variants (4%), ovotesticular DSD (2%), testicular regression syndrome (2%), and partial androgen insensitivity syndrome (1%). An anatomical diagnosis without a definitive etiology was made in 68% of these patients, Dr. Bhullar said.
The most common diagnosis among children raised as females was congenital adrenal hyperplasia (CAH) (47%), followed by Turner syndrome and its variants (18%), cloacal and bladder exstrophy (12%), and ovotesticular DSD (6%). Other less common diagnoses included complete androgen insensitivity (CAIS) (4%), complete gonadal dysgenesis (1%), and partial/mixed gonadal dysgenesis (1%). About 11% of those raised as females had an anatomical diagnosis without any etiology established, she said.
Except for certain conditions such as CAH and CAIS, a female sex rearing is strongly preferred based on long-term outcomes, Dr. Warne said. For most other conditions, there are either insufficient long-term outcomes data or the diagnosis is so uncertain that it is impossible to be sure how things will turn out.
During a discussion of the analysis, an audience member said the data provide a good starting point for research aimed at better classifying these disorders, but pointed out that contention still exists regarding the consensus guidelines and the inclusion of isolated hypospadias with palpable gonads and the placement of coital entropies in the labial adhesion category.
Dr. Warne said it is important for guidelines to be evidence based as far as possible, and acknowledged that mistakes have been made in the past, resulting in postoperative gender dysphoria that is extremely difficult to treat and leaves many patients, understandably, feeling deeply aggrieved.
“There are movements dedicated to opposing what is perceived to be current medical practice,” he said. “Having said that, the medical profession accepts that practices need to change, and is trying very hard to develop protocols that better protect the best interests of patients.”
The researchers published a set of ethical principles for the management of infants with DSD (Horm. Res. Paediatr. 2010;74:412-8) that were endorsed by the Fifth World Congress on Family Law and Children's Rights, and are looking to test the principles in Australia and other cultural settings. They also are studying new methods of molecular diagnosis using Next-Gen Sequencing and gene chip technology that may provide swift and accurate diagnoses, he said.
Major Finding: An etiologic diagnosis was made in 87.5% of patients with an XX disorder, but only 29% of those with an XY disorder.
Data Source: Ten-year retrospective analysis of 199 patients with disorders of sexual development.
Disclosures: The authors said they had no relevant financial disclosures.
CHICAGO – Etiology remains elusive in many patients with disorders of sexual development, according to data from one of the largest cohorts reported to date.
The analysis found that most patients with an XX disorder of sexual development (DSD) have an etiologic diagnosis, but that more than two-thirds of those with an XY disorder have only an anatomical diagnosis.
“We as clinicians should be aiming for an etiological diagnosis rather than an anatomical diagnosis in such patients to provide better care,” Dr. Karamdeep Bhullar said.
Recent consensus guidelines stress the importance of early diagnosis and coined the term DSD to describe any congenital condition in which the development of chromosomal, gonadal, or anatomical sex is atypical (Arch. Dis. Child. 2006;91:554-63). Although most cases of DSD are identified in infancy, individuals with normal male or female genitalia and discordant internal anatomy are often not identified until adulthood. A girl might present with primary amenorrhea in the case of vaginal agenesis or present with inguinal hernia that is actually testes in cases of complete androgen insensitivity syndrome, said Dr. Bhullar of the department of pediatrics at the University of Melbourne.
She presented an analysis of 199 patients, born between 1999 and 2008 and managed at the Royal Children's Hospital in Melbourne, one of the world leaders in DSD research. In all, 107 (54%) presented with XY DSD, 64 (32%) with XX DSD, and 28 (14%) as sex chromosome aneuploidy DSD. A definitive diagnosis was made in only 57% of the cohort, Dr. Bhullar said.
An etiologic diagnosis was made in 87.5% of patients with XX DSD, but only 29% of those with XY DSD.
Of the XY children, 92% were raised as males and 8% as females, while only one (2%) XX DSD child was raised as a male. Of the chromosome aneuploidy DSD children, 68%were assigned female sex and 32%, male sex.
The consensus guidelines stress that all children with DSD should receive a sex assignment, and that evaluation and long-term management should be carried out at a center with an experienced multidisciplinary team. Senior author Dr. Garry Warne, director of Royal Children's Hospital International, Melbourne, said that early assignment of sex is thought to be the best way to prevent psychosocial harm to the child. In addition, there is a significant risk of gonadal malignancy in 46, XY DSD and sex chromosome aneuploidy DSD when there is a Y chromosome. In two conditions – partial androgen insensitivity syndrome and Y chromosome–positive gonadal dysgenesis – the risk of cancer is around 50% if the gonad is intraabdominal.
“If the decision is made to retain a gonad in such circumstances, it is essential that a risk-management strategy be prepared and clearly communicated to the patient,” Dr. Warne said in an interview. “This is done to prevent physical harm to the patient.”
In the current analysis, the spectrum of diagnoses among children raised as males included cloacal and bladder exstrophy (17%), partial/mixed gonadal dysgenesis (6%), Klinefelter syndrome and its variants (4%), ovotesticular DSD (2%), testicular regression syndrome (2%), and partial androgen insensitivity syndrome (1%). An anatomical diagnosis without a definitive etiology was made in 68% of these patients, Dr. Bhullar said.
The most common diagnosis among children raised as females was congenital adrenal hyperplasia (CAH) (47%), followed by Turner syndrome and its variants (18%), cloacal and bladder exstrophy (12%), and ovotesticular DSD (6%). Other less common diagnoses included complete androgen insensitivity (CAIS) (4%), complete gonadal dysgenesis (1%), and partial/mixed gonadal dysgenesis (1%). About 11% of those raised as females had an anatomical diagnosis without any etiology established, she said.
Except for certain conditions such as CAH and CAIS, a female sex rearing is strongly preferred based on long-term outcomes, Dr. Warne said. For most other conditions, there are either insufficient long-term outcomes data or the diagnosis is so uncertain that it is impossible to be sure how things will turn out.
During a discussion of the analysis, an audience member said the data provide a good starting point for research aimed at better classifying these disorders, but pointed out that contention still exists regarding the consensus guidelines and the inclusion of isolated hypospadias with palpable gonads and the placement of coital entropies in the labial adhesion category.
Dr. Warne said it is important for guidelines to be evidence based as far as possible, and acknowledged that mistakes have been made in the past, resulting in postoperative gender dysphoria that is extremely difficult to treat and leaves many patients, understandably, feeling deeply aggrieved.
“There are movements dedicated to opposing what is perceived to be current medical practice,” he said. “Having said that, the medical profession accepts that practices need to change, and is trying very hard to develop protocols that better protect the best interests of patients.”
The researchers published a set of ethical principles for the management of infants with DSD (Horm. Res. Paediatr. 2010;74:412-8) that were endorsed by the Fifth World Congress on Family Law and Children's Rights, and are looking to test the principles in Australia and other cultural settings. They also are studying new methods of molecular diagnosis using Next-Gen Sequencing and gene chip technology that may provide swift and accurate diagnoses, he said.
From the Annual Meeting of the North American Society for Pediatric and Adolescent Gynecology
Is Labioplasty the Best Option in Adolescence?
Major Finding: There were no intraoperative or major postoperative complications, and 10 patients (27%) experienced minor postoperative complications.
Data Source: Retrospective analysis of 37 girls with symptomatic labial hypertrophy who underwent bilateral or unilateral labioplasty with or without clitoral hood revision.
Disclosures: Dr. Santos and Dr. Dietrich reported no relevant financial disclosures.
CHICAGO – Labioplasty resulted in high rates of satisfaction and few complications in what is being described as the largest series of pediatric and adolescent females undergoing labioplasty for symptomatic labial hypertrophy.
The study in 37 girls, aged 7–17 years, evoked strong responses when presented at the meeting.
One audience member said she was disturbed by the age range of the participants, and questioned why labioplasty was even performed in a 7-year-old.
Principal investigator Dr. Xiomara M. Santos replied that the child had extensive labial hypertrophy due to chronic masturbation and experienced no complications as a result of surgery. The girl also had been diagnosed with precocious adrenarche. Dr. Santos stressed that in no case was a procedure performed for cosmetic reasons, and that patients and their mothers received extensive counseling on the risks and benefits prior to surgery.
Senior author Dr. Jennifer Dietrich, chief of gynecology at Texas Children's Hospital in Houston, said in an interview that labioplasty in adolescents is safe and effective for symptomatic labial hypertrophy, but that counseling and education cannot be emphasized enough. She noted that only two girls in the series were prepubertal: the 7-year-old and an 8-year-old with precocious puberty who developed symptomatic labial hypertrophy after vulvar trauma. Both girls had failed conservative management and underwent surgery because of considerable hygiene difficulties and chronic discomfort.
“Ultimately, these are procedures for patients who are symptomatic enough that it affects their daily life,” she said. “Patients and parents who consent regardless of conservative measures attempted are making a very private choice in this matter based on quality of life issues.”
The 37 girls underwent either bilateral or unilateral labioplasty with or without clitoral hood revision under general anesthesia between July 2007 and June 2010. Symptomatic labial hypertrophy was defined as labia minora of more than 4 cm, with 60% of patients having labia of 7–8 cm. The mean age was 12.6 years.
The straight surgical technique was used bilaterally in 17 patients and unilaterally in 5, the wedge excision technique bilaterally in 1 and unilaterally in 3, the elliptical technique in only 3 patients bilaterally, and the contoured technique bilaterally in only 1 patient. Clitoral hood revision for clitoral hood hypertrophy was performed in six patients. One patient underwent surgery after trauma.
Postoperative perineal care included conjugated estrogen cream and bacitracin in 34 patients and Silvadene cream in 3 patients, with sitz baths twice daily.
No intraoperative or major postoperative complications were reported among the 37 patients, with 10 (27%) experiencing minor postoperative complications, said Dr. Santos, a clinical fellow at Texas Children's Hospital. The complications included three wound infections, two cases of wound dehiscence, two wound hematomas, reaction to the prescribed cream in two patients, and severe postoperative pain requiring admission in one patient. All complications resolved with minor interventions by 6 weeks post procedure, with 70% resolving by 3 weeks.
Noncompliance with postoperative perineal care occurred in 27% of patients and was significantly correlated with having a minor postoperative complication, Dr. Santos said. No statistically significant correlation was identified with complication rates and surgical technique, suture type, type of procedure, body mass index (BMI), age, and age at menarche. Two patients were not satisfied with the surgery, resulting in an overall satisfaction rate of 94%.
Among 34 patients with long-term follow-up available, 3 patients (9%) experienced a recurrence, Dr. Santos reported. However, Dr. Dietrich told this news agency that her fellow misspoke and that only two patients (5.8%) experienced a recurrence, one 2 months after surgery and one 2 years later. Only one patient underwent a repeat procedure, both women said.
“Labial hypertrophy can cause significant physical and social discomfort,” Dr. Santos concluded. “Providers should perform the technique which he or she is comfortable with and best suits the patient's anatomy.”
When asked by the audience how satisfaction was measured, Dr. Santos replied that they asked the patient if she was happy with the result. The audience also asked how compliance with postoperative care was measured, to which Dr. Santos replied that they assumed the patients were following instructions. Her responses failed to satisfy the audience, with an attendee suggesting that resolution of symptoms would have been a more rigorous clinical end point than overall satisfaction and cautioning the authors about making assumptions that can change clinical practice. Dr. Santos agreed that satisfaction is a complex construct to measure, and said they did ask patients whether their symptoms resolved.
In a separate interview, Dr. Julie Strickland, immediate past-president of the North American Society for Pediatric and Adolescent Gynecology (NASPAG), also questioned the vigor of the study's methodology, and said part of the controversy lies in the use of plastic surgery in girls prior to menarche when they are neither physically or psychologically mature.
“There aren't rigid criteria of what is normal and abnormal, so we get this request a lot,” she said. “During adolescence it is really normal [for girls] to question their body composition and to worry about normalcy. They go to gym and they look slightly different from someone else, and that can really become a psychological issue that they grow out of. “So it's controversial if it should be done at all, except in extreme cases, and particularly below the age of 18 because it is a plastic procedure.”
Dr. Dietrich said that for every patient who presents with symptomatic hypertrophy, there are probably two patients who are concerned about appearance, but with counseling and education do not undergo a procedure.
The age of menarche for the group overall was about 11.5 years, but as early as 10 years, Dr. Dietrich said. Although BMI was not associated with complications, she noted that 60% of adolescents falling in the early adolescent category (10–14 years) were overweight or obese, which is a risk factor for earlier puberty and in line with girls developing earlier in the last few decades.
Recurrence in such young patients is also a critical issue, said Dr. Strickland of the University of Missouri–Kansas City. This can be particularly troublesome if a unilateral labioplasty is performed and repeat surgery is needed for the contralateral side. She observed that most recommendations and textbooks discuss labioplasty in cases of extreme symptomatic labial hypertrophy, but that it is segregated after growth is complete. Dr. Strickland defined extreme as labia that have undergone marked anatomic changes; are typically at least 8–9 cm in size; and can be pinched, difficult to clean, and eroded or irritated because of exposure to clothing.
