Sharon Worcester

ORLANDO – A systemwide medical error disclosure program that successfully reduced the rate of claims and improved claim resolution time for a large university health system had similar effects on gastroenterology-specific claims, a retrospective study has shown.

The findings suggest that error disclosure programs can benefit even procedure-based specialties like gastroenterology, Dr. Megan A. Adams reported at the annual Digestive Disease Week.

The medical error disclosure program, which included incident reporting and disclosure, internal investigation of all claims, an offer of apology and compensation for all reasonable claims, and vigorous defense of all unreasonable claims, was adopted at the University of Michigan Health System (UMHS) in 2001 following a 1999 Institute of Medicine report calling for efforts to reduce medical errors. The program was developed in light of an increasing realization that traditional "deny-and-defend" approaches to claims were failing to achieve the goal of improving patient care.

A hospitalwide analysis published in 2010 showed a statistically significant 36% decrease in the average monthly rate of new claims per patient encounter, 30% decrease in the median time from claim reporting to resolution, and 44% decrease in the average cost per lawsuit following program implementation (Ann. Intern. Med. 2010;153:213-21).

"But the question remained: ‘Can we apply these systemwide findings to gastroenterology?’ First, we have a procedure-based specialty. We also do many open-access procedures where we have no preexisting or established relationship with our patients. And, finally, we treat gastrointestinal-specific diseases, such as [those in] patients with functional bowel disorders, who represent a complex patient population," said Dr. Adams of the University of Michigan Medical Center, Ann Arbor.

A review of gastroenterology-specific claims in the UMHS Risk Management database from 1990 to 2010 showed that despite a 72% increase in encounters in the 10 years after implementation, compared with the 10 years prior (412,000 vs. 240,000 encounters), only 28 claims were made after, versus 38 before, implementation.

The rate of claims declined significantly from 0.16% to 0.068% per 1,000 patient encounters. Moreover, after adjustment for inflation, total settlement dollars decreased by 54%, overall claims-related costs decreased by 94%, mean total liability per claim decreased by 52%, and time to claim resolution decreased by 50%.

Although the findings are limited by the small number of claims and an inability to determine causality, and did not consider statewide or national trends in the filing of claims, the results do demonstrate that the systemwide findings at UMHS were "reproduced in a dramatic way in the procedure-based specialty of gastroenterology," Dr. Adams said.

"When properly implemented as part of a systemwide quality improvement effort, medical error disclosure programs help to foster a culture of transparency, and in doing so, strengthen patients’ trust in the health care system. They also help to promote ongoing medical error prevention in a way that does not lead to increased medical liability," she said, adding that further research looking at the generalizability of these findings to other health systems is warranted.

Dr. Adams reported having no relevant financial disclosures.

ORLANDO – A systemwide medical error disclosure program that successfully reduced the rate of claims and improved claim resolution time for a large university health system had similar effects on gastroenterology-specific claims, a retrospective study has shown.

The findings suggest that error disclosure programs can benefit even procedure-based specialties like gastroenterology, Dr. Megan A. Adams reported at the annual Digestive Disease Week.

The medical error disclosure program, which included incident reporting and disclosure, internal investigation of all claims, an offer of apology and compensation for all reasonable claims, and vigorous defense of all unreasonable claims, was adopted at the University of Michigan Health System (UMHS) in 2001 following a 1999 Institute of Medicine report calling for efforts to reduce medical errors. The program was developed in light of an increasing realization that traditional "deny-and-defend" approaches to claims were failing to achieve the goal of improving patient care.

A hospitalwide analysis published in 2010 showed a statistically significant 36% decrease in the average monthly rate of new claims per patient encounter, 30% decrease in the median time from claim reporting to resolution, and 44% decrease in the average cost per lawsuit following program implementation (Ann. Intern. Med. 2010;153:213-21).

"But the question remained: ‘Can we apply these systemwide findings to gastroenterology?’ First, we have a procedure-based specialty. We also do many open-access procedures where we have no preexisting or established relationship with our patients. And, finally, we treat gastrointestinal-specific diseases, such as [those in] patients with functional bowel disorders, who represent a complex patient population," said Dr. Adams of the University of Michigan Medical Center, Ann Arbor.

A review of gastroenterology-specific claims in the UMHS Risk Management database from 1990 to 2010 showed that despite a 72% increase in encounters in the 10 years after implementation, compared with the 10 years prior (412,000 vs. 240,000 encounters), only 28 claims were made after, versus 38 before, implementation.

The rate of claims declined significantly from 0.16% to 0.068% per 1,000 patient encounters. Moreover, after adjustment for inflation, total settlement dollars decreased by 54%, overall claims-related costs decreased by 94%, mean total liability per claim decreased by 52%, and time to claim resolution decreased by 50%.

Although the findings are limited by the small number of claims and an inability to determine causality, and did not consider statewide or national trends in the filing of claims, the results do demonstrate that the systemwide findings at UMHS were "reproduced in a dramatic way in the procedure-based specialty of gastroenterology," Dr. Adams said.

"When properly implemented as part of a systemwide quality improvement effort, medical error disclosure programs help to foster a culture of transparency, and in doing so, strengthen patients’ trust in the health care system. They also help to promote ongoing medical error prevention in a way that does not lead to increased medical liability," she said, adding that further research looking at the generalizability of these findings to other health systems is warranted.

Dr. Adams reported having no relevant financial disclosures.

ORLANDO – A systemwide medical error disclosure program that successfully reduced the rate of claims and improved claim resolution time for a large university health system had similar effects on gastroenterology-specific claims, a retrospective study has shown.

The findings suggest that error disclosure programs can benefit even procedure-based specialties like gastroenterology, Dr. Megan A. Adams reported at the annual Digestive Disease Week.

The medical error disclosure program, which included incident reporting and disclosure, internal investigation of all claims, an offer of apology and compensation for all reasonable claims, and vigorous defense of all unreasonable claims, was adopted at the University of Michigan Health System (UMHS) in 2001 following a 1999 Institute of Medicine report calling for efforts to reduce medical errors. The program was developed in light of an increasing realization that traditional "deny-and-defend" approaches to claims were failing to achieve the goal of improving patient care.

A hospitalwide analysis published in 2010 showed a statistically significant 36% decrease in the average monthly rate of new claims per patient encounter, 30% decrease in the median time from claim reporting to resolution, and 44% decrease in the average cost per lawsuit following program implementation (Ann. Intern. Med. 2010;153:213-21).

"But the question remained: ‘Can we apply these systemwide findings to gastroenterology?’ First, we have a procedure-based specialty. We also do many open-access procedures where we have no preexisting or established relationship with our patients. And, finally, we treat gastrointestinal-specific diseases, such as [those in] patients with functional bowel disorders, who represent a complex patient population," said Dr. Adams of the University of Michigan Medical Center, Ann Arbor.

A review of gastroenterology-specific claims in the UMHS Risk Management database from 1990 to 2010 showed that despite a 72% increase in encounters in the 10 years after implementation, compared with the 10 years prior (412,000 vs. 240,000 encounters), only 28 claims were made after, versus 38 before, implementation.

The rate of claims declined significantly from 0.16% to 0.068% per 1,000 patient encounters. Moreover, after adjustment for inflation, total settlement dollars decreased by 54%, overall claims-related costs decreased by 94%, mean total liability per claim decreased by 52%, and time to claim resolution decreased by 50%.

Although the findings are limited by the small number of claims and an inability to determine causality, and did not consider statewide or national trends in the filing of claims, the results do demonstrate that the systemwide findings at UMHS were "reproduced in a dramatic way in the procedure-based specialty of gastroenterology," Dr. Adams said.

"When properly implemented as part of a systemwide quality improvement effort, medical error disclosure programs help to foster a culture of transparency, and in doing so, strengthen patients’ trust in the health care system. They also help to promote ongoing medical error prevention in a way that does not lead to increased medical liability," she said, adding that further research looking at the generalizability of these findings to other health systems is warranted.

Dr. Adams reported having no relevant financial disclosures.

ORLANDO – Immunoablation and hematopoietic stem cell transplantation is highly effective – but also risky – for patients with intractable Crohn’s disease, according to interim findings from the randomized controlled ASTIC (Autologous Stem Cell Transplantation International Crohn’s Disease) trial.

At 1-year follow-up in the 5-year study, the treatment was associated with significant improvements as measured by the Crohn’s Disease Activity Index (CDAI) and Simple Endoscopic Score for Crohn’s Disease (SES-CD), Dr. Christopher J. Hawkey reported at the annual Digestive Disease Week. However, patients experienced more than three serious adverse events per person, and one death occurred 2 weeks after transplantation, he said.

Of 45 patients with impaired quality of life due to moderate to severe Crohn’s disease activity despite treatment with at least three immunosuppressive agents, all underwent stem cell mobilization treatment and were then randomized to receive either immediate or delayed immunoablation and hematopoietic stem cell transplantation (HSCT). The delayed-treatment group served as a control group.

In 22 patients who received immediate treatment and survived until 1-year follow-up, the CDAI score was halved to a median value of 162, compared with only about a 50-point drop in 13 patients in the control group who continued in the study (9 patients withdrew early – mainly because of disease worsening – and some went on to early HSCT). Furthermore, an "encouraging number" of patients in the treatment group were able to discontinue all immunosuppressive drugs and steroids (about two-thirds of patients, compared with 15% in the control group), said Dr. Hawkey of the University of Nottingham, England.

Almost half of the patients in the treatment group achieved a CDAI score of 150 or less, signaling clinical remission.

"Strikingly, most of these patients were not taking any drugs at the time, either," Dr. Hawkey said.

The SES-CD score also decreased markedly in the treatment group, falling from a mean of 13 to 4 points, with four patients achieving complete absence of any evidence of involvement or ulceration, compared with no patients in the control group.

Complete mucosal healing, defined as lack of erosions or ulcerations on endoscopy, occurred in 40% of treatment-group patients, compared with only 15% of control-group patients, but several of these patients were still taking anti–tumor necrosis factor (anti-TNF) drugs or steroids, Dr. Hawkey said.

"Nevertheless, these are quite substantial findings," he said.

Patients included in the trial were adults who had undergone up to 12 surgeries each but who still had disease-related impairments to quality of life.

"For such an extreme technique, we wanted to enroll the most resistant patients," Dr. Hawkey said.

The treatment and control groups were well matched with respect to major demographics as well as CDAI and SES-CD scores, and patients were relatively young, having been diagnosed with Crohn’s disease at an early age, he noted.

Stem cell mobilization was achieved using 4 g/m² of intravenous cyclophosphamide delivered over 2 days, followed by 10 mcg/kg filgrastim daily until randomization. The conditioning regimen in the treatment group was 50 mg/kg per day of intravenous cyclophosphamide for 4 days, 2.5 mg/kg per day of antithymocyte globulin, and 1 mg/kg of methyl prednisolone on days 3-5. The bone marrow was reconstituted by infusion of an unselected graft of 3-8 × 10⁶ CD34-positive cells/kg.

One patient in the treatment group died 2 weeks after HSCT due to sepsis, and a significantly greater number of serious adverse events – usually infectious – occurred during follow-up in the treatment group than in the control group (an average of 3.3 per person).

The findings could have important implications for the treatment of Crohn’s disease.

"Immunoablation and repopulation of the bone marrow by uncommitted stem cells has excited a lot of interest in Crohn’s disease lately, and some of the case reports are undoubtedly so dramatic that it’s reasonable to talk about a cure in those patients," Dr. Hawkey said.

HSCT has been shown in controlled clinical trials to be effective – albeit with major toxicities – in systemic sclerosis and multiple sclerosis, but this is the first randomized controlled trial to evaluate the technique in Crohn’s disease.

"Our goal was quite an ambitious one. If we could achieve clinical remission, and patients were off drugs, that would be something of a game-changer," he said.

Indeed, the findings thus far suggest that stem cell transplantation is highly effective for patients with resistant Crohn’s disease, but in most cases, there is evidence of disease persistence.

"So this is seldom a cure, although sometimes it clearly is," he said, adding that given the significant number of serious adverse events, weighing the risks and benefits will be the key to successful clinical use in the future.

Outcomes following HSCT in the delayed-treatment group will be presented at a later date, he said.

Dr. Hawkey serves on advisory committees or review panels for Atlantic Healthcare, Bayer AG, GlaxoSmithKline, Novartis Pharmaceuticals, Boehringer Ingelheim, and Takeda Pharmaceuticals.

ORLANDO – Immunoablation and hematopoietic stem cell transplantation is highly effective – but also risky – for patients with intractable Crohn’s disease, according to interim findings from the randomized controlled ASTIC (Autologous Stem Cell Transplantation International Crohn’s Disease) trial.

