Sharon Worcester

ORLANDO – Risk-based drug treatment with colonoscopy at 6 months – and treatment step-up for recurrence – was significantly more effective in preventing postoperative recurrence of Crohn’s disease, compared with standard drug therapy alone, based on data from the POCER (Post-Operative Crohn’s Endoscopic Recurrence) study.

At an 18-month follow-up colonoscopy, 49% of patients randomized to a risk-based intervention had endoscopic recurrence, compared with 67% of those in a standard drug therapy arm, Dr. Peter De Cruz reported during a late-breaking abstract session at the annual Digestive Disease Week.

Researchers compared the two recurrence-prevention strategies in 174 subjects who were stratified as high risk or low risk based on smoking status, presence of perforating disease, and previous surgeries. The participants were randomized 2:1 to either active care or standard drug therapy. Approximately one-third of patients in the active care arm showed signs of early recurrence at a 6-month colonoscopy and thus received step-up treatment.

Complete mucosal normality was observed in 22% of those in the risk-based treatment arm, compared with 8% in the standard therapy arm; no significant differences were noted with respect to severe endoscopic recurrence or clinical recurrence, said Dr. De Cruz of St. Vincent’s Hospital, Melbourne, Australia.

Patients in the multicenter POCER study were adults undergoing intestinal resection of all macroscopic disease. The treatment arms were similar in terms of demographics, disease characteristics, and prior drug therapy. Of 122 patients in the risk-based treatment arm, 101 were high-risk, and 21 were low-risk. Of 52 patients in the standard drug therapy arm, 44 were high-risk, and 8 were low-risk.

All patients were treated beginning postoperatively with 3 months of 400 mg metronidazole twice daily. High-risk patients also received 2 mg/kg of azathioprine daily, or 1.5 mg/kg of 6 mercaptopurine. Those intolerant of thiopurine were treated with adalimumab induction, followed by 40 mg every 2 weeks. Low-risk patients received no additional treatment following the 3 months of metronidazole.

For recurrence at 6 months, low-risk patients were stepped up to thiopurine; high-risk patients on thiopurine were stepped up to 40 mg adalimumab every 2 weeks, and high-risk patients on adalimumab every 2 weeks stepped up to weekly adalimumab.

The endoscopic remission rate at 18 months was 25% for the low-risk patients who stepped up to thiopurine 41% for high-risk patients who stepped up to thiopurine, and 50% for those who stepped up to weekly adalimumab.

Overall, 39% of patients who stepped up at 6 months were in remission at 1 year. Notably, 31% of the low-risk patients with endoscopic remission at the 6-month colonoscopy, 46% of the high-risk patients on thiopurine, and 41% of the high-risk patients on adalimumab with endoscopic remission at 6 months had endoscopic recurrence 1 year later.

"We can’t afford to relax," Dr. De Cruz said regarding those patients with remission 6 months postoperatively.

This study also allowed for comparison of the efficacy of adalimumab and thiopurine given immediately postoperatively in the high-risk patients. At 6 months, adalimumab was associated with a nearly 80% endoscopic remission rate, compared with 55% for thiopurine, Dr. De Cruz noted.

At 18 months, there was no significant difference in the recurrence rates between patients treated with adalimumab immediately postoperatively and those stepped up to adalimumab in combination with thiopurine. There was, however, a trend toward reduced recurrence rates among those on immediate postoperative adalimumab.

A multivariate analysis showed that active smoking was significantly associated with an increased endoscopic recurrence rate at 18 months, whereas the intervention of endoscopy at 6 months was significantly associated with a reduced recurrence risk at 18 months.

Most prior studies of postoperative recurrence prevention in Crohn’s surgery patients have focused on drug therapy compared with placebo; few have focused on risk-based strategies, Dr. De Cruz noted.

The findings indicate that step-up therapy based on endoscopy is a viable postoperative strategy in patients at high risk of recurrence, he said. No unexpected serious adverse events occurred in this study.

Dr. De Cruz warned, however, that remission at 6 months is no guarantee of remission 1 year later.