In an interview, Dr. Santos reiterated that all of the patients were symptomatic, that they and their parents were told about the risks and benefits of surgery, and that labial hypertrophy can be managed without surgery.
'Labial hypertrophy can cause significant physical and social discomfort.'
Source DR. SANTOS
Major Finding: There were no intraoperative or major postoperative complications, and 10 patients (27%) experienced minor postoperative complications.
Data Source: Retrospective analysis of 37 girls with symptomatic labial hypertrophy who underwent bilateral or unilateral labioplasty with or without clitoral hood revision.
Disclosures: Dr. Santos and Dr. Dietrich reported no relevant financial disclosures.
CHICAGO – Labioplasty resulted in high rates of satisfaction and few complications in what is being described as the largest series of pediatric and adolescent females undergoing labioplasty for symptomatic labial hypertrophy.
The study in 37 girls, aged 7–17 years, evoked strong responses when presented at the meeting.
One audience member said she was disturbed by the age range of the participants, and questioned why labioplasty was even performed in a 7-year-old.
Principal investigator Dr. Xiomara M. Santos replied that the child had extensive labial hypertrophy due to chronic masturbation and experienced no complications as a result of surgery. The girl also had been diagnosed with precocious adrenarche. Dr. Santos stressed that in no case was a procedure performed for cosmetic reasons, and that patients and their mothers received extensive counseling on the risks and benefits prior to surgery.
Senior author Dr. Jennifer Dietrich, chief of gynecology at Texas Children's Hospital in Houston, said in an interview that labioplasty in adolescents is safe and effective for symptomatic labial hypertrophy, but that counseling and education cannot be emphasized enough. She noted that only two girls in the series were prepubertal: the 7-year-old and an 8-year-old with precocious puberty who developed symptomatic labial hypertrophy after vulvar trauma. Both girls had failed conservative management and underwent surgery because of considerable hygiene difficulties and chronic discomfort.
“Ultimately, these are procedures for patients who are symptomatic enough that it affects their daily life,” she said. “Patients and parents who consent regardless of conservative measures attempted are making a very private choice in this matter based on quality of life issues.”
The 37 girls underwent either bilateral or unilateral labioplasty with or without clitoral hood revision under general anesthesia between July 2007 and June 2010. Symptomatic labial hypertrophy was defined as labia minora of more than 4 cm, with 60% of patients having labia of 7–8 cm. The mean age was 12.6 years.
The straight surgical technique was used bilaterally in 17 patients and unilaterally in 5, the wedge excision technique bilaterally in 1 and unilaterally in 3, the elliptical technique in only 3 patients bilaterally, and the contoured technique bilaterally in only 1 patient. Clitoral hood revision for clitoral hood hypertrophy was performed in six patients. One patient underwent surgery after trauma.
Postoperative perineal care included conjugated estrogen cream and bacitracin in 34 patients and Silvadene cream in 3 patients, with sitz baths twice daily.
No intraoperative or major postoperative complications were reported among the 37 patients, with 10 (27%) experiencing minor postoperative complications, said Dr. Santos, a clinical fellow at Texas Children's Hospital. The complications included three wound infections, two cases of wound dehiscence, two wound hematomas, reaction to the prescribed cream in two patients, and severe postoperative pain requiring admission in one patient. All complications resolved with minor interventions by 6 weeks post procedure, with 70% resolving by 3 weeks.
Noncompliance with postoperative perineal care occurred in 27% of patients and was significantly correlated with having a minor postoperative complication, Dr. Santos said. No statistically significant correlation was identified with complication rates and surgical technique, suture type, type of procedure, body mass index (BMI), age, and age at menarche. Two patients were not satisfied with the surgery, resulting in an overall satisfaction rate of 94%.
Among 34 patients with long-term follow-up available, 3 patients (9%) experienced a recurrence, Dr. Santos reported. However, Dr. Dietrich told this news agency that her fellow misspoke and that only two patients (5.8%) experienced a recurrence, one 2 months after surgery and one 2 years later. Only one patient underwent a repeat procedure, both women said.
“Labial hypertrophy can cause significant physical and social discomfort,” Dr. Santos concluded. “Providers should perform the technique which he or she is comfortable with and best suits the patient's anatomy.”
When asked by the audience how satisfaction was measured, Dr. Santos replied that they asked the patient if she was happy with the result. The audience also asked how compliance with postoperative care was measured, to which Dr. Santos replied that they assumed the patients were following instructions. Her responses failed to satisfy the audience, with an attendee suggesting that resolution of symptoms would have been a more rigorous clinical end point than overall satisfaction and cautioning the authors about making assumptions that can change clinical practice. Dr. Santos agreed that satisfaction is a complex construct to measure, and said they did ask patients whether their symptoms resolved.
In a separate interview, Dr. Julie Strickland, immediate past-president of the North American Society for Pediatric and Adolescent Gynecology (NASPAG), also questioned the vigor of the study's methodology, and said part of the controversy lies in the use of plastic surgery in girls prior to menarche when they are neither physically or psychologically mature.
“There aren't rigid criteria of what is normal and abnormal, so we get this request a lot,” she said. “During adolescence it is really normal [for girls] to question their body composition and to worry about normalcy. They go to gym and they look slightly different from someone else, and that can really become a psychological issue that they grow out of. “So it's controversial if it should be done at all, except in extreme cases, and particularly below the age of 18 because it is a plastic procedure.”
Dr. Dietrich said that for every patient who presents with symptomatic hypertrophy, there are probably two patients who are concerned about appearance, but with counseling and education do not undergo a procedure.
The age of menarche for the group overall was about 11.5 years, but as early as 10 years, Dr. Dietrich said. Although BMI was not associated with complications, she noted that 60% of adolescents falling in the early adolescent category (10–14 years) were overweight or obese, which is a risk factor for earlier puberty and in line with girls developing earlier in the last few decades.
Recurrence in such young patients is also a critical issue, said Dr. Strickland of the University of Missouri–Kansas City. This can be particularly troublesome if a unilateral labioplasty is performed and repeat surgery is needed for the contralateral side. She observed that most recommendations and textbooks discuss labioplasty in cases of extreme symptomatic labial hypertrophy, but that it is segregated after growth is complete. Dr. Strickland defined extreme as labia that have undergone marked anatomic changes; are typically at least 8–9 cm in size; and can be pinched, difficult to clean, and eroded or irritated because of exposure to clothing.
In an interview, Dr. Santos reiterated that all of the patients were symptomatic, that they and their parents were told about the risks and benefits of surgery, and that labial hypertrophy can be managed without surgery.
'Labial hypertrophy can cause significant physical and social discomfort.'
Source DR. SANTOS
Major Finding: There were no intraoperative or major postoperative complications, and 10 patients (27%) experienced minor postoperative complications.
Data Source: Retrospective analysis of 37 girls with symptomatic labial hypertrophy who underwent bilateral or unilateral labioplasty with or without clitoral hood revision.
Disclosures: Dr. Santos and Dr. Dietrich reported no relevant financial disclosures.
CHICAGO – Labioplasty resulted in high rates of satisfaction and few complications in what is being described as the largest series of pediatric and adolescent females undergoing labioplasty for symptomatic labial hypertrophy.
The study in 37 girls, aged 7–17 years, evoked strong responses when presented at the meeting.
One audience member said she was disturbed by the age range of the participants, and questioned why labioplasty was even performed in a 7-year-old.
Principal investigator Dr. Xiomara M. Santos replied that the child had extensive labial hypertrophy due to chronic masturbation and experienced no complications as a result of surgery. The girl also had been diagnosed with precocious adrenarche. Dr. Santos stressed that in no case was a procedure performed for cosmetic reasons, and that patients and their mothers received extensive counseling on the risks and benefits prior to surgery.
Senior author Dr. Jennifer Dietrich, chief of gynecology at Texas Children's Hospital in Houston, said in an interview that labioplasty in adolescents is safe and effective for symptomatic labial hypertrophy, but that counseling and education cannot be emphasized enough. She noted that only two girls in the series were prepubertal: the 7-year-old and an 8-year-old with precocious puberty who developed symptomatic labial hypertrophy after vulvar trauma. Both girls had failed conservative management and underwent surgery because of considerable hygiene difficulties and chronic discomfort.
“Ultimately, these are procedures for patients who are symptomatic enough that it affects their daily life,” she said. “Patients and parents who consent regardless of conservative measures attempted are making a very private choice in this matter based on quality of life issues.”
The 37 girls underwent either bilateral or unilateral labioplasty with or without clitoral hood revision under general anesthesia between July 2007 and June 2010. Symptomatic labial hypertrophy was defined as labia minora of more than 4 cm, with 60% of patients having labia of 7–8 cm. The mean age was 12.6 years.
The straight surgical technique was used bilaterally in 17 patients and unilaterally in 5, the wedge excision technique bilaterally in 1 and unilaterally in 3, the elliptical technique in only 3 patients bilaterally, and the contoured technique bilaterally in only 1 patient. Clitoral hood revision for clitoral hood hypertrophy was performed in six patients. One patient underwent surgery after trauma.
Postoperative perineal care included conjugated estrogen cream and bacitracin in 34 patients and Silvadene cream in 3 patients, with sitz baths twice daily.
No intraoperative or major postoperative complications were reported among the 37 patients, with 10 (27%) experiencing minor postoperative complications, said Dr. Santos, a clinical fellow at Texas Children's Hospital. The complications included three wound infections, two cases of wound dehiscence, two wound hematomas, reaction to the prescribed cream in two patients, and severe postoperative pain requiring admission in one patient. All complications resolved with minor interventions by 6 weeks post procedure, with 70% resolving by 3 weeks.
Noncompliance with postoperative perineal care occurred in 27% of patients and was significantly correlated with having a minor postoperative complication, Dr. Santos said. No statistically significant correlation was identified with complication rates and surgical technique, suture type, type of procedure, body mass index (BMI), age, and age at menarche. Two patients were not satisfied with the surgery, resulting in an overall satisfaction rate of 94%.
Among 34 patients with long-term follow-up available, 3 patients (9%) experienced a recurrence, Dr. Santos reported. However, Dr. Dietrich told this news agency that her fellow misspoke and that only two patients (5.8%) experienced a recurrence, one 2 months after surgery and one 2 years later. Only one patient underwent a repeat procedure, both women said.
“Labial hypertrophy can cause significant physical and social discomfort,” Dr. Santos concluded. “Providers should perform the technique which he or she is comfortable with and best suits the patient's anatomy.”
When asked by the audience how satisfaction was measured, Dr. Santos replied that they asked the patient if she was happy with the result. The audience also asked how compliance with postoperative care was measured, to which Dr. Santos replied that they assumed the patients were following instructions. Her responses failed to satisfy the audience, with an attendee suggesting that resolution of symptoms would have been a more rigorous clinical end point than overall satisfaction and cautioning the authors about making assumptions that can change clinical practice. Dr. Santos agreed that satisfaction is a complex construct to measure, and said they did ask patients whether their symptoms resolved.
In a separate interview, Dr. Julie Strickland, immediate past-president of the North American Society for Pediatric and Adolescent Gynecology (NASPAG), also questioned the vigor of the study's methodology, and said part of the controversy lies in the use of plastic surgery in girls prior to menarche when they are neither physically or psychologically mature.
“There aren't rigid criteria of what is normal and abnormal, so we get this request a lot,” she said. “During adolescence it is really normal [for girls] to question their body composition and to worry about normalcy. They go to gym and they look slightly different from someone else, and that can really become a psychological issue that they grow out of. “So it's controversial if it should be done at all, except in extreme cases, and particularly below the age of 18 because it is a plastic procedure.”
Dr. Dietrich said that for every patient who presents with symptomatic hypertrophy, there are probably two patients who are concerned about appearance, but with counseling and education do not undergo a procedure.
The age of menarche for the group overall was about 11.5 years, but as early as 10 years, Dr. Dietrich said. Although BMI was not associated with complications, she noted that 60% of adolescents falling in the early adolescent category (10–14 years) were overweight or obese, which is a risk factor for earlier puberty and in line with girls developing earlier in the last few decades.
Recurrence in such young patients is also a critical issue, said Dr. Strickland of the University of Missouri–Kansas City. This can be particularly troublesome if a unilateral labioplasty is performed and repeat surgery is needed for the contralateral side. She observed that most recommendations and textbooks discuss labioplasty in cases of extreme symptomatic labial hypertrophy, but that it is segregated after growth is complete. Dr. Strickland defined extreme as labia that have undergone marked anatomic changes; are typically at least 8–9 cm in size; and can be pinched, difficult to clean, and eroded or irritated because of exposure to clothing.
In an interview, Dr. Santos reiterated that all of the patients were symptomatic, that they and their parents were told about the risks and benefits of surgery, and that labial hypertrophy can be managed without surgery.
