Denise Napoli

Smoking tobacco more than doubles the risk that Barrett’s esophagus will progress to adenocarcinoma or high-grade dysplasia, Dr. Helen G. Coleman and her colleagues wrote in the February issue of Gastroenterology.

The study also found that alcohol consumption – despite its known association with esophageal squamous cell carcinoma – was not linked to adenocarcinoma (Gastroenterology 2011 [Epub ahead of print, doi:10.1053/j.gastro.2011.10.034]).

Dr. Coleman of Queen’s University Belfast, United Kingdom, reviewed the medical records of patients in the population-based Northern Ireland BE register. The register includes all adults diagnosed with columnar-lined epithelium of the esophagus between 1993 and 2005 in that region, making it "one of the largest population-based cohorts of BE patients worldwide."

This cohort was then linked to the Northern Ireland Cancer Registry, and the researchers were able to identify patients in the former registry who subsequently developed adenocarcinomas or unspecified malignancies of the esophagus and gastric cardia adenocarcinomas.

Squamous cell esophageal carcinomas were not included as outcomes, and the results were tallied through Dec. 31, 2008.

Overall, 3,167 BE patients were included in the analysis, and were followed up for a total of 23,692 person-years up to 16 years, with a mean follow-up of 7.5 years.

In total, 117 patients developed high-grade dysplasia or cancer of the esophagus or gastric cardia, wrote the authors, including 70 adenocarcinomas or unspecified cancers of the esophagus, 10 adenocarcinomas of the gastric cardia and 37 cases of esophageal high-grade dysplasia.

The mean time from BE diagnosis to diagnosis of cancer or dysplasia was 4.5 years.

Those patients who progressed from BE were significantly more likely to be between 50 and 60 years old (P = .003), to be male (P = .001), and to have a Barrett’s segment length of 3 cm or greater (P = .006).

They were also much more likely (P less than .001) to have low-grade or indefinite dysplasia at their index BE diagnosis, wrote the authors.

Among the modifiable risk factors, smoking carried the greatest weight.

After researchers adjusted for demographics, presence of low-grade dysplasia, reflux symptoms, and Barrett’s segment length at diagnosis, current cigarette smokers had a more than twofold risk of BE progression, compared with patients who never smoked (hazard ratio, 2.02; 95% confidence interval, 1.13-3.11).

Pipe smokers had an even greater risk and were nearly three times as likely to have their BE progress, compared with patients who never smoked a pipe (HR, 2.95; 95% CI, 1.39-6.25).

Any current smoking status – be it pipe or cigarette – had a hazard ratio of 2.29, compared with nonsmokers (95% CI, 1.32-4.00).

Alcohol intake, in contrast, was not correlated with BE progression, even among patients who said they drank 10 units or more per week (HR, 0.82; 95% CI, 0.41-1.62).

That finding is in agreement with other studies, wrote the investigators, in which alcohol has been "consistently refuted as a risk factor for [esophageal adenocarcinoma], in contrast to its known direct association with esophageal squamous cell carcinoma," wrote the authors.

"Therefore we can only recommend that BE patients follow the advice of current public health guidelines for cancer prevention to consume alcohol in moderation, if taken," they added.

On the other hand, wrote Dr. Coleman, smoking has previously been "specifically demonstrated to inflict DNA damage on Barrett’s mucosa."

Additionally, she postulated that smoking may be "associated with an increased number of reflux episodes and that nicotine may reduce lower esophageal sphincter pressure, which would contribute to excess acid/bile exposure that may consequently increase neoplastic progression risk in BE."

The authors wrote that the study was funded by the Ulster Cancer Foundation and the Health and Social Care Research and Development Office. They added that they have no conflicts to declare.

Smoking tobacco more than doubles the risk that Barrett’s esophagus will progress to adenocarcinoma or high-grade dysplasia, Dr. Helen G. Coleman and her colleagues wrote in the February issue of Gastroenterology.

The study also found that alcohol consumption – despite its known association with esophageal squamous cell carcinoma – was not linked to adenocarcinoma (Gastroenterology 2011 [Epub ahead of print, doi:10.1053/j.gastro.2011.10.034]).

Dr. Coleman of Queen’s University Belfast, United Kingdom, reviewed the medical records of patients in the population-based Northern Ireland BE register. The register includes all adults diagnosed with columnar-lined epithelium of the esophagus between 1993 and 2005 in that region, making it "one of the largest population-based cohorts of BE patients worldwide."

This cohort was then linked to the Northern Ireland Cancer Registry, and the researchers were able to identify patients in the former registry who subsequently developed adenocarcinomas or unspecified malignancies of the esophagus and gastric cardia adenocarcinomas.

Squamous cell esophageal carcinomas were not included as outcomes, and the results were tallied through Dec. 31, 2008.

Overall, 3,167 BE patients were included in the analysis, and were followed up for a total of 23,692 person-years up to 16 years, with a mean follow-up of 7.5 years.

In total, 117 patients developed high-grade dysplasia or cancer of the esophagus or gastric cardia, wrote the authors, including 70 adenocarcinomas or unspecified cancers of the esophagus, 10 adenocarcinomas of the gastric cardia and 37 cases of esophageal high-grade dysplasia.

The mean time from BE diagnosis to diagnosis of cancer or dysplasia was 4.5 years.

Those patients who progressed from BE were significantly more likely to be between 50 and 60 years old (P = .003), to be male (P = .001), and to have a Barrett’s segment length of 3 cm or greater (P = .006).

They were also much more likely (P less than .001) to have low-grade or indefinite dysplasia at their index BE diagnosis, wrote the authors.

Among the modifiable risk factors, smoking carried the greatest weight.

After researchers adjusted for demographics, presence of low-grade dysplasia, reflux symptoms, and Barrett’s segment length at diagnosis, current cigarette smokers had a more than twofold risk of BE progression, compared with patients who never smoked (hazard ratio, 2.02; 95% confidence interval, 1.13-3.11).

Pipe smokers had an even greater risk and were nearly three times as likely to have their BE progress, compared with patients who never smoked a pipe (HR, 2.95; 95% CI, 1.39-6.25).

Any current smoking status – be it pipe or cigarette – had a hazard ratio of 2.29, compared with nonsmokers (95% CI, 1.32-4.00).

Alcohol intake, in contrast, was not correlated with BE progression, even among patients who said they drank 10 units or more per week (HR, 0.82; 95% CI, 0.41-1.62).

That finding is in agreement with other studies, wrote the investigators, in which alcohol has been "consistently refuted as a risk factor for [esophageal adenocarcinoma], in contrast to its known direct association with esophageal squamous cell carcinoma," wrote the authors.

"Therefore we can only recommend that BE patients follow the advice of current public health guidelines for cancer prevention to consume alcohol in moderation, if taken," they added.

On the other hand, wrote Dr. Coleman, smoking has previously been "specifically demonstrated to inflict DNA damage on Barrett’s mucosa."

Additionally, she postulated that smoking may be "associated with an increased number of reflux episodes and that nicotine may reduce lower esophageal sphincter pressure, which would contribute to excess acid/bile exposure that may consequently increase neoplastic progression risk in BE."

The authors wrote that the study was funded by the Ulster Cancer Foundation and the Health and Social Care Research and Development Office. They added that they have no conflicts to declare.

Smoking tobacco more than doubles the risk that Barrett’s esophagus will progress to adenocarcinoma or high-grade dysplasia, Dr. Helen G. Coleman and her colleagues wrote in the February issue of Gastroenterology.

The study also found that alcohol consumption – despite its known association with esophageal squamous cell carcinoma – was not linked to adenocarcinoma (Gastroenterology 2011 [Epub ahead of print, doi:10.1053/j.gastro.2011.10.034]).

Dr. Coleman of Queen’s University Belfast, United Kingdom, reviewed the medical records of patients in the population-based Northern Ireland BE register. The register includes all adults diagnosed with columnar-lined epithelium of the esophagus between 1993 and 2005 in that region, making it "one of the largest population-based cohorts of BE patients worldwide."

This cohort was then linked to the Northern Ireland Cancer Registry, and the researchers were able to identify patients in the former registry who subsequently developed adenocarcinomas or unspecified malignancies of the esophagus and gastric cardia adenocarcinomas.

Squamous cell esophageal carcinomas were not included as outcomes, and the results were tallied through Dec. 31, 2008.

Overall, 3,167 BE patients were included in the analysis, and were followed up for a total of 23,692 person-years up to 16 years, with a mean follow-up of 7.5 years.

In total, 117 patients developed high-grade dysplasia or cancer of the esophagus or gastric cardia, wrote the authors, including 70 adenocarcinomas or unspecified cancers of the esophagus, 10 adenocarcinomas of the gastric cardia and 37 cases of esophageal high-grade dysplasia.

The mean time from BE diagnosis to diagnosis of cancer or dysplasia was 4.5 years.

Those patients who progressed from BE were significantly more likely to be between 50 and 60 years old (P = .003), to be male (P = .001), and to have a Barrett’s segment length of 3 cm or greater (P = .006).

They were also much more likely (P less than .001) to have low-grade or indefinite dysplasia at their index BE diagnosis, wrote the authors.

Among the modifiable risk factors, smoking carried the greatest weight.

After researchers adjusted for demographics, presence of low-grade dysplasia, reflux symptoms, and Barrett’s segment length at diagnosis, current cigarette smokers had a more than twofold risk of BE progression, compared with patients who never smoked (hazard ratio, 2.02; 95% confidence interval, 1.13-3.11).

Pipe smokers had an even greater risk and were nearly three times as likely to have their BE progress, compared with patients who never smoked a pipe (HR, 2.95; 95% CI, 1.39-6.25).

Any current smoking status – be it pipe or cigarette – had a hazard ratio of 2.29, compared with nonsmokers (95% CI, 1.32-4.00).

Alcohol intake, in contrast, was not correlated with BE progression, even among patients who said they drank 10 units or more per week (HR, 0.82; 95% CI, 0.41-1.62).

That finding is in agreement with other studies, wrote the investigators, in which alcohol has been "consistently refuted as a risk factor for [esophageal adenocarcinoma], in contrast to its known direct association with esophageal squamous cell carcinoma," wrote the authors.

"Therefore we can only recommend that BE patients follow the advice of current public health guidelines for cancer prevention to consume alcohol in moderation, if taken," they added.

On the other hand, wrote Dr. Coleman, smoking has previously been "specifically demonstrated to inflict DNA damage on Barrett’s mucosa."

Additionally, she postulated that smoking may be "associated with an increased number of reflux episodes and that nicotine may reduce lower esophageal sphincter pressure, which would contribute to excess acid/bile exposure that may consequently increase neoplastic progression risk in BE."

The authors wrote that the study was funded by the Ulster Cancer Foundation and the Health and Social Care Research and Development Office. They added that they have no conflicts to declare.

For acute diverticular bleeding, first-line diagnostic colonoscopy plus endoscopic clipping of actively bleeding diverticulum appears safe and efficacious and also reduces hospital stays, reported Dr. Tonya Kaltenbach and colleagues in the February issue of Clinical Gastroenterology and Hepatology.

The authors wrote that they hope this finding "may aid in the development of a management algorithm for patients with acute severe [lower gastrointestinal bleed]."

Dr. Kaltenbach of the Veterans Affairs Palo Alto (Calif.) Health Care System studied data from 250 patients from her facility as well as the VA San Francisco, who presented with signs and symptoms indicative of acute lower GI bleed over a 5-year period.

The symptoms included tachycardia, systolic hypotension, syncope, nontender abdominal examination, rectal bleeding during the first 4 hours of evaluation, aspirin use, and multiple comorbid illnesses, the investigators said.

According to a protocol developed by the GI section chiefs at these institutions, all patients presenting with lower GI bleed symptoms underwent a rapid purge of the bowel over 3 hours, followed by colonoscopy. The median time to colonoscopy was 24 hours. The procedures were performed by 12 different endoscopists.

"Throughout colonoscope insertion and withdrawal, we systematically irrigated diverticula and surveyed for diverticular stigmata of recent hemorrhage, including active bleeding, nonbleeding visible vessel, and adherent clot, as well as other potential (though unproven) stigmata such as pigmented spot or erosion," wrote the authors.

If diverticular stigmata of recent hemorrhage were discovered, the authors attempted to clip the diverticulum. Other patients were classified as having presumptive diverticular hemorrhage if a diverticulum with a spot or erosion was found and no other bleeding source was identified.

Overall, diverticular bleeding was diagnosed in 64 patients (61 male) with an average age of 76 years. Of these, 24 had diverticular stigmata of recent hemorrhage visible on colonoscopy, including active bleeding in 12 cases, nonbleeding visible vessels in 3 cases, and adherent clots in 9 cases.

Among the active bleeders, "We achieved primary hemostasis with endoscopic clip application in 9 of the 12 (75%)," wrote the authors. Clipping was unsuccessful in the other three patients, two of whom required emergent hemicolectomy; the remaining patient underwent angiographic embolization.

The 21 patients who were successfully clipped had a significantly shorter mean length of hospital stay than the 3 who were not treated successfully with clipping (6.4 days vs. 36.3 days; P less than .001).

"There were no perforations or episodes of early [less than 30 days post-procedure] rebleeding," noted Dr. Kaltenbach and colleagues (Clin. Gastro. Hepatol. 2012 [doi:10.1016/j.cgh.2011.10.029]).