"Intensifying treatment at 6 months brings about 40% of patients with recurrence into remission, and we found that a small group of patients had recurrent disease despite endoscopic monitoring and intense treatment," he said.

Dr. De Cruz reported having no disclosures. Several study coauthors disclosed relationships with multiple pharmaceutical companies.

ORLANDO – Risk-based drug treatment with colonoscopy at 6 months – and treatment step-up for recurrence – was significantly more effective in preventing postoperative recurrence of Crohn’s disease, compared with standard drug therapy alone, based on data from the POCER (Post-Operative Crohn’s Endoscopic Recurrence) study.

At an 18-month follow-up colonoscopy, 49% of patients randomized to a risk-based intervention had endoscopic recurrence, compared with 67% of those in a standard drug therapy arm, Dr. Peter De Cruz reported during a late-breaking abstract session at the annual Digestive Disease Week.

Researchers compared the two recurrence-prevention strategies in 174 subjects who were stratified as high risk or low risk based on smoking status, presence of perforating disease, and previous surgeries. The participants were randomized 2:1 to either active care or standard drug therapy. Approximately one-third of patients in the active care arm showed signs of early recurrence at a 6-month colonoscopy and thus received step-up treatment.

Complete mucosal normality was observed in 22% of those in the risk-based treatment arm, compared with 8% in the standard therapy arm; no significant differences were noted with respect to severe endoscopic recurrence or clinical recurrence, said Dr. De Cruz of St. Vincent’s Hospital, Melbourne, Australia.

Patients in the multicenter POCER study were adults undergoing intestinal resection of all macroscopic disease. The treatment arms were similar in terms of demographics, disease characteristics, and prior drug therapy. Of 122 patients in the risk-based treatment arm, 101 were high-risk, and 21 were low-risk. Of 52 patients in the standard drug therapy arm, 44 were high-risk, and 8 were low-risk.

All patients were treated beginning postoperatively with 3 months of 400 mg metronidazole twice daily. High-risk patients also received 2 mg/kg of azathioprine daily, or 1.5 mg/kg of 6 mercaptopurine. Those intolerant of thiopurine were treated with adalimumab induction, followed by 40 mg every 2 weeks. Low-risk patients received no additional treatment following the 3 months of metronidazole.

For recurrence at 6 months, low-risk patients were stepped up to thiopurine; high-risk patients on thiopurine were stepped up to 40 mg adalimumab every 2 weeks, and high-risk patients on adalimumab every 2 weeks stepped up to weekly adalimumab.

The endoscopic remission rate at 18 months was 25% for the low-risk patients who stepped up to thiopurine 41% for high-risk patients who stepped up to thiopurine, and 50% for those who stepped up to weekly adalimumab.

Overall, 39% of patients who stepped up at 6 months were in remission at 1 year. Notably, 31% of the low-risk patients with endoscopic remission at the 6-month colonoscopy, 46% of the high-risk patients on thiopurine, and 41% of the high-risk patients on adalimumab with endoscopic remission at 6 months had endoscopic recurrence 1 year later.

"We can’t afford to relax," Dr. De Cruz said regarding those patients with remission 6 months postoperatively.

This study also allowed for comparison of the efficacy of adalimumab and thiopurine given immediately postoperatively in the high-risk patients. At 6 months, adalimumab was associated with a nearly 80% endoscopic remission rate, compared with 55% for thiopurine, Dr. De Cruz noted.

At 18 months, there was no significant difference in the recurrence rates between patients treated with adalimumab immediately postoperatively and those stepped up to adalimumab in combination with thiopurine. There was, however, a trend toward reduced recurrence rates among those on immediate postoperative adalimumab.

A multivariate analysis showed that active smoking was significantly associated with an increased endoscopic recurrence rate at 18 months, whereas the intervention of endoscopy at 6 months was significantly associated with a reduced recurrence risk at 18 months.

Most prior studies of postoperative recurrence prevention in Crohn’s surgery patients have focused on drug therapy compared with placebo; few have focused on risk-based strategies, Dr. De Cruz noted.