At 1-year follow-up in the 5-year study, the treatment was associated with significant improvements as measured by the Crohn’s Disease Activity Index (CDAI) and Simple Endoscopic Score for Crohn’s Disease (SES-CD), Dr. Christopher J. Hawkey reported at the annual Digestive Disease Week. However, patients experienced more than three serious adverse events per person, and one death occurred 2 weeks after transplantation, he said.

Of 45 patients with impaired quality of life due to moderate to severe Crohn’s disease activity despite treatment with at least three immunosuppressive agents, all underwent stem cell mobilization treatment and were then randomized to receive either immediate or delayed immunoablation and hematopoietic stem cell transplantation (HSCT). The delayed-treatment group served as a control group.

In 22 patients who received immediate treatment and survived until 1-year follow-up, the CDAI score was halved to a median value of 162, compared with only about a 50-point drop in 13 patients in the control group who continued in the study (9 patients withdrew early – mainly because of disease worsening – and some went on to early HSCT). Furthermore, an "encouraging number" of patients in the treatment group were able to discontinue all immunosuppressive drugs and steroids (about two-thirds of patients, compared with 15% in the control group), said Dr. Hawkey of the University of Nottingham, England.

Almost half of the patients in the treatment group achieved a CDAI score of 150 or less, signaling clinical remission.

"Strikingly, most of these patients were not taking any drugs at the time, either," Dr. Hawkey said.

The SES-CD score also decreased markedly in the treatment group, falling from a mean of 13 to 4 points, with four patients achieving complete absence of any evidence of involvement or ulceration, compared with no patients in the control group.

Complete mucosal healing, defined as lack of erosions or ulcerations on endoscopy, occurred in 40% of treatment-group patients, compared with only 15% of control-group patients, but several of these patients were still taking anti–tumor necrosis factor (anti-TNF) drugs or steroids, Dr. Hawkey said.

"Nevertheless, these are quite substantial findings," he said.

Patients included in the trial were adults who had undergone up to 12 surgeries each but who still had disease-related impairments to quality of life.

"For such an extreme technique, we wanted to enroll the most resistant patients," Dr. Hawkey said.

The treatment and control groups were well matched with respect to major demographics as well as CDAI and SES-CD scores, and patients were relatively young, having been diagnosed with Crohn’s disease at an early age, he noted.

Stem cell mobilization was achieved using 4 g/m² of intravenous cyclophosphamide delivered over 2 days, followed by 10 mcg/kg filgrastim daily until randomization. The conditioning regimen in the treatment group was 50 mg/kg per day of intravenous cyclophosphamide for 4 days, 2.5 mg/kg per day of antithymocyte globulin, and 1 mg/kg of methyl prednisolone on days 3-5. The bone marrow was reconstituted by infusion of an unselected graft of 3-8 × 10⁶ CD34-positive cells/kg.

One patient in the treatment group died 2 weeks after HSCT due to sepsis, and a significantly greater number of serious adverse events – usually infectious – occurred during follow-up in the treatment group than in the control group (an average of 3.3 per person).

The findings could have important implications for the treatment of Crohn’s disease.

"Immunoablation and repopulation of the bone marrow by uncommitted stem cells has excited a lot of interest in Crohn’s disease lately, and some of the case reports are undoubtedly so dramatic that it’s reasonable to talk about a cure in those patients," Dr. Hawkey said.

HSCT has been shown in controlled clinical trials to be effective – albeit with major toxicities – in systemic sclerosis and multiple sclerosis, but this is the first randomized controlled trial to evaluate the technique in Crohn’s disease.

"Our goal was quite an ambitious one. If we could achieve clinical remission, and patients were off drugs, that would be something of a game-changer," he said.

Indeed, the findings thus far suggest that stem cell transplantation is highly effective for patients with resistant Crohn’s disease, but in most cases, there is evidence of disease persistence.

"So this is seldom a cure, although sometimes it clearly is," he said, adding that given the significant number of serious adverse events, weighing the risks and benefits will be the key to successful clinical use in the future.

Outcomes following HSCT in the delayed-treatment group will be presented at a later date, he said.

Dr. Hawkey serves on advisory committees or review panels for Atlantic Healthcare, Bayer AG, GlaxoSmithKline, Novartis Pharmaceuticals, Boehringer Ingelheim, and Takeda Pharmaceuticals.

ORLANDO – Immunoablation and hematopoietic stem cell transplantation is highly effective – but also risky – for patients with intractable Crohn’s disease, according to interim findings from the randomized controlled ASTIC (Autologous Stem Cell Transplantation International Crohn’s Disease) trial.

At 1-year follow-up in the 5-year study, the treatment was associated with significant improvements as measured by the Crohn’s Disease Activity Index (CDAI) and Simple Endoscopic Score for Crohn’s Disease (SES-CD), Dr. Christopher J. Hawkey reported at the annual Digestive Disease Week. However, patients experienced more than three serious adverse events per person, and one death occurred 2 weeks after transplantation, he said.

Of 45 patients with impaired quality of life due to moderate to severe Crohn’s disease activity despite treatment with at least three immunosuppressive agents, all underwent stem cell mobilization treatment and were then randomized to receive either immediate or delayed immunoablation and hematopoietic stem cell transplantation (HSCT). The delayed-treatment group served as a control group.

In 22 patients who received immediate treatment and survived until 1-year follow-up, the CDAI score was halved to a median value of 162, compared with only about a 50-point drop in 13 patients in the control group who continued in the study (9 patients withdrew early – mainly because of disease worsening – and some went on to early HSCT). Furthermore, an "encouraging number" of patients in the treatment group were able to discontinue all immunosuppressive drugs and steroids (about two-thirds of patients, compared with 15% in the control group), said Dr. Hawkey of the University of Nottingham, England.

Almost half of the patients in the treatment group achieved a CDAI score of 150 or less, signaling clinical remission.

"Strikingly, most of these patients were not taking any drugs at the time, either," Dr. Hawkey said.

The SES-CD score also decreased markedly in the treatment group, falling from a mean of 13 to 4 points, with four patients achieving complete absence of any evidence of involvement or ulceration, compared with no patients in the control group.

Complete mucosal healing, defined as lack of erosions or ulcerations on endoscopy, occurred in 40% of treatment-group patients, compared with only 15% of control-group patients, but several of these patients were still taking anti–tumor necrosis factor (anti-TNF) drugs or steroids, Dr. Hawkey said.

"Nevertheless, these are quite substantial findings," he said.

Patients included in the trial were adults who had undergone up to 12 surgeries each but who still had disease-related impairments to quality of life.

"For such an extreme technique, we wanted to enroll the most resistant patients," Dr. Hawkey said.

The treatment and control groups were well matched with respect to major demographics as well as CDAI and SES-CD scores, and patients were relatively young, having been diagnosed with Crohn’s disease at an early age, he noted.

Stem cell mobilization was achieved using 4 g/m² of intravenous cyclophosphamide delivered over 2 days, followed by 10 mcg/kg filgrastim daily until randomization. The conditioning regimen in the treatment group was 50 mg/kg per day of intravenous cyclophosphamide for 4 days, 2.5 mg/kg per day of antithymocyte globulin, and 1 mg/kg of methyl prednisolone on days 3-5. The bone marrow was reconstituted by infusion of an unselected graft of 3-8 × 10⁶ CD34-positive cells/kg.

One patient in the treatment group died 2 weeks after HSCT due to sepsis, and a significantly greater number of serious adverse events – usually infectious – occurred during follow-up in the treatment group than in the control group (an average of 3.3 per person).

The findings could have important implications for the treatment of Crohn’s disease.

"Immunoablation and repopulation of the bone marrow by uncommitted stem cells has excited a lot of interest in Crohn’s disease lately, and some of the case reports are undoubtedly so dramatic that it’s reasonable to talk about a cure in those patients," Dr. Hawkey said.

HSCT has been shown in controlled clinical trials to be effective – albeit with major toxicities – in systemic sclerosis and multiple sclerosis, but this is the first randomized controlled trial to evaluate the technique in Crohn’s disease.

"Our goal was quite an ambitious one. If we could achieve clinical remission, and patients were off drugs, that would be something of a game-changer," he said.

Indeed, the findings thus far suggest that stem cell transplantation is highly effective for patients with resistant Crohn’s disease, but in most cases, there is evidence of disease persistence.

"So this is seldom a cure, although sometimes it clearly is," he said, adding that given the significant number of serious adverse events, weighing the risks and benefits will be the key to successful clinical use in the future.

Outcomes following HSCT in the delayed-treatment group will be presented at a later date, he said.

Dr. Hawkey serves on advisory committees or review panels for Atlantic Healthcare, Bayer AG, GlaxoSmithKline, Novartis Pharmaceuticals, Boehringer Ingelheim, and Takeda Pharmaceuticals.

ORLANDO – Researchers have identified a novel genetic marker for increased pancreatic cancer risk.

The marker, a single nucleotide polymorphism (SNP) of the cholecystokinin-B (CCK-B) receptor, could serve as a screening test for high-risk subjects, Dr. Jill P. Smith reported at the annual Digestive Disease Week.

The CCK-B receptor is a G-protein coupled receptor through which the effects of the peptide gastrin – which regulates pancreatic cancer growth – are mediated. Both gastrin and the CCK-B receptor are overexpressed in pancreatic cancer.

Dr. Smith and her colleagues discovered a splice variant of the CCK-B receptor, known as the CCK-C receptor, which results from retention of the fourth intron on the CCK-B receptor and the insertion of 69 amino acids to the third intracellular loop, she explained.

This change increases the affinity to gastrin and is associated with a more aggressive pancreatic cancer phenotype.

"So we hypothesized that the missplicing of the fourth intron of the CCK-B receptor was the result of a genetic mutation. We also felt that the translation of the additional 69 amino acids in the third intracellular loop of the CCK-B receptor would then contribute to the aggressive phenotype that we know of as pancreatic cancer," said Dr. Smith of the National Institutes of Health.

The investigators analyzed DNA extracted from blood or surgical cancer tissue specimens of 962 pancreatic cancer patients with ductal adenocarcinoma who were treated at three major medical centers, as well as from samples of normal pancreas tissue. The analysis confirmed that the etiology of the misspliced receptor was due to a SNP (involving a transition from C to A) at position 32 of the fourth intron that corresponded to the known SNP rs1800843. The newly identified SNP was not previously identified in genomewide association studies due to its location within an intron, rather than an exon, she noted.

The frequency of the A allele was significantly greater among those with pancreatic cancer than among controls (odds ratio, 1.57).

In addition, survival was significantly reduced in subjects who had the A allele (either AA or AC), compared with subjects with the CC genotype: Survival was about 14 months for patients with AA and 17 months for those with AC, compared with nearly 20 months for CC, Dr. Smith said.

The reduced survival was not a result of more advanced disease state at diagnosis, as the mean stage of subjects with two A alleles (AA) was slightly lower than in those with the CC genotype, she noted.

The findings are notable given that survival from pancreatic cancer has not improved over the past several decades, and that no test exists to diagnose pancreatic cancer in the early stages; more than 90% of patients have advanced disease at the time of diagnosis. Also, no screening tests without radiation are available for high-risk patients, Dr. Smith said.

"The finding of a germline mutation linked to a phenotype that’s significantly increased in patients with pancreatic cancer makes the CCK-B receptor relevant for clinical screening in high-risk subjects or families. Use of this new genetic marker may lead to early detection or even prevention of pancreatic cancer," she concluded.

This study was supported by a National Institutes of Health grant. Dr. Smith disclosed that she is a TNI Biotech stock shareholder.

ORLANDO – Researchers have identified a novel genetic marker for increased pancreatic cancer risk.

The marker, a single nucleotide polymorphism (SNP) of the cholecystokinin-B (CCK-B) receptor, could serve as a screening test for high-risk subjects, Dr. Jill P. Smith reported at the annual Digestive Disease Week.

The CCK-B receptor is a G-protein coupled receptor through which the effects of the peptide gastrin – which regulates pancreatic cancer growth – are mediated. Both gastrin and the CCK-B receptor are overexpressed in pancreatic cancer.

Dr. Smith and her colleagues discovered a splice variant of the CCK-B receptor, known as the CCK-C receptor, which results from retention of the fourth intron on the CCK-B receptor and the insertion of 69 amino acids to the third intracellular loop, she explained.

This change increases the affinity to gastrin and is associated with a more aggressive pancreatic cancer phenotype.

"So we hypothesized that the missplicing of the fourth intron of the CCK-B receptor was the result of a genetic mutation. We also felt that the translation of the additional 69 amino acids in the third intracellular loop of the CCK-B receptor would then contribute to the aggressive phenotype that we know of as pancreatic cancer," said Dr. Smith of the National Institutes of Health.