And while the clipped patients had recurrent bleeding rates that were similar to those of their nonbleeding, nonclipped counterparts – about 20% – the 21 clipped patients had longer mean bleeding-free intervals (43 months vs. 15 months, respectively; P less than .001).

Among the patients who did rebleed, all were treated with the protocol again. Four of these patients underwent diverticulum clipping, and had an even shorter length of hospital stay compared to their index bleed, wrote the authors.

Throughout the study period, no patients died due to diverticular bleeding, wrote the authors, nor were there any complications arising from the colonoscopy itself.

"Currently, clinicians are faced with uncertainty as to the optimal diagnostic modality to choose in the management of patients with acute severe lower GI bleed," wrote the authors. "As such, other diagnostic modalities are used – often with high risk and low benefit."

And while the study is limited by its retrospective nature, as well as by differences in practice among endoscopists, it adds to what the authors called a paucity of data showing that first-line endoscopic therapy can reduce the incidence of further bleeding, "thereby preventing the need for emergent colectomy."

The authors reported no conflicts of interest relating to this study.

For acute diverticular bleeding, first-line diagnostic colonoscopy plus endoscopic clipping of actively bleeding diverticulum appears safe and efficacious and also reduces hospital stays, reported Dr. Tonya Kaltenbach and colleagues in the February issue of Clinical Gastroenterology and Hepatology.

The authors wrote that they hope this finding "may aid in the development of a management algorithm for patients with acute severe [lower gastrointestinal bleed]."

Dr. Kaltenbach of the Veterans Affairs Palo Alto (Calif.) Health Care System studied data from 250 patients from her facility as well as the VA San Francisco, who presented with signs and symptoms indicative of acute lower GI bleed over a 5-year period.

The symptoms included tachycardia, systolic hypotension, syncope, nontender abdominal examination, rectal bleeding during the first 4 hours of evaluation, aspirin use, and multiple comorbid illnesses, the investigators said.

According to a protocol developed by the GI section chiefs at these institutions, all patients presenting with lower GI bleed symptoms underwent a rapid purge of the bowel over 3 hours, followed by colonoscopy. The median time to colonoscopy was 24 hours. The procedures were performed by 12 different endoscopists.

"Throughout colonoscope insertion and withdrawal, we systematically irrigated diverticula and surveyed for diverticular stigmata of recent hemorrhage, including active bleeding, nonbleeding visible vessel, and adherent clot, as well as other potential (though unproven) stigmata such as pigmented spot or erosion," wrote the authors.

If diverticular stigmata of recent hemorrhage were discovered, the authors attempted to clip the diverticulum. Other patients were classified as having presumptive diverticular hemorrhage if a diverticulum with a spot or erosion was found and no other bleeding source was identified.

Overall, diverticular bleeding was diagnosed in 64 patients (61 male) with an average age of 76 years. Of these, 24 had diverticular stigmata of recent hemorrhage visible on colonoscopy, including active bleeding in 12 cases, nonbleeding visible vessels in 3 cases, and adherent clots in 9 cases.

Among the active bleeders, "We achieved primary hemostasis with endoscopic clip application in 9 of the 12 (75%)," wrote the authors. Clipping was unsuccessful in the other three patients, two of whom required emergent hemicolectomy; the remaining patient underwent angiographic embolization.

The 21 patients who were successfully clipped had a significantly shorter mean length of hospital stay than the 3 who were not treated successfully with clipping (6.4 days vs. 36.3 days; P less than .001).

"There were no perforations or episodes of early [less than 30 days post-procedure] rebleeding," noted Dr. Kaltenbach and colleagues (Clin. Gastro. Hepatol. 2012 [doi:10.1016/j.cgh.2011.10.029]).

And while the clipped patients had recurrent bleeding rates that were similar to those of their nonbleeding, nonclipped counterparts – about 20% – the 21 clipped patients had longer mean bleeding-free intervals (43 months vs. 15 months, respectively; P less than .001).

Among the patients who did rebleed, all were treated with the protocol again. Four of these patients underwent diverticulum clipping, and had an even shorter length of hospital stay compared to their index bleed, wrote the authors.

Throughout the study period, no patients died due to diverticular bleeding, wrote the authors, nor were there any complications arising from the colonoscopy itself.

"Currently, clinicians are faced with uncertainty as to the optimal diagnostic modality to choose in the management of patients with acute severe lower GI bleed," wrote the authors. "As such, other diagnostic modalities are used – often with high risk and low benefit."

And while the study is limited by its retrospective nature, as well as by differences in practice among endoscopists, it adds to what the authors called a paucity of data showing that first-line endoscopic therapy can reduce the incidence of further bleeding, "thereby preventing the need for emergent colectomy."

The authors reported no conflicts of interest relating to this study.

For acute diverticular bleeding, first-line diagnostic colonoscopy plus endoscopic clipping of actively bleeding diverticulum appears safe and efficacious and also reduces hospital stays, reported Dr. Tonya Kaltenbach and colleagues in the February issue of Clinical Gastroenterology and Hepatology.

The authors wrote that they hope this finding "may aid in the development of a management algorithm for patients with acute severe [lower gastrointestinal bleed]."

Dr. Kaltenbach of the Veterans Affairs Palo Alto (Calif.) Health Care System studied data from 250 patients from her facility as well as the VA San Francisco, who presented with signs and symptoms indicative of acute lower GI bleed over a 5-year period.

The symptoms included tachycardia, systolic hypotension, syncope, nontender abdominal examination, rectal bleeding during the first 4 hours of evaluation, aspirin use, and multiple comorbid illnesses, the investigators said.

According to a protocol developed by the GI section chiefs at these institutions, all patients presenting with lower GI bleed symptoms underwent a rapid purge of the bowel over 3 hours, followed by colonoscopy. The median time to colonoscopy was 24 hours. The procedures were performed by 12 different endoscopists.

"Throughout colonoscope insertion and withdrawal, we systematically irrigated diverticula and surveyed for diverticular stigmata of recent hemorrhage, including active bleeding, nonbleeding visible vessel, and adherent clot, as well as other potential (though unproven) stigmata such as pigmented spot or erosion," wrote the authors.

If diverticular stigmata of recent hemorrhage were discovered, the authors attempted to clip the diverticulum. Other patients were classified as having presumptive diverticular hemorrhage if a diverticulum with a spot or erosion was found and no other bleeding source was identified.

Overall, diverticular bleeding was diagnosed in 64 patients (61 male) with an average age of 76 years. Of these, 24 had diverticular stigmata of recent hemorrhage visible on colonoscopy, including active bleeding in 12 cases, nonbleeding visible vessels in 3 cases, and adherent clots in 9 cases.

Among the active bleeders, "We achieved primary hemostasis with endoscopic clip application in 9 of the 12 (75%)," wrote the authors. Clipping was unsuccessful in the other three patients, two of whom required emergent hemicolectomy; the remaining patient underwent angiographic embolization.

The 21 patients who were successfully clipped had a significantly shorter mean length of hospital stay than the 3 who were not treated successfully with clipping (6.4 days vs. 36.3 days; P less than .001).

"There were no perforations or episodes of early [less than 30 days post-procedure] rebleeding," noted Dr. Kaltenbach and colleagues (Clin. Gastro. Hepatol. 2012 [doi:10.1016/j.cgh.2011.10.029]).

And while the clipped patients had recurrent bleeding rates that were similar to those of their nonbleeding, nonclipped counterparts – about 20% – the 21 clipped patients had longer mean bleeding-free intervals (43 months vs. 15 months, respectively; P less than .001).

Among the patients who did rebleed, all were treated with the protocol again. Four of these patients underwent diverticulum clipping, and had an even shorter length of hospital stay compared to their index bleed, wrote the authors.

Throughout the study period, no patients died due to diverticular bleeding, wrote the authors, nor were there any complications arising from the colonoscopy itself.

"Currently, clinicians are faced with uncertainty as to the optimal diagnostic modality to choose in the management of patients with acute severe lower GI bleed," wrote the authors. "As such, other diagnostic modalities are used – often with high risk and low benefit."

And while the study is limited by its retrospective nature, as well as by differences in practice among endoscopists, it adds to what the authors called a paucity of data showing that first-line endoscopic therapy can reduce the incidence of further bleeding, "thereby preventing the need for emergent colectomy."

The authors reported no conflicts of interest relating to this study.

The incidence of inflammatory bowel disease is on the rise worldwide, particularly in developed regions, Natalie A. Molodecky and colleagues reported in the journal Gastroenterology.

"Because mortality in IBD is low and the disease is most often diagnosed in the young, these findings suggest that the global prevalence of IBD will continue to increase substantially," the authors noted.

The pathogenesis of IBD is not fully understood, but these diseases are thought to occur in genetically susceptible individuals exposed to environmental risk factors. Environmental exposures are markedly different in developed versus underdeveloped regions, the authors noted (Gastroenterology 2011 [doi:10.1053/j.gastro.2011.10.001]).

Ms. Molodecky, then a graduate student at the University of Calgary (Alta.), and associates conducted a systematic literature review that identified 260 studies on the incidence and prevalence of Crohn’s disease (CD) and ulcerative colitis (UC). The studies were culled from searches of two databases: MEDLINE (1950 to December 2010) and EMBASE (1980 to December 2010).

Among the 260 included publications, 238 addressed incidence. Of those, 185 investigated the incidence of CD and 161 studied UC incidence.

Of the 122 prevalence studies, 96 investigated the prevalence of CD and 79 studied UC prevalence.

For both diseases, the majority of the studies were from European regions, followed by Asia and the Middle East, then North America. African and South American regions and nations accounted for a small percentage (5% or less) of both incidence and prevalence studies.

"These findings suggest that the global prevalence of IBD will continue to increase substantially."

The researchers found that in Europe, the annual incidence of UC ranged widely, from 0.6 to 24.3 per 100,000 person-years. In Asia and the Middle East, in contrast, the annual incidence rate for UC varied from 0.11 to 6.3 cases per 100,000 person-years. In North America, which was similar to Europe, incidence ranged from 0 to 19.2 per 100,000 person-years.

Looking at CD, incidence ranged from 0.3 to 12.7 per 100,000 person-years in Europe, 0.04 to 5.0 in Asia and the Middle East, and 0 to 20.2 in North America, wrote the authors.

Prevalence studies also showed great heterogeneity. "UC estimates ranged from 4.9 to 505 per 100,000 in Europe; 4.9 to 168.3 per 100,000 in Asia and the Middle East; and 37.5 to 248.6 per 100,000 in North America," wrote the authors.

Similarly, CD prevalence estimates ranged from 0.6 to 322 per 100,000 at-risk persons in Europe, 0.88 to 67.9 per 100,000 in Asia and the Middle East, and 16.7 to 318.5 per 100,000 in North America.

The researchers also uncovered increasing incidence rates over time. Among those studies that examined incidence rates over time, 75% of the CD studies and 60% of the UC studies showed statistically significant (P less than .05) increases, with average annual percentage changes ranging from 1.2% to 23.3% in CD and 2.4% to 18.1% in UC. In contrast, three UC studies (6%) and no CD studies found statistically significant decreases in incidence over time, they added.

In conclusion, wrote the authors, "Emergence of IBD in traditionally low prevalent regions (e.g., Asia), suggests that the development of IBD may be influenced by environmental risk factors.

"However, this increase could be due to increased awareness of IBD by physicians and the public, as well as advancements in diagnostic methods for IBD," they wrote, adding that future studies should "adjust incidence rates by diagnostic procedure (e.g., colonoscopy) utilization."

The authors conceded that unpublished manuscripts and abstracts were not included in this review, and they were not able to conduct a meta-analysis because of variability in the study design of the included studies. However, they described their research as a comprehensive review of CD and UC prevalence and incidence that spans both time and geography.

The review was funded by the Alberta IBD Consortium. No individual conflicts of interest were disclosed.

The incidence of inflammatory bowel disease is on the rise worldwide, particularly in developed regions, Natalie A. Molodecky and colleagues reported in the journal Gastroenterology.

"Because mortality in IBD is low and the disease is most often diagnosed in the young, these findings suggest that the global prevalence of IBD will continue to increase substantially," the authors noted.

The pathogenesis of IBD is not fully understood, but these diseases are thought to occur in genetically susceptible individuals exposed to environmental risk factors. Environmental exposures are markedly different in developed versus underdeveloped regions, the authors noted (Gastroenterology 2011 [doi:10.1053/j.gastro.2011.10.001]).

Ms. Molodecky, then a graduate student at the University of Calgary (Alta.), and associates conducted a systematic literature review that identified 260 studies on the incidence and prevalence of Crohn’s disease (CD) and ulcerative colitis (UC). The studies were culled from searches of two databases: MEDLINE (1950 to December 2010) and EMBASE (1980 to December 2010).

Among the 260 included publications, 238 addressed incidence. Of those, 185 investigated the incidence of CD and 161 studied UC incidence.

Of the 122 prevalence studies, 96 investigated the prevalence of CD and 79 studied UC prevalence.

For both diseases, the majority of the studies were from European regions, followed by Asia and the Middle East, then North America. African and South American regions and nations accounted for a small percentage (5% or less) of both incidence and prevalence studies.

"These findings suggest that the global prevalence of IBD will continue to increase substantially."

