From the AGA Journals

Genetic factors accounted for about 40% of variability in the risk of colorectal cancer (CRC) in an analysis of monozygotic and same-sex dizygotic twins from the Nordic Twin Study of Cancer to reported in the August issue of Clinical Gastroenterology and Hepatology (2017 Jan. doi: 10.1016/j.cgh.2016.12.041).

Thus, CRC “has a substantial heritable component, and may be more heritable in women than men,” Rebecca E. Graff, ScD, of the Harvard T.H. Chan School of Public Health, Boston, and the University of California, San Francisco, and her colleagues wrote. “Siblings, and particularly monozygotic cotwins, of individuals with colon or rectal cancer should consider personalized screening,” they added.

©Christian Jasiuk/Thinkstock

Genetic factors accounted for about 40% of variability in the risk of colorectal cancer (CRC) in an analysis of monozygotic and same-sex dizygotic twins from the Nordic Twin Study of Cancer to reported in the August issue of Clinical Gastroenterology and Hepatology (2017 Jan. doi: 10.1016/j.cgh.2016.12.041).

Thus, CRC “has a substantial heritable component, and may be more heritable in women than men,” Rebecca E. Graff, ScD, of the Harvard T.H. Chan School of Public Health, Boston, and the University of California, San Francisco, and her colleagues wrote. “Siblings, and particularly monozygotic cotwins, of individuals with colon or rectal cancer should consider personalized screening,” they added.

©Christian Jasiuk/Thinkstock

Genetic factors accounted for about 40% of variability in the risk of colorectal cancer (CRC) in an analysis of monozygotic and same-sex dizygotic twins from the Nordic Twin Study of Cancer to reported in the August issue of Clinical Gastroenterology and Hepatology (2017 Jan. doi: 10.1016/j.cgh.2016.12.041).

Thus, CRC “has a substantial heritable component, and may be more heritable in women than men,” Rebecca E. Graff, ScD, of the Harvard T.H. Chan School of Public Health, Boston, and the University of California, San Francisco, and her colleagues wrote. “Siblings, and particularly monozygotic cotwins, of individuals with colon or rectal cancer should consider personalized screening,” they added.

©Christian Jasiuk/Thinkstock

Endoscopists who took about a minute longer during screening esophagogastroduodenoscopy (EGD) detected significantly more upper gastrointestinal neoplasms than their quicker colleagues, in a retrospective study reported in the August issue of Gastroenterology (doi: 10.1053/j.gastro.2017.05.009).

Detection rates were 0.28% and 0.20%, respectively (P = .005), and this difference remained statistically significant after the investigators controlled for numerous factors that also can affect the chances of detecting gastric neoplasms during upper endoscopy, reported Jae Myung Park, MD, and his colleagues at Seoul (Korea) St. Mary’s Hospital.

Gastric cancer is the second leading cause of cancer mortality worldwide, they noted. Although EGD has been practiced globally for decades, there is no consensus on which performance metrics optimize diagnostic yield. Both Korea and Japan have adopted screening EGD to help diagnose gastric cancer, but interval cancers and false-positive results remain concerns, and the field lacks rigorous analyses comparing EGD time with gastric cancer detection rates. Therefore, the researchers studied 111,962 consecutive patients who underwent EGD at one hospital in Seoul from 2009 through 2015. Fourteen board-certified endoscopists performed these procedures at a single endoscopy unit.A total of 262 patients (0.23%) were diagnosed with gastric neoplasia or dysplasia, duodenal neoplasia, or esophageal carcinoma. This finding closely resembled a prior report from Korea, the investigators noted. Detection rates among individual endoscopists ranged from 0.14% to 0.32%, and longer EGD time was associated with a higher detection rate with an R value of 0.54 (P = .046). During the first year of the study, EGDs without biopsies averaged 2 minutes, 53 seconds. Based on this finding, the researchers set a cutoff time of 3 minutes and classified eight endoscopists as fast (mean EGD duration, 2 minutes and 38 seconds; standard deviation, 21 seconds) and six endoscopists as slow (mean duration, 3 minutes and 25 seconds; SD, 19 seconds). Slower endoscopists were significantly more likely to detect gastric adenomas or carcinomas, even after the investigators controlled for the biopsy rates and experience level of these endoscopists and patients’ age, sex, smoking status, alcohol use, and family history of cancer (odds ratio, 1.52; 95% confidence interval, 1.17-1.97; P = .0018).