'Labial hypertrophy can cause significant physical and social discomfort.'
Source DR. SANTOS
From the Annual Meeting of the North American Society for Pediatric and Adolescent Gynecology
RAPS: Radial Artery Tops Saphenous Vein Graft
Major Finding: Functional graft occlusion at 5 years was 12% in radial artery grafts and nearly 19% in saphenous vein grafts.
Data Source: Multicenter, randomized Radial Artery Patency Study in 269 patients.
Disclosures: The Canadian Institutes of Health Research funded the study. Dr. Fremes reported no conflicts.
NEW ORLEANS – Long-term data from the Radial Artery Patency Study show that radial arteries, compared with saphenous veins, are associated with reduced rates of functional and complete graft occlusion in patients undergoing coronary artery bypass surgery.
Radial arteries also are associated with lower rates of graft disease, lead author Dr. Stephen E. Fremes said during a late-breaking trial session at the meeting.
The issue of which conduit provides the best long-term graft outcomes has been a subject of debate. Several trials have indicated that radial artery grafts are no better than saphenous vein grafts, including a Veterans Affairs study showing similar 1-year graft patency among 757 patients undergoing first-time, elective coronary artery bypass grafting (JAMA 2011;305:167-74). One-year data from the Radial Artery Patency Study (RAPS) showed that complete graft occlusion was significantly reduced in radial artery grafts compared with saphenous vein grafts (8.2% vs. 13.6%), but that partial graft occlusion was similar (12.3% vs. 14.3%) between the two conduits (N. Engl. J. Med. 2004;351:2302-9).
When Dr. Fremes was asked how to reconcile the results of RAPS with those from the VA study, he replied that the VA study was conducted almost exclusively in men (99%), vein grafts performed better than predicted, and there were very high rates of evidence-based medicine. Adherence to evidence-based medicine was good in RAPS, but the trial accrued much earlier, from November 1996 to January 2001. The mean age of the 269 patients in the current analysis was 60 years, and 15% were women.
RAPS enrolled 561 patients with isolated triple-vessel disease and a left ventricular fraction of more than 35% from 12 Canadian centers and 1 in New Zealand. Randomization was unique in that it was performed within patients and not between patients, said Dr. Fremes, head of the cardiovascular surgery division at Sunnybrook Health Sciences Centre and research director at the Schulich Heart Centre at Sunnybrook, Toronto. Patients were randomized to receive either a radial artery to the right coronary territory and a saphenous vein to the circumflex territory or a saphenous vein to the right coronary territory and a radial artery to the circumflex territory.
Late angiography was performed on 440 patients at 1 year and on 269 patients at a mean of 7.6 years after surgery. Grafts were considered occluded if they had a TIMI (Thrombolysis in Myocardial Infarction) score of 0-2, and were considered patent with a TIMI score of 3.
At 5 years, the primary end point of functional graft occlusion was significantly decreased in radial artery grafts at 12%, compared with saphenous vein grafts at 18.8% (odds ratio, 0.64), Dr. Fremes said. Significantly fewer radial artery grafts also became completely occluded at 9%, compared with saphenous-vein grafts at 18% (OR, 0.50).
Among 164 patients who had completely patent grafts at follow-up, graft stenosis was similar for both conduits for proximal and distal anastomotic lesions. There were fewer graft-body lesions at 6.7% in radial arteries, vs. saphenous veins at 15.2% (OR, 0.42). Consequently, radial artery grafts were significantly less likely to be either stenotic or completely occluded at 22%, compared with saphenous vein grafts at 34% (OR, 0.58), he said.
Target vessel stenosis, an important risk factor for graft occlusion at 1 year, was evaluated in a subgroup analysis. Target vessels with stenosis were classified a priori as those with 70%-89% narrowing and those with at least 90% narrowing. Although graft occlusion was reduced almost 50% for either graft in target vessels with at least 90% narrowing, radial artery grafts had much lower functional (8.8%) and complete (6.3%) occlusion rates, as did saphenous vein grafts (14.6% and 14.5%, respectively), in the more severely narrowed vessels.
The incidence of cardiac death beyond 1 year was 5%, of nonfatal myocardial infarction was 1.5%, and of major adverse cardiac events was 15%. Dr. Fremes pointed out that the clinical event findings were descriptive rather than explanatory since each patient received both graft types.
Overall survival in the entire cohort was 96% at 5 years, 91% at 7.5 years, and 78% at 10 years. Event-free survival was 95%, 90%, and 78%, respectively.
“This [study] lends credence to utilizing the radial artery, with obvious caveats that it is important to place it in highly obstructed vessels so there is not competitive flow and to maintain patency for the longest period of time,” Dr. James McClurken, professor and vice-chair of surgery at Temple University, Philadelphia, said in a panel discussion. “This is not quite as good as internal mammary artery patency data, but certainly better than vein-graft data.”
Fellow discussant Dr. Steven Bolling, a thoracic surgeon at the University of Michigan, Ann Arbor, said he expects the data will shift practice and increase utilization of the radial artery graft.
When asked about this point at a press conference, Dr. Fremes said that radial artery utilization varies by jurisdiction at about 20%, compared with more than 95% for the internal mammary artery. He noted that the evidence to date on radial artery grafts has been mixed and comes mainly from observational studies.
“The study we presented is the first multi-institutional, longitudinal, randomized comparison, so this is fairly unique data,” he said. “Hopefully, it will be persuasive.”
Major Finding: Functional graft occlusion at 5 years was 12% in radial artery grafts and nearly 19% in saphenous vein grafts.
Data Source: Multicenter, randomized Radial Artery Patency Study in 269 patients.
Disclosures: The Canadian Institutes of Health Research funded the study. Dr. Fremes reported no conflicts.
NEW ORLEANS – Long-term data from the Radial Artery Patency Study show that radial arteries, compared with saphenous veins, are associated with reduced rates of functional and complete graft occlusion in patients undergoing coronary artery bypass surgery.
Radial arteries also are associated with lower rates of graft disease, lead author Dr. Stephen E. Fremes said during a late-breaking trial session at the meeting.
The issue of which conduit provides the best long-term graft outcomes has been a subject of debate. Several trials have indicated that radial artery grafts are no better than saphenous vein grafts, including a Veterans Affairs study showing similar 1-year graft patency among 757 patients undergoing first-time, elective coronary artery bypass grafting (JAMA 2011;305:167-74). One-year data from the Radial Artery Patency Study (RAPS) showed that complete graft occlusion was significantly reduced in radial artery grafts compared with saphenous vein grafts (8.2% vs. 13.6%), but that partial graft occlusion was similar (12.3% vs. 14.3%) between the two conduits (N. Engl. J. Med. 2004;351:2302-9).
When Dr. Fremes was asked how to reconcile the results of RAPS with those from the VA study, he replied that the VA study was conducted almost exclusively in men (99%), vein grafts performed better than predicted, and there were very high rates of evidence-based medicine. Adherence to evidence-based medicine was good in RAPS, but the trial accrued much earlier, from November 1996 to January 2001. The mean age of the 269 patients in the current analysis was 60 years, and 15% were women.
RAPS enrolled 561 patients with isolated triple-vessel disease and a left ventricular fraction of more than 35% from 12 Canadian centers and 1 in New Zealand. Randomization was unique in that it was performed within patients and not between patients, said Dr. Fremes, head of the cardiovascular surgery division at Sunnybrook Health Sciences Centre and research director at the Schulich Heart Centre at Sunnybrook, Toronto. Patients were randomized to receive either a radial artery to the right coronary territory and a saphenous vein to the circumflex territory or a saphenous vein to the right coronary territory and a radial artery to the circumflex territory.
Late angiography was performed on 440 patients at 1 year and on 269 patients at a mean of 7.6 years after surgery. Grafts were considered occluded if they had a TIMI (Thrombolysis in Myocardial Infarction) score of 0-2, and were considered patent with a TIMI score of 3.
At 5 years, the primary end point of functional graft occlusion was significantly decreased in radial artery grafts at 12%, compared with saphenous vein grafts at 18.8% (odds ratio, 0.64), Dr. Fremes said. Significantly fewer radial artery grafts also became completely occluded at 9%, compared with saphenous-vein grafts at 18% (OR, 0.50).
Among 164 patients who had completely patent grafts at follow-up, graft stenosis was similar for both conduits for proximal and distal anastomotic lesions. There were fewer graft-body lesions at 6.7% in radial arteries, vs. saphenous veins at 15.2% (OR, 0.42). Consequently, radial artery grafts were significantly less likely to be either stenotic or completely occluded at 22%, compared with saphenous vein grafts at 34% (OR, 0.58), he said.
Target vessel stenosis, an important risk factor for graft occlusion at 1 year, was evaluated in a subgroup analysis. Target vessels with stenosis were classified a priori as those with 70%-89% narrowing and those with at least 90% narrowing. Although graft occlusion was reduced almost 50% for either graft in target vessels with at least 90% narrowing, radial artery grafts had much lower functional (8.8%) and complete (6.3%) occlusion rates, as did saphenous vein grafts (14.6% and 14.5%, respectively), in the more severely narrowed vessels.
The incidence of cardiac death beyond 1 year was 5%, of nonfatal myocardial infarction was 1.5%, and of major adverse cardiac events was 15%. Dr. Fremes pointed out that the clinical event findings were descriptive rather than explanatory since each patient received both graft types.
Overall survival in the entire cohort was 96% at 5 years, 91% at 7.5 years, and 78% at 10 years. Event-free survival was 95%, 90%, and 78%, respectively.
“This [study] lends credence to utilizing the radial artery, with obvious caveats that it is important to place it in highly obstructed vessels so there is not competitive flow and to maintain patency for the longest period of time,” Dr. James McClurken, professor and vice-chair of surgery at Temple University, Philadelphia, said in a panel discussion. “This is not quite as good as internal mammary artery patency data, but certainly better than vein-graft data.”
Fellow discussant Dr. Steven Bolling, a thoracic surgeon at the University of Michigan, Ann Arbor, said he expects the data will shift practice and increase utilization of the radial artery graft.
When asked about this point at a press conference, Dr. Fremes said that radial artery utilization varies by jurisdiction at about 20%, compared with more than 95% for the internal mammary artery. He noted that the evidence to date on radial artery grafts has been mixed and comes mainly from observational studies.
“The study we presented is the first multi-institutional, longitudinal, randomized comparison, so this is fairly unique data,” he said. “Hopefully, it will be persuasive.”
Major Finding: Functional graft occlusion at 5 years was 12% in radial artery grafts and nearly 19% in saphenous vein grafts.
Data Source: Multicenter, randomized Radial Artery Patency Study in 269 patients.
Disclosures: The Canadian Institutes of Health Research funded the study. Dr. Fremes reported no conflicts.
NEW ORLEANS – Long-term data from the Radial Artery Patency Study show that radial arteries, compared with saphenous veins, are associated with reduced rates of functional and complete graft occlusion in patients undergoing coronary artery bypass surgery.
Radial arteries also are associated with lower rates of graft disease, lead author Dr. Stephen E. Fremes said during a late-breaking trial session at the meeting.
The issue of which conduit provides the best long-term graft outcomes has been a subject of debate. Several trials have indicated that radial artery grafts are no better than saphenous vein grafts, including a Veterans Affairs study showing similar 1-year graft patency among 757 patients undergoing first-time, elective coronary artery bypass grafting (JAMA 2011;305:167-74). One-year data from the Radial Artery Patency Study (RAPS) showed that complete graft occlusion was significantly reduced in radial artery grafts compared with saphenous vein grafts (8.2% vs. 13.6%), but that partial graft occlusion was similar (12.3% vs. 14.3%) between the two conduits (N. Engl. J. Med. 2004;351:2302-9).
When Dr. Fremes was asked how to reconcile the results of RAPS with those from the VA study, he replied that the VA study was conducted almost exclusively in men (99%), vein grafts performed better than predicted, and there were very high rates of evidence-based medicine. Adherence to evidence-based medicine was good in RAPS, but the trial accrued much earlier, from November 1996 to January 2001. The mean age of the 269 patients in the current analysis was 60 years, and 15% were women.
RAPS enrolled 561 patients with isolated triple-vessel disease and a left ventricular fraction of more than 35% from 12 Canadian centers and 1 in New Zealand. Randomization was unique in that it was performed within patients and not between patients, said Dr. Fremes, head of the cardiovascular surgery division at Sunnybrook Health Sciences Centre and research director at the Schulich Heart Centre at Sunnybrook, Toronto. Patients were randomized to receive either a radial artery to the right coronary territory and a saphenous vein to the circumflex territory or a saphenous vein to the right coronary territory and a radial artery to the circumflex territory.
Late angiography was performed on 440 patients at 1 year and on 269 patients at a mean of 7.6 years after surgery. Grafts were considered occluded if they had a TIMI (Thrombolysis in Myocardial Infarction) score of 0-2, and were considered patent with a TIMI score of 3.