The findings indicate that step-up therapy based on endoscopy is a viable postoperative strategy in patients at high risk of recurrence, he said. No unexpected serious adverse events occurred in this study.

Dr. De Cruz warned, however, that remission at 6 months is no guarantee of remission 1 year later.

"Intensifying treatment at 6 months brings about 40% of patients with recurrence into remission, and we found that a small group of patients had recurrent disease despite endoscopic monitoring and intense treatment," he said.

Dr. De Cruz reported having no disclosures. Several study coauthors disclosed relationships with multiple pharmaceutical companies.

ORLANDO – Risk-based drug treatment with colonoscopy at 6 months – and treatment step-up for recurrence – was significantly more effective in preventing postoperative recurrence of Crohn’s disease, compared with standard drug therapy alone, based on data from the POCER (Post-Operative Crohn’s Endoscopic Recurrence) study.

At an 18-month follow-up colonoscopy, 49% of patients randomized to a risk-based intervention had endoscopic recurrence, compared with 67% of those in a standard drug therapy arm, Dr. Peter De Cruz reported during a late-breaking abstract session at the annual Digestive Disease Week.

Researchers compared the two recurrence-prevention strategies in 174 subjects who were stratified as high risk or low risk based on smoking status, presence of perforating disease, and previous surgeries. The participants were randomized 2:1 to either active care or standard drug therapy. Approximately one-third of patients in the active care arm showed signs of early recurrence at a 6-month colonoscopy and thus received step-up treatment.

Complete mucosal normality was observed in 22% of those in the risk-based treatment arm, compared with 8% in the standard therapy arm; no significant differences were noted with respect to severe endoscopic recurrence or clinical recurrence, said Dr. De Cruz of St. Vincent’s Hospital, Melbourne, Australia.

Patients in the multicenter POCER study were adults undergoing intestinal resection of all macroscopic disease. The treatment arms were similar in terms of demographics, disease characteristics, and prior drug therapy. Of 122 patients in the risk-based treatment arm, 101 were high-risk, and 21 were low-risk. Of 52 patients in the standard drug therapy arm, 44 were high-risk, and 8 were low-risk.

All patients were treated beginning postoperatively with 3 months of 400 mg metronidazole twice daily. High-risk patients also received 2 mg/kg of azathioprine daily, or 1.5 mg/kg of 6 mercaptopurine. Those intolerant of thiopurine were treated with adalimumab induction, followed by 40 mg every 2 weeks. Low-risk patients received no additional treatment following the 3 months of metronidazole.

For recurrence at 6 months, low-risk patients were stepped up to thiopurine; high-risk patients on thiopurine were stepped up to 40 mg adalimumab every 2 weeks, and high-risk patients on adalimumab every 2 weeks stepped up to weekly adalimumab.

The endoscopic remission rate at 18 months was 25% for the low-risk patients who stepped up to thiopurine 41% for high-risk patients who stepped up to thiopurine, and 50% for those who stepped up to weekly adalimumab.

Overall, 39% of patients who stepped up at 6 months were in remission at 1 year. Notably, 31% of the low-risk patients with endoscopic remission at the 6-month colonoscopy, 46% of the high-risk patients on thiopurine, and 41% of the high-risk patients on adalimumab with endoscopic remission at 6 months had endoscopic recurrence 1 year later.

"We can’t afford to relax," Dr. De Cruz said regarding those patients with remission 6 months postoperatively.

This study also allowed for comparison of the efficacy of adalimumab and thiopurine given immediately postoperatively in the high-risk patients. At 6 months, adalimumab was associated with a nearly 80% endoscopic remission rate, compared with 55% for thiopurine, Dr. De Cruz noted.

At 18 months, there was no significant difference in the recurrence rates between patients treated with adalimumab immediately postoperatively and those stepped up to adalimumab in combination with thiopurine. There was, however, a trend toward reduced recurrence rates among those on immediate postoperative adalimumab.

A multivariate analysis showed that active smoking was significantly associated with an increased endoscopic recurrence rate at 18 months, whereas the intervention of endoscopy at 6 months was significantly associated with a reduced recurrence risk at 18 months.