Older age, male sex, and smoking also were significant correlates of cancer detection in the multivariable model. Biopsy rates among endoscopists ranged from 7% to 28%, and taking a biopsy was an even stronger predictor of detecting an upper GI neoplasm than was EGD duration, with an R value of 0.76 (P = .002). Although this study was observational and retrospective and lacked data on prior EGD examinations, surveillance intervals, and rates of false-negative results, it “supports the hypothesis that examination duration affects the diagnostic accuracy of EGD,” Dr. Park and his coinvestigators reported. “Prolonging the examination time will allow more careful examination by the endoscopist, which will enable the detection of more subtle lesions. Based on our data, we believe that these indicators can improve the quality of EGD.”

Funders included the Ministry of Education, Science, and Technology; the Ministry of Science, ICT, and Future Planning; and the Ministry of Health & Welfare, Republic of Korea. The investigators reported having no conflicts of interest.

Endoscopists who took about a minute longer during screening esophagogastroduodenoscopy (EGD) detected significantly more upper gastrointestinal neoplasms than their quicker colleagues, in a retrospective study reported in the August issue of Gastroenterology (doi: 10.1053/j.gastro.2017.05.009).

Detection rates were 0.28% and 0.20%, respectively (P = .005), and this difference remained statistically significant after the investigators controlled for numerous factors that also can affect the chances of detecting gastric neoplasms during upper endoscopy, reported Jae Myung Park, MD, and his colleagues at Seoul (Korea) St. Mary’s Hospital.

Gastric cancer is the second leading cause of cancer mortality worldwide, they noted. Although EGD has been practiced globally for decades, there is no consensus on which performance metrics optimize diagnostic yield. Both Korea and Japan have adopted screening EGD to help diagnose gastric cancer, but interval cancers and false-positive results remain concerns, and the field lacks rigorous analyses comparing EGD time with gastric cancer detection rates. Therefore, the researchers studied 111,962 consecutive patients who underwent EGD at one hospital in Seoul from 2009 through 2015. Fourteen board-certified endoscopists performed these procedures at a single endoscopy unit.A total of 262 patients (0.23%) were diagnosed with gastric neoplasia or dysplasia, duodenal neoplasia, or esophageal carcinoma. This finding closely resembled a prior report from Korea, the investigators noted. Detection rates among individual endoscopists ranged from 0.14% to 0.32%, and longer EGD time was associated with a higher detection rate with an R value of 0.54 (P = .046). During the first year of the study, EGDs without biopsies averaged 2 minutes, 53 seconds. Based on this finding, the researchers set a cutoff time of 3 minutes and classified eight endoscopists as fast (mean EGD duration, 2 minutes and 38 seconds; standard deviation, 21 seconds) and six endoscopists as slow (mean duration, 3 minutes and 25 seconds; SD, 19 seconds). Slower endoscopists were significantly more likely to detect gastric adenomas or carcinomas, even after the investigators controlled for the biopsy rates and experience level of these endoscopists and patients’ age, sex, smoking status, alcohol use, and family history of cancer (odds ratio, 1.52; 95% confidence interval, 1.17-1.97; P = .0018).

Older age, male sex, and smoking also were significant correlates of cancer detection in the multivariable model. Biopsy rates among endoscopists ranged from 7% to 28%, and taking a biopsy was an even stronger predictor of detecting an upper GI neoplasm than was EGD duration, with an R value of 0.76 (P = .002). Although this study was observational and retrospective and lacked data on prior EGD examinations, surveillance intervals, and rates of false-negative results, it “supports the hypothesis that examination duration affects the diagnostic accuracy of EGD,” Dr. Park and his coinvestigators reported. “Prolonging the examination time will allow more careful examination by the endoscopist, which will enable the detection of more subtle lesions. Based on our data, we believe that these indicators can improve the quality of EGD.”

Funders included the Ministry of Education, Science, and Technology; the Ministry of Science, ICT, and Future Planning; and the Ministry of Health & Welfare, Republic of Korea. The investigators reported having no conflicts of interest.

Endoscopists who took about a minute longer during screening esophagogastroduodenoscopy (EGD) detected significantly more upper gastrointestinal neoplasms than their quicker colleagues, in a retrospective study reported in the August issue of Gastroenterology (doi: 10.1053/j.gastro.2017.05.009).