At 5 years, the primary end point of functional graft occlusion was significantly decreased in radial artery grafts at 12%, compared with saphenous vein grafts at 18.8% (odds ratio, 0.64), Dr. Fremes said. Significantly fewer radial artery grafts also became completely occluded at 9%, compared with saphenous-vein grafts at 18% (OR, 0.50).
Among 164 patients who had completely patent grafts at follow-up, graft stenosis was similar for both conduits for proximal and distal anastomotic lesions. There were fewer graft-body lesions at 6.7% in radial arteries, vs. saphenous veins at 15.2% (OR, 0.42). Consequently, radial artery grafts were significantly less likely to be either stenotic or completely occluded at 22%, compared with saphenous vein grafts at 34% (OR, 0.58), he said.
Target vessel stenosis, an important risk factor for graft occlusion at 1 year, was evaluated in a subgroup analysis. Target vessels with stenosis were classified a priori as those with 70%-89% narrowing and those with at least 90% narrowing. Although graft occlusion was reduced almost 50% for either graft in target vessels with at least 90% narrowing, radial artery grafts had much lower functional (8.8%) and complete (6.3%) occlusion rates, as did saphenous vein grafts (14.6% and 14.5%, respectively), in the more severely narrowed vessels.
The incidence of cardiac death beyond 1 year was 5%, of nonfatal myocardial infarction was 1.5%, and of major adverse cardiac events was 15%. Dr. Fremes pointed out that the clinical event findings were descriptive rather than explanatory since each patient received both graft types.
Overall survival in the entire cohort was 96% at 5 years, 91% at 7.5 years, and 78% at 10 years. Event-free survival was 95%, 90%, and 78%, respectively.
“This [study] lends credence to utilizing the radial artery, with obvious caveats that it is important to place it in highly obstructed vessels so there is not competitive flow and to maintain patency for the longest period of time,” Dr. James McClurken, professor and vice-chair of surgery at Temple University, Philadelphia, said in a panel discussion. “This is not quite as good as internal mammary artery patency data, but certainly better than vein-graft data.”
Fellow discussant Dr. Steven Bolling, a thoracic surgeon at the University of Michigan, Ann Arbor, said he expects the data will shift practice and increase utilization of the radial artery graft.
When asked about this point at a press conference, Dr. Fremes said that radial artery utilization varies by jurisdiction at about 20%, compared with more than 95% for the internal mammary artery. He noted that the evidence to date on radial artery grafts has been mixed and comes mainly from observational studies.
“The study we presented is the first multi-institutional, longitudinal, randomized comparison, so this is fairly unique data,” he said. “Hopefully, it will be persuasive.”
Teduglutide Cuts Parenteral Nutrition Needs in Short-Bowel Syndrome
CHICAGO – Phase III data from a randomized, placebo-controlled trial indicate that the novel agent teduglutide reduces the need for parenteral support in patients with short-bowel syndrome.
At week 20 and week 24, 63% of patients who were randomized to teduglutide (Gattex) achieved at least a 20% reduction in the volume of parenteral fluid required, compared with baseline. Only 30% of patients receiving the placebo achieved this degree of reduction in their parenteral nutrition needs (P = .002), said lead author Dr. Palle B. Jeppesen during a late-breaking abstract session at the annual Digestive Disease Week.
Short-bowel syndrome (SBS) results from removal of the small intestine because of Crohn’s disease, cancer, or other conditions, and is characterized by malabsorption of nutrients, fluids, and electrolytes, as well as diarrhea. An estimated 10,000-15,000 SBS patients in North America are dependent on parenteral nutrition (PN) for their fluid and nutritional needs, at an annual cost that can exceed $100,000 per patient.
"This has a tremendous impact on their life situation, and of course, what we would like to do is provide them with some treatment, getting them off their parental support," said Dr. Jeppesen, with the Copenhagen University Hospital.
Teduglutide is a recombinant analogue of glucagonlike peptide 2, a peptide that enhances intestinal absorption by thickening the intestinal mucosa and increasing villus height and crypt depth.
Teduglutide has been designated an orphan drug for the treatment of SBS by the Food and Drug Administration and the European Medicines Agency. An application was submitted in March to market teduglutide with the brand name Revestive in Europe as a once-daily subcutaneous treatment for SBS, with a similar application under the brand name Gattex expected later this year in the United States, according to study sponsor NPS Pharmaceuticals. In the STEPS (Study of Teduglutide in PN-Dependent Short-Bowel Syndrome) trial, patients had at least 12 continuous months of PN support prior to enrollment; required PN at least three times weekly to meet caloric, fluid, or electrolyte needs; and had a body mass index of at least 15 kg/m2.
After an initial 30-day stabilization period, 86 patients were randomized to subcutaneous teduglutide 0.05 mg/kg or placebo once daily for 24 weeks. One patient in the teduglutide group was randomized in error and not treated.
At baseline, the teduglutide and placebo groups were similar in age (51 years vs. 50 years), weight (63 kg vs. 62 kg), estimated mean small bowel length (84 cm vs. 69 cm), and mean baseline liters of intravenous PN fluid per week (12.5 L vs. 13.4 L).
At week 24, the mean absolute reduction in PN fluid required by the patient was 4.4 L in the teduglutide group vs.2.3 L in the placebo group (P less than .001), Dr. Jeppesen said.
Significantly more patients who were treated with teduglutide had one or more additional days off parenteral infusions (54% vs. 23%; P = .0047). "Having days off parenteral support is an important issue for their social life," he said.
During a discussion of the study, an attendee asked whether patients will be able to take teduglutide cyclically or will need the drug continually for the rest of their lives. Dr. Jeppesen replied that "it is going to be like treating diabetes. It only works when you give them insulin, and it’s the same case with this drug. It works as long as you give it, and when you take it off they go back to their baseline."
Audience members then asked whether there are any long-term effects of teduglutide, particularly in light of concerns that were raised early on about tumor promotion, which have been reportedly addressed by NPS Pharmaceuticals. Dr. Jeppesen said there is no reason to expect any problems and that the drug has a very good safety profile.
Another attendee asked whether teduglutide is likely to be helpful for unstable patients, and Dr. Jeppesen responded that yes, this is likely.
The most common treatment-emergent adverse events in the teduglutide and placebo groups were abdominal pain (31% vs. 23%), nausea (29% vs. 19%), and stoma complications (24% vs. 7%). Physicians should explain to teduglutide patients that abdominal discomfort resulting from growth of the bowel is to be expected, Dr. Jeppesen said.
Three patients discontinued teduglutide; the reasons were abdominal distention, abdominal pain, and investigator decision. Four patients discontinued placebo treatment. There were no deaths in the study.
Dr. Jeppesen disclosed consulting for the study sponsor, NPS Pharmaceuticals.
CHICAGO – Phase III data from a randomized, placebo-controlled trial indicate that the novel agent teduglutide reduces the need for parenteral support in patients with short-bowel syndrome.
At week 20 and week 24, 63% of patients who were randomized to teduglutide (Gattex) achieved at least a 20% reduction in the volume of parenteral fluid required, compared with baseline. Only 30% of patients receiving the placebo achieved this degree of reduction in their parenteral nutrition needs (P = .002), said lead author Dr. Palle B. Jeppesen during a late-breaking abstract session at the annual Digestive Disease Week.
Short-bowel syndrome (SBS) results from removal of the small intestine because of Crohn’s disease, cancer, or other conditions, and is characterized by malabsorption of nutrients, fluids, and electrolytes, as well as diarrhea. An estimated 10,000-15,000 SBS patients in North America are dependent on parenteral nutrition (PN) for their fluid and nutritional needs, at an annual cost that can exceed $100,000 per patient.
"This has a tremendous impact on their life situation, and of course, what we would like to do is provide them with some treatment, getting them off their parental support," said Dr. Jeppesen, with the Copenhagen University Hospital.
Teduglutide is a recombinant analogue of glucagonlike peptide 2, a peptide that enhances intestinal absorption by thickening the intestinal mucosa and increasing villus height and crypt depth.
Teduglutide has been designated an orphan drug for the treatment of SBS by the Food and Drug Administration and the European Medicines Agency. An application was submitted in March to market teduglutide with the brand name Revestive in Europe as a once-daily subcutaneous treatment for SBS, with a similar application under the brand name Gattex expected later this year in the United States, according to study sponsor NPS Pharmaceuticals. In the STEPS (Study of Teduglutide in PN-Dependent Short-Bowel Syndrome) trial, patients had at least 12 continuous months of PN support prior to enrollment; required PN at least three times weekly to meet caloric, fluid, or electrolyte needs; and had a body mass index of at least 15 kg/m2.
After an initial 30-day stabilization period, 86 patients were randomized to subcutaneous teduglutide 0.05 mg/kg or placebo once daily for 24 weeks. One patient in the teduglutide group was randomized in error and not treated.
At baseline, the teduglutide and placebo groups were similar in age (51 years vs. 50 years), weight (63 kg vs. 62 kg), estimated mean small bowel length (84 cm vs. 69 cm), and mean baseline liters of intravenous PN fluid per week (12.5 L vs. 13.4 L).
At week 24, the mean absolute reduction in PN fluid required by the patient was 4.4 L in the teduglutide group vs.2.3 L in the placebo group (P less than .001), Dr. Jeppesen said.
Significantly more patients who were treated with teduglutide had one or more additional days off parenteral infusions (54% vs. 23%; P = .0047). "Having days off parenteral support is an important issue for their social life," he said.
During a discussion of the study, an attendee asked whether patients will be able to take teduglutide cyclically or will need the drug continually for the rest of their lives. Dr. Jeppesen replied that "it is going to be like treating diabetes. It only works when you give them insulin, and it’s the same case with this drug. It works as long as you give it, and when you take it off they go back to their baseline."
Audience members then asked whether there are any long-term effects of teduglutide, particularly in light of concerns that were raised early on about tumor promotion, which have been reportedly addressed by NPS Pharmaceuticals. Dr. Jeppesen said there is no reason to expect any problems and that the drug has a very good safety profile.
Another attendee asked whether teduglutide is likely to be helpful for unstable patients, and Dr. Jeppesen responded that yes, this is likely.
The most common treatment-emergent adverse events in the teduglutide and placebo groups were abdominal pain (31% vs. 23%), nausea (29% vs. 19%), and stoma complications (24% vs. 7%). Physicians should explain to teduglutide patients that abdominal discomfort resulting from growth of the bowel is to be expected, Dr. Jeppesen said.
Three patients discontinued teduglutide; the reasons were abdominal distention, abdominal pain, and investigator decision. Four patients discontinued placebo treatment. There were no deaths in the study.
Dr. Jeppesen disclosed consulting for the study sponsor, NPS Pharmaceuticals.
CHICAGO – Phase III data from a randomized, placebo-controlled trial indicate that the novel agent teduglutide reduces the need for parenteral support in patients with short-bowel syndrome.
At week 20 and week 24, 63% of patients who were randomized to teduglutide (Gattex) achieved at least a 20% reduction in the volume of parenteral fluid required, compared with baseline. Only 30% of patients receiving the placebo achieved this degree of reduction in their parenteral nutrition needs (P = .002), said lead author Dr. Palle B. Jeppesen during a late-breaking abstract session at the annual Digestive Disease Week.
Short-bowel syndrome (SBS) results from removal of the small intestine because of Crohn’s disease, cancer, or other conditions, and is characterized by malabsorption of nutrients, fluids, and electrolytes, as well as diarrhea. An estimated 10,000-15,000 SBS patients in North America are dependent on parenteral nutrition (PN) for their fluid and nutritional needs, at an annual cost that can exceed $100,000 per patient.
"This has a tremendous impact on their life situation, and of course, what we would like to do is provide them with some treatment, getting them off their parental support," said Dr. Jeppesen, with the Copenhagen University Hospital.
Teduglutide is a recombinant analogue of glucagonlike peptide 2, a peptide that enhances intestinal absorption by thickening the intestinal mucosa and increasing villus height and crypt depth.
Teduglutide has been designated an orphan drug for the treatment of SBS by the Food and Drug Administration and the European Medicines Agency. An application was submitted in March to market teduglutide with the brand name Revestive in Europe as a once-daily subcutaneous treatment for SBS, with a similar application under the brand name Gattex expected later this year in the United States, according to study sponsor NPS Pharmaceuticals. In the STEPS (Study of Teduglutide in PN-Dependent Short-Bowel Syndrome) trial, patients had at least 12 continuous months of PN support prior to enrollment; required PN at least three times weekly to meet caloric, fluid, or electrolyte needs; and had a body mass index of at least 15 kg/m2.
After an initial 30-day stabilization period, 86 patients were randomized to subcutaneous teduglutide 0.05 mg/kg or placebo once daily for 24 weeks. One patient in the teduglutide group was randomized in error and not treated.
At baseline, the teduglutide and placebo groups were similar in age (51 years vs. 50 years), weight (63 kg vs. 62 kg), estimated mean small bowel length (84 cm vs. 69 cm), and mean baseline liters of intravenous PN fluid per week (12.5 L vs. 13.4 L).