Most prior studies of postoperative recurrence prevention in Crohn’s surgery patients have focused on drug therapy compared with placebo; few have focused on risk-based strategies, Dr. De Cruz noted.

The findings indicate that step-up therapy based on endoscopy is a viable postoperative strategy in patients at high risk of recurrence, he said. No unexpected serious adverse events occurred in this study.

Dr. De Cruz warned, however, that remission at 6 months is no guarantee of remission 1 year later.

"Intensifying treatment at 6 months brings about 40% of patients with recurrence into remission, and we found that a small group of patients had recurrent disease despite endoscopic monitoring and intense treatment," he said.

Dr. De Cruz reported having no disclosures. Several study coauthors disclosed relationships with multiple pharmaceutical companies.

MIAMI BEACH – American men are showing an increased interest in skin care products, according to Dr. Ivan Camacho.

Men are becoming more aware of the importance of skin care, and they are actively seeking information and products. In fact, the men’s skin care market increased 9% from 2009 to 2010, and is expected to grow 16% by 2014, Dr. Camacho said at the annual meeting of the American Academy of Dermatology.

One point for dermatologists to keep in mind when it comes to introducing men to a skin care routine is that simple is best. Using multipurpose products, keeping regimens to one or two steps – three at most – and incorporating new products into an established routine, such as shaving, will likely improve compliance and results, said Dr. Camacho of the University of Miami.

Dr. Camacho’s additional tips for better skin care for men include:

• Recommend multifunctional products, such as those that combine antioxidants and botanicals, as well as other cosmeceuticals that can enhance anti-aging, provide anti-inflammatory effects, and hydrate the skin.

• Suggest fragrance-free or subtly scented products.

• Incorporate a broad-spectrum sunscreen (also unscented or subtly scented) with a sun protection factor (SPF) of at least 30. A product with botanical and other cosmeceutical ingredients or with anti-inflammatory properties may be a good choice, especially in patients with inflammatory conditions like acne or rosacea.

• Incorporate a moisturizer, which is very important for restoring facial hydration and improving the skin barrier. A moisturizer can be included in the sunscreen or other products.

"Tell patients to moisturize, moisturize, moisturize," Dr. Camacho said, noting: "If you tell them they need to do it three times a day, they will probably do it once a day, because this is a practice very neglected by many men. As we know, moisturizers will benefit all skin types."

For men with oily skin, recommend an oil-absorbing or mattifying formulation; for those with drier skin, recommend a lipid-based formulation. Given that more men are seeking information about skin care, dermatologists would do well to become knowledgeable about the various products available that may be most appealing to and effective for men, said Dr. Camacho.

Products currently attracting attention include moisturizers with topical caffeine, which has been shown to reduce the transepidermal water loss that is greater in men than in women, he noted.

Also, glycerin-based and niacinamide-based moisturizers have been shown in several studies to reduce transepidermal water loss, which may increase after shaving, he said.

In addition, many men can benefit from cleansers and toners developed for their particular skin types, shaving products that prevent or relieve irritation, oil-absorbing primers to provide temporary relief for skin oiliness, and exfoliating products and retinoids to improve an uneven complexion, said Dr. Camacho.

In addition, antiaging formulations containing alpha-hydroxy acids, retinoids, growth factors, antioxidants, peptides, and/or botanicals can be used to help reverse ultraviolet-related damage and help improve the appearance of fine lines, he said.

Dr. Camacho reported having no disclosures.

MIAMI BEACH – American men are showing an increased interest in skin care products, according to Dr. Ivan Camacho.

Men are becoming more aware of the importance of skin care, and they are actively seeking information and products. In fact, the men’s skin care market increased 9% from 2009 to 2010, and is expected to grow 16% by 2014, Dr. Camacho said at the annual meeting of the American Academy of Dermatology.

One point for dermatologists to keep in mind when it comes to introducing men to a skin care routine is that simple is best. Using multipurpose products, keeping regimens to one or two steps – three at most – and incorporating new products into an established routine, such as shaving, will likely improve compliance and results, said Dr. Camacho of the University of Miami.