Detection rates were 0.28% and 0.20%, respectively (P = .005), and this difference remained statistically significant after the investigators controlled for numerous factors that also can affect the chances of detecting gastric neoplasms during upper endoscopy, reported Jae Myung Park, MD, and his colleagues at Seoul (Korea) St. Mary’s Hospital.

Gastric cancer is the second leading cause of cancer mortality worldwide, they noted. Although EGD has been practiced globally for decades, there is no consensus on which performance metrics optimize diagnostic yield. Both Korea and Japan have adopted screening EGD to help diagnose gastric cancer, but interval cancers and false-positive results remain concerns, and the field lacks rigorous analyses comparing EGD time with gastric cancer detection rates. Therefore, the researchers studied 111,962 consecutive patients who underwent EGD at one hospital in Seoul from 2009 through 2015. Fourteen board-certified endoscopists performed these procedures at a single endoscopy unit.A total of 262 patients (0.23%) were diagnosed with gastric neoplasia or dysplasia, duodenal neoplasia, or esophageal carcinoma. This finding closely resembled a prior report from Korea, the investigators noted. Detection rates among individual endoscopists ranged from 0.14% to 0.32%, and longer EGD time was associated with a higher detection rate with an R value of 0.54 (P = .046). During the first year of the study, EGDs without biopsies averaged 2 minutes, 53 seconds. Based on this finding, the researchers set a cutoff time of 3 minutes and classified eight endoscopists as fast (mean EGD duration, 2 minutes and 38 seconds; standard deviation, 21 seconds) and six endoscopists as slow (mean duration, 3 minutes and 25 seconds; SD, 19 seconds). Slower endoscopists were significantly more likely to detect gastric adenomas or carcinomas, even after the investigators controlled for the biopsy rates and experience level of these endoscopists and patients’ age, sex, smoking status, alcohol use, and family history of cancer (odds ratio, 1.52; 95% confidence interval, 1.17-1.97; P = .0018).

Older age, male sex, and smoking also were significant correlates of cancer detection in the multivariable model. Biopsy rates among endoscopists ranged from 7% to 28%, and taking a biopsy was an even stronger predictor of detecting an upper GI neoplasm than was EGD duration, with an R value of 0.76 (P = .002). Although this study was observational and retrospective and lacked data on prior EGD examinations, surveillance intervals, and rates of false-negative results, it “supports the hypothesis that examination duration affects the diagnostic accuracy of EGD,” Dr. Park and his coinvestigators reported. “Prolonging the examination time will allow more careful examination by the endoscopist, which will enable the detection of more subtle lesions. Based on our data, we believe that these indicators can improve the quality of EGD.”

Funders included the Ministry of Education, Science, and Technology; the Ministry of Science, ICT, and Future Planning; and the Ministry of Health & Welfare, Republic of Korea. The investigators reported having no conflicts of interest.

Obeticholic acid failed to prevent the development of short-bowel syndrome–associated liver disease in a preliminary study using piglet models. The findings were published in the July issue of Cellular and Molecular Gastroenterology and Hepatology (doi: 10.1016/j.jcmgh.2017.02.008).

Current treatment options for short-bowel syndrome-associated liver disease are limited, wrote Prue M. Pereira-Fantini, PhD, of Murdoch Childrens Research Institute, Victoria, Australia, and colleagues. However, the farnesoid X receptor, which regulates genes involved in bile acid synthesis, absorption, and transport in the intestine and liver, has shown promise as a pharmaceutical target.

“Recently, we described SBS-ALD-associated alterations in bile acid composition associated with disrupted farnesoid X receptor (FXR) signaling mechanisms,” the researchers said. Obeticholic acid (OCA) has been shown to prevent liver disease in mouse models and human disease, and the researchers explored whether it would be effective in the context of short-bowel syndrome associated liver disease (SBS-ALD).

The researchers randomized piglets into four groups to receive small-bowel resection or sham surgery, and either a daily dose of 2.4 mg/kg per day of OCA or no treatment. The pigs were euthanized 2 weeks after their surgeries, and the researchers collected portal plasma samples, bile samples, and liver samples.