The researchers found that in Europe, the annual incidence of UC ranged widely, from 0.6 to 24.3 per 100,000 person-years. In Asia and the Middle East, in contrast, the annual incidence rate for UC varied from 0.11 to 6.3 cases per 100,000 person-years. In North America, which was similar to Europe, incidence ranged from 0 to 19.2 per 100,000 person-years.

Looking at CD, incidence ranged from 0.3 to 12.7 per 100,000 person-years in Europe, 0.04 to 5.0 in Asia and the Middle East, and 0 to 20.2 in North America, wrote the authors.

Prevalence studies also showed great heterogeneity. "UC estimates ranged from 4.9 to 505 per 100,000 in Europe; 4.9 to 168.3 per 100,000 in Asia and the Middle East; and 37.5 to 248.6 per 100,000 in North America," wrote the authors.

Similarly, CD prevalence estimates ranged from 0.6 to 322 per 100,000 at-risk persons in Europe, 0.88 to 67.9 per 100,000 in Asia and the Middle East, and 16.7 to 318.5 per 100,000 in North America.

The researchers also uncovered increasing incidence rates over time. Among those studies that examined incidence rates over time, 75% of the CD studies and 60% of the UC studies showed statistically significant (P less than .05) increases, with average annual percentage changes ranging from 1.2% to 23.3% in CD and 2.4% to 18.1% in UC. In contrast, three UC studies (6%) and no CD studies found statistically significant decreases in incidence over time, they added.

In conclusion, wrote the authors, "Emergence of IBD in traditionally low prevalent regions (e.g., Asia), suggests that the development of IBD may be influenced by environmental risk factors.

"However, this increase could be due to increased awareness of IBD by physicians and the public, as well as advancements in diagnostic methods for IBD," they wrote, adding that future studies should "adjust incidence rates by diagnostic procedure (e.g., colonoscopy) utilization."

The authors conceded that unpublished manuscripts and abstracts were not included in this review, and they were not able to conduct a meta-analysis because of variability in the study design of the included studies. However, they described their research as a comprehensive review of CD and UC prevalence and incidence that spans both time and geography.

The review was funded by the Alberta IBD Consortium. No individual conflicts of interest were disclosed.

The incidence of inflammatory bowel disease is on the rise worldwide, particularly in developed regions, Natalie A. Molodecky and colleagues reported in the journal Gastroenterology.

"Because mortality in IBD is low and the disease is most often diagnosed in the young, these findings suggest that the global prevalence of IBD will continue to increase substantially," the authors noted.

The pathogenesis of IBD is not fully understood, but these diseases are thought to occur in genetically susceptible individuals exposed to environmental risk factors. Environmental exposures are markedly different in developed versus underdeveloped regions, the authors noted (Gastroenterology 2011 [doi:10.1053/j.gastro.2011.10.001]).

Ms. Molodecky, then a graduate student at the University of Calgary (Alta.), and associates conducted a systematic literature review that identified 260 studies on the incidence and prevalence of Crohn’s disease (CD) and ulcerative colitis (UC). The studies were culled from searches of two databases: MEDLINE (1950 to December 2010) and EMBASE (1980 to December 2010).

Among the 260 included publications, 238 addressed incidence. Of those, 185 investigated the incidence of CD and 161 studied UC incidence.

Of the 122 prevalence studies, 96 investigated the prevalence of CD and 79 studied UC prevalence.

For both diseases, the majority of the studies were from European regions, followed by Asia and the Middle East, then North America. African and South American regions and nations accounted for a small percentage (5% or less) of both incidence and prevalence studies.

"These findings suggest that the global prevalence of IBD will continue to increase substantially."

The researchers found that in Europe, the annual incidence of UC ranged widely, from 0.6 to 24.3 per 100,000 person-years. In Asia and the Middle East, in contrast, the annual incidence rate for UC varied from 0.11 to 6.3 cases per 100,000 person-years. In North America, which was similar to Europe, incidence ranged from 0 to 19.2 per 100,000 person-years.

Looking at CD, incidence ranged from 0.3 to 12.7 per 100,000 person-years in Europe, 0.04 to 5.0 in Asia and the Middle East, and 0 to 20.2 in North America, wrote the authors.

Prevalence studies also showed great heterogeneity. "UC estimates ranged from 4.9 to 505 per 100,000 in Europe; 4.9 to 168.3 per 100,000 in Asia and the Middle East; and 37.5 to 248.6 per 100,000 in North America," wrote the authors.

Similarly, CD prevalence estimates ranged from 0.6 to 322 per 100,000 at-risk persons in Europe, 0.88 to 67.9 per 100,000 in Asia and the Middle East, and 16.7 to 318.5 per 100,000 in North America.

The researchers also uncovered increasing incidence rates over time. Among those studies that examined incidence rates over time, 75% of the CD studies and 60% of the UC studies showed statistically significant (P less than .05) increases, with average annual percentage changes ranging from 1.2% to 23.3% in CD and 2.4% to 18.1% in UC. In contrast, three UC studies (6%) and no CD studies found statistically significant decreases in incidence over time, they added.

In conclusion, wrote the authors, "Emergence of IBD in traditionally low prevalent regions (e.g., Asia), suggests that the development of IBD may be influenced by environmental risk factors.

"However, this increase could be due to increased awareness of IBD by physicians and the public, as well as advancements in diagnostic methods for IBD," they wrote, adding that future studies should "adjust incidence rates by diagnostic procedure (e.g., colonoscopy) utilization."

The authors conceded that unpublished manuscripts and abstracts were not included in this review, and they were not able to conduct a meta-analysis because of variability in the study design of the included studies. However, they described their research as a comprehensive review of CD and UC prevalence and incidence that spans both time and geography.

The review was funded by the Alberta IBD Consortium. No individual conflicts of interest were disclosed.

At 5 years old, the children of mothers who smoked in pregnancy had significantly greater carotid intima-media thickness and lower arterial distensibility than did unexposed offspring.

"Moreover, there was a clear positive trend between the number of cigarettes smoked by mothers in pregnancy and adverse vascular health, a finding that adds to the credibility of gestational smoking being causally related to offspring vascular damage," wrote Dr. Caroline C. Geerts and colleagues in a study published online Dec. 26 in the journal Pediatrics.

In what the researchers called the first study to report on prenatal smoking and arterial characteristics in nonsmoking offspring, Dr. Geerts of the University Medical Center Utrecht (the Netherlands), and colleagues looked at 259 children who underwent ultrasound at age 5 years to determine carotid artery intima-media thickness (CIMT) and arterial wall distensibility (Pediatrics 2011 Dec. 26 [doi:10.1542/peds.2011-0249]).

The subject’s mothers had previously completed surveys when their children were 4 weeks of age, answering questions about smoking status at that time and during the pregnancy.

A similar questionnaire was administered at the time of the child’s ultrasound.

The majority of mothers (244 of 259) reported that they did not smoke during pregnancy, according to the questionnaire.

At birth, children born to smokers did not differ significantly from their counterparts in terms of weight, length, or gestational age, although there was a trend for these children to be lighter in weight and shorter.

"There was a clear positive trend between the number of cigarettes smoked by mothers in pregnancy and adverse vascular health."

They were, however, significantly less likely to be breastfed than babies of nonsmoking mothers.

By 5 years, among the 258 children with CIMT values available, children of mothers who smoked during pregnancy (n = 15) had a CIMT that was 18.8 mcm thicker than that of their counterparts.

Additionally, the children of mothers who smoked both during pregnancy and in the postnatal period (n = 11) had an even thicker CIMT (23.3 mcm) compared with that of completely nonexposed children.

In contrast, the children of 16 women who did not smoke in pregnancy but did smoke currently had no differences in CIMT, compared with children of nonsmoking mothers.

The finding was similar when investigators looked at vascular function: The arteries of children whose mothers smoked during pregnancy had significantly (16%) less stretch than did those of nonexposed peers, and the effect was compounded for children whose mothers smoked both during pregnancy and at the 5-year follow-up (19% lower distensibility).

Meanwhile, children of mothers who did not smoke during pregnancy but took it up afterward had no significant difference in distensibility, compared with their unexposed peers.

Finally, the authors found that compared with the children of mothers who smoked five or fewer cigarettes per day during pregnancy, the children of mothers who smoked more than five per day exhibited a statistically significant trend of lower mean arterial distensibility, as well as a nonsignificant trend toward greater CIMT, according to Dr. Geerts.

The authors conceded that the use of nicotine and cotinine as maternal and neonatal hair biomarkers for active smoking would have given a more reliable picture of smoking activity than did the questionnaires.

However, "that technology was unknown at the time of the [study] design, and it is not known if measurements at inclusion (weeks postpartum) accurately reflect smoke exposure in pregnancy," they wrote.

Indeed, "underreporting of smoking cannot be excluded but would most likely mean dilution of the association."

The investigators also added that CIMT and distensibility at age 5 years – known markers of cardiovascular disease risk in adulthood – may not correlate to disease in adulthood.

Such associations "can only be assumed," they added.

The authors stated they had no individual financial relationships relevant to this article to disclose. The study was partly funded by the Netherlands Organization for Health Research and Development, as well as the University Medical Center Utrecht.

At 5 years old, the children of mothers who smoked in pregnancy had significantly greater carotid intima-media thickness and lower arterial distensibility than did unexposed offspring.

"Moreover, there was a clear positive trend between the number of cigarettes smoked by mothers in pregnancy and adverse vascular health, a finding that adds to the credibility of gestational smoking being causally related to offspring vascular damage," wrote Dr. Caroline C. Geerts and colleagues in a study published online Dec. 26 in the journal Pediatrics.

In what the researchers called the first study to report on prenatal smoking and arterial characteristics in nonsmoking offspring, Dr. Geerts of the University Medical Center Utrecht (the Netherlands), and colleagues looked at 259 children who underwent ultrasound at age 5 years to determine carotid artery intima-media thickness (CIMT) and arterial wall distensibility (Pediatrics 2011 Dec. 26 [doi:10.1542/peds.2011-0249]).

The subject’s mothers had previously completed surveys when their children were 4 weeks of age, answering questions about smoking status at that time and during the pregnancy.

A similar questionnaire was administered at the time of the child’s ultrasound.

The majority of mothers (244 of 259) reported that they did not smoke during pregnancy, according to the questionnaire.

At birth, children born to smokers did not differ significantly from their counterparts in terms of weight, length, or gestational age, although there was a trend for these children to be lighter in weight and shorter.

"There was a clear positive trend between the number of cigarettes smoked by mothers in pregnancy and adverse vascular health."

They were, however, significantly less likely to be breastfed than babies of nonsmoking mothers.

By 5 years, among the 258 children with CIMT values available, children of mothers who smoked during pregnancy (n = 15) had a CIMT that was 18.8 mcm thicker than that of their counterparts.

Additionally, the children of mothers who smoked both during pregnancy and in the postnatal period (n = 11) had an even thicker CIMT (23.3 mcm) compared with that of completely nonexposed children.

In contrast, the children of 16 women who did not smoke in pregnancy but did smoke currently had no differences in CIMT, compared with children of nonsmoking mothers.

The finding was similar when investigators looked at vascular function: The arteries of children whose mothers smoked during pregnancy had significantly (16%) less stretch than did those of nonexposed peers, and the effect was compounded for children whose mothers smoked both during pregnancy and at the 5-year follow-up (19% lower distensibility).

Meanwhile, children of mothers who did not smoke during pregnancy but took it up afterward had no significant difference in distensibility, compared with their unexposed peers.

Finally, the authors found that compared with the children of mothers who smoked five or fewer cigarettes per day during pregnancy, the children of mothers who smoked more than five per day exhibited a statistically significant trend of lower mean arterial distensibility, as well as a nonsignificant trend toward greater CIMT, according to Dr. Geerts.

The authors conceded that the use of nicotine and cotinine as maternal and neonatal hair biomarkers for active smoking would have given a more reliable picture of smoking activity than did the questionnaires.

However, "that technology was unknown at the time of the [study] design, and it is not known if measurements at inclusion (weeks postpartum) accurately reflect smoke exposure in pregnancy," they wrote.

Indeed, "underreporting of smoking cannot be excluded but would most likely mean dilution of the association."

The investigators also added that CIMT and distensibility at age 5 years – known markers of cardiovascular disease risk in adulthood – may not correlate to disease in adulthood.

Such associations "can only be assumed," they added.

The authors stated they had no individual financial relationships relevant to this article to disclose. The study was partly funded by the Netherlands Organization for Health Research and Development, as well as the University Medical Center Utrecht.

At 5 years old, the children of mothers who smoked in pregnancy had significantly greater carotid intima-media thickness and lower arterial distensibility than did unexposed offspring.

"Moreover, there was a clear positive trend between the number of cigarettes smoked by mothers in pregnancy and adverse vascular health, a finding that adds to the credibility of gestational smoking being causally related to offspring vascular damage," wrote Dr. Caroline C. Geerts and colleagues in a study published online Dec. 26 in the journal Pediatrics.

In what the researchers called the first study to report on prenatal smoking and arterial characteristics in nonsmoking offspring, Dr. Geerts of the University Medical Center Utrecht (the Netherlands), and colleagues looked at 259 children who underwent ultrasound at age 5 years to determine carotid artery intima-media thickness (CIMT) and arterial wall distensibility (Pediatrics 2011 Dec. 26 [doi:10.1542/peds.2011-0249]).