The investigators analyzed DNA extracted from blood or surgical cancer tissue specimens of 962 pancreatic cancer patients with ductal adenocarcinoma who were treated at three major medical centers, as well as from samples of normal pancreas tissue. The analysis confirmed that the etiology of the misspliced receptor was due to a SNP (involving a transition from C to A) at position 32 of the fourth intron that corresponded to the known SNP rs1800843. The newly identified SNP was not previously identified in genomewide association studies due to its location within an intron, rather than an exon, she noted.

The frequency of the A allele was significantly greater among those with pancreatic cancer than among controls (odds ratio, 1.57).

In addition, survival was significantly reduced in subjects who had the A allele (either AA or AC), compared with subjects with the CC genotype: Survival was about 14 months for patients with AA and 17 months for those with AC, compared with nearly 20 months for CC, Dr. Smith said.

The reduced survival was not a result of more advanced disease state at diagnosis, as the mean stage of subjects with two A alleles (AA) was slightly lower than in those with the CC genotype, she noted.

The findings are notable given that survival from pancreatic cancer has not improved over the past several decades, and that no test exists to diagnose pancreatic cancer in the early stages; more than 90% of patients have advanced disease at the time of diagnosis. Also, no screening tests without radiation are available for high-risk patients, Dr. Smith said.

"The finding of a germline mutation linked to a phenotype that’s significantly increased in patients with pancreatic cancer makes the CCK-B receptor relevant for clinical screening in high-risk subjects or families. Use of this new genetic marker may lead to early detection or even prevention of pancreatic cancer," she concluded.

This study was supported by a National Institutes of Health grant. Dr. Smith disclosed that she is a TNI Biotech stock shareholder.

ORLANDO – Researchers have identified a novel genetic marker for increased pancreatic cancer risk.

The marker, a single nucleotide polymorphism (SNP) of the cholecystokinin-B (CCK-B) receptor, could serve as a screening test for high-risk subjects, Dr. Jill P. Smith reported at the annual Digestive Disease Week.

The CCK-B receptor is a G-protein coupled receptor through which the effects of the peptide gastrin – which regulates pancreatic cancer growth – are mediated. Both gastrin and the CCK-B receptor are overexpressed in pancreatic cancer.

Dr. Smith and her colleagues discovered a splice variant of the CCK-B receptor, known as the CCK-C receptor, which results from retention of the fourth intron on the CCK-B receptor and the insertion of 69 amino acids to the third intracellular loop, she explained.

This change increases the affinity to gastrin and is associated with a more aggressive pancreatic cancer phenotype.

"So we hypothesized that the missplicing of the fourth intron of the CCK-B receptor was the result of a genetic mutation. We also felt that the translation of the additional 69 amino acids in the third intracellular loop of the CCK-B receptor would then contribute to the aggressive phenotype that we know of as pancreatic cancer," said Dr. Smith of the National Institutes of Health.

The investigators analyzed DNA extracted from blood or surgical cancer tissue specimens of 962 pancreatic cancer patients with ductal adenocarcinoma who were treated at three major medical centers, as well as from samples of normal pancreas tissue. The analysis confirmed that the etiology of the misspliced receptor was due to a SNP (involving a transition from C to A) at position 32 of the fourth intron that corresponded to the known SNP rs1800843. The newly identified SNP was not previously identified in genomewide association studies due to its location within an intron, rather than an exon, she noted.

The frequency of the A allele was significantly greater among those with pancreatic cancer than among controls (odds ratio, 1.57).

In addition, survival was significantly reduced in subjects who had the A allele (either AA or AC), compared with subjects with the CC genotype: Survival was about 14 months for patients with AA and 17 months for those with AC, compared with nearly 20 months for CC, Dr. Smith said.

The reduced survival was not a result of more advanced disease state at diagnosis, as the mean stage of subjects with two A alleles (AA) was slightly lower than in those with the CC genotype, she noted.

The findings are notable given that survival from pancreatic cancer has not improved over the past several decades, and that no test exists to diagnose pancreatic cancer in the early stages; more than 90% of patients have advanced disease at the time of diagnosis. Also, no screening tests without radiation are available for high-risk patients, Dr. Smith said.

"The finding of a germline mutation linked to a phenotype that’s significantly increased in patients with pancreatic cancer makes the CCK-B receptor relevant for clinical screening in high-risk subjects or families. Use of this new genetic marker may lead to early detection or even prevention of pancreatic cancer," she concluded.

This study was supported by a National Institutes of Health grant. Dr. Smith disclosed that she is a TNI Biotech stock shareholder.

DESTIN, FLORIDA – Central nervous system manifestations in patients with systemic lupus erythematosus should always trigger an evaluation for infection and other non–SLE-related etiologies, according to Dr. Julius Birnbaum.

That’s because between 33% and 50% of SLE patients will have a CNS syndrome that is not caused by SLE, Dr. Birnbaum said at the annual Congress of Clinical Rheumatology.

Infection is among the top causes of such syndromes.

"Because lupus patients are on immunosuppressive therapy, there always needs to be this paranoia for this lurking possibility of an infection," stressed Dr. Birnbaum of the departments of medicine and neurology at Johns Hopkins University, Baltimore.

The VITAMIN mnemonic device, similar to the VITAMINS mnemonic device he recommends for developing the differential diagnosis for peripheral nervous system manifestations, can also help with the differential diagnosis for CNS manifestation in neuropsychiatric SLE, he said.

"The stakes are a little bit higher now when we’re dealing with a lupus patient because we really want to make sure that we’re not overlooking a syndrome which would be exacerbated and not helped if we start immunosuppressive therapy," he said.

VITAMIN in this case represents:

• V – Vascular. In terms of stroke, it is important to think about septic emboli, subarachnoid hemorrhage from mycotic aneurysms, and septic thrombophlebitis.

• I – Infections. These should be classified by etiology (that is, bacterial, fungal, viral) and by anatomic region (is it parenchymal or meningeal, or does it have a vascular distribution, as in the case of septic emboli or thrombophlebitis?).

• T – Trauma. In SLE, this cause of CNS symptoms is similar to the general population.

• A – Autoimmune disorders. Always look for other autoimmune diseases as a cause.

• M – Metabolic disorders. These are uncommon as a cause of CNS symptoms, but may include hyperhomocysteinemia and B₁₂ deficiency.

• I – Iatrogenic complications. These are a major concern, and can include metabolic complications associated with steroid use or infections caused by immunosuppressive therapy.

• N – Neoplastic syndromes.

Dr. Birnbaum suggested using the VITAMIN mnemonic to get ideas for potentially useful diagnostic strategies, including routine serologic studies (such as an evaluation for uremia as a cause for encephalopathy or seizures); a work-up for infection (possibly including lumbar puncture); neuroimaging studies (such as CT to exclude a hemorrhage and MRI to further characterize space occupying lesions using specific sequences for strokes, for example); and diagnostic-specific strategies for distinct CNS disorders, such as EEG for the evaluation of seizures.

"Everything germinates from the patient’s symptoms ... you start with the symptoms, you do your neurological examination, and all of these tests that you’re going to order should be subordinated under a unifying strategy based on just the symptom and the examination," he said.

The next step, after reviewing the differential diagnosis, is to consider the specificity of a particular CNS syndrome for neuropsychiatric SLE, Dr. Birnbaum said.

Importantly, among the syndromes included in the American College of Rheumatology neuropsychiatric SLE nomenclature and case definition for the CNS neuropsychiatric SLE spectrum are several that have been shown – since the list was developed 15 years ago – to be nonspecific in that they are seen with similar frequency in non-SLE controls, he said.

These include headache, mood disorders, anxiety disorders, and mild cognitive impairment. In most cases, once "sinister causes" are ruled out using the VITAMIN mnemonic, these can be evaluated and treated as if the patient does not have SLE.

Only rarely are these nonspecific syndromes actually a manifestation of pathologic mechanism specific to SLE. In the right clinical context, examples may include an intractable "lupus headache" and depression or depression with unusual catatonic features, Dr. Birnbaum said.

"These are extraordinarily uncommon ... I want to emphasize that a neurological work-up can be standardized, but it is layered with some nuance, so there is no substitute for individual judgment," he said.

As for decisions regarding instituting symptomatic vs. immunosuppressive therapy, much of the decision will be based on the timing of the onset of symptoms relative to the onset of lupus.

"By and large, neurological symptoms that occur early into the onset of lupus tend to be more associated with lupus disease. Those neurological symptoms that occur later tend to be associated with damage," he said.

Seizures that occur in a young adult within 2 years of the onset of lupus, for example, tend to be associated with extraneurologic disease activity and increased organ activity. In this context, institution of immunosuppressive therapy for the extraneurologic disease should be considered.

Somewhat paradoxically, symptomatic therapy is usually needed only short term in cases with onset early in the course of lupus, because neurologic syndromes that occur early in disease onset are generally inflammatory and respond well, Dr. Birnbaum said.

Conversely, immunosuppressive therapy is usually not needed in cases of CNS symptom onset at 2 or more years after lupus onset, but these patients may require prolonged symptomatic therapy, he said, explaining that the symptoms often are due to permanent damage.

Dr. Birnbaum reported having no disclosures.

DESTIN, FLORIDA – Central nervous system manifestations in patients with systemic lupus erythematosus should always trigger an evaluation for infection and other non–SLE-related etiologies, according to Dr. Julius Birnbaum.

That’s because between 33% and 50% of SLE patients will have a CNS syndrome that is not caused by SLE, Dr. Birnbaum said at the annual Congress of Clinical Rheumatology.

Infection is among the top causes of such syndromes.

"Because lupus patients are on immunosuppressive therapy, there always needs to be this paranoia for this lurking possibility of an infection," stressed Dr. Birnbaum of the departments of medicine and neurology at Johns Hopkins University, Baltimore.

The VITAMIN mnemonic device, similar to the VITAMINS mnemonic device he recommends for developing the differential diagnosis for peripheral nervous system manifestations, can also help with the differential diagnosis for CNS manifestation in neuropsychiatric SLE, he said.

"The stakes are a little bit higher now when we’re dealing with a lupus patient because we really want to make sure that we’re not overlooking a syndrome which would be exacerbated and not helped if we start immunosuppressive therapy," he said.

VITAMIN in this case represents:

• V – Vascular. In terms of stroke, it is important to think about septic emboli, subarachnoid hemorrhage from mycotic aneurysms, and septic thrombophlebitis.

• I – Infections. These should be classified by etiology (that is, bacterial, fungal, viral) and by anatomic region (is it parenchymal or meningeal, or does it have a vascular distribution, as in the case of septic emboli or thrombophlebitis?).

• T – Trauma. In SLE, this cause of CNS symptoms is similar to the general population.

• A – Autoimmune disorders. Always look for other autoimmune diseases as a cause.

• M – Metabolic disorders. These are uncommon as a cause of CNS symptoms, but may include hyperhomocysteinemia and B₁₂ deficiency.

• I – Iatrogenic complications. These are a major concern, and can include metabolic complications associated with steroid use or infections caused by immunosuppressive therapy.

• N – Neoplastic syndromes.

Dr. Birnbaum suggested using the VITAMIN mnemonic to get ideas for potentially useful diagnostic strategies, including routine serologic studies (such as an evaluation for uremia as a cause for encephalopathy or seizures); a work-up for infection (possibly including lumbar puncture); neuroimaging studies (such as CT to exclude a hemorrhage and MRI to further characterize space occupying lesions using specific sequences for strokes, for example); and diagnostic-specific strategies for distinct CNS disorders, such as EEG for the evaluation of seizures.

"Everything germinates from the patient’s symptoms ... you start with the symptoms, you do your neurological examination, and all of these tests that you’re going to order should be subordinated under a unifying strategy based on just the symptom and the examination," he said.

The next step, after reviewing the differential diagnosis, is to consider the specificity of a particular CNS syndrome for neuropsychiatric SLE, Dr. Birnbaum said.

Importantly, among the syndromes included in the American College of Rheumatology neuropsychiatric SLE nomenclature and case definition for the CNS neuropsychiatric SLE spectrum are several that have been shown – since the list was developed 15 years ago – to be nonspecific in that they are seen with similar frequency in non-SLE controls, he said.

These include headache, mood disorders, anxiety disorders, and mild cognitive impairment. In most cases, once "sinister causes" are ruled out using the VITAMIN mnemonic, these can be evaluated and treated as if the patient does not have SLE.

Only rarely are these nonspecific syndromes actually a manifestation of pathologic mechanism specific to SLE. In the right clinical context, examples may include an intractable "lupus headache" and depression or depression with unusual catatonic features, Dr. Birnbaum said.