OCA treatment in piglets in the SBS surgery group was associated with decreased stool fat that suggested improved fat absorption, but impacted liver morphology, the researchers noted. “Untreated, sham-operated piglets showed normal liver histology when compared with SBS piglets who showed decreased hepatic lobule area and small clusters of inflammatory cells together with mild-to-moderate vesicular zone 2 lipidosis,” they wrote.

Overall, OCA treatment prevented the depletion of taurine; taurine concentration was approximately 8 ng/mL for piglets with SBS treated with OCA compared with 8 ng/mL in the sham group, 9 ng/mL in the sham plus OCA group, and 3 ng/mL in the SBS-only group. However, bile acid dysmetabolism occurred as shown by HDCA levels, which increased with OCA treatment compared to sham controls but were significantly reduced in SBS piglets treated with OCA vs. untreated SBS piglets.

In addition, the researchers found that small-bowel resection did not impact gene expression levels of FXR targets in the intestine or liver. However, “intestinal FXR gene expression was 11-fold higher in untreated SBS piglets when compared with untreated sham piglets,” they wrote. OCA treatment had no significant impact on FXR gene expression in the OCA-treated group vs. the untreated group and in the OCA-treated SBS group.

Although the findings were limited by use of an animal model, the results suggest that OCA treatment may have clinical benefits for SBS patients by reducing fat malabsorption, which remains a challenge, the researchers wrote. However, OCA “did not prevent the development of SBS-ALD, thereby limiting the potential therapeutic benefit in patients with SBS,” they concluded.

The researchers had no financial conflicts to disclose. The study was supported in part by the National Health and Medical Research Council of Australia and by a research grant from the Science Foundation Ireland.

Obeticholic acid failed to prevent the development of short-bowel syndrome–associated liver disease in a preliminary study using piglet models. The findings were published in the July issue of Cellular and Molecular Gastroenterology and Hepatology (doi: 10.1016/j.jcmgh.2017.02.008).

Current treatment options for short-bowel syndrome-associated liver disease are limited, wrote Prue M. Pereira-Fantini, PhD, of Murdoch Childrens Research Institute, Victoria, Australia, and colleagues. However, the farnesoid X receptor, which regulates genes involved in bile acid synthesis, absorption, and transport in the intestine and liver, has shown promise as a pharmaceutical target.

“Recently, we described SBS-ALD-associated alterations in bile acid composition associated with disrupted farnesoid X receptor (FXR) signaling mechanisms,” the researchers said. Obeticholic acid (OCA) has been shown to prevent liver disease in mouse models and human disease, and the researchers explored whether it would be effective in the context of short-bowel syndrome associated liver disease (SBS-ALD).

The researchers randomized piglets into four groups to receive small-bowel resection or sham surgery, and either a daily dose of 2.4 mg/kg per day of OCA or no treatment. The pigs were euthanized 2 weeks after their surgeries, and the researchers collected portal plasma samples, bile samples, and liver samples.

OCA treatment in piglets in the SBS surgery group was associated with decreased stool fat that suggested improved fat absorption, but impacted liver morphology, the researchers noted. “Untreated, sham-operated piglets showed normal liver histology when compared with SBS piglets who showed decreased hepatic lobule area and small clusters of inflammatory cells together with mild-to-moderate vesicular zone 2 lipidosis,” they wrote.

Overall, OCA treatment prevented the depletion of taurine; taurine concentration was approximately 8 ng/mL for piglets with SBS treated with OCA compared with 8 ng/mL in the sham group, 9 ng/mL in the sham plus OCA group, and 3 ng/mL in the SBS-only group. However, bile acid dysmetabolism occurred as shown by HDCA levels, which increased with OCA treatment compared to sham controls but were significantly reduced in SBS piglets treated with OCA vs. untreated SBS piglets.

In addition, the researchers found that small-bowel resection did not impact gene expression levels of FXR targets in the intestine or liver. However, “intestinal FXR gene expression was 11-fold higher in untreated SBS piglets when compared with untreated sham piglets,” they wrote. OCA treatment had no significant impact on FXR gene expression in the OCA-treated group vs. the untreated group and in the OCA-treated SBS group.

Although the findings were limited by use of an animal model, the results suggest that OCA treatment may have clinical benefits for SBS patients by reducing fat malabsorption, which remains a challenge, the researchers wrote. However, OCA “did not prevent the development of SBS-ALD, thereby limiting the potential therapeutic benefit in patients with SBS,” they concluded.