At week 24, the mean absolute reduction in PN fluid required by the patient was 4.4 L in the teduglutide group vs.2.3 L in the placebo group (P less than .001), Dr. Jeppesen said.
Significantly more patients who were treated with teduglutide had one or more additional days off parenteral infusions (54% vs. 23%; P = .0047). "Having days off parenteral support is an important issue for their social life," he said.
During a discussion of the study, an attendee asked whether patients will be able to take teduglutide cyclically or will need the drug continually for the rest of their lives. Dr. Jeppesen replied that "it is going to be like treating diabetes. It only works when you give them insulin, and it’s the same case with this drug. It works as long as you give it, and when you take it off they go back to their baseline."
Audience members then asked whether there are any long-term effects of teduglutide, particularly in light of concerns that were raised early on about tumor promotion, which have been reportedly addressed by NPS Pharmaceuticals. Dr. Jeppesen said there is no reason to expect any problems and that the drug has a very good safety profile.
Another attendee asked whether teduglutide is likely to be helpful for unstable patients, and Dr. Jeppesen responded that yes, this is likely.
The most common treatment-emergent adverse events in the teduglutide and placebo groups were abdominal pain (31% vs. 23%), nausea (29% vs. 19%), and stoma complications (24% vs. 7%). Physicians should explain to teduglutide patients that abdominal discomfort resulting from growth of the bowel is to be expected, Dr. Jeppesen said.
Three patients discontinued teduglutide; the reasons were abdominal distention, abdominal pain, and investigator decision. Four patients discontinued placebo treatment. There were no deaths in the study.
Dr. Jeppesen disclosed consulting for the study sponsor, NPS Pharmaceuticals.
FROM THE ANNUAL DIGESTIVE DISEASE WEEK
Major Finding: Nearly two-thirds of patients (63%) who were randomized to teduglutide achieved at least a 20% reduction in weekly parenteral support volume at weeks 20 and 24, compared with only 30% of patients receiving the placebo (P = .002).
Data Source: Phase III STEPS trial in 86 patients with short-bowel syndrome.
Disclosures: Dr. Jeppesen reported consulting for the study sponsor, NPS Pharmaceuticals.
Teduglutide Cuts Parenteral Nutrition Needs in Short-Bowel Syndrome
CHICAGO – Phase III data from a randomized, placebo-controlled trial indicate that the novel agent teduglutide reduces the need for parenteral support in patients with short-bowel syndrome.
At week 20 and week 24, 63% of patients who were randomized to teduglutide (Gattex) achieved at least a 20% reduction in the volume of parenteral fluid required, compared with baseline. Only 30% of patients receiving the placebo achieved this degree of reduction in their parenteral nutrition needs (P = .002), said lead author Dr. Palle B. Jeppesen during a late-breaking abstract session at the annual Digestive Disease Week.
Short-bowel syndrome (SBS) results from removal of the small intestine because of Crohn’s disease, cancer, or other conditions, and is characterized by malabsorption of nutrients, fluids, and electrolytes, as well as diarrhea. An estimated 10,000-15,000 SBS patients in North America are dependent on parenteral nutrition (PN) for their fluid and nutritional needs, at an annual cost that can exceed $100,000 per patient.
"This has a tremendous impact on their life situation, and of course, what we would like to do is provide them with some treatment, getting them off their parental support," said Dr. Jeppesen, with the Copenhagen University Hospital.
Teduglutide is a recombinant analogue of glucagonlike peptide 2, a peptide that enhances intestinal absorption by thickening the intestinal mucosa and increasing villus height and crypt depth.
Teduglutide has been designated an orphan drug for the treatment of SBS by the Food and Drug Administration and the European Medicines Agency. An application was submitted in March to market teduglutide with the brand name Revestive in Europe as a once-daily subcutaneous treatment for SBS, with a similar application under the brand name Gattex expected later this year in the United States, according to study sponsor NPS Pharmaceuticals. In the STEPS (Study of Teduglutide in PN-Dependent Short-Bowel Syndrome) trial, patients had at least 12 continuous months of PN support prior to enrollment; required PN at least three times weekly to meet caloric, fluid, or electrolyte needs; and had a body mass index of at least 15 kg/m2.
After an initial 30-day stabilization period, 86 patients were randomized to subcutaneous teduglutide 0.05 mg/kg or placebo once daily for 24 weeks. One patient in the teduglutide group was randomized in error and not treated.
At baseline, the teduglutide and placebo groups were similar in age (51 years vs. 50 years), weight (63 kg vs. 62 kg), estimated mean small bowel length (84 cm vs. 69 cm), and mean baseline liters of intravenous PN fluid per week (12.5 L vs. 13.4 L).
At week 24, the mean absolute reduction in PN fluid required by the patient was 4.4 L in the teduglutide group vs.2.3 L in the placebo group (P less than .001), Dr. Jeppesen said.
Significantly more patients who were treated with teduglutide had one or more additional days off parenteral infusions (54% vs. 23%; P = .0047). "Having days off parenteral support is an important issue for their social life," he said.
During a discussion of the study, an attendee asked whether patients will be able to take teduglutide cyclically or will need the drug continually for the rest of their lives. Dr. Jeppesen replied that "it is going to be like treating diabetes. It only works when you give them insulin, and it’s the same case with this drug. It works as long as you give it, and when you take it off they go back to their baseline."
Audience members then asked whether there are any long-term effects of teduglutide, particularly in light of concerns that were raised early on about tumor promotion, which have been reportedly addressed by NPS Pharmaceuticals. Dr. Jeppesen said there is no reason to expect any problems and that the drug has a very good safety profile.
Another attendee asked whether teduglutide is likely to be helpful for unstable patients, and Dr. Jeppesen responded that yes, this is likely.
The most common treatment-emergent adverse events in the teduglutide and placebo groups were abdominal pain (31% vs. 23%), nausea (29% vs. 19%), and stoma complications (24% vs. 7%). Physicians should explain to teduglutide patients that abdominal discomfort resulting from growth of the bowel is to be expected, Dr. Jeppesen said.
Three patients discontinued teduglutide; the reasons were abdominal distention, abdominal pain, and investigator decision. Four patients discontinued placebo treatment. There were no deaths in the study.
Dr. Jeppesen disclosed consulting for the study sponsor, NPS Pharmaceuticals.
CHICAGO – Phase III data from a randomized, placebo-controlled trial indicate that the novel agent teduglutide reduces the need for parenteral support in patients with short-bowel syndrome.
At week 20 and week 24, 63% of patients who were randomized to teduglutide (Gattex) achieved at least a 20% reduction in the volume of parenteral fluid required, compared with baseline. Only 30% of patients receiving the placebo achieved this degree of reduction in their parenteral nutrition needs (P = .002), said lead author Dr. Palle B. Jeppesen during a late-breaking abstract session at the annual Digestive Disease Week.
Short-bowel syndrome (SBS) results from removal of the small intestine because of Crohn’s disease, cancer, or other conditions, and is characterized by malabsorption of nutrients, fluids, and electrolytes, as well as diarrhea. An estimated 10,000-15,000 SBS patients in North America are dependent on parenteral nutrition (PN) for their fluid and nutritional needs, at an annual cost that can exceed $100,000 per patient.
"This has a tremendous impact on their life situation, and of course, what we would like to do is provide them with some treatment, getting them off their parental support," said Dr. Jeppesen, with the Copenhagen University Hospital.
Teduglutide is a recombinant analogue of glucagonlike peptide 2, a peptide that enhances intestinal absorption by thickening the intestinal mucosa and increasing villus height and crypt depth.
Teduglutide has been designated an orphan drug for the treatment of SBS by the Food and Drug Administration and the European Medicines Agency. An application was submitted in March to market teduglutide with the brand name Revestive in Europe as a once-daily subcutaneous treatment for SBS, with a similar application under the brand name Gattex expected later this year in the United States, according to study sponsor NPS Pharmaceuticals. In the STEPS (Study of Teduglutide in PN-Dependent Short-Bowel Syndrome) trial, patients had at least 12 continuous months of PN support prior to enrollment; required PN at least three times weekly to meet caloric, fluid, or electrolyte needs; and had a body mass index of at least 15 kg/m2.
After an initial 30-day stabilization period, 86 patients were randomized to subcutaneous teduglutide 0.05 mg/kg or placebo once daily for 24 weeks. One patient in the teduglutide group was randomized in error and not treated.
At baseline, the teduglutide and placebo groups were similar in age (51 years vs. 50 years), weight (63 kg vs. 62 kg), estimated mean small bowel length (84 cm vs. 69 cm), and mean baseline liters of intravenous PN fluid per week (12.5 L vs. 13.4 L).
At week 24, the mean absolute reduction in PN fluid required by the patient was 4.4 L in the teduglutide group vs.2.3 L in the placebo group (P less than .001), Dr. Jeppesen said.
Significantly more patients who were treated with teduglutide had one or more additional days off parenteral infusions (54% vs. 23%; P = .0047). "Having days off parenteral support is an important issue for their social life," he said.
During a discussion of the study, an attendee asked whether patients will be able to take teduglutide cyclically or will need the drug continually for the rest of their lives. Dr. Jeppesen replied that "it is going to be like treating diabetes. It only works when you give them insulin, and it’s the same case with this drug. It works as long as you give it, and when you take it off they go back to their baseline."
Audience members then asked whether there are any long-term effects of teduglutide, particularly in light of concerns that were raised early on about tumor promotion, which have been reportedly addressed by NPS Pharmaceuticals. Dr. Jeppesen said there is no reason to expect any problems and that the drug has a very good safety profile.
Another attendee asked whether teduglutide is likely to be helpful for unstable patients, and Dr. Jeppesen responded that yes, this is likely.
The most common treatment-emergent adverse events in the teduglutide and placebo groups were abdominal pain (31% vs. 23%), nausea (29% vs. 19%), and stoma complications (24% vs. 7%). Physicians should explain to teduglutide patients that abdominal discomfort resulting from growth of the bowel is to be expected, Dr. Jeppesen said.
Three patients discontinued teduglutide; the reasons were abdominal distention, abdominal pain, and investigator decision. Four patients discontinued placebo treatment. There were no deaths in the study.
Dr. Jeppesen disclosed consulting for the study sponsor, NPS Pharmaceuticals.
CHICAGO – Phase III data from a randomized, placebo-controlled trial indicate that the novel agent teduglutide reduces the need for parenteral support in patients with short-bowel syndrome.
At week 20 and week 24, 63% of patients who were randomized to teduglutide (Gattex) achieved at least a 20% reduction in the volume of parenteral fluid required, compared with baseline. Only 30% of patients receiving the placebo achieved this degree of reduction in their parenteral nutrition needs (P = .002), said lead author Dr. Palle B. Jeppesen during a late-breaking abstract session at the annual Digestive Disease Week.
Short-bowel syndrome (SBS) results from removal of the small intestine because of Crohn’s disease, cancer, or other conditions, and is characterized by malabsorption of nutrients, fluids, and electrolytes, as well as diarrhea. An estimated 10,000-15,000 SBS patients in North America are dependent on parenteral nutrition (PN) for their fluid and nutritional needs, at an annual cost that can exceed $100,000 per patient.
"This has a tremendous impact on their life situation, and of course, what we would like to do is provide them with some treatment, getting them off their parental support," said Dr. Jeppesen, with the Copenhagen University Hospital.
Teduglutide is a recombinant analogue of glucagonlike peptide 2, a peptide that enhances intestinal absorption by thickening the intestinal mucosa and increasing villus height and crypt depth.
Teduglutide has been designated an orphan drug for the treatment of SBS by the Food and Drug Administration and the European Medicines Agency. An application was submitted in March to market teduglutide with the brand name Revestive in Europe as a once-daily subcutaneous treatment for SBS, with a similar application under the brand name Gattex expected later this year in the United States, according to study sponsor NPS Pharmaceuticals. In the STEPS (Study of Teduglutide in PN-Dependent Short-Bowel Syndrome) trial, patients had at least 12 continuous months of PN support prior to enrollment; required PN at least three times weekly to meet caloric, fluid, or electrolyte needs; and had a body mass index of at least 15 kg/m2.
After an initial 30-day stabilization period, 86 patients were randomized to subcutaneous teduglutide 0.05 mg/kg or placebo once daily for 24 weeks. One patient in the teduglutide group was randomized in error and not treated.
At baseline, the teduglutide and placebo groups were similar in age (51 years vs. 50 years), weight (63 kg vs. 62 kg), estimated mean small bowel length (84 cm vs. 69 cm), and mean baseline liters of intravenous PN fluid per week (12.5 L vs. 13.4 L).
At week 24, the mean absolute reduction in PN fluid required by the patient was 4.4 L in the teduglutide group vs.2.3 L in the placebo group (P less than .001), Dr. Jeppesen said.