"These are extraordinarily uncommon ... I want to emphasize that a neurological work-up can be standardized, but it is layered with some nuance, so there is no substitute for individual judgment," he said.

As for decisions regarding instituting symptomatic vs. immunosuppressive therapy, much of the decision will be based on the timing of the onset of symptoms relative to the onset of lupus.

"By and large, neurological symptoms that occur early into the onset of lupus tend to be more associated with lupus disease. Those neurological symptoms that occur later tend to be associated with damage," he said.

Seizures that occur in a young adult within 2 years of the onset of lupus, for example, tend to be associated with extraneurologic disease activity and increased organ activity. In this context, institution of immunosuppressive therapy for the extraneurologic disease should be considered.

Somewhat paradoxically, symptomatic therapy is usually needed only short term in cases with onset early in the course of lupus, because neurologic syndromes that occur early in disease onset are generally inflammatory and respond well, Dr. Birnbaum said.

Conversely, immunosuppressive therapy is usually not needed in cases of CNS symptom onset at 2 or more years after lupus onset, but these patients may require prolonged symptomatic therapy, he said, explaining that the symptoms often are due to permanent damage.

Dr. Birnbaum reported having no disclosures.

DESTIN, FLORIDA – Central nervous system manifestations in patients with systemic lupus erythematosus should always trigger an evaluation for infection and other non–SLE-related etiologies, according to Dr. Julius Birnbaum.

That’s because between 33% and 50% of SLE patients will have a CNS syndrome that is not caused by SLE, Dr. Birnbaum said at the annual Congress of Clinical Rheumatology.

Infection is among the top causes of such syndromes.

"Because lupus patients are on immunosuppressive therapy, there always needs to be this paranoia for this lurking possibility of an infection," stressed Dr. Birnbaum of the departments of medicine and neurology at Johns Hopkins University, Baltimore.

The VITAMIN mnemonic device, similar to the VITAMINS mnemonic device he recommends for developing the differential diagnosis for peripheral nervous system manifestations, can also help with the differential diagnosis for CNS manifestation in neuropsychiatric SLE, he said.

"The stakes are a little bit higher now when we’re dealing with a lupus patient because we really want to make sure that we’re not overlooking a syndrome which would be exacerbated and not helped if we start immunosuppressive therapy," he said.

VITAMIN in this case represents:

• V – Vascular. In terms of stroke, it is important to think about septic emboli, subarachnoid hemorrhage from mycotic aneurysms, and septic thrombophlebitis.

• I – Infections. These should be classified by etiology (that is, bacterial, fungal, viral) and by anatomic region (is it parenchymal or meningeal, or does it have a vascular distribution, as in the case of septic emboli or thrombophlebitis?).

• T – Trauma. In SLE, this cause of CNS symptoms is similar to the general population.

• A – Autoimmune disorders. Always look for other autoimmune diseases as a cause.

• M – Metabolic disorders. These are uncommon as a cause of CNS symptoms, but may include hyperhomocysteinemia and B₁₂ deficiency.

• I – Iatrogenic complications. These are a major concern, and can include metabolic complications associated with steroid use or infections caused by immunosuppressive therapy.

• N – Neoplastic syndromes.

Dr. Birnbaum suggested using the VITAMIN mnemonic to get ideas for potentially useful diagnostic strategies, including routine serologic studies (such as an evaluation for uremia as a cause for encephalopathy or seizures); a work-up for infection (possibly including lumbar puncture); neuroimaging studies (such as CT to exclude a hemorrhage and MRI to further characterize space occupying lesions using specific sequences for strokes, for example); and diagnostic-specific strategies for distinct CNS disorders, such as EEG for the evaluation of seizures.

"Everything germinates from the patient’s symptoms ... you start with the symptoms, you do your neurological examination, and all of these tests that you’re going to order should be subordinated under a unifying strategy based on just the symptom and the examination," he said.

The next step, after reviewing the differential diagnosis, is to consider the specificity of a particular CNS syndrome for neuropsychiatric SLE, Dr. Birnbaum said.

Importantly, among the syndromes included in the American College of Rheumatology neuropsychiatric SLE nomenclature and case definition for the CNS neuropsychiatric SLE spectrum are several that have been shown – since the list was developed 15 years ago – to be nonspecific in that they are seen with similar frequency in non-SLE controls, he said.

These include headache, mood disorders, anxiety disorders, and mild cognitive impairment. In most cases, once "sinister causes" are ruled out using the VITAMIN mnemonic, these can be evaluated and treated as if the patient does not have SLE.

Only rarely are these nonspecific syndromes actually a manifestation of pathologic mechanism specific to SLE. In the right clinical context, examples may include an intractable "lupus headache" and depression or depression with unusual catatonic features, Dr. Birnbaum said.

"These are extraordinarily uncommon ... I want to emphasize that a neurological work-up can be standardized, but it is layered with some nuance, so there is no substitute for individual judgment," he said.

As for decisions regarding instituting symptomatic vs. immunosuppressive therapy, much of the decision will be based on the timing of the onset of symptoms relative to the onset of lupus.

"By and large, neurological symptoms that occur early into the onset of lupus tend to be more associated with lupus disease. Those neurological symptoms that occur later tend to be associated with damage," he said.

Seizures that occur in a young adult within 2 years of the onset of lupus, for example, tend to be associated with extraneurologic disease activity and increased organ activity. In this context, institution of immunosuppressive therapy for the extraneurologic disease should be considered.

Somewhat paradoxically, symptomatic therapy is usually needed only short term in cases with onset early in the course of lupus, because neurologic syndromes that occur early in disease onset are generally inflammatory and respond well, Dr. Birnbaum said.

Conversely, immunosuppressive therapy is usually not needed in cases of CNS symptom onset at 2 or more years after lupus onset, but these patients may require prolonged symptomatic therapy, he said, explaining that the symptoms often are due to permanent damage.

Dr. Birnbaum reported having no disclosures.

DESTIN, FLA. – A simple mnemonic device can help to distinguish whether peripheral nervous system manifestations in patients with lupus and Sjögren’s syndrome are caused by the diseases themselves or by an alternate comorbidity, according to Dr. Julius Birnbaum.

The mnemonic device VITAMINS incorporates the spectrum of peripheral nervous system manifestations in lupus and Sjögren’s syndrome, and assists with the important task of fashioning a broad differential diagnosis and identifying the appropriate treatment, Dr. Birnbaum said at the Congress of Clinical Rheumatology.

Typically included in that spectrum of peripheral nervous system manifestations of lupus and Sjögren’s are a number of conditions that actually occur in less than 1% of patients, such as Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, plexopathy myasthenia gravis, and polyneuropathy without electrodiagnostic confirmation (except in cases of small-fiber neuropathy). Those conditions should therefore be considered as secondary and coincidental disease manifestations that can be managed as if the patient did not have lupus or Sjögren’s, said Dr. Birnbaum, associate professor of neurology at Johns Hopkins University, Baltimore.

Conversely, small-fiber neuropathies – painful sensory neuropathies that selectively or predominantly affect unmyelinated nociceptive fibers, are typically not included in that spectrum, but likely represent an underappreciated part of the spectrum of peripheral nervous system manifestations, he said. Small-fiber neuropathies are not detected by electrodiagnostic studies, which only test the integrity of larger-fiber myelinated nerves, he said.

In fact, in the context of supportive symptoms and physical examination, normal electromyography/nerve conduction velocity tests may actually support a diagnosis of small-fiber neuropathy. Furthermore, these neuropathies can cause unorthodox patterns of neuropathic pain, he said.

For example, in Sjögren’s syndrome, the patterns don’t always follow the typical “stocking and glove” distribution, and Sjögren’s patients with clinical features suggestive of small-fiber dysfunction may have normal skin biopsy studies.

Once these neuropathies are identified, the VITAMINS mnemonic can help in developing a differential. For small-fiber neuropathies, the mnemonic represents the following possible alternative causes:

 V – Vascular diagnoses, namely systemic vasculitides, but this is probably uncommon, according to Dr. Birnbaum.

 I – Infection, such as HIV and hepatitis C virus.

 T – Trauma, although this is very rare.

 A – Autoimmune/inflammatory disorders, especially celiac disease, sarcoidosis, and other rheumatic syndromes.

 M – Metabolic disorders. This typically means diabetes, but impaired glucose tolerance can also be the culprit, so a 2-hour glucose tolerance test is important. Other possible metabolic causes of small-fiber neuropathy are vitamin B₁₂ deficiency and hypothyroidism.

 I – Inflammatory disorders, including amyloidosis, paraproteinemia, and cryoglobulinemia.

 N – Neoplastic disorders, particularly paraneoplastic disorders.

 S – Structural “mimics” such as syringomyelia and myeloradiculopathies.

Using this mnemonic, which “literally takes about 5 minutes,” is much easier than memorizing these numerous differential entities, he said.

A slightly altered version of the VITAMINS mnemonic can be used to identify the differential diagnoses for symmetric axonal polyneuropathies in lupus and Sjögren’s patients. In this case, the mnemonic represents the following alternative causes:

 V – Vasculitis. “Sometimes a very rapidly coalescing vasculitis can give the facsimile of a polyneuropathy,” Dr. Birnbaum said.

 I – Infection. As with small-fiber neuropathies, HIV and hepatitis C virus – even when not related to cryoglobulin – can cause symmetric axonal polyneuropathies.

 T – Trauma, although this is very rare.

 A – Autoimmune diseases, such as sarcoidosis.

 M – Metabolic disorders, namely diabetes and impaired glucose tolerance. A 2-hour glucose tolerance test should be ordered.

 I – Inflammatory disorders, including amyloidosis, paraproteinemia, and type 1 cryoglobulinemia.

 N – Neoplastic disorders, particularly lymphomatous or other infiltrative neuropathies (although these are usually associated with asymmetric symptoms), chemotherapy, and/or paraneoplastic syndromes.

 S – Structural causes. Compressive neuropathies are an example, although these are rare.

“Again you could use this mnemonic, and you’ll have the ability to really start honing in on pertinent and salient diagnoses, which might mimic a rheumatic disease,” Dr. Birnbaum said.

When it comes to treatment of these neuropathies and determining whether to use immunosuppressive therapies or symptomatic management, “it is useful to try to understand the relationship of a particular peripheral nervous system phenotype to disease activity versus disease damage,” he said.

Understanding differences in the characteristics of axonal neuropathy and mononeuritis multiplex can be helpful. For example, the prevalence of axonal polyneuropathies ranges from 1% to 10% in lupus and Sjögren’s, compared with a prevalence of less than 1% for mononeuritis multiplex. Also, lupus and Sjögren’s disease activity tends to be lower in the presence of axonal polyneuropathies and higher with mononeuritis multiplex.

Furthermore, disease-specific autoantibodies and immunological markers are not present in cases of axonal polyneuropathies, but Sjögren’s patients with mononeuritis multiplex may have cryoglobulinemia types II or III, high anti–rheumatoid factor, and low C4, Dr. Birnbaum said.

“By and large, most symmetric axonal polyneuropathies that you will see in lupus and Sjögren’s will tend to start distally, they will tend to start symmetrically. If they start in the feet, they usually stay restricted to the feet. If there is any migration it is very slow and occurs over years, if at all, and it usually tends to be much more sensory rather than motor,” he said.

Based on this more distal and sensory distribution, these patients can be managed, from the standpoint of their neuropathy, with symptomatic therapy, he added.

However, therapy in these patients needs to be “contextualized in the background of disease activity,” he said.

“Obviously, if the lupus patient has other extraneurological lupus disease activity, then you will institute immunosuppressive therapy, but just from the standpoint of symmetric axonal polyneuropathy, you usually do not have to,” he said.

In contrast, mononeuritis multiplex, much like antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, represents a jeopardized organ that is being targeted.

“You treat with immunosuppressive therapy for induction” in these cases, Dr. Birnbaum said.

Keep in mind, however, that even when immunosuppressive therapies are warranted, symptomatic management of neuropathic pain may still be necessary, he said.

Dr. Birnbaum reported having no disclosures.

DESTIN, FLA. – A simple mnemonic device can help to distinguish whether peripheral nervous system manifestations in patients with lupus and Sjögren’s syndrome are caused by the diseases themselves or by an alternate comorbidity, according to Dr. Julius Birnbaum.

The mnemonic device VITAMINS incorporates the spectrum of peripheral nervous system manifestations in lupus and Sjögren’s syndrome, and assists with the important task of fashioning a broad differential diagnosis and identifying the appropriate treatment, Dr. Birnbaum said at the Congress of Clinical Rheumatology.