Dr. Camacho’s additional tips for better skin care for men include:

• Recommend multifunctional products, such as those that combine antioxidants and botanicals, as well as other cosmeceuticals that can enhance anti-aging, provide anti-inflammatory effects, and hydrate the skin.

• Suggest fragrance-free or subtly scented products.

• Incorporate a broad-spectrum sunscreen (also unscented or subtly scented) with a sun protection factor (SPF) of at least 30. A product with botanical and other cosmeceutical ingredients or with anti-inflammatory properties may be a good choice, especially in patients with inflammatory conditions like acne or rosacea.

• Incorporate a moisturizer, which is very important for restoring facial hydration and improving the skin barrier. A moisturizer can be included in the sunscreen or other products.

"Tell patients to moisturize, moisturize, moisturize," Dr. Camacho said, noting: "If you tell them they need to do it three times a day, they will probably do it once a day, because this is a practice very neglected by many men. As we know, moisturizers will benefit all skin types."

For men with oily skin, recommend an oil-absorbing or mattifying formulation; for those with drier skin, recommend a lipid-based formulation. Given that more men are seeking information about skin care, dermatologists would do well to become knowledgeable about the various products available that may be most appealing to and effective for men, said Dr. Camacho.

Products currently attracting attention include moisturizers with topical caffeine, which has been shown to reduce the transepidermal water loss that is greater in men than in women, he noted.

Also, glycerin-based and niacinamide-based moisturizers have been shown in several studies to reduce transepidermal water loss, which may increase after shaving, he said.

In addition, many men can benefit from cleansers and toners developed for their particular skin types, shaving products that prevent or relieve irritation, oil-absorbing primers to provide temporary relief for skin oiliness, and exfoliating products and retinoids to improve an uneven complexion, said Dr. Camacho.

In addition, antiaging formulations containing alpha-hydroxy acids, retinoids, growth factors, antioxidants, peptides, and/or botanicals can be used to help reverse ultraviolet-related damage and help improve the appearance of fine lines, he said.

Dr. Camacho reported having no disclosures.

MIAMI BEACH – American men are showing an increased interest in skin care products, according to Dr. Ivan Camacho.

Men are becoming more aware of the importance of skin care, and they are actively seeking information and products. In fact, the men’s skin care market increased 9% from 2009 to 2010, and is expected to grow 16% by 2014, Dr. Camacho said at the annual meeting of the American Academy of Dermatology.

One point for dermatologists to keep in mind when it comes to introducing men to a skin care routine is that simple is best. Using multipurpose products, keeping regimens to one or two steps – three at most – and incorporating new products into an established routine, such as shaving, will likely improve compliance and results, said Dr. Camacho of the University of Miami.

Dr. Camacho’s additional tips for better skin care for men include:

• Recommend multifunctional products, such as those that combine antioxidants and botanicals, as well as other cosmeceuticals that can enhance anti-aging, provide anti-inflammatory effects, and hydrate the skin.

• Suggest fragrance-free or subtly scented products.

• Incorporate a broad-spectrum sunscreen (also unscented or subtly scented) with a sun protection factor (SPF) of at least 30. A product with botanical and other cosmeceutical ingredients or with anti-inflammatory properties may be a good choice, especially in patients with inflammatory conditions like acne or rosacea.

• Incorporate a moisturizer, which is very important for restoring facial hydration and improving the skin barrier. A moisturizer can be included in the sunscreen or other products.

"Tell patients to moisturize, moisturize, moisturize," Dr. Camacho said, noting: "If you tell them they need to do it three times a day, they will probably do it once a day, because this is a practice very neglected by many men. As we know, moisturizers will benefit all skin types."

For men with oily skin, recommend an oil-absorbing or mattifying formulation; for those with drier skin, recommend a lipid-based formulation. Given that more men are seeking information about skin care, dermatologists would do well to become knowledgeable about the various products available that may be most appealing to and effective for men, said Dr. Camacho.