Significantly more patients who were treated with teduglutide had one or more additional days off parenteral infusions (54% vs. 23%; P = .0047). "Having days off parenteral support is an important issue for their social life," he said.
During a discussion of the study, an attendee asked whether patients will be able to take teduglutide cyclically or will need the drug continually for the rest of their lives. Dr. Jeppesen replied that "it is going to be like treating diabetes. It only works when you give them insulin, and it’s the same case with this drug. It works as long as you give it, and when you take it off they go back to their baseline."
Audience members then asked whether there are any long-term effects of teduglutide, particularly in light of concerns that were raised early on about tumor promotion, which have been reportedly addressed by NPS Pharmaceuticals. Dr. Jeppesen said there is no reason to expect any problems and that the drug has a very good safety profile.
Another attendee asked whether teduglutide is likely to be helpful for unstable patients, and Dr. Jeppesen responded that yes, this is likely.
The most common treatment-emergent adverse events in the teduglutide and placebo groups were abdominal pain (31% vs. 23%), nausea (29% vs. 19%), and stoma complications (24% vs. 7%). Physicians should explain to teduglutide patients that abdominal discomfort resulting from growth of the bowel is to be expected, Dr. Jeppesen said.
Three patients discontinued teduglutide; the reasons were abdominal distention, abdominal pain, and investigator decision. Four patients discontinued placebo treatment. There were no deaths in the study.
Dr. Jeppesen disclosed consulting for the study sponsor, NPS Pharmaceuticals.
FROM THE ANNUAL DIGESTIVE DISEASE WEEK
Major Finding: Nearly two-thirds of patients (63%) who were randomized to teduglutide achieved at least a 20% reduction in weekly parenteral support volume at weeks 20 and 24, compared with only 30% of patients receiving the placebo (P = .002).
Data Source: Phase III STEPS trial in 86 patients with short-bowel syndrome.
Disclosures: Dr. Jeppesen reported consulting for the study sponsor, NPS Pharmaceuticals.
Flex Sig Misses More Colorectal Cancers than Colonoscopy
CHICAGO – Among older patients, the rate of new or missed left-sided colorectal cancers quadrupled with flexible sigmoidoscopy compared with colonoscopy in a retrospective analysis of 25,541 cases.
The overall interval colorectal cancer (CRC) rate, defined as colorectal cancer diagnosed 6-36 months after a lower endoscopy, was 11.7% after flexible sigmoidoscopy vs. 2.6% after colonoscopy, Dr. Yize Richard Wang reported in a late-breaking abstract session at the annual Digestive Disease Week.
The rate of interval CRCs was higher after sigmoidoscopy than colonoscopy in all locations: the descending colon (18.7% vs. 3.3%), rectum (12.5% vs. 2.7%), left colon combined (11.7% vs. 2.6%), sigmoid colon (11.3% vs. 2.4%) and rectosigmoid junction (8% vs. 2.2%).
"Despite the imperfections of colonoscopy, it remains the gold standard for colorectal cancer detection and prevention," concluded Dr. Wang, a fellow with the Mayo Clinic in Jacksonville, Fla.
Although some news reports hailed the study as a boon for colonoscopy, it is unlikely to resolve the long-standing debate over which screening method is optimal. Sigmoidoscopy requires no sedation and less time and bowel preparation for the patient, but cannot visualize the entire colon. Colonoscopy typically requires sedation and has a higher perforation rate, but allows for examination of the entire colon and removal of any detected polyps. Still, these benefits have not translated into an unequivocal reduction in the incidence and mortality from cancer beyond the reach of sigmoidoscopy.
A recent commentary on colonoscopy vs. sigmoidoscopy screening (JAMA 2010;304:461-2) states that if "further evidence supports a lack of efficacy of colonoscopy for reducing incidence and mortality for right-sided colorectal cancer, the medical community should be prepared to consider returning to sigmoidoscopy for endoscopic screening of average-risk individuals."
Just 2 years ago at the same meeting, researchers with the Norwegian Colorectal Cancer Prevention Centre reported that the use of flexible sigmoidoscopy among 55,736 patients aged 55-64 years reduced colorectal cancer mortality 27% after 6 years, compared with no screening. The trend was not statistically significant, but when the researchers limited the analysis to patients who were randomized and actually underwent flexible sigmoidoscopy, there was a significant 59% reduction in total colorectal cancer mortality and significant 76% reduction in rectosigmoid cancer (BMJ 2009 May 29;338:b1846 [doi:10.1136/bmj.b1846]).
The current study included 25,541 patients 67 years and older at the time of a lower endoscopy during 1988-2005, who were subsequently diagnosed within 36 months with CRC distal to the splenic flexure. All but 841 of the 25,541 cases were detected within the first 6 months.
The patients were identified in the Surveillance, Epidemiology, and End Results–Medicare linked database. Exclusion criteria included participation in an HMO, no Medicare Part B coverage for the 24 months preceding the exam, inflammatory bowel disease, and a history of polyps or family history of colorectal cancer.
Compared with the colonoscopy group, the flexible sigmoidoscopy group was slightly older (78 vs. 77 years), included more women (53% vs. 50%) and fewer nonwhites (14% vs. 16%), lived in ZIP codes with higher income/education (no data given), and were more likely to be seen by nongastroenterologists (66% vs. 33%), Dr. Wang said.
In multivariate logistic analysis, women were at 15% higher risk of interval CRC (odds ratio 1.15), while undergoing an inpatient procedure reduced the risk by 47% (OR 0.53).
The odds ratio for an interval CRC with flexible sigmoidoscopy was 4.0 (95% confidence interval 3.51-4.55).
During a discussion of the study, attendees asked whether detection rates were different among gastroenterologists and nongastroenterologists. Dr. Wang replied that there was no difference (OR 1.09 for nongastroenterologists), but that a difference was observed in the right-side colon in another study presented at the meeting.
Dr. Wang pointed out that the retrospective study had several limitations including the inability to determine the indication for, or findings of, the lower endoscopy. It also does not apply to patients undergoing screening colonoscopy for detection and removal of polyps, and does not reflect recent advances in endoscopy such as high-definition colonoscopy.
"Whether our findings reflect differences in bowel preparation quality, lack of sedation, or depth reached during sigmoidoscopy, warrants future research," he said.
Two independent randomized trials of screening colonoscopy are ongoing (NCT00906997 and NCT00883792), but results are not expected until 2021 and 2026.
Dr. Wang disclosed no relevant conflicts of interest.
CHICAGO – Among older patients, the rate of new or missed left-sided colorectal cancers quadrupled with flexible sigmoidoscopy compared with colonoscopy in a retrospective analysis of 25,541 cases.
The overall interval colorectal cancer (CRC) rate, defined as colorectal cancer diagnosed 6-36 months after a lower endoscopy, was 11.7% after flexible sigmoidoscopy vs. 2.6% after colonoscopy, Dr. Yize Richard Wang reported in a late-breaking abstract session at the annual Digestive Disease Week.
The rate of interval CRCs was higher after sigmoidoscopy than colonoscopy in all locations: the descending colon (18.7% vs. 3.3%), rectum (12.5% vs. 2.7%), left colon combined (11.7% vs. 2.6%), sigmoid colon (11.3% vs. 2.4%) and rectosigmoid junction (8% vs. 2.2%).
"Despite the imperfections of colonoscopy, it remains the gold standard for colorectal cancer detection and prevention," concluded Dr. Wang, a fellow with the Mayo Clinic in Jacksonville, Fla.
Although some news reports hailed the study as a boon for colonoscopy, it is unlikely to resolve the long-standing debate over which screening method is optimal. Sigmoidoscopy requires no sedation and less time and bowel preparation for the patient, but cannot visualize the entire colon. Colonoscopy typically requires sedation and has a higher perforation rate, but allows for examination of the entire colon and removal of any detected polyps. Still, these benefits have not translated into an unequivocal reduction in the incidence and mortality from cancer beyond the reach of sigmoidoscopy.
A recent commentary on colonoscopy vs. sigmoidoscopy screening (JAMA 2010;304:461-2) states that if "further evidence supports a lack of efficacy of colonoscopy for reducing incidence and mortality for right-sided colorectal cancer, the medical community should be prepared to consider returning to sigmoidoscopy for endoscopic screening of average-risk individuals."
Just 2 years ago at the same meeting, researchers with the Norwegian Colorectal Cancer Prevention Centre reported that the use of flexible sigmoidoscopy among 55,736 patients aged 55-64 years reduced colorectal cancer mortality 27% after 6 years, compared with no screening. The trend was not statistically significant, but when the researchers limited the analysis to patients who were randomized and actually underwent flexible sigmoidoscopy, there was a significant 59% reduction in total colorectal cancer mortality and significant 76% reduction in rectosigmoid cancer (BMJ 2009 May 29;338:b1846 [doi:10.1136/bmj.b1846]).
The current study included 25,541 patients 67 years and older at the time of a lower endoscopy during 1988-2005, who were subsequently diagnosed within 36 months with CRC distal to the splenic flexure. All but 841 of the 25,541 cases were detected within the first 6 months.
The patients were identified in the Surveillance, Epidemiology, and End Results–Medicare linked database. Exclusion criteria included participation in an HMO, no Medicare Part B coverage for the 24 months preceding the exam, inflammatory bowel disease, and a history of polyps or family history of colorectal cancer.
Compared with the colonoscopy group, the flexible sigmoidoscopy group was slightly older (78 vs. 77 years), included more women (53% vs. 50%) and fewer nonwhites (14% vs. 16%), lived in ZIP codes with higher income/education (no data given), and were more likely to be seen by nongastroenterologists (66% vs. 33%), Dr. Wang said.
In multivariate logistic analysis, women were at 15% higher risk of interval CRC (odds ratio 1.15), while undergoing an inpatient procedure reduced the risk by 47% (OR 0.53).
The odds ratio for an interval CRC with flexible sigmoidoscopy was 4.0 (95% confidence interval 3.51-4.55).
During a discussion of the study, attendees asked whether detection rates were different among gastroenterologists and nongastroenterologists. Dr. Wang replied that there was no difference (OR 1.09 for nongastroenterologists), but that a difference was observed in the right-side colon in another study presented at the meeting.
Dr. Wang pointed out that the retrospective study had several limitations including the inability to determine the indication for, or findings of, the lower endoscopy. It also does not apply to patients undergoing screening colonoscopy for detection and removal of polyps, and does not reflect recent advances in endoscopy such as high-definition colonoscopy.
"Whether our findings reflect differences in bowel preparation quality, lack of sedation, or depth reached during sigmoidoscopy, warrants future research," he said.
Two independent randomized trials of screening colonoscopy are ongoing (NCT00906997 and NCT00883792), but results are not expected until 2021 and 2026.
Dr. Wang disclosed no relevant conflicts of interest.
CHICAGO – Among older patients, the rate of new or missed left-sided colorectal cancers quadrupled with flexible sigmoidoscopy compared with colonoscopy in a retrospective analysis of 25,541 cases.
The overall interval colorectal cancer (CRC) rate, defined as colorectal cancer diagnosed 6-36 months after a lower endoscopy, was 11.7% after flexible sigmoidoscopy vs. 2.6% after colonoscopy, Dr. Yize Richard Wang reported in a late-breaking abstract session at the annual Digestive Disease Week.
The rate of interval CRCs was higher after sigmoidoscopy than colonoscopy in all locations: the descending colon (18.7% vs. 3.3%), rectum (12.5% vs. 2.7%), left colon combined (11.7% vs. 2.6%), sigmoid colon (11.3% vs. 2.4%) and rectosigmoid junction (8% vs. 2.2%).
"Despite the imperfections of colonoscopy, it remains the gold standard for colorectal cancer detection and prevention," concluded Dr. Wang, a fellow with the Mayo Clinic in Jacksonville, Fla.
Although some news reports hailed the study as a boon for colonoscopy, it is unlikely to resolve the long-standing debate over which screening method is optimal. Sigmoidoscopy requires no sedation and less time and bowel preparation for the patient, but cannot visualize the entire colon. Colonoscopy typically requires sedation and has a higher perforation rate, but allows for examination of the entire colon and removal of any detected polyps. Still, these benefits have not translated into an unequivocal reduction in the incidence and mortality from cancer beyond the reach of sigmoidoscopy.
A recent commentary on colonoscopy vs. sigmoidoscopy screening (JAMA 2010;304:461-2) states that if "further evidence supports a lack of efficacy of colonoscopy for reducing incidence and mortality for right-sided colorectal cancer, the medical community should be prepared to consider returning to sigmoidoscopy for endoscopic screening of average-risk individuals."
Just 2 years ago at the same meeting, researchers with the Norwegian Colorectal Cancer Prevention Centre reported that the use of flexible sigmoidoscopy among 55,736 patients aged 55-64 years reduced colorectal cancer mortality 27% after 6 years, compared with no screening. The trend was not statistically significant, but when the researchers limited the analysis to patients who were randomized and actually underwent flexible sigmoidoscopy, there was a significant 59% reduction in total colorectal cancer mortality and significant 76% reduction in rectosigmoid cancer (BMJ 2009 May 29;338:b1846 [doi:10.1136/bmj.b1846]).