Typically included in that spectrum of peripheral nervous system manifestations of lupus and Sjögren’s are a number of conditions that actually occur in less than 1% of patients, such as Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, plexopathy myasthenia gravis, and polyneuropathy without electrodiagnostic confirmation (except in cases of small-fiber neuropathy). Those conditions should therefore be considered as secondary and coincidental disease manifestations that can be managed as if the patient did not have lupus or Sjögren’s, said Dr. Birnbaum, associate professor of neurology at Johns Hopkins University, Baltimore.

Conversely, small-fiber neuropathies – painful sensory neuropathies that selectively or predominantly affect unmyelinated nociceptive fibers, are typically not included in that spectrum, but likely represent an underappreciated part of the spectrum of peripheral nervous system manifestations, he said. Small-fiber neuropathies are not detected by electrodiagnostic studies, which only test the integrity of larger-fiber myelinated nerves, he said.

In fact, in the context of supportive symptoms and physical examination, normal electromyography/nerve conduction velocity tests may actually support a diagnosis of small-fiber neuropathy. Furthermore, these neuropathies can cause unorthodox patterns of neuropathic pain, he said.

For example, in Sjögren’s syndrome, the patterns don’t always follow the typical “stocking and glove” distribution, and Sjögren’s patients with clinical features suggestive of small-fiber dysfunction may have normal skin biopsy studies.

Once these neuropathies are identified, the VITAMINS mnemonic can help in developing a differential. For small-fiber neuropathies, the mnemonic represents the following possible alternative causes:

 V – Vascular diagnoses, namely systemic vasculitides, but this is probably uncommon, according to Dr. Birnbaum.

 I – Infection, such as HIV and hepatitis C virus.

 T – Trauma, although this is very rare.

 A – Autoimmune/inflammatory disorders, especially celiac disease, sarcoidosis, and other rheumatic syndromes.

 M – Metabolic disorders. This typically means diabetes, but impaired glucose tolerance can also be the culprit, so a 2-hour glucose tolerance test is important. Other possible metabolic causes of small-fiber neuropathy are vitamin B₁₂ deficiency and hypothyroidism.

 I – Inflammatory disorders, including amyloidosis, paraproteinemia, and cryoglobulinemia.

 N – Neoplastic disorders, particularly paraneoplastic disorders.

 S – Structural “mimics” such as syringomyelia and myeloradiculopathies.

Using this mnemonic, which “literally takes about 5 minutes,” is much easier than memorizing these numerous differential entities, he said.

A slightly altered version of the VITAMINS mnemonic can be used to identify the differential diagnoses for symmetric axonal polyneuropathies in lupus and Sjögren’s patients. In this case, the mnemonic represents the following alternative causes:

 V – Vasculitis. “Sometimes a very rapidly coalescing vasculitis can give the facsimile of a polyneuropathy,” Dr. Birnbaum said.

 I – Infection. As with small-fiber neuropathies, HIV and hepatitis C virus – even when not related to cryoglobulin – can cause symmetric axonal polyneuropathies.

 T – Trauma, although this is very rare.

 A – Autoimmune diseases, such as sarcoidosis.

 M – Metabolic disorders, namely diabetes and impaired glucose tolerance. A 2-hour glucose tolerance test should be ordered.

 I – Inflammatory disorders, including amyloidosis, paraproteinemia, and type 1 cryoglobulinemia.

 N – Neoplastic disorders, particularly lymphomatous or other infiltrative neuropathies (although these are usually associated with asymmetric symptoms), chemotherapy, and/or paraneoplastic syndromes.

 S – Structural causes. Compressive neuropathies are an example, although these are rare.

“Again you could use this mnemonic, and you’ll have the ability to really start honing in on pertinent and salient diagnoses, which might mimic a rheumatic disease,” Dr. Birnbaum said.

When it comes to treatment of these neuropathies and determining whether to use immunosuppressive therapies or symptomatic management, “it is useful to try to understand the relationship of a particular peripheral nervous system phenotype to disease activity versus disease damage,” he said.

Understanding differences in the characteristics of axonal neuropathy and mononeuritis multiplex can be helpful. For example, the prevalence of axonal polyneuropathies ranges from 1% to 10% in lupus and Sjögren’s, compared with a prevalence of less than 1% for mononeuritis multiplex. Also, lupus and Sjögren’s disease activity tends to be lower in the presence of axonal polyneuropathies and higher with mononeuritis multiplex.

Furthermore, disease-specific autoantibodies and immunological markers are not present in cases of axonal polyneuropathies, but Sjögren’s patients with mononeuritis multiplex may have cryoglobulinemia types II or III, high anti–rheumatoid factor, and low C4, Dr. Birnbaum said.

“By and large, most symmetric axonal polyneuropathies that you will see in lupus and Sjögren’s will tend to start distally, they will tend to start symmetrically. If they start in the feet, they usually stay restricted to the feet. If there is any migration it is very slow and occurs over years, if at all, and it usually tends to be much more sensory rather than motor,” he said.

Based on this more distal and sensory distribution, these patients can be managed, from the standpoint of their neuropathy, with symptomatic therapy, he added.

However, therapy in these patients needs to be “contextualized in the background of disease activity,” he said.

“Obviously, if the lupus patient has other extraneurological lupus disease activity, then you will institute immunosuppressive therapy, but just from the standpoint of symmetric axonal polyneuropathy, you usually do not have to,” he said.

In contrast, mononeuritis multiplex, much like antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, represents a jeopardized organ that is being targeted.

“You treat with immunosuppressive therapy for induction” in these cases, Dr. Birnbaum said.

Keep in mind, however, that even when immunosuppressive therapies are warranted, symptomatic management of neuropathic pain may still be necessary, he said.

Dr. Birnbaum reported having no disclosures.

DESTIN, FLA. – A simple mnemonic device can help to distinguish whether peripheral nervous system manifestations in patients with lupus and Sjögren’s syndrome are caused by the diseases themselves or by an alternate comorbidity, according to Dr. Julius Birnbaum.

The mnemonic device VITAMINS incorporates the spectrum of peripheral nervous system manifestations in lupus and Sjögren’s syndrome, and assists with the important task of fashioning a broad differential diagnosis and identifying the appropriate treatment, Dr. Birnbaum said at the Congress of Clinical Rheumatology.

Typically included in that spectrum of peripheral nervous system manifestations of lupus and Sjögren’s are a number of conditions that actually occur in less than 1% of patients, such as Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, plexopathy myasthenia gravis, and polyneuropathy without electrodiagnostic confirmation (except in cases of small-fiber neuropathy). Those conditions should therefore be considered as secondary and coincidental disease manifestations that can be managed as if the patient did not have lupus or Sjögren’s, said Dr. Birnbaum, associate professor of neurology at Johns Hopkins University, Baltimore.

Conversely, small-fiber neuropathies – painful sensory neuropathies that selectively or predominantly affect unmyelinated nociceptive fibers, are typically not included in that spectrum, but likely represent an underappreciated part of the spectrum of peripheral nervous system manifestations, he said. Small-fiber neuropathies are not detected by electrodiagnostic studies, which only test the integrity of larger-fiber myelinated nerves, he said.

In fact, in the context of supportive symptoms and physical examination, normal electromyography/nerve conduction velocity tests may actually support a diagnosis of small-fiber neuropathy. Furthermore, these neuropathies can cause unorthodox patterns of neuropathic pain, he said.

For example, in Sjögren’s syndrome, the patterns don’t always follow the typical “stocking and glove” distribution, and Sjögren’s patients with clinical features suggestive of small-fiber dysfunction may have normal skin biopsy studies.

Once these neuropathies are identified, the VITAMINS mnemonic can help in developing a differential. For small-fiber neuropathies, the mnemonic represents the following possible alternative causes:

 V – Vascular diagnoses, namely systemic vasculitides, but this is probably uncommon, according to Dr. Birnbaum.

 I – Infection, such as HIV and hepatitis C virus.

 T – Trauma, although this is very rare.

 A – Autoimmune/inflammatory disorders, especially celiac disease, sarcoidosis, and other rheumatic syndromes.

 M – Metabolic disorders. This typically means diabetes, but impaired glucose tolerance can also be the culprit, so a 2-hour glucose tolerance test is important. Other possible metabolic causes of small-fiber neuropathy are vitamin B₁₂ deficiency and hypothyroidism.

 I – Inflammatory disorders, including amyloidosis, paraproteinemia, and cryoglobulinemia.

 N – Neoplastic disorders, particularly paraneoplastic disorders.

 S – Structural “mimics” such as syringomyelia and myeloradiculopathies.

Using this mnemonic, which “literally takes about 5 minutes,” is much easier than memorizing these numerous differential entities, he said.

A slightly altered version of the VITAMINS mnemonic can be used to identify the differential diagnoses for symmetric axonal polyneuropathies in lupus and Sjögren’s patients. In this case, the mnemonic represents the following alternative causes:

 V – Vasculitis. “Sometimes a very rapidly coalescing vasculitis can give the facsimile of a polyneuropathy,” Dr. Birnbaum said.

 I – Infection. As with small-fiber neuropathies, HIV and hepatitis C virus – even when not related to cryoglobulin – can cause symmetric axonal polyneuropathies.

 T – Trauma, although this is very rare.

 A – Autoimmune diseases, such as sarcoidosis.

 M – Metabolic disorders, namely diabetes and impaired glucose tolerance. A 2-hour glucose tolerance test should be ordered.

 I – Inflammatory disorders, including amyloidosis, paraproteinemia, and type 1 cryoglobulinemia.

 N – Neoplastic disorders, particularly lymphomatous or other infiltrative neuropathies (although these are usually associated with asymmetric symptoms), chemotherapy, and/or paraneoplastic syndromes.

 S – Structural causes. Compressive neuropathies are an example, although these are rare.

“Again you could use this mnemonic, and you’ll have the ability to really start honing in on pertinent and salient diagnoses, which might mimic a rheumatic disease,” Dr. Birnbaum said.

When it comes to treatment of these neuropathies and determining whether to use immunosuppressive therapies or symptomatic management, “it is useful to try to understand the relationship of a particular peripheral nervous system phenotype to disease activity versus disease damage,” he said.

Understanding differences in the characteristics of axonal neuropathy and mononeuritis multiplex can be helpful. For example, the prevalence of axonal polyneuropathies ranges from 1% to 10% in lupus and Sjögren’s, compared with a prevalence of less than 1% for mononeuritis multiplex. Also, lupus and Sjögren’s disease activity tends to be lower in the presence of axonal polyneuropathies and higher with mononeuritis multiplex.

Furthermore, disease-specific autoantibodies and immunological markers are not present in cases of axonal polyneuropathies, but Sjögren’s patients with mononeuritis multiplex may have cryoglobulinemia types II or III, high anti–rheumatoid factor, and low C4, Dr. Birnbaum said.

“By and large, most symmetric axonal polyneuropathies that you will see in lupus and Sjögren’s will tend to start distally, they will tend to start symmetrically. If they start in the feet, they usually stay restricted to the feet. If there is any migration it is very slow and occurs over years, if at all, and it usually tends to be much more sensory rather than motor,” he said.

Based on this more distal and sensory distribution, these patients can be managed, from the standpoint of their neuropathy, with symptomatic therapy, he added.

However, therapy in these patients needs to be “contextualized in the background of disease activity,” he said.

“Obviously, if the lupus patient has other extraneurological lupus disease activity, then you will institute immunosuppressive therapy, but just from the standpoint of symmetric axonal polyneuropathy, you usually do not have to,” he said.

In contrast, mononeuritis multiplex, much like antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, represents a jeopardized organ that is being targeted.

“You treat with immunosuppressive therapy for induction” in these cases, Dr. Birnbaum said.

Keep in mind, however, that even when immunosuppressive therapies are warranted, symptomatic management of neuropathic pain may still be necessary, he said.

Dr. Birnbaum reported having no disclosures.

ORLANDO – Colorectal cancers that are identified 6 months or more after a colonoscopy due to either a missed lesion or a new cancer development occur in 3.5%-6% of patients in the United States, findings from a large population-based retrospective cohort study suggest.

Characteristics of these missed or newly developed cancers, or "missed interval" cancers, suggest that tumor biology, rather than patient or physician factors, plays an important role in their development, Dr. N. Jewel Samadder said at the annual Digestive Disease Week.

Of 129,936 patients aged 50-80 years who underwent colonoscopy in Utah between Feb. 15, 1995, and Jan. 31, 2009, 2,659 were diagnosed with colorectal cancer, and 37 cases of a missed interval cancer that occurred 6-60 months after the index colonoscopy were identified. Using a 6- to 36-month window following the index colonoscopy, the rate of missed interval cancers was 3.5%; using a 6- to 60-month window, the rate was 6%, said Dr. Samadder of Huntsman Cancer Institute, Salt Lake City.