Products currently attracting attention include moisturizers with topical caffeine, which has been shown to reduce the transepidermal water loss that is greater in men than in women, he noted.

Also, glycerin-based and niacinamide-based moisturizers have been shown in several studies to reduce transepidermal water loss, which may increase after shaving, he said.

In addition, many men can benefit from cleansers and toners developed for their particular skin types, shaving products that prevent or relieve irritation, oil-absorbing primers to provide temporary relief for skin oiliness, and exfoliating products and retinoids to improve an uneven complexion, said Dr. Camacho.

In addition, antiaging formulations containing alpha-hydroxy acids, retinoids, growth factors, antioxidants, peptides, and/or botanicals can be used to help reverse ultraviolet-related damage and help improve the appearance of fine lines, he said.

Dr. Camacho reported having no disclosures.

ORLANDO – Cold snare polypectomy is clearly superior to double biopsy cold forceps polypectomy for the complete removal of small colorectal polyps, according to findings from a single-center, prospective, randomized controlled study involving 54 patients.

The rates of both visual polyp eradication and complete histologic eradication were significantly higher in patients randomized to the cold snare polypectomy (CSP) group than in those randomized to the cold forceps polypectomy (CFP) group (91.5% vs. 78.3%, and 93.2% vs. 75.9%, respectively), Dr. Chang Kyun Lee reported at the annual Digestive Disease Week.

Additional analysis in the CFP group showed a histologic eradication rate of 92% for 1- to 3-mm polyps, and 50% for 4- to 5-mm polyps.

On logistic regression analysis, CFP and polyp size of 4 mm or larger were associated with incomplete polyp eradication (odds ratios 4.75 and 4.38, respectively), whereas lesion location and histologic diagnosis were not, said Dr. Lee of Kyung Hee University, Seoul, Republic of Korea.

The 54 study subjects were adults (mean age, 53.7 years) and a total of 115 1- to 5-mm polyps. Most polyps (88%) were 0-IIa type, and most (70.1%) were tubular adenomas. The mean polyp size was 3.66 mm.

The treatment groups did not differ significantly with respect to sex, age, indication for colonoscopy, or procedure time, and no differences were noted in the size, location, and diagnosis of polyps.

Only one polyp with advanced histologic features was identified. The 5-mm lesion – a tubular adenoma – was located in the proximal colon and was removed completely via CFP.

CSP was performed using a minisnare, and CFP was performed using standard large-capacity forceps and a double biopsy technique (two "bites" per forceps pass). Polyp removal time was significantly shorter with CSP than with CFP (14.29 vs. 22.03 seconds), though this difference was not clinically meaningful. The rate of successful retrieval of polypectomy samples was lower in the CSP group (93.2% vs. 100% for CFP), Dr. Lee noted.

While cold techniques are widely used in clinical practice, few studies have directly compared outcomes with different techniques. These findings indicate that choice of technique is clinically important to the endoscopic removal of diminutive polyps, he said.

"Based on the findings, we recommend that cold snaring be considered as the primary method for endoscopic treatment of polyps in the 4- to 5-mm size range. However, given the incomplete polypectomy rate in this study – about 15% – further technical refinements and instrumental innovations are required for future studies," Dr. Lee concluded.

Dr. Lee reported having no disclosures.

ORLANDO – Cold snare polypectomy is clearly superior to double biopsy cold forceps polypectomy for the complete removal of small colorectal polyps, according to findings from a single-center, prospective, randomized controlled study involving 54 patients.

The rates of both visual polyp eradication and complete histologic eradication were significantly higher in patients randomized to the cold snare polypectomy (CSP) group than in those randomized to the cold forceps polypectomy (CFP) group (91.5% vs. 78.3%, and 93.2% vs. 75.9%, respectively), Dr. Chang Kyun Lee reported at the annual Digestive Disease Week.

Additional analysis in the CFP group showed a histologic eradication rate of 92% for 1- to 3-mm polyps, and 50% for 4- to 5-mm polyps.