The current study included 25,541 patients 67 years and older at the time of a lower endoscopy during 1988-2005, who were subsequently diagnosed within 36 months with CRC distal to the splenic flexure. All but 841 of the 25,541 cases were detected within the first 6 months.
The patients were identified in the Surveillance, Epidemiology, and End Results–Medicare linked database. Exclusion criteria included participation in an HMO, no Medicare Part B coverage for the 24 months preceding the exam, inflammatory bowel disease, and a history of polyps or family history of colorectal cancer.
Compared with the colonoscopy group, the flexible sigmoidoscopy group was slightly older (78 vs. 77 years), included more women (53% vs. 50%) and fewer nonwhites (14% vs. 16%), lived in ZIP codes with higher income/education (no data given), and were more likely to be seen by nongastroenterologists (66% vs. 33%), Dr. Wang said.
In multivariate logistic analysis, women were at 15% higher risk of interval CRC (odds ratio 1.15), while undergoing an inpatient procedure reduced the risk by 47% (OR 0.53).
The odds ratio for an interval CRC with flexible sigmoidoscopy was 4.0 (95% confidence interval 3.51-4.55).
During a discussion of the study, attendees asked whether detection rates were different among gastroenterologists and nongastroenterologists. Dr. Wang replied that there was no difference (OR 1.09 for nongastroenterologists), but that a difference was observed in the right-side colon in another study presented at the meeting.
Dr. Wang pointed out that the retrospective study had several limitations including the inability to determine the indication for, or findings of, the lower endoscopy. It also does not apply to patients undergoing screening colonoscopy for detection and removal of polyps, and does not reflect recent advances in endoscopy such as high-definition colonoscopy.
"Whether our findings reflect differences in bowel preparation quality, lack of sedation, or depth reached during sigmoidoscopy, warrants future research," he said.
Two independent randomized trials of screening colonoscopy are ongoing (NCT00906997 and NCT00883792), but results are not expected until 2021 and 2026.
Dr. Wang disclosed no relevant conflicts of interest.
FROM THE ANNUAL DIGESTIVE DISEASE WEEK
Major Finding: The rate of missed or new left-sided colorectal cancers was 11.7% after flexible sigmoidoscopy vs. 2.6% after screening colonoscopy.
Data Source: Retrospective analysis of 25,541 patients aged 67 or older, with left-sided colorectal cancer, who underwent screening flexible sigmoidoscopy or colonoscopy.
Disclosures: Dr. Wang disclosed no relevant conflicts of interest.
Flex Sig Misses More Colorectal Cancers than Colonoscopy
CHICAGO – Among older patients, the rate of new or missed left-sided colorectal cancers quadrupled with flexible sigmoidoscopy compared with colonoscopy in a retrospective analysis of 25,541 cases.
The overall interval colorectal cancer (CRC) rate, defined as colorectal cancer diagnosed 6-36 months after a lower endoscopy, was 11.7% after flexible sigmoidoscopy vs. 2.6% after colonoscopy, Dr. Yize Richard Wang reported in a late-breaking abstract session at the annual Digestive Disease Week.
The rate of interval CRCs was higher after sigmoidoscopy than colonoscopy in all locations: the descending colon (18.7% vs. 3.3%), rectum (12.5% vs. 2.7%), left colon combined (11.7% vs. 2.6%), sigmoid colon (11.3% vs. 2.4%) and rectosigmoid junction (8% vs. 2.2%).
"Despite the imperfections of colonoscopy, it remains the gold standard for colorectal cancer detection and prevention," concluded Dr. Wang, a fellow with the Mayo Clinic in Jacksonville, Fla.
Although some news reports hailed the study as a boon for colonoscopy, it is unlikely to resolve the long-standing debate over which screening method is optimal. Sigmoidoscopy requires no sedation and less time and bowel preparation for the patient, but cannot visualize the entire colon. Colonoscopy typically requires sedation and has a higher perforation rate, but allows for examination of the entire colon and removal of any detected polyps. Still, these benefits have not translated into an unequivocal reduction in the incidence and mortality from cancer beyond the reach of sigmoidoscopy.
A recent commentary on colonoscopy vs. sigmoidoscopy screening (JAMA 2010;304:461-2) states that if "further evidence supports a lack of efficacy of colonoscopy for reducing incidence and mortality for right-sided colorectal cancer, the medical community should be prepared to consider returning to sigmoidoscopy for endoscopic screening of average-risk individuals."
Just 2 years ago at the same meeting, researchers with the Norwegian Colorectal Cancer Prevention Centre reported that the use of flexible sigmoidoscopy among 55,736 patients aged 55-64 years reduced colorectal cancer mortality 27% after 6 years, compared with no screening. The trend was not statistically significant, but when the researchers limited the analysis to patients who were randomized and actually underwent flexible sigmoidoscopy, there was a significant 59% reduction in total colorectal cancer mortality and significant 76% reduction in rectosigmoid cancer (BMJ 2009 May 29;338:b1846 [doi:10.1136/bmj.b1846]).
The current study included 25,541 patients 67 years and older at the time of a lower endoscopy during 1988-2005, who were subsequently diagnosed within 36 months with CRC distal to the splenic flexure. All but 841 of the 25,541 cases were detected within the first 6 months.
The patients were identified in the Surveillance, Epidemiology, and End Results–Medicare linked database. Exclusion criteria included participation in an HMO, no Medicare Part B coverage for the 24 months preceding the exam, inflammatory bowel disease, and a history of polyps or family history of colorectal cancer.
Compared with the colonoscopy group, the flexible sigmoidoscopy group was slightly older (78 vs. 77 years), included more women (53% vs. 50%) and fewer nonwhites (14% vs. 16%), lived in ZIP codes with higher income/education (no data given), and were more likely to be seen by nongastroenterologists (66% vs. 33%), Dr. Wang said.
In multivariate logistic analysis, women were at 15% higher risk of interval CRC (odds ratio 1.15), while undergoing an inpatient procedure reduced the risk by 47% (OR 0.53).
The odds ratio for an interval CRC with flexible sigmoidoscopy was 4.0 (95% confidence interval 3.51-4.55).
During a discussion of the study, attendees asked whether detection rates were different among gastroenterologists and nongastroenterologists. Dr. Wang replied that there was no difference (OR 1.09 for nongastroenterologists), but that a difference was observed in the right-side colon in another study presented at the meeting.
Dr. Wang pointed out that the retrospective study had several limitations including the inability to determine the indication for, or findings of, the lower endoscopy. It also does not apply to patients undergoing screening colonoscopy for detection and removal of polyps, and does not reflect recent advances in endoscopy such as high-definition colonoscopy.
"Whether our findings reflect differences in bowel preparation quality, lack of sedation, or depth reached during sigmoidoscopy, warrants future research," he said.
Two independent randomized trials of screening colonoscopy are ongoing (NCT00906997 and NCT00883792), but results are not expected until 2021 and 2026.
Dr. Wang disclosed no relevant conflicts of interest.
CHICAGO – Among older patients, the rate of new or missed left-sided colorectal cancers quadrupled with flexible sigmoidoscopy compared with colonoscopy in a retrospective analysis of 25,541 cases.
The overall interval colorectal cancer (CRC) rate, defined as colorectal cancer diagnosed 6-36 months after a lower endoscopy, was 11.7% after flexible sigmoidoscopy vs. 2.6% after colonoscopy, Dr. Yize Richard Wang reported in a late-breaking abstract session at the annual Digestive Disease Week.
The rate of interval CRCs was higher after sigmoidoscopy than colonoscopy in all locations: the descending colon (18.7% vs. 3.3%), rectum (12.5% vs. 2.7%), left colon combined (11.7% vs. 2.6%), sigmoid colon (11.3% vs. 2.4%) and rectosigmoid junction (8% vs. 2.2%).
"Despite the imperfections of colonoscopy, it remains the gold standard for colorectal cancer detection and prevention," concluded Dr. Wang, a fellow with the Mayo Clinic in Jacksonville, Fla.
Although some news reports hailed the study as a boon for colonoscopy, it is unlikely to resolve the long-standing debate over which screening method is optimal. Sigmoidoscopy requires no sedation and less time and bowel preparation for the patient, but cannot visualize the entire colon. Colonoscopy typically requires sedation and has a higher perforation rate, but allows for examination of the entire colon and removal of any detected polyps. Still, these benefits have not translated into an unequivocal reduction in the incidence and mortality from cancer beyond the reach of sigmoidoscopy.
A recent commentary on colonoscopy vs. sigmoidoscopy screening (JAMA 2010;304:461-2) states that if "further evidence supports a lack of efficacy of colonoscopy for reducing incidence and mortality for right-sided colorectal cancer, the medical community should be prepared to consider returning to sigmoidoscopy for endoscopic screening of average-risk individuals."
Just 2 years ago at the same meeting, researchers with the Norwegian Colorectal Cancer Prevention Centre reported that the use of flexible sigmoidoscopy among 55,736 patients aged 55-64 years reduced colorectal cancer mortality 27% after 6 years, compared with no screening. The trend was not statistically significant, but when the researchers limited the analysis to patients who were randomized and actually underwent flexible sigmoidoscopy, there was a significant 59% reduction in total colorectal cancer mortality and significant 76% reduction in rectosigmoid cancer (BMJ 2009 May 29;338:b1846 [doi:10.1136/bmj.b1846]).
The current study included 25,541 patients 67 years and older at the time of a lower endoscopy during 1988-2005, who were subsequently diagnosed within 36 months with CRC distal to the splenic flexure. All but 841 of the 25,541 cases were detected within the first 6 months.
The patients were identified in the Surveillance, Epidemiology, and End Results–Medicare linked database. Exclusion criteria included participation in an HMO, no Medicare Part B coverage for the 24 months preceding the exam, inflammatory bowel disease, and a history of polyps or family history of colorectal cancer.
Compared with the colonoscopy group, the flexible sigmoidoscopy group was slightly older (78 vs. 77 years), included more women (53% vs. 50%) and fewer nonwhites (14% vs. 16%), lived in ZIP codes with higher income/education (no data given), and were more likely to be seen by nongastroenterologists (66% vs. 33%), Dr. Wang said.
In multivariate logistic analysis, women were at 15% higher risk of interval CRC (odds ratio 1.15), while undergoing an inpatient procedure reduced the risk by 47% (OR 0.53).
The odds ratio for an interval CRC with flexible sigmoidoscopy was 4.0 (95% confidence interval 3.51-4.55).
During a discussion of the study, attendees asked whether detection rates were different among gastroenterologists and nongastroenterologists. Dr. Wang replied that there was no difference (OR 1.09 for nongastroenterologists), but that a difference was observed in the right-side colon in another study presented at the meeting.
Dr. Wang pointed out that the retrospective study had several limitations including the inability to determine the indication for, or findings of, the lower endoscopy. It also does not apply to patients undergoing screening colonoscopy for detection and removal of polyps, and does not reflect recent advances in endoscopy such as high-definition colonoscopy.
"Whether our findings reflect differences in bowel preparation quality, lack of sedation, or depth reached during sigmoidoscopy, warrants future research," he said.
Two independent randomized trials of screening colonoscopy are ongoing (NCT00906997 and NCT00883792), but results are not expected until 2021 and 2026.
Dr. Wang disclosed no relevant conflicts of interest.
CHICAGO – Among older patients, the rate of new or missed left-sided colorectal cancers quadrupled with flexible sigmoidoscopy compared with colonoscopy in a retrospective analysis of 25,541 cases.
The overall interval colorectal cancer (CRC) rate, defined as colorectal cancer diagnosed 6-36 months after a lower endoscopy, was 11.7% after flexible sigmoidoscopy vs. 2.6% after colonoscopy, Dr. Yize Richard Wang reported in a late-breaking abstract session at the annual Digestive Disease Week.
The rate of interval CRCs was higher after sigmoidoscopy than colonoscopy in all locations: the descending colon (18.7% vs. 3.3%), rectum (12.5% vs. 2.7%), left colon combined (11.7% vs. 2.6%), sigmoid colon (11.3% vs. 2.4%) and rectosigmoid junction (8% vs. 2.2%).
"Despite the imperfections of colonoscopy, it remains the gold standard for colorectal cancer detection and prevention," concluded Dr. Wang, a fellow with the Mayo Clinic in Jacksonville, Fla.
Although some news reports hailed the study as a boon for colonoscopy, it is unlikely to resolve the long-standing debate over which screening method is optimal. Sigmoidoscopy requires no sedation and less time and bowel preparation for the patient, but cannot visualize the entire colon. Colonoscopy typically requires sedation and has a higher perforation rate, but allows for examination of the entire colon and removal of any detected polyps. Still, these benefits have not translated into an unequivocal reduction in the incidence and mortality from cancer beyond the reach of sigmoidoscopy.