Nearly 85% of the missed cancers occurred in patients who underwent polypectomy at a prior colonoscopy, meaning only about 15% occurred in patients with a prior clean colonoscopy. Furthermore, missed interval colorectal cancers were significantly associated with a lower stage than were those detected at the index colonoscopy (advanced-stage odds ratio, 0.70), and were significantly more likely to be proximally located (OR, 2.24), he said.

Missed interval cancers also were associated with distinctly better survival than were detected cancers, both overall (hazard ratio, 0.63), and by stage (HR: 0.77, 0.54, 0.50, and 0.48 for cancer stages 1, 2, 3, and 4, respectively), he noted.

The findings are noteworthy because while prior studies from other countries have shown similar rates of missed interval colorectal cancers, those findings weren’t necessarily generalizable to U.S. populations, and the rate in the United States has been unclear, Dr. Samadder said. The size of the current study and the use of statewide data reflect clinical practice and make the findings generalizable to the U.S. population and routine GI clinical practice, he noted.

Although colonoscopy is the preferred screening option for colorectal cancer, controversy exists about its effectiveness, particularly with respect to missed interval cancer, he said.

Several factors have been suggested as to the cause of missed interval cancers, including a low adenoma detection rate, incomplete colonoscopy, poor bowel preparation, and differences in tumor biology.

In this study, neither age nor gender was associated with missed interval versus detected cancer. Also, the cecal intubation rate was 92% in the missed interval cases, and bowel prep was rated as good or excellent in 92% of cases. All procedures were performed by a gastroenterologist.

"Thus, our study suggests that a low adenoma detection rate, incomplete colonoscopy, and poor bowel prep may not be the complete estimation of the missed interval cancer issue; tumor biology may play a greater role," Dr. Samadder said. The results are consistent with missed interval colorectal cancers developing from either microsatellite instability or the serrated pathway, he added.

"Future directions include determining molecular predictors of missed interval colorectal cancer, thus identifying patients and communities at greatest risk and needing increased surveillance," he said.

Dr. Samadder has served as a speaker and teacher for Cook.

ORLANDO – Colorectal cancers that are identified 6 months or more after a colonoscopy due to either a missed lesion or a new cancer development occur in 3.5%-6% of patients in the United States, findings from a large population-based retrospective cohort study suggest.

Characteristics of these missed or newly developed cancers, or "missed interval" cancers, suggest that tumor biology, rather than patient or physician factors, plays an important role in their development, Dr. N. Jewel Samadder said at the annual Digestive Disease Week.

Of 129,936 patients aged 50-80 years who underwent colonoscopy in Utah between Feb. 15, 1995, and Jan. 31, 2009, 2,659 were diagnosed with colorectal cancer, and 37 cases of a missed interval cancer that occurred 6-60 months after the index colonoscopy were identified. Using a 6- to 36-month window following the index colonoscopy, the rate of missed interval cancers was 3.5%; using a 6- to 60-month window, the rate was 6%, said Dr. Samadder of Huntsman Cancer Institute, Salt Lake City.

Nearly 85% of the missed cancers occurred in patients who underwent polypectomy at a prior colonoscopy, meaning only about 15% occurred in patients with a prior clean colonoscopy. Furthermore, missed interval colorectal cancers were significantly associated with a lower stage than were those detected at the index colonoscopy (advanced-stage odds ratio, 0.70), and were significantly more likely to be proximally located (OR, 2.24), he said.

Missed interval cancers also were associated with distinctly better survival than were detected cancers, both overall (hazard ratio, 0.63), and by stage (HR: 0.77, 0.54, 0.50, and 0.48 for cancer stages 1, 2, 3, and 4, respectively), he noted.

The findings are noteworthy because while prior studies from other countries have shown similar rates of missed interval colorectal cancers, those findings weren’t necessarily generalizable to U.S. populations, and the rate in the United States has been unclear, Dr. Samadder said. The size of the current study and the use of statewide data reflect clinical practice and make the findings generalizable to the U.S. population and routine GI clinical practice, he noted.

Although colonoscopy is the preferred screening option for colorectal cancer, controversy exists about its effectiveness, particularly with respect to missed interval cancer, he said.

Several factors have been suggested as to the cause of missed interval cancers, including a low adenoma detection rate, incomplete colonoscopy, poor bowel preparation, and differences in tumor biology.

In this study, neither age nor gender was associated with missed interval versus detected cancer. Also, the cecal intubation rate was 92% in the missed interval cases, and bowel prep was rated as good or excellent in 92% of cases. All procedures were performed by a gastroenterologist.

"Thus, our study suggests that a low adenoma detection rate, incomplete colonoscopy, and poor bowel prep may not be the complete estimation of the missed interval cancer issue; tumor biology may play a greater role," Dr. Samadder said. The results are consistent with missed interval colorectal cancers developing from either microsatellite instability or the serrated pathway, he added.

"Future directions include determining molecular predictors of missed interval colorectal cancer, thus identifying patients and communities at greatest risk and needing increased surveillance," he said.

Dr. Samadder has served as a speaker and teacher for Cook.

ORLANDO – Colorectal cancers that are identified 6 months or more after a colonoscopy due to either a missed lesion or a new cancer development occur in 3.5%-6% of patients in the United States, findings from a large population-based retrospective cohort study suggest.

Characteristics of these missed or newly developed cancers, or "missed interval" cancers, suggest that tumor biology, rather than patient or physician factors, plays an important role in their development, Dr. N. Jewel Samadder said at the annual Digestive Disease Week.

Of 129,936 patients aged 50-80 years who underwent colonoscopy in Utah between Feb. 15, 1995, and Jan. 31, 2009, 2,659 were diagnosed with colorectal cancer, and 37 cases of a missed interval cancer that occurred 6-60 months after the index colonoscopy were identified. Using a 6- to 36-month window following the index colonoscopy, the rate of missed interval cancers was 3.5%; using a 6- to 60-month window, the rate was 6%, said Dr. Samadder of Huntsman Cancer Institute, Salt Lake City.

Nearly 85% of the missed cancers occurred in patients who underwent polypectomy at a prior colonoscopy, meaning only about 15% occurred in patients with a prior clean colonoscopy. Furthermore, missed interval colorectal cancers were significantly associated with a lower stage than were those detected at the index colonoscopy (advanced-stage odds ratio, 0.70), and were significantly more likely to be proximally located (OR, 2.24), he said.

Missed interval cancers also were associated with distinctly better survival than were detected cancers, both overall (hazard ratio, 0.63), and by stage (HR: 0.77, 0.54, 0.50, and 0.48 for cancer stages 1, 2, 3, and 4, respectively), he noted.

The findings are noteworthy because while prior studies from other countries have shown similar rates of missed interval colorectal cancers, those findings weren’t necessarily generalizable to U.S. populations, and the rate in the United States has been unclear, Dr. Samadder said. The size of the current study and the use of statewide data reflect clinical practice and make the findings generalizable to the U.S. population and routine GI clinical practice, he noted.

Although colonoscopy is the preferred screening option for colorectal cancer, controversy exists about its effectiveness, particularly with respect to missed interval cancer, he said.

Several factors have been suggested as to the cause of missed interval cancers, including a low adenoma detection rate, incomplete colonoscopy, poor bowel preparation, and differences in tumor biology.

In this study, neither age nor gender was associated with missed interval versus detected cancer. Also, the cecal intubation rate was 92% in the missed interval cases, and bowel prep was rated as good or excellent in 92% of cases. All procedures were performed by a gastroenterologist.

"Thus, our study suggests that a low adenoma detection rate, incomplete colonoscopy, and poor bowel prep may not be the complete estimation of the missed interval cancer issue; tumor biology may play a greater role," Dr. Samadder said. The results are consistent with missed interval colorectal cancers developing from either microsatellite instability or the serrated pathway, he added.

"Future directions include determining molecular predictors of missed interval colorectal cancer, thus identifying patients and communities at greatest risk and needing increased surveillance," he said.

Dr. Samadder has served as a speaker and teacher for Cook.

ORLANDO – The rate at which physicians detect adenomas during colonoscopy is an independent risk factor for their patients’ risk of developing colorectal cancer following a negative colonoscopy, according to findings from a large observational study.

Physicians with low rates of adenoma detection during screening colonoscopies were more likely to have patients who developed interval colorectal cancers. For every 1% decline in the physician adenoma detection rate, colorectal cancer risk increased by about 3%, and the risk of death related to colorectal cancer increased by about 4%, Dr. Douglas A. Corley reported at the annual Digestive Disease Week.

The findings suggest that adenoma detection rates – the proportion of screening colonoscopies in which a physician detects at least one adenoma – could be a useful quality metric, he said.

The findings were noted in a study of 314,872 colonoscopy exams in which 8,708 colorectal cancers were detected. Interval colorectal cancers – cancers diagnosed at examinations that took place at least 6 months after the index colonoscopy – were seen in 712 patients, said Dr. Corley, of the Kaiser Permanente Division of Research, Oakland, Calif.

Most (60%) interval cancers were proximal. In total, 34% were advanced cancers, and about 20% led to colorectal cancer–related deaths. About one-third were diagnosed in the early interval period, between 6 months and 3 years. The remaining two-thirds were diagnosed 3-10 years after an initial negative screening colonoscopy, Dr. Corley said.

Physician adenoma detection rates ranged from 7% to 52%, which are rates consistent with prior reports in the literature. There was a linear association across five quintiles of physician adenoma detection rates and subsequent patient colorectal cancer risk. "There’s no threshold effect above which increases in adenoma detection rate were without benefit," Dr. Corley said.

After adjusting for colonoscopy indication and patient age, sex, race/ethnicity, family history of colorectal cancer, and Charlson comorbidity score, the risk was about 80%-90% higher among patients of physicians whose adenoma detection rates were in the first or second quintile, as compared with patients of physicians with detection rates in the highest quintile.

A similar pattern was seen for advanced colorectal cancers, and the correlation was even stronger. The risk was increased more than twofold among patients of physicians in the bottom two quintiles of adenoma detection rates, compared with patients whose physicians were in the top quintile, he said.

Risk of death from colorectal cancer followed a similar pattern. Patients of physicians in the first and second quintiles had more than a 2.5-fold increased risk of colorectal cancer death compared with patients of physicians in the top quintile. Risk did not differ by patient status or by cancer location, Dr. Corley said.

Patients included in the study were aged 50 years or older, had been members of the Kaiser Permanente Northern California health plan for at least 2 years, and had a negative colonoscopy for any indication between 1998 and 2010. Only those colonoscopies performed by experienced endoscopists – those who had performed more than 300 colonoscopies and more than 75 screening exams during the study period – were included in the study.

Patients were followed for 10 years or until another negative colonoscopy was performed, health plan membership was terminated, a diagnosis of colorectal cancer was made, or Jan. 31, 2011 – whichever came first.

Dr. Corley has received grant or research support from Pfizer Pharmaceuticals.

ORLANDO – The rate at which physicians detect adenomas during colonoscopy is an independent risk factor for their patients’ risk of developing colorectal cancer following a negative colonoscopy, according to findings from a large observational study.

Physicians with low rates of adenoma detection during screening colonoscopies were more likely to have patients who developed interval colorectal cancers. For every 1% decline in the physician adenoma detection rate, colorectal cancer risk increased by about 3%, and the risk of death related to colorectal cancer increased by about 4%, Dr. Douglas A. Corley reported at the annual Digestive Disease Week.

The findings suggest that adenoma detection rates – the proportion of screening colonoscopies in which a physician detects at least one adenoma – could be a useful quality metric, he said.

The findings were noted in a study of 314,872 colonoscopy exams in which 8,708 colorectal cancers were detected. Interval colorectal cancers – cancers diagnosed at examinations that took place at least 6 months after the index colonoscopy – were seen in 712 patients, said Dr. Corley, of the Kaiser Permanente Division of Research, Oakland, Calif.

Most (60%) interval cancers were proximal. In total, 34% were advanced cancers, and about 20% led to colorectal cancer–related deaths. About one-third were diagnosed in the early interval period, between 6 months and 3 years. The remaining two-thirds were diagnosed 3-10 years after an initial negative screening colonoscopy, Dr. Corley said.

Physician adenoma detection rates ranged from 7% to 52%, which are rates consistent with prior reports in the literature. There was a linear association across five quintiles of physician adenoma detection rates and subsequent patient colorectal cancer risk. "There’s no threshold effect above which increases in adenoma detection rate were without benefit," Dr. Corley said.