The subject’s mothers had previously completed surveys when their children were 4 weeks of age, answering questions about smoking status at that time and during the pregnancy.

A similar questionnaire was administered at the time of the child’s ultrasound.

The majority of mothers (244 of 259) reported that they did not smoke during pregnancy, according to the questionnaire.

At birth, children born to smokers did not differ significantly from their counterparts in terms of weight, length, or gestational age, although there was a trend for these children to be lighter in weight and shorter.

"There was a clear positive trend between the number of cigarettes smoked by mothers in pregnancy and adverse vascular health."

They were, however, significantly less likely to be breastfed than babies of nonsmoking mothers.

By 5 years, among the 258 children with CIMT values available, children of mothers who smoked during pregnancy (n = 15) had a CIMT that was 18.8 mcm thicker than that of their counterparts.

Additionally, the children of mothers who smoked both during pregnancy and in the postnatal period (n = 11) had an even thicker CIMT (23.3 mcm) compared with that of completely nonexposed children.

In contrast, the children of 16 women who did not smoke in pregnancy but did smoke currently had no differences in CIMT, compared with children of nonsmoking mothers.

The finding was similar when investigators looked at vascular function: The arteries of children whose mothers smoked during pregnancy had significantly (16%) less stretch than did those of nonexposed peers, and the effect was compounded for children whose mothers smoked both during pregnancy and at the 5-year follow-up (19% lower distensibility).

Meanwhile, children of mothers who did not smoke during pregnancy but took it up afterward had no significant difference in distensibility, compared with their unexposed peers.

Finally, the authors found that compared with the children of mothers who smoked five or fewer cigarettes per day during pregnancy, the children of mothers who smoked more than five per day exhibited a statistically significant trend of lower mean arterial distensibility, as well as a nonsignificant trend toward greater CIMT, according to Dr. Geerts.

The authors conceded that the use of nicotine and cotinine as maternal and neonatal hair biomarkers for active smoking would have given a more reliable picture of smoking activity than did the questionnaires.

However, "that technology was unknown at the time of the [study] design, and it is not known if measurements at inclusion (weeks postpartum) accurately reflect smoke exposure in pregnancy," they wrote.

Indeed, "underreporting of smoking cannot be excluded but would most likely mean dilution of the association."

The investigators also added that CIMT and distensibility at age 5 years – known markers of cardiovascular disease risk in adulthood – may not correlate to disease in adulthood.

Such associations "can only be assumed," they added.

The authors stated they had no individual financial relationships relevant to this article to disclose. The study was partly funded by the Netherlands Organization for Health Research and Development, as well as the University Medical Center Utrecht.

Women with recurrent spontaneous abortions in the setting of antiphospholipid syndrome have a 15-fold greater risk of thrombotic events over the long term, compared with women who have had multiple miscarriages but who don’t have the syndrome.

If the finding is confirmed, "further studies would be warranted to assess the efficacy and risks of long-term thromboprophylaxis with aspirin and/or heparin in patients with [recurrent spontaneous abortion] associated with antiphospholipid syndrome," according to the investigators writing in the January issue of Annals of the Rheumatic Diseases.

Dr. Maria Angeles Martinez-Zamora of the University of Barcelona and colleagues looked at 57 women seen at a single tertiary-care center who had antiphospholipid syndrome (APS) and associated recurrent spontaneous abortion (Ann. Rheum. Dis. 2012;71:61-6).

APS was defined according to the 2006 international consensus statement (J. Thromb. Haemost. 2006;4:295-306).

Briefly, the criteria stipulate that the diagnosis can be made only when the patient has had at least one thrombotic event, plus pregnancy morbidity, plus all of the following: positive lupus anticoagulant; anticardiolipin antibody of IgG and/or IgM isotype present in medium or high titer; and anti-beta₂ glycoprotein-I antibody of IgG and/or IgM isotype in titers greater than the 99th percentile.

This group was then compared to three separate control groups. The first (n = 86) included patients with recurrent spontaneous abortions of unknown etiology who were negative for APS.

The second (n = 42) also had recurrent spontaneous abortions, but with known thrombophilic genetic defects.

"Thrombophilia in this group was defined as factor V Leiden (heterozygote) mutation (n = 17), prothrombin G20210A gene (heterozygote) mutation (n = 12), protein C deficiency (n = 9), or protein S deficiency (n = 4)," wrote the authors.

However, "No woman in this group had combined thrombophilia (two or more findings)."

Finally, the third group (n = 30) were antiphospholipid (APL)-positive on laboratory tests but had no history of thrombotic or obstetric morbidity.

Overall, 100% of women in all groups were white, and their mean ages were between 32 and 34 years at the time of their first miscarriage (or study inclusion, in the case of the APL group). Patients were followed for up to 12 years, with a mean follow-up ranging from 6 years among those with recurrent spontaneous abortions of unknown origin to 8.2 years among the patients who were antiphospholipid positive without thrombotic events of obstetric morbidity.

The researchers found that 11 patients (19.3%) with APS with recurrent spontaneous abortion had thrombotic events over the study period, including four cerebral arterial infarctions, one cerebellar arterial infarction, and two deep vein thromboses, pulmonary embolisms, and ischemic myocardial infarctions each.

In contrast, deep vein thromboses occurred in two of the women with recurrent spontaneous abortion with known thrombophilic genetic defects but in none of the patients with recurrent spontaneous abortions of unknown origin or antiphospholipid positive without thrombotic events or obstetric morbidity.

That correlated to a greatly increased risk for thrombosis among the women with APS and recurrent spontaneous abortions, with an odds ratio of 15.06, compared with the women with either recurrent spontaneous abortions of unknown origin who were negative for APL or antiphospholipid positivity without thrombotic events or obstetric morbidity (95% confidence interval, 3.2-70.5; P less than .0001).

"This was still true when only patients with thrombophilic disorders other than APL [recurrent spontaneous abortion with known thrombophilic genetic defects] were considered (OR, 4.8; 95% CI, 1-22.8; P less than .05)," wrote the authors.

The OR was even higher when the women with APS and recurrent spontaneous abortions were compared with the women with recurrent spontaneous abortions of unknown origin who were negative for APL (OR, 42.8; 95% CI, 2.5-742; P less than .0001), they added.

Nor did the use of aspirin therapy alter the outcome, as "the occurrence of thrombotic events among women with recurrent spontaneous abortion [all groups] treated with aspirin (16% or 2 of 12 patients) did not differ from patients who did not receive this treatment (6% or 11 of 173 women) (OR, 2.9; 95% CI, 0.5-15.1)," wrote the investigators.

Dr. Martinez-Zamora concluded that the findings of the current study support the "two-hit hypothesis," used to explain why thrombotic events occur only occasionally, despite the persistent presence of APL.

According to the hypothesis, antiphospholipid syndrome – the "first hit" – increases patients’ thrombophilic risk, and clotting takes place in the presence of another thrombophilic condition, that is, recurrent spontaneous abortion, the "second-hit."

"This would explain previous epidemiological studies suggesting that a woman’s reproductive history may indicate future cardiovascular risk," added the authors.

On the other hand, they pointed out that 80% of patients with recurrent spontaneous abortion associated with APL in their study did not develop a thrombotic event.

"Therefore, whether an individual will develop a thrombotic event depends on the concomitant presence of additional factors that may increase the whole thrombotic risk," they wrote.

The authors declared no funding for this study and stated that they had no competing interests to disclose.

Women with recurrent spontaneous abortions in the setting of antiphospholipid syndrome have a 15-fold greater risk of thrombotic events over the long term, compared with women who have had multiple miscarriages but who don’t have the syndrome.

If the finding is confirmed, "further studies would be warranted to assess the efficacy and risks of long-term thromboprophylaxis with aspirin and/or heparin in patients with [recurrent spontaneous abortion] associated with antiphospholipid syndrome," according to the investigators writing in the January issue of Annals of the Rheumatic Diseases.

Dr. Maria Angeles Martinez-Zamora of the University of Barcelona and colleagues looked at 57 women seen at a single tertiary-care center who had antiphospholipid syndrome (APS) and associated recurrent spontaneous abortion (Ann. Rheum. Dis. 2012;71:61-6).

APS was defined according to the 2006 international consensus statement (J. Thromb. Haemost. 2006;4:295-306).

Briefly, the criteria stipulate that the diagnosis can be made only when the patient has had at least one thrombotic event, plus pregnancy morbidity, plus all of the following: positive lupus anticoagulant; anticardiolipin antibody of IgG and/or IgM isotype present in medium or high titer; and anti-beta₂ glycoprotein-I antibody of IgG and/or IgM isotype in titers greater than the 99th percentile.

This group was then compared to three separate control groups. The first (n = 86) included patients with recurrent spontaneous abortions of unknown etiology who were negative for APS.

The second (n = 42) also had recurrent spontaneous abortions, but with known thrombophilic genetic defects.

"Thrombophilia in this group was defined as factor V Leiden (heterozygote) mutation (n = 17), prothrombin G20210A gene (heterozygote) mutation (n = 12), protein C deficiency (n = 9), or protein S deficiency (n = 4)," wrote the authors.

However, "No woman in this group had combined thrombophilia (two or more findings)."

Finally, the third group (n = 30) were antiphospholipid (APL)-positive on laboratory tests but had no history of thrombotic or obstetric morbidity.

Overall, 100% of women in all groups were white, and their mean ages were between 32 and 34 years at the time of their first miscarriage (or study inclusion, in the case of the APL group). Patients were followed for up to 12 years, with a mean follow-up ranging from 6 years among those with recurrent spontaneous abortions of unknown origin to 8.2 years among the patients who were antiphospholipid positive without thrombotic events of obstetric morbidity.

The researchers found that 11 patients (19.3%) with APS with recurrent spontaneous abortion had thrombotic events over the study period, including four cerebral arterial infarctions, one cerebellar arterial infarction, and two deep vein thromboses, pulmonary embolisms, and ischemic myocardial infarctions each.

In contrast, deep vein thromboses occurred in two of the women with recurrent spontaneous abortion with known thrombophilic genetic defects but in none of the patients with recurrent spontaneous abortions of unknown origin or antiphospholipid positive without thrombotic events or obstetric morbidity.

That correlated to a greatly increased risk for thrombosis among the women with APS and recurrent spontaneous abortions, with an odds ratio of 15.06, compared with the women with either recurrent spontaneous abortions of unknown origin who were negative for APL or antiphospholipid positivity without thrombotic events or obstetric morbidity (95% confidence interval, 3.2-70.5; P less than .0001).

"This was still true when only patients with thrombophilic disorders other than APL [recurrent spontaneous abortion with known thrombophilic genetic defects] were considered (OR, 4.8; 95% CI, 1-22.8; P less than .05)," wrote the authors.

The OR was even higher when the women with APS and recurrent spontaneous abortions were compared with the women with recurrent spontaneous abortions of unknown origin who were negative for APL (OR, 42.8; 95% CI, 2.5-742; P less than .0001), they added.

Nor did the use of aspirin therapy alter the outcome, as "the occurrence of thrombotic events among women with recurrent spontaneous abortion [all groups] treated with aspirin (16% or 2 of 12 patients) did not differ from patients who did not receive this treatment (6% or 11 of 173 women) (OR, 2.9; 95% CI, 0.5-15.1)," wrote the investigators.

Dr. Martinez-Zamora concluded that the findings of the current study support the "two-hit hypothesis," used to explain why thrombotic events occur only occasionally, despite the persistent presence of APL.

According to the hypothesis, antiphospholipid syndrome – the "first hit" – increases patients’ thrombophilic risk, and clotting takes place in the presence of another thrombophilic condition, that is, recurrent spontaneous abortion, the "second-hit."

"This would explain previous epidemiological studies suggesting that a woman’s reproductive history may indicate future cardiovascular risk," added the authors.

On the other hand, they pointed out that 80% of patients with recurrent spontaneous abortion associated with APL in their study did not develop a thrombotic event.

"Therefore, whether an individual will develop a thrombotic event depends on the concomitant presence of additional factors that may increase the whole thrombotic risk," they wrote.

The authors declared no funding for this study and stated that they had no competing interests to disclose.

Women with recurrent spontaneous abortions in the setting of antiphospholipid syndrome have a 15-fold greater risk of thrombotic events over the long term, compared with women who have had multiple miscarriages but who don’t have the syndrome.

If the finding is confirmed, "further studies would be warranted to assess the efficacy and risks of long-term thromboprophylaxis with aspirin and/or heparin in patients with [recurrent spontaneous abortion] associated with antiphospholipid syndrome," according to the investigators writing in the January issue of Annals of the Rheumatic Diseases.

Dr. Maria Angeles Martinez-Zamora of the University of Barcelona and colleagues looked at 57 women seen at a single tertiary-care center who had antiphospholipid syndrome (APS) and associated recurrent spontaneous abortion (Ann. Rheum. Dis. 2012;71:61-6).

APS was defined according to the 2006 international consensus statement (J. Thromb. Haemost. 2006;4:295-306).

Briefly, the criteria stipulate that the diagnosis can be made only when the patient has had at least one thrombotic event, plus pregnancy morbidity, plus all of the following: positive lupus anticoagulant; anticardiolipin antibody of IgG and/or IgM isotype present in medium or high titer; and anti-beta₂ glycoprotein-I antibody of IgG and/or IgM isotype in titers greater than the 99th percentile.