A recent commentary on colonoscopy vs. sigmoidoscopy screening (JAMA 2010;304:461-2) states that if "further evidence supports a lack of efficacy of colonoscopy for reducing incidence and mortality for right-sided colorectal cancer, the medical community should be prepared to consider returning to sigmoidoscopy for endoscopic screening of average-risk individuals."
Just 2 years ago at the same meeting, researchers with the Norwegian Colorectal Cancer Prevention Centre reported that the use of flexible sigmoidoscopy among 55,736 patients aged 55-64 years reduced colorectal cancer mortality 27% after 6 years, compared with no screening. The trend was not statistically significant, but when the researchers limited the analysis to patients who were randomized and actually underwent flexible sigmoidoscopy, there was a significant 59% reduction in total colorectal cancer mortality and significant 76% reduction in rectosigmoid cancer (BMJ 2009 May 29;338:b1846 [doi:10.1136/bmj.b1846]).
The current study included 25,541 patients 67 years and older at the time of a lower endoscopy during 1988-2005, who were subsequently diagnosed within 36 months with CRC distal to the splenic flexure. All but 841 of the 25,541 cases were detected within the first 6 months.
The patients were identified in the Surveillance, Epidemiology, and End Results–Medicare linked database. Exclusion criteria included participation in an HMO, no Medicare Part B coverage for the 24 months preceding the exam, inflammatory bowel disease, and a history of polyps or family history of colorectal cancer.
Compared with the colonoscopy group, the flexible sigmoidoscopy group was slightly older (78 vs. 77 years), included more women (53% vs. 50%) and fewer nonwhites (14% vs. 16%), lived in ZIP codes with higher income/education (no data given), and were more likely to be seen by nongastroenterologists (66% vs. 33%), Dr. Wang said.
In multivariate logistic analysis, women were at 15% higher risk of interval CRC (odds ratio 1.15), while undergoing an inpatient procedure reduced the risk by 47% (OR 0.53).
The odds ratio for an interval CRC with flexible sigmoidoscopy was 4.0 (95% confidence interval 3.51-4.55).
During a discussion of the study, attendees asked whether detection rates were different among gastroenterologists and nongastroenterologists. Dr. Wang replied that there was no difference (OR 1.09 for nongastroenterologists), but that a difference was observed in the right-side colon in another study presented at the meeting.
Dr. Wang pointed out that the retrospective study had several limitations including the inability to determine the indication for, or findings of, the lower endoscopy. It also does not apply to patients undergoing screening colonoscopy for detection and removal of polyps, and does not reflect recent advances in endoscopy such as high-definition colonoscopy.
"Whether our findings reflect differences in bowel preparation quality, lack of sedation, or depth reached during sigmoidoscopy, warrants future research," he said.
Two independent randomized trials of screening colonoscopy are ongoing (NCT00906997 and NCT00883792), but results are not expected until 2021 and 2026.
Dr. Wang disclosed no relevant conflicts of interest.
FROM THE ANNUAL DIGESTIVE DISEASE WEEK
Major Finding: The rate of missed or new left-sided colorectal cancers was 11.7% after flexible sigmoidoscopy vs. 2.6% after screening colonoscopy.
Data Source: Retrospective analysis of 25,541 patients aged 67 or older, with left-sided colorectal cancer, who underwent screening flexible sigmoidoscopy or colonoscopy.
Disclosures: Dr. Wang disclosed no relevant conflicts of interest.
College Students Earn Failing Grade for Gynecologic Knowledge
CHICAGO – Less than 40% of female college students and just 20% of their male counterparts responded correctly when asked to label the vagina on an anatomical diagram.
This startling finding, taken from a brief survey conducted among 236 students at a Midwestern university, highlights the general lack of gynecologic knowledge among today’s college students, according to lead author Dr. Jill S. Huppert.
"Although they report a high level of sexual activity, they have a significant knowledge deficit," she said at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology. "Addressing this gap in knowledge might be an important strategy in improving the sexual and reproductive health of many young women and men."
The 40-item survey was distributed to six health, physical education, and recreation classes; it was completed by 138 women and 98 men. A knowledge score was generated by totaling correct responses to nine items on menstruation, Pap smear, sexually transmitted diseases (STDs), and pregnancy, and using a word bank to correctly label 11 spots on a diagram of the female anatomy. The anatomy score ranged from 0 to 11, and the total knowledge score ranged from 0 to 20, and included the nine knowledge items plus the anatomy score.
The median age of the respondents was 20 years (range, 18-36 years), and 84% reported prior vaginal intercourse, Dr. Huppert noted. Men were significantly more likely to report having more than one lifetime sexual partner (61% vs. 39%), and less likely to have prior STD testing (30% vs. 43%). Notably, 10% of respondents had a parent who was a physician, and one-third of those were ob.gyns.
In general, women did better at identifying their own anatomy than men. The mean anatomy knowledge score was 7.2 for women vs. 4.5 for men, which was significantly different, said Dr. Huppert of Cincinnati Children’s Hospital Medical Center. The ovary was correctly identified by both sexes the most frequently and the vagina the least often. Just about 70% of women and less than 60% of men could find the clitoris. Scores were low overall, with only 53% of women and 29% of men correctly identifying more than 80% of the anatomical structures on the diagram.
With regard to general knowledge, half of the men and women knew that a Pap smear detects cancer, 60% knew that menarche usually occurs at age 12 years, and 73% understood that 25% of women aged 18-24 years were infected with an STD, she said. A majority, or 94%, of both sexes knew that pregnancy delays periods, while 68% knew that depot medroxyprogesterone acetate (Depo-Provera) can do likewise.
There were significant differences between the sexes, with 24% of men recognizing that the risk of pregnancy with unprotected sex for a year is at least 75%, compared with just 13% of women, Dr. Huppert said. Women, however, were significantly more likely than men to know that menstrual periods can be delayed by stress (94% vs. 76%), losing weight/anorexia (91% vs. 66%), or high levels of exercise (80% vs. 46%).
The mean total knowledge score was significantly lower at 10 for men vs. 13.4 for women. In regression analysis, scores were not influenced by sexual experience or STD testing, Dr. Huppert said.
When the researchers looked at the influence of parents, there was a trend for higher anatomy scores among both sexes if a parent was an ob.gyn. Total knowledge scores also trended higher among women if a parent was an ob.gyn., and were significantly higher among men if their mother or father was an ob.gyn. at 15.7, vs. 9.9 if a parent was not an ob.gyn., she said.
Dr. Huppert and her associates reported no relevant financial disclosures.
CHICAGO – Less than 40% of female college students and just 20% of their male counterparts responded correctly when asked to label the vagina on an anatomical diagram.
This startling finding, taken from a brief survey conducted among 236 students at a Midwestern university, highlights the general lack of gynecologic knowledge among today’s college students, according to lead author Dr. Jill S. Huppert.
"Although they report a high level of sexual activity, they have a significant knowledge deficit," she said at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology. "Addressing this gap in knowledge might be an important strategy in improving the sexual and reproductive health of many young women and men."
The 40-item survey was distributed to six health, physical education, and recreation classes; it was completed by 138 women and 98 men. A knowledge score was generated by totaling correct responses to nine items on menstruation, Pap smear, sexually transmitted diseases (STDs), and pregnancy, and using a word bank to correctly label 11 spots on a diagram of the female anatomy. The anatomy score ranged from 0 to 11, and the total knowledge score ranged from 0 to 20, and included the nine knowledge items plus the anatomy score.
The median age of the respondents was 20 years (range, 18-36 years), and 84% reported prior vaginal intercourse, Dr. Huppert noted. Men were significantly more likely to report having more than one lifetime sexual partner (61% vs. 39%), and less likely to have prior STD testing (30% vs. 43%). Notably, 10% of respondents had a parent who was a physician, and one-third of those were ob.gyns.
In general, women did better at identifying their own anatomy than men. The mean anatomy knowledge score was 7.2 for women vs. 4.5 for men, which was significantly different, said Dr. Huppert of Cincinnati Children’s Hospital Medical Center. The ovary was correctly identified by both sexes the most frequently and the vagina the least often. Just about 70% of women and less than 60% of men could find the clitoris. Scores were low overall, with only 53% of women and 29% of men correctly identifying more than 80% of the anatomical structures on the diagram.
With regard to general knowledge, half of the men and women knew that a Pap smear detects cancer, 60% knew that menarche usually occurs at age 12 years, and 73% understood that 25% of women aged 18-24 years were infected with an STD, she said. A majority, or 94%, of both sexes knew that pregnancy delays periods, while 68% knew that depot medroxyprogesterone acetate (Depo-Provera) can do likewise.
There were significant differences between the sexes, with 24% of men recognizing that the risk of pregnancy with unprotected sex for a year is at least 75%, compared with just 13% of women, Dr. Huppert said. Women, however, were significantly more likely than men to know that menstrual periods can be delayed by stress (94% vs. 76%), losing weight/anorexia (91% vs. 66%), or high levels of exercise (80% vs. 46%).
The mean total knowledge score was significantly lower at 10 for men vs. 13.4 for women. In regression analysis, scores were not influenced by sexual experience or STD testing, Dr. Huppert said.
When the researchers looked at the influence of parents, there was a trend for higher anatomy scores among both sexes if a parent was an ob.gyn. Total knowledge scores also trended higher among women if a parent was an ob.gyn., and were significantly higher among men if their mother or father was an ob.gyn. at 15.7, vs. 9.9 if a parent was not an ob.gyn., she said.
Dr. Huppert and her associates reported no relevant financial disclosures.
CHICAGO – Less than 40% of female college students and just 20% of their male counterparts responded correctly when asked to label the vagina on an anatomical diagram.
This startling finding, taken from a brief survey conducted among 236 students at a Midwestern university, highlights the general lack of gynecologic knowledge among today’s college students, according to lead author Dr. Jill S. Huppert.
"Although they report a high level of sexual activity, they have a significant knowledge deficit," she said at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology. "Addressing this gap in knowledge might be an important strategy in improving the sexual and reproductive health of many young women and men."
The 40-item survey was distributed to six health, physical education, and recreation classes; it was completed by 138 women and 98 men. A knowledge score was generated by totaling correct responses to nine items on menstruation, Pap smear, sexually transmitted diseases (STDs), and pregnancy, and using a word bank to correctly label 11 spots on a diagram of the female anatomy. The anatomy score ranged from 0 to 11, and the total knowledge score ranged from 0 to 20, and included the nine knowledge items plus the anatomy score.
The median age of the respondents was 20 years (range, 18-36 years), and 84% reported prior vaginal intercourse, Dr. Huppert noted. Men were significantly more likely to report having more than one lifetime sexual partner (61% vs. 39%), and less likely to have prior STD testing (30% vs. 43%). Notably, 10% of respondents had a parent who was a physician, and one-third of those were ob.gyns.
In general, women did better at identifying their own anatomy than men. The mean anatomy knowledge score was 7.2 for women vs. 4.5 for men, which was significantly different, said Dr. Huppert of Cincinnati Children’s Hospital Medical Center. The ovary was correctly identified by both sexes the most frequently and the vagina the least often. Just about 70% of women and less than 60% of men could find the clitoris. Scores were low overall, with only 53% of women and 29% of men correctly identifying more than 80% of the anatomical structures on the diagram.
With regard to general knowledge, half of the men and women knew that a Pap smear detects cancer, 60% knew that menarche usually occurs at age 12 years, and 73% understood that 25% of women aged 18-24 years were infected with an STD, she said. A majority, or 94%, of both sexes knew that pregnancy delays periods, while 68% knew that depot medroxyprogesterone acetate (Depo-Provera) can do likewise.
There were significant differences between the sexes, with 24% of men recognizing that the risk of pregnancy with unprotected sex for a year is at least 75%, compared with just 13% of women, Dr. Huppert said. Women, however, were significantly more likely than men to know that menstrual periods can be delayed by stress (94% vs. 76%), losing weight/anorexia (91% vs. 66%), or high levels of exercise (80% vs. 46%).
The mean total knowledge score was significantly lower at 10 for men vs. 13.4 for women. In regression analysis, scores were not influenced by sexual experience or STD testing, Dr. Huppert said.
When the researchers looked at the influence of parents, there was a trend for higher anatomy scores among both sexes if a parent was an ob.gyn. Total knowledge scores also trended higher among women if a parent was an ob.gyn., and were significantly higher among men if their mother or father was an ob.gyn. at 15.7, vs. 9.9 if a parent was not an ob.gyn., she said.
Dr. Huppert and her associates reported no relevant financial disclosures.
FROM THE ANNUAL MEETING OF THE NORTH AMERICAN SOCIETY FOR PEDIATRIC AND ADOLESCENT GYNECOLOGY
Major Finding: Only 53% of women and 29% of men correctly identified more than 80% of female anatomical structures on a diagram.
Data Source: Survey of gynecologic knowledge among 236 college students.
Disclosures: Dr. Huppert and her associates reported no relevant financial disclosures.