After adjusting for colonoscopy indication and patient age, sex, race/ethnicity, family history of colorectal cancer, and Charlson comorbidity score, the risk was about 80%-90% higher among patients of physicians whose adenoma detection rates were in the first or second quintile, as compared with patients of physicians with detection rates in the highest quintile.

A similar pattern was seen for advanced colorectal cancers, and the correlation was even stronger. The risk was increased more than twofold among patients of physicians in the bottom two quintiles of adenoma detection rates, compared with patients whose physicians were in the top quintile, he said.

Risk of death from colorectal cancer followed a similar pattern. Patients of physicians in the first and second quintiles had more than a 2.5-fold increased risk of colorectal cancer death compared with patients of physicians in the top quintile. Risk did not differ by patient status or by cancer location, Dr. Corley said.

Patients included in the study were aged 50 years or older, had been members of the Kaiser Permanente Northern California health plan for at least 2 years, and had a negative colonoscopy for any indication between 1998 and 2010. Only those colonoscopies performed by experienced endoscopists – those who had performed more than 300 colonoscopies and more than 75 screening exams during the study period – were included in the study.

Patients were followed for 10 years or until another negative colonoscopy was performed, health plan membership was terminated, a diagnosis of colorectal cancer was made, or Jan. 31, 2011 – whichever came first.

Dr. Corley has received grant or research support from Pfizer Pharmaceuticals.

ORLANDO – The rate at which physicians detect adenomas during colonoscopy is an independent risk factor for their patients’ risk of developing colorectal cancer following a negative colonoscopy, according to findings from a large observational study.

Physicians with low rates of adenoma detection during screening colonoscopies were more likely to have patients who developed interval colorectal cancers. For every 1% decline in the physician adenoma detection rate, colorectal cancer risk increased by about 3%, and the risk of death related to colorectal cancer increased by about 4%, Dr. Douglas A. Corley reported at the annual Digestive Disease Week.

The findings suggest that adenoma detection rates – the proportion of screening colonoscopies in which a physician detects at least one adenoma – could be a useful quality metric, he said.

The findings were noted in a study of 314,872 colonoscopy exams in which 8,708 colorectal cancers were detected. Interval colorectal cancers – cancers diagnosed at examinations that took place at least 6 months after the index colonoscopy – were seen in 712 patients, said Dr. Corley, of the Kaiser Permanente Division of Research, Oakland, Calif.

Most (60%) interval cancers were proximal. In total, 34% were advanced cancers, and about 20% led to colorectal cancer–related deaths. About one-third were diagnosed in the early interval period, between 6 months and 3 years. The remaining two-thirds were diagnosed 3-10 years after an initial negative screening colonoscopy, Dr. Corley said.

Physician adenoma detection rates ranged from 7% to 52%, which are rates consistent with prior reports in the literature. There was a linear association across five quintiles of physician adenoma detection rates and subsequent patient colorectal cancer risk. "There’s no threshold effect above which increases in adenoma detection rate were without benefit," Dr. Corley said.

After adjusting for colonoscopy indication and patient age, sex, race/ethnicity, family history of colorectal cancer, and Charlson comorbidity score, the risk was about 80%-90% higher among patients of physicians whose adenoma detection rates were in the first or second quintile, as compared with patients of physicians with detection rates in the highest quintile.

A similar pattern was seen for advanced colorectal cancers, and the correlation was even stronger. The risk was increased more than twofold among patients of physicians in the bottom two quintiles of adenoma detection rates, compared with patients whose physicians were in the top quintile, he said.

Risk of death from colorectal cancer followed a similar pattern. Patients of physicians in the first and second quintiles had more than a 2.5-fold increased risk of colorectal cancer death compared with patients of physicians in the top quintile. Risk did not differ by patient status or by cancer location, Dr. Corley said.

Patients included in the study were aged 50 years or older, had been members of the Kaiser Permanente Northern California health plan for at least 2 years, and had a negative colonoscopy for any indication between 1998 and 2010. Only those colonoscopies performed by experienced endoscopists – those who had performed more than 300 colonoscopies and more than 75 screening exams during the study period – were included in the study.

Patients were followed for 10 years or until another negative colonoscopy was performed, health plan membership was terminated, a diagnosis of colorectal cancer was made, or Jan. 31, 2011 – whichever came first.

Dr. Corley has received grant or research support from Pfizer Pharmaceuticals.

ORLANDO – Use of a novel colonoscope that offers 330-degree viewing, as compared to the 140- to 170-degree viewing of traditional forward-viewing colonoscopes, was associated with a 71% improvement in adenoma detection, according to late-breaking data from a randomized, prospective multicenter study reported at the annual Digestive Disease Week.

In addition to its expanded viewing capability, the device has the same technical features as traditional colonoscopes, including scope length and diameter, full tip deflection, working channel, suction, and forward water-jet irrigation, reported Dr. Ian M. Gralnek of the Technion-Israel Institute of Technology and Elisha Hospital, both in Haifa, Israel.

For the study, 185 patients underwent colonoscopies via both traditional forward-viewing and EndoChoice’s full-spectrum endoscopy (FUSE) colonoscopy in random order on the same day. The overall polyp detection rate was 52.5%, and the adenoma detection rate was 31.7%.

In 88 subjects who underwent traditional colonoscopy followed by FUSE colonoscopy, traditional colonoscopy detected 28 adenomas and the subsequent FUSE colonoscopy detected an additional 20 adenomas, for a 71.4% increase in adenomas found with subsequent FUSE colonoscopy.

In 97 subjects who were randomly assigned to receive FUSE colonoscopy first, 59 adenomas and 2 cancers were detected. On subsequent traditional colonoscopy, 5 additional adenomas were found, yielding an 8.2% increase in adenomas found with subsequent traditional colonoscopy.

Thus, significantly more adenomas were detected by FUSE colonoscopy than with traditional colonoscopy (71.4% vs. 8.2% incremental detection rates), and significantly fewer adenomas were missed by FUSE colonoscopy as compared with traditional colonoscopy (7.6% vs. 42%).

The differences were highly statistically significant, Dr. Gralnek said.

Study subjects were adults aged 18-70 years who were referred between January 2012 and March 2013 for colorectal cancer screening, polyp surveillance, or diagnostic evaluation to one of three sites in Israel, one site in the Netherlands, or two in the United States. Subjects were randomly assigned to receive FUSE or traditional colonoscopy, then to receive the alternative modality on the same day. The same endoscopist performed both examinations.

Though the study findings are limited by the lack of blinding, the fact that the same endoscopist performed both colonoscopies in each patient, and the lack of per-patient analysis, the results highlight the value of the improved visualization afforded by the FUSE colonoscope, Dr. Gralnek concluded.

Developed by EndoChoice, the FUSE colonoscope has a CE marking in Europe, and it recently received 510(k) marketing approval from the U.S. Food and Drug Administration. Commercial availability is expected as early as summer 2013.

The study was sponsored by EndoChoice.

Dr. Gralnek is a member of advisory committees or review panels for Given Imaging and Motus GI, and is a consultant for Given Imaging, Peer Medical, and AstraZeneca.

ORLANDO – Use of a novel colonoscope that offers 330-degree viewing, as compared to the 140- to 170-degree viewing of traditional forward-viewing colonoscopes, was associated with a 71% improvement in adenoma detection, according to late-breaking data from a randomized, prospective multicenter study reported at the annual Digestive Disease Week.

In addition to its expanded viewing capability, the device has the same technical features as traditional colonoscopes, including scope length and diameter, full tip deflection, working channel, suction, and forward water-jet irrigation, reported Dr. Ian M. Gralnek of the Technion-Israel Institute of Technology and Elisha Hospital, both in Haifa, Israel.

For the study, 185 patients underwent colonoscopies via both traditional forward-viewing and EndoChoice’s full-spectrum endoscopy (FUSE) colonoscopy in random order on the same day. The overall polyp detection rate was 52.5%, and the adenoma detection rate was 31.7%.

In 88 subjects who underwent traditional colonoscopy followed by FUSE colonoscopy, traditional colonoscopy detected 28 adenomas and the subsequent FUSE colonoscopy detected an additional 20 adenomas, for a 71.4% increase in adenomas found with subsequent FUSE colonoscopy.

In 97 subjects who were randomly assigned to receive FUSE colonoscopy first, 59 adenomas and 2 cancers were detected. On subsequent traditional colonoscopy, 5 additional adenomas were found, yielding an 8.2% increase in adenomas found with subsequent traditional colonoscopy.

Thus, significantly more adenomas were detected by FUSE colonoscopy than with traditional colonoscopy (71.4% vs. 8.2% incremental detection rates), and significantly fewer adenomas were missed by FUSE colonoscopy as compared with traditional colonoscopy (7.6% vs. 42%).

The differences were highly statistically significant, Dr. Gralnek said.

Study subjects were adults aged 18-70 years who were referred between January 2012 and March 2013 for colorectal cancer screening, polyp surveillance, or diagnostic evaluation to one of three sites in Israel, one site in the Netherlands, or two in the United States. Subjects were randomly assigned to receive FUSE or traditional colonoscopy, then to receive the alternative modality on the same day. The same endoscopist performed both examinations.

Though the study findings are limited by the lack of blinding, the fact that the same endoscopist performed both colonoscopies in each patient, and the lack of per-patient analysis, the results highlight the value of the improved visualization afforded by the FUSE colonoscope, Dr. Gralnek concluded.

Developed by EndoChoice, the FUSE colonoscope has a CE marking in Europe, and it recently received 510(k) marketing approval from the U.S. Food and Drug Administration. Commercial availability is expected as early as summer 2013.

The study was sponsored by EndoChoice.

Dr. Gralnek is a member of advisory committees or review panels for Given Imaging and Motus GI, and is a consultant for Given Imaging, Peer Medical, and AstraZeneca.

ORLANDO – Use of a novel colonoscope that offers 330-degree viewing, as compared to the 140- to 170-degree viewing of traditional forward-viewing colonoscopes, was associated with a 71% improvement in adenoma detection, according to late-breaking data from a randomized, prospective multicenter study reported at the annual Digestive Disease Week.

In addition to its expanded viewing capability, the device has the same technical features as traditional colonoscopes, including scope length and diameter, full tip deflection, working channel, suction, and forward water-jet irrigation, reported Dr. Ian M. Gralnek of the Technion-Israel Institute of Technology and Elisha Hospital, both in Haifa, Israel.

For the study, 185 patients underwent colonoscopies via both traditional forward-viewing and EndoChoice’s full-spectrum endoscopy (FUSE) colonoscopy in random order on the same day. The overall polyp detection rate was 52.5%, and the adenoma detection rate was 31.7%.

In 88 subjects who underwent traditional colonoscopy followed by FUSE colonoscopy, traditional colonoscopy detected 28 adenomas and the subsequent FUSE colonoscopy detected an additional 20 adenomas, for a 71.4% increase in adenomas found with subsequent FUSE colonoscopy.

In 97 subjects who were randomly assigned to receive FUSE colonoscopy first, 59 adenomas and 2 cancers were detected. On subsequent traditional colonoscopy, 5 additional adenomas were found, yielding an 8.2% increase in adenomas found with subsequent traditional colonoscopy.

Thus, significantly more adenomas were detected by FUSE colonoscopy than with traditional colonoscopy (71.4% vs. 8.2% incremental detection rates), and significantly fewer adenomas were missed by FUSE colonoscopy as compared with traditional colonoscopy (7.6% vs. 42%).

The differences were highly statistically significant, Dr. Gralnek said.

Study subjects were adults aged 18-70 years who were referred between January 2012 and March 2013 for colorectal cancer screening, polyp surveillance, or diagnostic evaluation to one of three sites in Israel, one site in the Netherlands, or two in the United States. Subjects were randomly assigned to receive FUSE or traditional colonoscopy, then to receive the alternative modality on the same day. The same endoscopist performed both examinations.

Though the study findings are limited by the lack of blinding, the fact that the same endoscopist performed both colonoscopies in each patient, and the lack of per-patient analysis, the results highlight the value of the improved visualization afforded by the FUSE colonoscope, Dr. Gralnek concluded.

Developed by EndoChoice, the FUSE colonoscope has a CE marking in Europe, and it recently received 510(k) marketing approval from the U.S. Food and Drug Administration. Commercial availability is expected as early as summer 2013.

The study was sponsored by EndoChoice.

Dr. Gralnek is a member of advisory committees or review panels for Given Imaging and Motus GI, and is a consultant for Given Imaging, Peer Medical, and AstraZeneca.

NEW ORLEANS – Use of an investigational vaginal misoprostol insert significantly reduced the time to vaginal delivery, compared with a vaginal dinoprostone insert, and also reduced the need for maternal and neonatal antibiotics in both nulliparous and parous women undergoing labor induction, according to findings from a randomized, double-blind, phase III study.