This group was then compared to three separate control groups. The first (n = 86) included patients with recurrent spontaneous abortions of unknown etiology who were negative for APS.

The second (n = 42) also had recurrent spontaneous abortions, but with known thrombophilic genetic defects.

"Thrombophilia in this group was defined as factor V Leiden (heterozygote) mutation (n = 17), prothrombin G20210A gene (heterozygote) mutation (n = 12), protein C deficiency (n = 9), or protein S deficiency (n = 4)," wrote the authors.

However, "No woman in this group had combined thrombophilia (two or more findings)."

Finally, the third group (n = 30) were antiphospholipid (APL)-positive on laboratory tests but had no history of thrombotic or obstetric morbidity.

Overall, 100% of women in all groups were white, and their mean ages were between 32 and 34 years at the time of their first miscarriage (or study inclusion, in the case of the APL group). Patients were followed for up to 12 years, with a mean follow-up ranging from 6 years among those with recurrent spontaneous abortions of unknown origin to 8.2 years among the patients who were antiphospholipid positive without thrombotic events of obstetric morbidity.

The researchers found that 11 patients (19.3%) with APS with recurrent spontaneous abortion had thrombotic events over the study period, including four cerebral arterial infarctions, one cerebellar arterial infarction, and two deep vein thromboses, pulmonary embolisms, and ischemic myocardial infarctions each.

In contrast, deep vein thromboses occurred in two of the women with recurrent spontaneous abortion with known thrombophilic genetic defects but in none of the patients with recurrent spontaneous abortions of unknown origin or antiphospholipid positive without thrombotic events or obstetric morbidity.

That correlated to a greatly increased risk for thrombosis among the women with APS and recurrent spontaneous abortions, with an odds ratio of 15.06, compared with the women with either recurrent spontaneous abortions of unknown origin who were negative for APL or antiphospholipid positivity without thrombotic events or obstetric morbidity (95% confidence interval, 3.2-70.5; P less than .0001).

"This was still true when only patients with thrombophilic disorders other than APL [recurrent spontaneous abortion with known thrombophilic genetic defects] were considered (OR, 4.8; 95% CI, 1-22.8; P less than .05)," wrote the authors.

The OR was even higher when the women with APS and recurrent spontaneous abortions were compared with the women with recurrent spontaneous abortions of unknown origin who were negative for APL (OR, 42.8; 95% CI, 2.5-742; P less than .0001), they added.

Nor did the use of aspirin therapy alter the outcome, as "the occurrence of thrombotic events among women with recurrent spontaneous abortion [all groups] treated with aspirin (16% or 2 of 12 patients) did not differ from patients who did not receive this treatment (6% or 11 of 173 women) (OR, 2.9; 95% CI, 0.5-15.1)," wrote the investigators.

Dr. Martinez-Zamora concluded that the findings of the current study support the "two-hit hypothesis," used to explain why thrombotic events occur only occasionally, despite the persistent presence of APL.

According to the hypothesis, antiphospholipid syndrome – the "first hit" – increases patients’ thrombophilic risk, and clotting takes place in the presence of another thrombophilic condition, that is, recurrent spontaneous abortion, the "second-hit."

"This would explain previous epidemiological studies suggesting that a woman’s reproductive history may indicate future cardiovascular risk," added the authors.

On the other hand, they pointed out that 80% of patients with recurrent spontaneous abortion associated with APL in their study did not develop a thrombotic event.

"Therefore, whether an individual will develop a thrombotic event depends on the concomitant presence of additional factors that may increase the whole thrombotic risk," they wrote.

The authors declared no funding for this study and stated that they had no competing interests to disclose.

In Takayasu arteritis, as in systemic lupus erythematosus, greater numbers of circulating plasmablasts coincided with increased disease activity.

The finding is the first to extensively describe B-cell disturbances in this poorly understood disease, "which was previously thought to have a mainly T-cell–mediated pathogenesis," according to the researchers.

Moreover, the finding offers hope that B-cell depletion therapy may be an option for these patients, added Dr. Bimba F. Hoyer in the January 2012 issue of Annals of the Rheumatic Diseases.

Dr. Hoyer of the Charité Universitätsmedizin Berlin and colleagues looked at blood samples from 17 women with Takayasu arteritis according to American College of Rheumatology disease criteria.

Patients’ median age at disease onset was 25 years, their median disease duration was 90 months, and the median age at analysis was 39 years.

A second cohort of nine women without Takayasu arteritis but with systemic lupus erythematosus (SLE) was also studied (mean age, 32 years), as was a control group of eight healthy women and one man (mean age, 35.5 years).

Cells were analyzed for expression of CD20, CD19, CD27, and HLA-DR.

"B-cell depletion therapy seems to be a useful option for refractory Takayasu arteritis."

"Unlike active SLE, which is characterized by lymphocytopenia, total lymphocyte and B-cell counts in patients with [Takayasu arteritis] were not significantly lower than those in healthy donors," wrote the authors (Ann. Rheum. Dis. 2012;71:75-9).

However, they did find that B-cell subsets were "considerably altered" in active Takayasu arteritis. For example, they found an increased number and frequency of CD19⁺/CD20^–/CD27^high antibody-secreting cells in patients with Takayasu arteritis compared with healthy donors (2,800 vs. 1,200, respectively; P = .027), as well as a lower total number of naive B cells (28,000 vs. 110,000; P = .012) and a higher number of memory B cells (78,000 vs. 48,000; P = .049).

They also found an increased number of plasmablasts among active Takayasu arteritis patients (11 of the 17 total patients), both in relation to healthy donors (7,800 vs. 975; P = .027) and in relation to the inactive Takayasu arteritis cohort (n = 6), where the mean was 535 (P = .0056).

"This strongly resembles the findings in SLE, where plasmablast expansion serves as a marker of disease activity," wrote the authors. Indeed, the number of plasmablasts in the active SLE patients was identical to that in the active Takayasu arteritis patients, at 7,800.

Based on these findings, three patients who were refractory to other treatments were subsequently treated with rituximab, "so far successfully," wrote the authors. The case studies of these patients were published in a supplement to the current study.

"The observed correlation between the plasmablast numbers and active Takayasu arteritis, as well as the beneficial effects of B-cell depletion therapy, suggests a potential of plasmablasts as biomarkers of disease activity and for interventions targeting B cells," they wrote.

Moreover, "B-cell depletion therapy seems to be a useful option for refractory Takayasu arteritis, and its potential should be evaluated in controlled trials," they added.

"Other factors influencing B-cell differentiation and plasma cells may also emerge as novel therapeutic targets."

The study was supported by the Deutsche Forschungsgemeinschaft (the German Research Foundation) and Roche Pharma AG, the maker of rituximab. The authors stated that they had no individual competing interests to disclose.

In Takayasu arteritis, as in systemic lupus erythematosus, greater numbers of circulating plasmablasts coincided with increased disease activity.

The finding is the first to extensively describe B-cell disturbances in this poorly understood disease, "which was previously thought to have a mainly T-cell–mediated pathogenesis," according to the researchers.

Moreover, the finding offers hope that B-cell depletion therapy may be an option for these patients, added Dr. Bimba F. Hoyer in the January 2012 issue of Annals of the Rheumatic Diseases.

Dr. Hoyer of the Charité Universitätsmedizin Berlin and colleagues looked at blood samples from 17 women with Takayasu arteritis according to American College of Rheumatology disease criteria.

Patients’ median age at disease onset was 25 years, their median disease duration was 90 months, and the median age at analysis was 39 years.

A second cohort of nine women without Takayasu arteritis but with systemic lupus erythematosus (SLE) was also studied (mean age, 32 years), as was a control group of eight healthy women and one man (mean age, 35.5 years).

Cells were analyzed for expression of CD20, CD19, CD27, and HLA-DR.

"B-cell depletion therapy seems to be a useful option for refractory Takayasu arteritis."

"Unlike active SLE, which is characterized by lymphocytopenia, total lymphocyte and B-cell counts in patients with [Takayasu arteritis] were not significantly lower than those in healthy donors," wrote the authors (Ann. Rheum. Dis. 2012;71:75-9).

However, they did find that B-cell subsets were "considerably altered" in active Takayasu arteritis. For example, they found an increased number and frequency of CD19⁺/CD20^–/CD27^high antibody-secreting cells in patients with Takayasu arteritis compared with healthy donors (2,800 vs. 1,200, respectively; P = .027), as well as a lower total number of naive B cells (28,000 vs. 110,000; P = .012) and a higher number of memory B cells (78,000 vs. 48,000; P = .049).

They also found an increased number of plasmablasts among active Takayasu arteritis patients (11 of the 17 total patients), both in relation to healthy donors (7,800 vs. 975; P = .027) and in relation to the inactive Takayasu arteritis cohort (n = 6), where the mean was 535 (P = .0056).

"This strongly resembles the findings in SLE, where plasmablast expansion serves as a marker of disease activity," wrote the authors. Indeed, the number of plasmablasts in the active SLE patients was identical to that in the active Takayasu arteritis patients, at 7,800.

Based on these findings, three patients who were refractory to other treatments were subsequently treated with rituximab, "so far successfully," wrote the authors. The case studies of these patients were published in a supplement to the current study.

"The observed correlation between the plasmablast numbers and active Takayasu arteritis, as well as the beneficial effects of B-cell depletion therapy, suggests a potential of plasmablasts as biomarkers of disease activity and for interventions targeting B cells," they wrote.

Moreover, "B-cell depletion therapy seems to be a useful option for refractory Takayasu arteritis, and its potential should be evaluated in controlled trials," they added.

"Other factors influencing B-cell differentiation and plasma cells may also emerge as novel therapeutic targets."

The study was supported by the Deutsche Forschungsgemeinschaft (the German Research Foundation) and Roche Pharma AG, the maker of rituximab. The authors stated that they had no individual competing interests to disclose.

In Takayasu arteritis, as in systemic lupus erythematosus, greater numbers of circulating plasmablasts coincided with increased disease activity.

The finding is the first to extensively describe B-cell disturbances in this poorly understood disease, "which was previously thought to have a mainly T-cell–mediated pathogenesis," according to the researchers.

Moreover, the finding offers hope that B-cell depletion therapy may be an option for these patients, added Dr. Bimba F. Hoyer in the January 2012 issue of Annals of the Rheumatic Diseases.

Dr. Hoyer of the Charité Universitätsmedizin Berlin and colleagues looked at blood samples from 17 women with Takayasu arteritis according to American College of Rheumatology disease criteria.

Patients’ median age at disease onset was 25 years, their median disease duration was 90 months, and the median age at analysis was 39 years.

A second cohort of nine women without Takayasu arteritis but with systemic lupus erythematosus (SLE) was also studied (mean age, 32 years), as was a control group of eight healthy women and one man (mean age, 35.5 years).

Cells were analyzed for expression of CD20, CD19, CD27, and HLA-DR.

"B-cell depletion therapy seems to be a useful option for refractory Takayasu arteritis."

"Unlike active SLE, which is characterized by lymphocytopenia, total lymphocyte and B-cell counts in patients with [Takayasu arteritis] were not significantly lower than those in healthy donors," wrote the authors (Ann. Rheum. Dis. 2012;71:75-9).

However, they did find that B-cell subsets were "considerably altered" in active Takayasu arteritis. For example, they found an increased number and frequency of CD19⁺/CD20^–/CD27^high antibody-secreting cells in patients with Takayasu arteritis compared with healthy donors (2,800 vs. 1,200, respectively; P = .027), as well as a lower total number of naive B cells (28,000 vs. 110,000; P = .012) and a higher number of memory B cells (78,000 vs. 48,000; P = .049).

They also found an increased number of plasmablasts among active Takayasu arteritis patients (11 of the 17 total patients), both in relation to healthy donors (7,800 vs. 975; P = .027) and in relation to the inactive Takayasu arteritis cohort (n = 6), where the mean was 535 (P = .0056).

"This strongly resembles the findings in SLE, where plasmablast expansion serves as a marker of disease activity," wrote the authors. Indeed, the number of plasmablasts in the active SLE patients was identical to that in the active Takayasu arteritis patients, at 7,800.

Based on these findings, three patients who were refractory to other treatments were subsequently treated with rituximab, "so far successfully," wrote the authors. The case studies of these patients were published in a supplement to the current study.

"The observed correlation between the plasmablast numbers and active Takayasu arteritis, as well as the beneficial effects of B-cell depletion therapy, suggests a potential of plasmablasts as biomarkers of disease activity and for interventions targeting B cells," they wrote.

Moreover, "B-cell depletion therapy seems to be a useful option for refractory Takayasu arteritis, and its potential should be evaluated in controlled trials," they added.

"Other factors influencing B-cell differentiation and plasma cells may also emerge as novel therapeutic targets."

The study was supported by the Deutsche Forschungsgemeinschaft (the German Research Foundation) and Roche Pharma AG, the maker of rituximab. The authors stated that they had no individual competing interests to disclose.

Overall, celiac disease patients are not at increased risk for gastrointestinal cancers beyond their first year after diagnosis, according to a review by Dr. Peter Elfström and colleagues in the journal Clinical Gastroenterology and Hepatology.

However, there is a significantly increased risk for GI cancer among celiac patients during that first year after the biopsy reveals the celiac diagnosis, according to this large, population-based study.