On logistic regression analysis, CFP and polyp size of 4 mm or larger were associated with incomplete polyp eradication (odds ratios 4.75 and 4.38, respectively), whereas lesion location and histologic diagnosis were not, said Dr. Lee of Kyung Hee University, Seoul, Republic of Korea.

The 54 study subjects were adults (mean age, 53.7 years) and a total of 115 1- to 5-mm polyps. Most polyps (88%) were 0-IIa type, and most (70.1%) were tubular adenomas. The mean polyp size was 3.66 mm.

The treatment groups did not differ significantly with respect to sex, age, indication for colonoscopy, or procedure time, and no differences were noted in the size, location, and diagnosis of polyps.

Only one polyp with advanced histologic features was identified. The 5-mm lesion – a tubular adenoma – was located in the proximal colon and was removed completely via CFP.

CSP was performed using a minisnare, and CFP was performed using standard large-capacity forceps and a double biopsy technique (two "bites" per forceps pass). Polyp removal time was significantly shorter with CSP than with CFP (14.29 vs. 22.03 seconds), though this difference was not clinically meaningful. The rate of successful retrieval of polypectomy samples was lower in the CSP group (93.2% vs. 100% for CFP), Dr. Lee noted.

While cold techniques are widely used in clinical practice, few studies have directly compared outcomes with different techniques. These findings indicate that choice of technique is clinically important to the endoscopic removal of diminutive polyps, he said.

"Based on the findings, we recommend that cold snaring be considered as the primary method for endoscopic treatment of polyps in the 4- to 5-mm size range. However, given the incomplete polypectomy rate in this study – about 15% – further technical refinements and instrumental innovations are required for future studies," Dr. Lee concluded.

Dr. Lee reported having no disclosures.

ORLANDO – Cold snare polypectomy is clearly superior to double biopsy cold forceps polypectomy for the complete removal of small colorectal polyps, according to findings from a single-center, prospective, randomized controlled study involving 54 patients.

The rates of both visual polyp eradication and complete histologic eradication were significantly higher in patients randomized to the cold snare polypectomy (CSP) group than in those randomized to the cold forceps polypectomy (CFP) group (91.5% vs. 78.3%, and 93.2% vs. 75.9%, respectively), Dr. Chang Kyun Lee reported at the annual Digestive Disease Week.

Additional analysis in the CFP group showed a histologic eradication rate of 92% for 1- to 3-mm polyps, and 50% for 4- to 5-mm polyps.

On logistic regression analysis, CFP and polyp size of 4 mm or larger were associated with incomplete polyp eradication (odds ratios 4.75 and 4.38, respectively), whereas lesion location and histologic diagnosis were not, said Dr. Lee of Kyung Hee University, Seoul, Republic of Korea.

The 54 study subjects were adults (mean age, 53.7 years) and a total of 115 1- to 5-mm polyps. Most polyps (88%) were 0-IIa type, and most (70.1%) were tubular adenomas. The mean polyp size was 3.66 mm.

The treatment groups did not differ significantly with respect to sex, age, indication for colonoscopy, or procedure time, and no differences were noted in the size, location, and diagnosis of polyps.

Only one polyp with advanced histologic features was identified. The 5-mm lesion – a tubular adenoma – was located in the proximal colon and was removed completely via CFP.

CSP was performed using a minisnare, and CFP was performed using standard large-capacity forceps and a double biopsy technique (two "bites" per forceps pass). Polyp removal time was significantly shorter with CSP than with CFP (14.29 vs. 22.03 seconds), though this difference was not clinically meaningful. The rate of successful retrieval of polypectomy samples was lower in the CSP group (93.2% vs. 100% for CFP), Dr. Lee noted.

While cold techniques are widely used in clinical practice, few studies have directly compared outcomes with different techniques. These findings indicate that choice of technique is clinically important to the endoscopic removal of diminutive polyps, he said.

"Based on the findings, we recommend that cold snaring be considered as the primary method for endoscopic treatment of polyps in the 4- to 5-mm size range. However, given the incomplete polypectomy rate in this study – about 15% – further technical refinements and instrumental innovations are required for future studies," Dr. Lee concluded.

Dr. Lee reported having no 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 – 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.