Time to vaginal delivery was a mean of 29.2 hours in 441 nulliparous women who were treated with the 200-mcg controlled-release misoprostol vaginal insert (MVI) for labor induction, compared with 43.1 hours in 451 nulliparous women treated with a 10-mg controlled-release dinoprostone vaginal insert (DVI). Time to vaginal delivery was a mean of 13.4 hours in 237 parous women treated with MVI, compared with 20.1 hours in 229 parous women treated with DVI, Dr. R. Lamar Parker reported in a poster at the annual meeting of the American College of Obstetricians and Gynecologists.

The rate of cesarean delivery did not differ between the treatment groups (34.5% vs. 37.3% for nulliparous women treated with MVI and DVI, respectively, and 10.1% and 7.0% for parous women treated with MVI and DVI, respectively), said Dr. Parker, a gynecologist in group practice in Winston-Salem, N.C.

The groups also did not differ with respect to the rates of intrapartum, postpartum, or neonatal adverse events, most of which were mild or moderate, but the MVI group did experience more uterine activity–related adverse events, including tachysystole requiring intervention (13.3% vs. 4% in the MVI vs. DVI groups).

In another analysis of the study data, Dr. Deborah A. Wing and her colleagues found that MVI also significantly shortened the time to any delivery mode, compared with DVI (18.3 vs. 27.3 hours), and significantly shortened the duration of both the latent and active phases of labor (12.1 vs. 18.6 hours, and 4.8 vs. 6.9 hours, for the latent and active phases, respectively).

Significant reductions in the duration of latent and active labor with MVI vs. DVI treatment occurred in both nulliparous and parous women.

Shorter duration of these labor phases, regardless of the treatment used for labor induction, was associated with a significant reduction in the need for intrapartum, postpartum, and neonatal antibiotics, Dr. Wing, professor of clinical obstetrics and gynecology at the University of California, Irvine, and Long Beach Memorial Medical Center in Long Beach, Calif., reported in a separate poster.

Significantly fewer women who received MVI, compared with those who received DVI, required antibiotics during the intrapartum period (relative risk, 0.65) and postpartum period (RR, 0.55).

Also, antibiotics were required less often during the intrapartum, postpartum, and neonatal periods for both women and neonates when active or latent labor was shorter than the median duration, and when the total time to delivery and the duration of labor from rupture of membranes to delivery was shorter than the median duration, Dr. Wing noted.

Women included in this multicenter study were aged 18 years or older (mean of 26 years), had reached 36 weeks’ or more gestation, had parity of 3 or less, and had body mass index of 50 kg/m² or less at study entry. All had a baseline modified Bishop score of 4 or less (mean of 2.4 and 2.3 in the MVI and DVI groups, respectively) and required labor induction.

Those with pregnancy-related or fetal complications were excluded.

The findings are of note, because in the United States nearly a quarter of deliveries involve labor induction.

"While many methods are used, the American College of Obstetricians and Gynecologists and the World Health Organization recommend low-dose prostaglandins for cervical ripening prior to induction of labor," the authors wrote.

Currently, DVI (PEG₂), which is available as a vaginal insert or a vaginal gel, is the only Food and Drug Administration–approved prostaglandin for this purpose. Oral misoprostol, a prostaglandin E, is approved for prevention of gastric ulcers in patients using NSAIDS, but misoprostol tablets are often used off-label either orally or vaginally to induce labor, they said.

The tablet splitting and repeat administration required for vaginal use of oral misoprostol increases the likelihood of inaccurate dosing, they explained.

MVI (PEG₁), however, is a controlled-release vaginal insert that can remain in place for 24 hours. It can also be removed – thereby terminating drug administration - at the onset of active labor or in the event of adverse effects, they said.

A new drug approval application for MVI was accepted for review by the FDA in October 2012.

This study was sponsored by Ferring Pharmaceuticals. Dr. Parker and Dr. Wing reported serving as consultants to Ferring Pharmaceuticals and formerly receiving research support from Cytokine PharmaSciences, which is a wholly owned subsidiary of Ferring Pharmaceuticals.

NEW ORLEANS – Use of an investigational vaginal misoprostol insert significantly reduced the time to vaginal delivery, compared with a vaginal dinoprostone insert, and also reduced the need for maternal and neonatal antibiotics in both nulliparous and parous women undergoing labor induction, according to findings from a randomized, double-blind, phase III study.

Time to vaginal delivery was a mean of 29.2 hours in 441 nulliparous women who were treated with the 200-mcg controlled-release misoprostol vaginal insert (MVI) for labor induction, compared with 43.1 hours in 451 nulliparous women treated with a 10-mg controlled-release dinoprostone vaginal insert (DVI). Time to vaginal delivery was a mean of 13.4 hours in 237 parous women treated with MVI, compared with 20.1 hours in 229 parous women treated with DVI, Dr. R. Lamar Parker reported in a poster at the annual meeting of the American College of Obstetricians and Gynecologists.

The rate of cesarean delivery did not differ between the treatment groups (34.5% vs. 37.3% for nulliparous women treated with MVI and DVI, respectively, and 10.1% and 7.0% for parous women treated with MVI and DVI, respectively), said Dr. Parker, a gynecologist in group practice in Winston-Salem, N.C.

The groups also did not differ with respect to the rates of intrapartum, postpartum, or neonatal adverse events, most of which were mild or moderate, but the MVI group did experience more uterine activity–related adverse events, including tachysystole requiring intervention (13.3% vs. 4% in the MVI vs. DVI groups).

In another analysis of the study data, Dr. Deborah A. Wing and her colleagues found that MVI also significantly shortened the time to any delivery mode, compared with DVI (18.3 vs. 27.3 hours), and significantly shortened the duration of both the latent and active phases of labor (12.1 vs. 18.6 hours, and 4.8 vs. 6.9 hours, for the latent and active phases, respectively).

Significant reductions in the duration of latent and active labor with MVI vs. DVI treatment occurred in both nulliparous and parous women.

Shorter duration of these labor phases, regardless of the treatment used for labor induction, was associated with a significant reduction in the need for intrapartum, postpartum, and neonatal antibiotics, Dr. Wing, professor of clinical obstetrics and gynecology at the University of California, Irvine, and Long Beach Memorial Medical Center in Long Beach, Calif., reported in a separate poster.

Significantly fewer women who received MVI, compared with those who received DVI, required antibiotics during the intrapartum period (relative risk, 0.65) and postpartum period (RR, 0.55).

Also, antibiotics were required less often during the intrapartum, postpartum, and neonatal periods for both women and neonates when active or latent labor was shorter than the median duration, and when the total time to delivery and the duration of labor from rupture of membranes to delivery was shorter than the median duration, Dr. Wing noted.

Women included in this multicenter study were aged 18 years or older (mean of 26 years), had reached 36 weeks’ or more gestation, had parity of 3 or less, and had body mass index of 50 kg/m² or less at study entry. All had a baseline modified Bishop score of 4 or less (mean of 2.4 and 2.3 in the MVI and DVI groups, respectively) and required labor induction.

Those with pregnancy-related or fetal complications were excluded.

The findings are of note, because in the United States nearly a quarter of deliveries involve labor induction.

"While many methods are used, the American College of Obstetricians and Gynecologists and the World Health Organization recommend low-dose prostaglandins for cervical ripening prior to induction of labor," the authors wrote.

Currently, DVI (PEG₂), which is available as a vaginal insert or a vaginal gel, is the only Food and Drug Administration–approved prostaglandin for this purpose. Oral misoprostol, a prostaglandin E, is approved for prevention of gastric ulcers in patients using NSAIDS, but misoprostol tablets are often used off-label either orally or vaginally to induce labor, they said.

The tablet splitting and repeat administration required for vaginal use of oral misoprostol increases the likelihood of inaccurate dosing, they explained.

MVI (PEG₁), however, is a controlled-release vaginal insert that can remain in place for 24 hours. It can also be removed – thereby terminating drug administration - at the onset of active labor or in the event of adverse effects, they said.

A new drug approval application for MVI was accepted for review by the FDA in October 2012.

This study was sponsored by Ferring Pharmaceuticals. Dr. Parker and Dr. Wing reported serving as consultants to Ferring Pharmaceuticals and formerly receiving research support from Cytokine PharmaSciences, which is a wholly owned subsidiary of Ferring Pharmaceuticals.

NEW ORLEANS – Use of an investigational vaginal misoprostol insert significantly reduced the time to vaginal delivery, compared with a vaginal dinoprostone insert, and also reduced the need for maternal and neonatal antibiotics in both nulliparous and parous women undergoing labor induction, according to findings from a randomized, double-blind, phase III study.

Time to vaginal delivery was a mean of 29.2 hours in 441 nulliparous women who were treated with the 200-mcg controlled-release misoprostol vaginal insert (MVI) for labor induction, compared with 43.1 hours in 451 nulliparous women treated with a 10-mg controlled-release dinoprostone vaginal insert (DVI). Time to vaginal delivery was a mean of 13.4 hours in 237 parous women treated with MVI, compared with 20.1 hours in 229 parous women treated with DVI, Dr. R. Lamar Parker reported in a poster at the annual meeting of the American College of Obstetricians and Gynecologists.

The rate of cesarean delivery did not differ between the treatment groups (34.5% vs. 37.3% for nulliparous women treated with MVI and DVI, respectively, and 10.1% and 7.0% for parous women treated with MVI and DVI, respectively), said Dr. Parker, a gynecologist in group practice in Winston-Salem, N.C.

The groups also did not differ with respect to the rates of intrapartum, postpartum, or neonatal adverse events, most of which were mild or moderate, but the MVI group did experience more uterine activity–related adverse events, including tachysystole requiring intervention (13.3% vs. 4% in the MVI vs. DVI groups).

In another analysis of the study data, Dr. Deborah A. Wing and her colleagues found that MVI also significantly shortened the time to any delivery mode, compared with DVI (18.3 vs. 27.3 hours), and significantly shortened the duration of both the latent and active phases of labor (12.1 vs. 18.6 hours, and 4.8 vs. 6.9 hours, for the latent and active phases, respectively).

Significant reductions in the duration of latent and active labor with MVI vs. DVI treatment occurred in both nulliparous and parous women.

Shorter duration of these labor phases, regardless of the treatment used for labor induction, was associated with a significant reduction in the need for intrapartum, postpartum, and neonatal antibiotics, Dr. Wing, professor of clinical obstetrics and gynecology at the University of California, Irvine, and Long Beach Memorial Medical Center in Long Beach, Calif., reported in a separate poster.

Significantly fewer women who received MVI, compared with those who received DVI, required antibiotics during the intrapartum period (relative risk, 0.65) and postpartum period (RR, 0.55).

Also, antibiotics were required less often during the intrapartum, postpartum, and neonatal periods for both women and neonates when active or latent labor was shorter than the median duration, and when the total time to delivery and the duration of labor from rupture of membranes to delivery was shorter than the median duration, Dr. Wing noted.

Women included in this multicenter study were aged 18 years or older (mean of 26 years), had reached 36 weeks’ or more gestation, had parity of 3 or less, and had body mass index of 50 kg/m² or less at study entry. All had a baseline modified Bishop score of 4 or less (mean of 2.4 and 2.3 in the MVI and DVI groups, respectively) and required labor induction.

Those with pregnancy-related or fetal complications were excluded.

The findings are of note, because in the United States nearly a quarter of deliveries involve labor induction.

"While many methods are used, the American College of Obstetricians and Gynecologists and the World Health Organization recommend low-dose prostaglandins for cervical ripening prior to induction of labor," the authors wrote.

Currently, DVI (PEG₂), which is available as a vaginal insert or a vaginal gel, is the only Food and Drug Administration–approved prostaglandin for this purpose. Oral misoprostol, a prostaglandin E, is approved for prevention of gastric ulcers in patients using NSAIDS, but misoprostol tablets are often used off-label either orally or vaginally to induce labor, they said.

The tablet splitting and repeat administration required for vaginal use of oral misoprostol increases the likelihood of inaccurate dosing, they explained.

MVI (PEG₁), however, is a controlled-release vaginal insert that can remain in place for 24 hours. It can also be removed – thereby terminating drug administration - at the onset of active labor or in the event of adverse effects, they said.

A new drug approval application for MVI was accepted for review by the FDA in October 2012.

This study was sponsored by Ferring Pharmaceuticals. Dr. Parker and Dr. Wing reported serving as consultants to Ferring Pharmaceuticals and formerly receiving research support from Cytokine PharmaSciences, which is a wholly owned subsidiary of Ferring Pharmaceuticals.