Dr. Elfström of Karolinska University Hospital in Stockholm and his colleagues reviewed data from 28,882 Swedish patients with celiac disease that was confirmed by biopsy showing villous atrophy in the small intestine (Clin. Gastroenterol. Hepatol. 2011 [doi:10.1016/j.cgh.2011.06.029]).

They also reviewed data on 12,860 patients whose biopsies did not show atrophy but did show inflammation of the small intestine, and another 3,705 patients with normal mucosa but serology indicative of celiac disease, including a positive IgA or IgG antigliadin, endomysial, or tissue transglutaminase test. The authors defined this third group as having "latent" celiac disease.

The study included children and adults. The percentage of children (aged 0-19 years) was 41% in the biopsy-confirmed celiac disease (villous atrophy) group, 10% in the inflammation group, and 25% in the latent celiac group.

Excluded from this study were all patients with a history of GI cancer before biopsy. Patients in the study were followed until the first incidence of GI cancer (according to the Swedish Cancer Registry), emigration, death, or the end of the study period on Dec. 31, 2007 – whichever came first.

Overall, during the entire follow-up period, the authors found 372 incident cancers in the villous atrophy–positive celiac disease patients, 347 cases in the inflammation-only cohort, and 38 cancers in the latent celiac group.

During the first year alone, there was a total of 125 incident cancers in the villous atrophy cohort, for a hazard ratio of 5.95 (95% confidence interval, 4.64-7.64).

In the inflammation-only group, the first year of follow-up after biopsy yielded 169 incident cancers (HR, 9.13; 95% CI, 7.19-11.6).

Similarly, latent celiac patients had a hazard ratio of 8.10 (95% CI, 4.69-14.0) for the first year of follow-up, with 23 incident cancers.

After the first year, however, the findings abruptly changed. "Excluding the first year of follow-up, patients undergoing small intestinal biopsy were at no increased risk of any GI cancer," wrote the authors, with the villous atrophy patients having a hazard ratio of 1.07 (95% CI, 0.93-1.23).

Similarly, the inflammation-only group’s HR fell to 1.16 (95% CI, 0.98-1.37), and the latent celiac disease group’s HR dropped to 0.96 (95% CI, 0.56-1.66).

This corresponded to an absolute risk for any GI cancer of 101 per 100,000 person-years in the group with villous atrophy, wrote the authors, or an excess risk over the nonceliac population of 2 per 100,000.

The absolute risk among the inflammation-only cohort was 192 per 100,000, whereas the latent disease group had an absolute risk of only 70 per 100,000.

The authors postulated that the lack of elevated risk after the first year could be due to patients starting and following a gluten-free diet. However, "this is unlikely, since a similar pattern was seen also in inflammation and latent" groups, they wrote," adding that "in Sweden, patients with inflammation and latent [celiac disease] have traditionally not received a gluten-free diet."

Additionally, "we cannot rule out that part of the early risk increase is due to confounding by indication, [that is,] that symptoms of a GI cancer may cause investigation leading to a diagnosis of [celiac disease]," they postulated, with a later diagnosis of cancer.

This study was supported by grants from several universities, foundations, and societies, including the Swedish Society of Medicine and the Swedish Celiac Society. The authors disclosed no individual conflicts relating to this study.

* This article was updated on Dec. 7, 2011.

Overall, celiac disease patients are not at increased risk for gastrointestinal cancers beyond their first year after diagnosis, according to a review by Dr. Peter Elfström and colleagues in the journal Clinical Gastroenterology and Hepatology.

However, there is a significantly increased risk for GI cancer among celiac patients during that first year after the biopsy reveals the celiac diagnosis, according to this large, population-based study.

Dr. Elfström of Karolinska University Hospital in Stockholm and his colleagues reviewed data from 28,882 Swedish patients with celiac disease that was confirmed by biopsy showing villous atrophy in the small intestine (Clin. Gastroenterol. Hepatol. 2011 [doi:10.1016/j.cgh.2011.06.029]).

They also reviewed data on 12,860 patients whose biopsies did not show atrophy but did show inflammation of the small intestine, and another 3,705 patients with normal mucosa but serology indicative of celiac disease, including a positive IgA or IgG antigliadin, endomysial, or tissue transglutaminase test. The authors defined this third group as having "latent" celiac disease.

The study included children and adults. The percentage of children (aged 0-19 years) was 41% in the biopsy-confirmed celiac disease (villous atrophy) group, 10% in the inflammation group, and 25% in the latent celiac group.

Excluded from this study were all patients with a history of GI cancer before biopsy. Patients in the study were followed until the first incidence of GI cancer (according to the Swedish Cancer Registry), emigration, death, or the end of the study period on Dec. 31, 2007 – whichever came first.

Overall, during the entire follow-up period, the authors found 372 incident cancers in the villous atrophy–positive celiac disease patients, 347 cases in the inflammation-only cohort, and 38 cancers in the latent celiac group.

During the first year alone, there was a total of 125 incident cancers in the villous atrophy cohort, for a hazard ratio of 5.95 (95% confidence interval, 4.64-7.64).

In the inflammation-only group, the first year of follow-up after biopsy yielded 169 incident cancers (HR, 9.13; 95% CI, 7.19-11.6).

Similarly, latent celiac patients had a hazard ratio of 8.10 (95% CI, 4.69-14.0) for the first year of follow-up, with 23 incident cancers.

After the first year, however, the findings abruptly changed. "Excluding the first year of follow-up, patients undergoing small intestinal biopsy were at no increased risk of any GI cancer," wrote the authors, with the villous atrophy patients having a hazard ratio of 1.07 (95% CI, 0.93-1.23).

Similarly, the inflammation-only group’s HR fell to 1.16 (95% CI, 0.98-1.37), and the latent celiac disease group’s HR dropped to 0.96 (95% CI, 0.56-1.66).

This corresponded to an absolute risk for any GI cancer of 101 per 100,000 person-years in the group with villous atrophy, wrote the authors, or an excess risk over the nonceliac population of 2 per 100,000.

The absolute risk among the inflammation-only cohort was 192 per 100,000, whereas the latent disease group had an absolute risk of only 70 per 100,000.

The authors postulated that the lack of elevated risk after the first year could be due to patients starting and following a gluten-free diet. However, "this is unlikely, since a similar pattern was seen also in inflammation and latent" groups, they wrote," adding that "in Sweden, patients with inflammation and latent [celiac disease] have traditionally not received a gluten-free diet."

Additionally, "we cannot rule out that part of the early risk increase is due to confounding by indication, [that is,] that symptoms of a GI cancer may cause investigation leading to a diagnosis of [celiac disease]," they postulated, with a later diagnosis of cancer.

This study was supported by grants from several universities, foundations, and societies, including the Swedish Society of Medicine and the Swedish Celiac Society. The authors disclosed no individual conflicts relating to this study.

* This article was updated on Dec. 7, 2011.

Overall, celiac disease patients are not at increased risk for gastrointestinal cancers beyond their first year after diagnosis, according to a review by Dr. Peter Elfström and colleagues in the journal Clinical Gastroenterology and Hepatology.

However, there is a significantly increased risk for GI cancer among celiac patients during that first year after the biopsy reveals the celiac diagnosis, according to this large, population-based study.

Dr. Elfström of Karolinska University Hospital in Stockholm and his colleagues reviewed data from 28,882 Swedish patients with celiac disease that was confirmed by biopsy showing villous atrophy in the small intestine (Clin. Gastroenterol. Hepatol. 2011 [doi:10.1016/j.cgh.2011.06.029]).

They also reviewed data on 12,860 patients whose biopsies did not show atrophy but did show inflammation of the small intestine, and another 3,705 patients with normal mucosa but serology indicative of celiac disease, including a positive IgA or IgG antigliadin, endomysial, or tissue transglutaminase test. The authors defined this third group as having "latent" celiac disease.

The study included children and adults. The percentage of children (aged 0-19 years) was 41% in the biopsy-confirmed celiac disease (villous atrophy) group, 10% in the inflammation group, and 25% in the latent celiac group.

Excluded from this study were all patients with a history of GI cancer before biopsy. Patients in the study were followed until the first incidence of GI cancer (according to the Swedish Cancer Registry), emigration, death, or the end of the study period on Dec. 31, 2007 – whichever came first.

Overall, during the entire follow-up period, the authors found 372 incident cancers in the villous atrophy–positive celiac disease patients, 347 cases in the inflammation-only cohort, and 38 cancers in the latent celiac group.

During the first year alone, there was a total of 125 incident cancers in the villous atrophy cohort, for a hazard ratio of 5.95 (95% confidence interval, 4.64-7.64).

In the inflammation-only group, the first year of follow-up after biopsy yielded 169 incident cancers (HR, 9.13; 95% CI, 7.19-11.6).

Similarly, latent celiac patients had a hazard ratio of 8.10 (95% CI, 4.69-14.0) for the first year of follow-up, with 23 incident cancers.

After the first year, however, the findings abruptly changed. "Excluding the first year of follow-up, patients undergoing small intestinal biopsy were at no increased risk of any GI cancer," wrote the authors, with the villous atrophy patients having a hazard ratio of 1.07 (95% CI, 0.93-1.23).

Similarly, the inflammation-only group’s HR fell to 1.16 (95% CI, 0.98-1.37), and the latent celiac disease group’s HR dropped to 0.96 (95% CI, 0.56-1.66).

This corresponded to an absolute risk for any GI cancer of 101 per 100,000 person-years in the group with villous atrophy, wrote the authors, or an excess risk over the nonceliac population of 2 per 100,000.

The absolute risk among the inflammation-only cohort was 192 per 100,000, whereas the latent disease group had an absolute risk of only 70 per 100,000.

The authors postulated that the lack of elevated risk after the first year could be due to patients starting and following a gluten-free diet. However, "this is unlikely, since a similar pattern was seen also in inflammation and latent" groups, they wrote," adding that "in Sweden, patients with inflammation and latent [celiac disease] have traditionally not received a gluten-free diet."

Additionally, "we cannot rule out that part of the early risk increase is due to confounding by indication, [that is,] that symptoms of a GI cancer may cause investigation leading to a diagnosis of [celiac disease]," they postulated, with a later diagnosis of cancer.

This study was supported by grants from several universities, foundations, and societies, including the Swedish Society of Medicine and the Swedish Celiac Society. The authors disclosed no individual conflicts relating to this study.

* This article was updated on Dec. 7, 2011.

Roughly half of Crohn’s disease patients who are in remission while being treated with infliximab will relapse after discontinuing this drug, reported Dr. Edouard Louis and colleagues reported online in the journal Gastroenterology.

However, following retreatment with infliximab, "almost all" patients were once again in remission 1 month later, "and none experienced a significant acute or delayed infusion reaction, despite a drug holiday longer than 6 months for half of them."

Dr. Louis of the Centre Hospitalier Universitaire de Liège, Belgium, and his associates studied 115 adult patients with active luminal Crohn’s disease (CD) who had received at least 1 year of therapy with infliximab and an antimetabolite (azathioprine, 6-mercaptopurine, or methotrexate).

All patients had received at least two infliximab infusions during the 6 months prior to study inclusion, and patients’ concurrent antimetabolite doses had been stable for at least 3 months, with corticosteroid-free remission for the last 6 months before inclusion.

"Clinical response was defined by a decrease in the Crohns Disease Activity Index (CDAI) of at least 70 points, and 25% from CDAI at relapse," whereas remission was defined as a CDAI below 150.

Overall, there were 62 reported relapses at the study centers. Five of these relapses were invalidated by the authors, and another five were not retreated with infliximab because of patient or physician decision, leaving 52 relapses which were retreated per study protocol (Gastroenterology 2011 [doi:10.1053/j.gastro.2011.09.034]).

Factors significantly associated with relapse included male gender, with a hazard ratio of 3.7 (95% confidence interval, 1.9-7.4; P less than .001) and baseline hemoglobin levels less than 145 g/L at study inclusion (such as infliximab cessation), with a hazard ratio of 6.0 (95% CI, 2.2-16.5; P less than .001).

A leukocyte count greater than 6 x 10⁹/L (hazard ratio, 2.4, 95% CI 1.2-4.7; P = .01) and a high sensitivity C-reactive protein level greater than or equal to 5 mg/L (HR, 3.2, 95% CI 1.6-6.4; P less than .001) were also associated with relapse, as were a lack of previous surgical resection and a fecal calprotectin level greater than or equal to 300 mcg/g.

By 30 days after restarting infliximab, 37 of the 40 patients with complete data available (93%) were in remission once again, and 39 of 40 (98%) had clinical response.

Of the remaining 12 patients, there was one consent withdrawal and 11 patients were assessed at alternate time points, with 9 found to be in remission and with clinical response, 1 with response only, and 1 patient not in remission or showing clinical response.

"No infusion reaction or significant delayed reaction was reported in the retreated patients up to third retreatment, despite a median drug holiday of 6.6 months," wrote Dr. Louis, adding that no other serious adverse event was reported during the study.

"In clinical practice, stopping infliximab may still be considered for various reasons including cost, fear of long-term side effects, and concerns about pregnancy," concluded the authors.

"However, simple parameters may be used to identify a subgroup of patients with a low risk of relapse and in whom infliximab withdrawal may be considered," they wrote, pointing out that "when patients relapsed, retreatment with infliximab was effective and well tolerated in the vast majority."

Dr. Louis reported receiving consultancy fees as well as research and educational grants from several pharmaceutical companies, as did several other authors. The research was sponsored by the Association François Aupetit and the Société Nationale Française de Gastroentérologie.

Roughly half of Crohn’s disease patients who are in remission while being treated with infliximab will relapse after discontinuing this drug, reported Dr. Edouard Louis and colleagues reported online in the journal Gastroenterology.

However, following retreatment with infliximab, "almost all" patients were once again in remission 1 month later, "and none experienced a significant acute or delayed infusion reaction, despite a drug holiday longer than 6 months for half of them."

Dr. Louis of the Centre Hospitalier Universitaire de Liège, Belgium, and his associates studied 115 adult patients with active luminal Crohn’s disease (CD) who had received at least 1 year of therapy with infliximab and an antimetabolite (azathioprine, 6-mercaptopurine, or methotrexate).

All patients had received at least two infliximab infusions during the 6 months prior to study inclusion, and patients’ concurrent antimetabolite doses had been stable for at least 3 months, with corticosteroid-free remission for the last 6 months before inclusion.

"Clinical response was defined by a decrease in the Crohns Disease Activity Index (CDAI) of at least 70 points, and 25% from CDAI at relapse," whereas remission was defined as a CDAI below 150.

Overall, there were 62 reported relapses at the study centers. Five of these relapses were invalidated by the authors, and another five were not retreated with infliximab because of patient or physician decision, leaving 52 relapses which were retreated per study protocol (Gastroenterology 2011 [doi:10.1053/j.gastro.2011.09.034]).

Factors significantly associated with relapse included male gender, with a hazard ratio of 3.7 (95% confidence interval, 1.9-7.4; P less than .001) and baseline hemoglobin levels less than 145 g/L at study inclusion (such as infliximab cessation), with a hazard ratio of 6.0 (95% CI, 2.2-16.5; P less than .001).

A leukocyte count greater than 6 x 10⁹/L (hazard ratio, 2.4, 95% CI 1.2-4.7; P = .01) and a high sensitivity C-reactive protein level greater than or equal to 5 mg/L (HR, 3.2, 95% CI 1.6-6.4; P less than .001) were also associated with relapse, as were a lack of previous surgical resection and a fecal calprotectin level greater than or equal to 300 mcg/g.

By 30 days after restarting infliximab, 37 of the 40 patients with complete data available (93%) were in remission once again, and 39 of 40 (98%) had clinical response.

Of the remaining 12 patients, there was one consent withdrawal and 11 patients were assessed at alternate time points, with 9 found to be in remission and with clinical response, 1 with response only, and 1 patient not in remission or showing clinical response.

"No infusion reaction or significant delayed reaction was reported in the retreated patients up to third retreatment, despite a median drug holiday of 6.6 months," wrote Dr. Louis, adding that no other serious adverse event was reported during the study.

"In clinical practice, stopping infliximab may still be considered for various reasons including cost, fear of long-term side effects, and concerns about pregnancy," concluded the authors.

"However, simple parameters may be used to identify a subgroup of patients with a low risk of relapse and in whom infliximab withdrawal may be considered," they wrote, pointing out that "when patients relapsed, retreatment with infliximab was effective and well tolerated in the vast majority."

Dr. Louis reported receiving consultancy fees as well as research and educational grants from several pharmaceutical companies, as did several other authors. The research was sponsored by the Association François Aupetit and the Société Nationale Française de Gastroentérologie.

Roughly half of Crohn’s disease patients who are in remission while being treated with infliximab will relapse after discontinuing this drug, reported Dr. Edouard Louis and colleagues reported online in the journal Gastroenterology.

However, following retreatment with infliximab, "almost all" patients were once again in remission 1 month later, "and none experienced a significant acute or delayed infusion reaction, despite a drug holiday longer than 6 months for half of them."

Dr. Louis of the Centre Hospitalier Universitaire de Liège, Belgium, and his associates studied 115 adult patients with active luminal Crohn’s disease (CD) who had received at least 1 year of therapy with infliximab and an antimetabolite (azathioprine, 6-mercaptopurine, or methotrexate).

All patients had received at least two infliximab infusions during the 6 months prior to study inclusion, and patients’ concurrent antimetabolite doses had been stable for at least 3 months, with corticosteroid-free remission for the last 6 months before inclusion.

"Clinical response was defined by a decrease in the Crohns Disease Activity Index (CDAI) of at least 70 points, and 25% from CDAI at relapse," whereas remission was defined as a CDAI below 150.

Overall, there were 62 reported relapses at the study centers. Five of these relapses were invalidated by the authors, and another five were not retreated with infliximab because of patient or physician decision, leaving 52 relapses which were retreated per study protocol (Gastroenterology 2011 [doi:10.1053/j.gastro.2011.09.034]).

Factors significantly associated with relapse included male gender, with a hazard ratio of 3.7 (95% confidence interval, 1.9-7.4; P less than .001) and baseline hemoglobin levels less than 145 g/L at study inclusion (such as infliximab cessation), with a hazard ratio of 6.0 (95% CI, 2.2-16.5; P less than .001).

A leukocyte count greater than 6 x 10⁹/L (hazard ratio, 2.4, 95% CI 1.2-4.7; P = .01) and a high sensitivity C-reactive protein level greater than or equal to 5 mg/L (HR, 3.2, 95% CI 1.6-6.4; P less than .001) were also associated with relapse, as were a lack of previous surgical resection and a fecal calprotectin level greater than or equal to 300 mcg/g.

By 30 days after restarting infliximab, 37 of the 40 patients with complete data available (93%) were in remission once again, and 39 of 40 (98%) had clinical response.

Of the remaining 12 patients, there was one consent withdrawal and 11 patients were assessed at alternate time points, with 9 found to be in remission and with clinical response, 1 with response only, and 1 patient not in remission or showing clinical response.

"No infusion reaction or significant delayed reaction was reported in the retreated patients up to third retreatment, despite a median drug holiday of 6.6 months," wrote Dr. Louis, adding that no other serious adverse event was reported during the study.

"In clinical practice, stopping infliximab may still be considered for various reasons including cost, fear of long-term side effects, and concerns about pregnancy," concluded the authors.

"However, simple parameters may be used to identify a subgroup of patients with a low risk of relapse and in whom infliximab withdrawal may be considered," they wrote, pointing out that "when patients relapsed, retreatment with infliximab was effective and well tolerated in the vast majority."

Dr. Louis reported receiving consultancy fees as well as research and educational grants from several pharmaceutical companies, as did several other authors. The research was sponsored by the Association François Aupetit and the Société Nationale Française de Gastroentérologie.

Anesthesiologist involvement in screening colonoscopy increased the cost of the procedure by about $100, or nearly 20%, wrote Dr. Vijay S. Khiani and his colleagues in the January issue of Clinical Gastroenterology and Hepatology.

Moreover, the percentage of screening colonoscopies with anesthesiologist involvement more than doubled over the period from 2001 to 2006, representing "a significant change in practice," wrote the authors.

Dr. Khiani of Yale University in New Haven, Conn., and his colleagues used the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Medicare linked database, which provides a compilation of data from geographic areas that represent approximately 28% of the U.S. population.

Patients were included in the study if they underwent a screening colonoscopy between 2001 and 2006, were on Medicare for at least 3 years prior to the screening, and had not had a prior screening within 3 years (Clin. Gastroenterol. Hepatol. 2011 [doi:10.1016/j.cgh.2011.07.005]).

Screening colonoscopies, as opposed to diagnostic colonoscopies, were defined as those performed in an outpatient setting without use of ICD-9 codes for gastrointestinal tract symptoms, weight loss, iron deficiency anemia, alteration in bowel habits, or gastrointestinal bleeding reported at any physician visits within the previous 3 months.

During the study period, there were 16,268 screening colonoscopies. Slightly more than half of the patients were female and 40% were between 70 and 74 years of age. Most (90%) were white, and more than 75% of the procedures were performed by a gastroenterologist.

Overall, 17.2% of these colonoscopies had anesthesiologist involvement, wrote the authors, with increases in anesthesiologist use over time. In 2001, 11.0% of claims included an anesthesiologist, whereas in 2006, the proportion was 23.4%.

The authors also found that involvement of an anesthesiologist varied according to provider characteristics. For example, "surgeons had anesthesiologist involvement in 24.2% of screening colonoscopies, compared to 18.0% in gastroenterologists and 11.3% in primary care providers."

Looking at regional characteristics, "Anesthesiologist involvement by registry ranged from 1.6% in San Francisco to 57.8% in New Jersey," they wrote. Utah; Seattle, Wash.; and San Jose, Calif., Medicare claims markets also logged low anesthesiologist usage rates, while Detroit and Los Angeles registered some of the highest.

Finally, the authors looked at cost. The average price tag for procedures without anesthesiologist involvement was $575.20, they wrote, compared with $678.20 with an anesthesiologist.

Based on those figures, they then calculated the total cost to Medicare during the study period for all screening colonoscopies nationally, assuming no anesthesiologist involvement: The total was $668,382,400.

However, assuming the 17.2% average anesthesiologist usage rate seen in this study, the total national cost to Medicare jumped to $688,968,392 – more than a $20 million increase.

The authors highlighted a recent position statement by the American Society for Gastrointestinal Endoscopy stating that "the use of anesthesiologist-administered propofol for healthy individuals undergoing elective endoscopy is very costly without demonstrated improvement in patient safety or procedural outcome." Dr. Khiani and his colleagues also noted that endoscopist-directed administration of propofol has been shown to be safe.

"An investigation of the potential benefits, including polyp detection rate, and potential risks, including the complication rate, with and without anesthesiologist involvement may help to determine the most safe and cost-effective approach to screening colonoscopies," Dr. Khiani and his associates concluded.

The study was funded by the National Institutes of Health. The authors made no individual disclosures.

Anesthesiologist involvement in screening colonoscopy increased the cost of the procedure by about $100, or nearly 20%, wrote Dr. Vijay S. Khiani and his colleagues in the January issue of Clinical Gastroenterology and Hepatology.

Moreover, the percentage of screening colonoscopies with anesthesiologist involvement more than doubled over the period from 2001 to 2006, representing "a significant change in practice," wrote the authors.

Dr. Khiani of Yale University in New Haven, Conn., and his colleagues used the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Medicare linked database, which provides a compilation of data from geographic areas that represent approximately 28% of the U.S. population.

Patients were included in the study if they underwent a screening colonoscopy between 2001 and 2006, were on Medicare for at least 3 years prior to the screening, and had not had a prior screening within 3 years (Clin. Gastroenterol. Hepatol. 2011 [doi:10.1016/j.cgh.2011.07.005]).

Screening colonoscopies, as opposed to diagnostic colonoscopies, were defined as those performed in an outpatient setting without use of ICD-9 codes for gastrointestinal tract symptoms, weight loss, iron deficiency anemia, alteration in bowel habits, or gastrointestinal bleeding reported at any physician visits within the previous 3 months.

During the study period, there were 16,268 screening colonoscopies. Slightly more than half of the patients were female and 40% were between 70 and 74 years of age. Most (90%) were white, and more than 75% of the procedures were performed by a gastroenterologist.

Overall, 17.2% of these colonoscopies had anesthesiologist involvement, wrote the authors, with increases in anesthesiologist use over time. In 2001, 11.0% of claims included an anesthesiologist, whereas in 2006, the proportion was 23.4%.

The authors also found that involvement of an anesthesiologist varied according to provider characteristics. For example, "surgeons had anesthesiologist involvement in 24.2% of screening colonoscopies, compared to 18.0% in gastroenterologists and 11.3% in primary care providers."

Looking at regional characteristics, "Anesthesiologist involvement by registry ranged from 1.6% in San Francisco to 57.8% in New Jersey," they wrote. Utah; Seattle, Wash.; and San Jose, Calif., Medicare claims markets also logged low anesthesiologist usage rates, while Detroit and Los Angeles registered some of the highest.

Finally, the authors looked at cost. The average price tag for procedures without anesthesiologist involvement was $575.20, they wrote, compared with $678.20 with an anesthesiologist.

Based on those figures, they then calculated the total cost to Medicare during the study period for all screening colonoscopies nationally, assuming no anesthesiologist involvement: The total was $668,382,400.

However, assuming the 17.2% average anesthesiologist usage rate seen in this study, the total national cost to Medicare jumped to $688,968,392 – more than a $20 million increase.

The authors highlighted a recent position statement by the American Society for Gastrointestinal Endoscopy stating that "the use of anesthesiologist-administered propofol for healthy individuals undergoing elective endoscopy is very costly without demonstrated improvement in patient safety or procedural outcome." Dr. Khiani and his colleagues also noted that endoscopist-directed administration of propofol has been shown to be safe.

"An investigation of the potential benefits, including polyp detection rate, and potential risks, including the complication rate, with and without anesthesiologist involvement may help to determine the most safe and cost-effective approach to screening colonoscopies," Dr. Khiani and his associates concluded.

The study was funded by the National Institutes of Health. The authors made no individual disclosures.

Anesthesiologist involvement in screening colonoscopy increased the cost of the procedure by about $100, or nearly 20%, wrote Dr. Vijay S. Khiani and his colleagues in the January issue of Clinical Gastroenterology and Hepatology.

Moreover, the percentage of screening colonoscopies with anesthesiologist involvement more than doubled over the period from 2001 to 2006, representing "a significant change in practice," wrote the authors.

Dr. Khiani of Yale University in New Haven, Conn., and his colleagues used the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Medicare linked database, which provides a compilation of data from geographic areas that represent approximately 28% of the U.S. population.

Patients were included in the study if they underwent a screening colonoscopy between 2001 and 2006, were on Medicare for at least 3 years prior to the screening, and had not had a prior screening within 3 years (Clin. Gastroenterol. Hepatol. 2011 [doi:10.1016/j.cgh.2011.07.005]).

Screening colonoscopies, as opposed to diagnostic colonoscopies, were defined as those performed in an outpatient setting without use of ICD-9 codes for gastrointestinal tract symptoms, weight loss, iron deficiency anemia, alteration in bowel habits, or gastrointestinal bleeding reported at any physician visits within the previous 3 months.

During the study period, there were 16,268 screening colonoscopies. Slightly more than half of the patients were female and 40% were between 70 and 74 years of age. Most (90%) were white, and more than 75% of the procedures were performed by a gastroenterologist.

Overall, 17.2% of these colonoscopies had anesthesiologist involvement, wrote the authors, with increases in anesthesiologist use over time. In 2001, 11.0% of claims included an anesthesiologist, whereas in 2006, the proportion was 23.4%.

The authors also found that involvement of an anesthesiologist varied according to provider characteristics. For example, "surgeons had anesthesiologist involvement in 24.2% of screening colonoscopies, compared to 18.0% in gastroenterologists and 11.3% in primary care providers."

Looking at regional characteristics, "Anesthesiologist involvement by registry ranged from 1.6% in San Francisco to 57.8% in New Jersey," they wrote. Utah; Seattle, Wash.; and San Jose, Calif., Medicare claims markets also logged low anesthesiologist usage rates, while Detroit and Los Angeles registered some of the highest.

Finally, the authors looked at cost. The average price tag for procedures without anesthesiologist involvement was $575.20, they wrote, compared with $678.20 with an anesthesiologist.

Based on those figures, they then calculated the total cost to Medicare during the study period for all screening colonoscopies nationally, assuming no anesthesiologist involvement: The total was $668,382,400.

However, assuming the 17.2% average anesthesiologist usage rate seen in this study, the total national cost to Medicare jumped to $688,968,392 – more than a $20 million increase.

The authors highlighted a recent position statement by the American Society for Gastrointestinal Endoscopy stating that "the use of anesthesiologist-administered propofol for healthy individuals undergoing elective endoscopy is very costly without demonstrated improvement in patient safety or procedural outcome." Dr. Khiani and his colleagues also noted that endoscopist-directed administration of propofol has been shown to be safe.

"An investigation of the potential benefits, including polyp detection rate, and potential risks, including the complication rate, with and without anesthesiologist involvement may help to determine the most safe and cost-effective approach to screening colonoscopies," Dr. Khiani and his associates concluded.

The study was funded by the National Institutes of Health. The authors made no individual disclosures.

Magnifying narrow-band imaging, when used in addition to conventional white-light imaging, greatly improves accuracy, sensitivity, and specificity in the detection of gastric mucosal cancers, Dr. Yasumasa Ezoe and colleagues reported in the December issue of Gastroenterology.

"This has enormous significance in clinical practice, because the examination with high positive predictive value and high negative predictive value might enable the clinician to make appropriate judgments as to which lesion needs pathology to confirm the diagnosis," the authors wrote (Gastroenterology 2011 Dec. 1 [10.1053/j.gastro.2011.08.007]).

Indeed, when combined, the two imaging modalities "might be the best approach for making accurate diagnoses of small gastric cancers," offering a so-called "optic biopsy" for gastric mucosal cancers, the authors suggested.

Dr. Ezoe of Kyoto University and colleagues studied patients aged 20 years or older seen at multiple institutions in Japan who had either untreated gastric cancers or a history of gastric cancer. Patients with prior surgical stomach resection were excluded from the study, although prior minimally invasive procedures, such as endoscopic mucosal resection and endoscopic submucosal dissection, were allowed.

All 353 patients included in the study initially underwent conventional white-light imaging (C-WLI). When a newly detected, undiagnosed, small (10 mm or less), depressed gastric lesion was detected, patients were immediately randomized to undergo detailed examination of the lesion using either C-WLI (n = 176) or magnifying narrow-band imaging (M-NBI) in a 1:1 ratio.

All lesions initially evaluated with C-WLI were subsequently evaluated with M-NBI, to ascertain the predictive value of both modalities together.

In the case of multiple lesions, only the first lesion was included in the study. Small, depressed lesions with apparent erosion or ulceration were also not evaluated, "as it is difficult to visualize surface changes in these lesions," wrote the authors.

After all the target lesions were examined, at least one biopsy specimen was collected and the revised Vienna classification system was used to diagnose C4 (mucosal high-grade neoplasia) or C5 (submucosal invasion by neoplasia) specimens as cancerous.

Overall, 20 patients in each group had a newly diagnosed gastric cancer (13% for both groups).

According to the authors, when compared with biopsy results, the diagnostic accuracy of M-NBI was significantly greater than that of C-WLI (90.4% versus 64.8%, respectively; P less than .001). M-NBI also beat C-WLI on specificity (94.3% vs. 67.9%, respectively; P less than .001).

However, in terms of sensitivity, the two techniques were similar, with M-NBI at 60.0% and C-WLI at 40.0%, respectively (P = .34).

The authors then looked at M-NBI plus C-WLI, and found that the former "significantly enhanced the diagnostic performance of the latter," with accuracy increasing to 96.6% when both were used together, specificity increasing to 96.8%, and sensitivity to 95%, with P less than .001 for all values when compared with C-WLI alone.

Similarly, "C-WLI followed by M-NBI dramatically improved the positive predictive value from 13.8% to 79.2%" compared with C-WLI alone (P less than .001). The negative predictive value also increased, from 89.8% with C-WLI alone to 99.3% when both techniques were used together (P less than .001).

The authors conceded that their sample size was small, and that larger studies will be needed to confirm the diagnostic utility of each modality. Additionally, they did not compare these modalities to dye-based imaging methods.

However, they added, dyes "are only used in a few countries and institutes, and then, the standard worldwide endoscopic method to diagnose early gastric cancer is still C-WLI without any dye use," they added.

The authors disclosed no personal conflicts of interest. The study was sponsored by a grant from the Ministry of Health, Labor, and Welfare of Japan.

Magnifying narrow-band imaging, when used in addition to conventional white-light imaging, greatly improves accuracy, sensitivity, and specificity in the detection of gastric mucosal cancers, Dr. Yasumasa Ezoe and colleagues reported in the December issue of Gastroenterology.

"This has enormous significance in clinical practice, because the examination with high positive predictive value and high negative predictive value might enable the clinician to make appropriate judgments as to which lesion needs pathology to confirm the diagnosis," the authors wrote (Gastroenterology 2011 Dec. 1 [10.1053/j.gastro.2011.08.007]).

Indeed, when combined, the two imaging modalities "might be the best approach for making accurate diagnoses of small gastric cancers," offering a so-called "optic biopsy" for gastric mucosal cancers, the authors suggested.

Dr. Ezoe of Kyoto University and colleagues studied patients aged 20 years or older seen at multiple institutions in Japan who had either untreated gastric cancers or a history of gastric cancer. Patients with prior surgical stomach resection were excluded from the study, although prior minimally invasive procedures, such as endoscopic mucosal resection and endoscopic submucosal dissection, were allowed.

All 353 patients included in the study initially underwent conventional white-light imaging (C-WLI). When a newly detected, undiagnosed, small (10 mm or less), depressed gastric lesion was detected, patients were immediately randomized to undergo detailed examination of the lesion using either C-WLI (n = 176) or magnifying narrow-band imaging (M-NBI) in a 1:1 ratio.

All lesions initially evaluated with C-WLI were subsequently evaluated with M-NBI, to ascertain the predictive value of both modalities together.

In the case of multiple lesions, only the first lesion was included in the study. Small, depressed lesions with apparent erosion or ulceration were also not evaluated, "as it is difficult to visualize surface changes in these lesions," wrote the authors.

After all the target lesions were examined, at least one biopsy specimen was collected and the revised Vienna classification system was used to diagnose C4 (mucosal high-grade neoplasia) or C5 (submucosal invasion by neoplasia) specimens as cancerous.

Overall, 20 patients in each group had a newly diagnosed gastric cancer (13% for both groups).

According to the authors, when compared with biopsy results, the diagnostic accuracy of M-NBI was significantly greater than that of C-WLI (90.4% versus 64.8%, respectively; P less than .001). M-NBI also beat C-WLI on specificity (94.3% vs. 67.9%, respectively; P less than .001).

However, in terms of sensitivity, the two techniques were similar, with M-NBI at 60.0% and C-WLI at 40.0%, respectively (P = .34).

The authors then looked at M-NBI plus C-WLI, and found that the former "significantly enhanced the diagnostic performance of the latter," with accuracy increasing to 96.6% when both were used together, specificity increasing to 96.8%, and sensitivity to 95%, with P less than .001 for all values when compared with C-WLI alone.

Similarly, "C-WLI followed by M-NBI dramatically improved the positive predictive value from 13.8% to 79.2%" compared with C-WLI alone (P less than .001). The negative predictive value also increased, from 89.8% with C-WLI alone to 99.3% when both techniques were used together (P less than .001).

The authors conceded that their sample size was small, and that larger studies will be needed to confirm the diagnostic utility of each modality. Additionally, they did not compare these modalities to dye-based imaging methods.

However, they added, dyes "are only used in a few countries and institutes, and then, the standard worldwide endoscopic method to diagnose early gastric cancer is still C-WLI without any dye use," they added.

The authors disclosed no personal conflicts of interest. The study was sponsored by a grant from the Ministry of Health, Labor, and Welfare of Japan.

Magnifying narrow-band imaging, when used in addition to conventional white-light imaging, greatly improves accuracy, sensitivity, and specificity in the detection of gastric mucosal cancers, Dr. Yasumasa Ezoe and colleagues reported in the December issue of Gastroenterology.

"This has enormous significance in clinical practice, because the examination with high positive predictive value and high negative predictive value might enable the clinician to make appropriate judgments as to which lesion needs pathology to confirm the diagnosis," the authors wrote (Gastroenterology 2011 Dec. 1 [10.1053/j.gastro.2011.08.007]).

Indeed, when combined, the two imaging modalities "might be the best approach for making accurate diagnoses of small gastric cancers," offering a so-called "optic biopsy" for gastric mucosal cancers, the authors suggested.

Dr. Ezoe of Kyoto University and colleagues studied patients aged 20 years or older seen at multiple institutions in Japan who had either untreated gastric cancers or a history of gastric cancer. Patients with prior surgical stomach resection were excluded from the study, although prior minimally invasive procedures, such as endoscopic mucosal resection and endoscopic submucosal dissection, were allowed.

All 353 patients included in the study initially underwent conventional white-light imaging (C-WLI). When a newly detected, undiagnosed, small (10 mm or less), depressed gastric lesion was detected, patients were immediately randomized to undergo detailed examination of the lesion using either C-WLI (n = 176) or magnifying narrow-band imaging (M-NBI) in a 1:1 ratio.

All lesions initially evaluated with C-WLI were subsequently evaluated with M-NBI, to ascertain the predictive value of both modalities together.

In the case of multiple lesions, only the first lesion was included in the study. Small, depressed lesions with apparent erosion or ulceration were also not evaluated, "as it is difficult to visualize surface changes in these lesions," wrote the authors.

After all the target lesions were examined, at least one biopsy specimen was collected and the revised Vienna classification system was used to diagnose C4 (mucosal high-grade neoplasia) or C5 (submucosal invasion by neoplasia) specimens as cancerous.

Overall, 20 patients in each group had a newly diagnosed gastric cancer (13% for both groups).

According to the authors, when compared with biopsy results, the diagnostic accuracy of M-NBI was significantly greater than that of C-WLI (90.4% versus 64.8%, respectively; P less than .001). M-NBI also beat C-WLI on specificity (94.3% vs. 67.9%, respectively; P less than .001).

However, in terms of sensitivity, the two techniques were similar, with M-NBI at 60.0% and C-WLI at 40.0%, respectively (P = .34).

The authors then looked at M-NBI plus C-WLI, and found that the former "significantly enhanced the diagnostic performance of the latter," with accuracy increasing to 96.6% when both were used together, specificity increasing to 96.8%, and sensitivity to 95%, with P less than .001 for all values when compared with C-WLI alone.

Similarly, "C-WLI followed by M-NBI dramatically improved the positive predictive value from 13.8% to 79.2%" compared with C-WLI alone (P less than .001). The negative predictive value also increased, from 89.8% with C-WLI alone to 99.3% when both techniques were used together (P less than .001).

The authors conceded that their sample size was small, and that larger studies will be needed to confirm the diagnostic utility of each modality. Additionally, they did not compare these modalities to dye-based imaging methods.

However, they added, dyes "are only used in a few countries and institutes, and then, the standard worldwide endoscopic method to diagnose early gastric cancer is still C-WLI without any dye use," they added.

The authors disclosed no personal conflicts of interest. The study was sponsored by a grant from the Ministry of Health, Labor, and Welfare of Japan.