The researchers had no financial conflicts to disclose. The study was supported in part by the National Health and Medical Research Council of Australia and by a research grant from the Science Foundation Ireland.

Obeticholic acid failed to prevent the development of short-bowel syndrome–associated liver disease in a preliminary study using piglet models. The findings were published in the July issue of Cellular and Molecular Gastroenterology and Hepatology (doi: 10.1016/j.jcmgh.2017.02.008).

Current treatment options for short-bowel syndrome-associated liver disease are limited, wrote Prue M. Pereira-Fantini, PhD, of Murdoch Childrens Research Institute, Victoria, Australia, and colleagues. However, the farnesoid X receptor, which regulates genes involved in bile acid synthesis, absorption, and transport in the intestine and liver, has shown promise as a pharmaceutical target.

“Recently, we described SBS-ALD-associated alterations in bile acid composition associated with disrupted farnesoid X receptor (FXR) signaling mechanisms,” the researchers said. Obeticholic acid (OCA) has been shown to prevent liver disease in mouse models and human disease, and the researchers explored whether it would be effective in the context of short-bowel syndrome associated liver disease (SBS-ALD).

The researchers randomized piglets into four groups to receive small-bowel resection or sham surgery, and either a daily dose of 2.4 mg/kg per day of OCA or no treatment. The pigs were euthanized 2 weeks after their surgeries, and the researchers collected portal plasma samples, bile samples, and liver samples.

OCA treatment in piglets in the SBS surgery group was associated with decreased stool fat that suggested improved fat absorption, but impacted liver morphology, the researchers noted. “Untreated, sham-operated piglets showed normal liver histology when compared with SBS piglets who showed decreased hepatic lobule area and small clusters of inflammatory cells together with mild-to-moderate vesicular zone 2 lipidosis,” they wrote.

Overall, OCA treatment prevented the depletion of taurine; taurine concentration was approximately 8 ng/mL for piglets with SBS treated with OCA compared with 8 ng/mL in the sham group, 9 ng/mL in the sham plus OCA group, and 3 ng/mL in the SBS-only group. However, bile acid dysmetabolism occurred as shown by HDCA levels, which increased with OCA treatment compared to sham controls but were significantly reduced in SBS piglets treated with OCA vs. untreated SBS piglets.

In addition, the researchers found that small-bowel resection did not impact gene expression levels of FXR targets in the intestine or liver. However, “intestinal FXR gene expression was 11-fold higher in untreated SBS piglets when compared with untreated sham piglets,” they wrote. OCA treatment had no significant impact on FXR gene expression in the OCA-treated group vs. the untreated group and in the OCA-treated SBS group.

Although the findings were limited by use of an animal model, the results suggest that OCA treatment may have clinical benefits for SBS patients by reducing fat malabsorption, which remains a challenge, the researchers wrote. However, OCA “did not prevent the development of SBS-ALD, thereby limiting the potential therapeutic benefit in patients with SBS,” they concluded.

The researchers had no financial conflicts to disclose. The study was supported in part by the National Health and Medical Research Council of Australia and by a research grant from the Science Foundation Ireland.

Seven weeks of treatment with delta-9-atetrahydrocannabinol (THC) did not improve chronic abdominal pain in a placebo-controlled trial of 65 adults.

Treatment “was safe and well tolerated,” but did not significantly reduce pain scores or secondary efficacy outcomes, Marjan de Vries, MSc, and her associates wrote in the July issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.09.147). Studies have not clearly shown that THC improves central pain sensitization, a key mechanism in chronic abdominal pain, they noted. Future studies of THC and central sensitization include quantitative sensory testing or electroencephalography, they added.

Source: American Gastroenterological Association

Treatment-refractory chronic abdominal pain is common after abdominal surgery or in chronic pancreatitis, wrote Ms. de Vries of Radboud University Medical Center, Nijmegen, the Netherlands. Affected patients tend to develop central sensitization, or hyper-responsive nociceptive central nervous system pathways. When this happens, pain no longer couples reliably with peripheral stimuli, and therapy targeting central nociceptive pathways is indicated. The main psychoactive compound of Cannabis sativa is THC, which interacts with CB1 receptors in the central nervous system, including in areas of the brain that help regulate emotions, such as the amygdala. Emotion-processing circuits are often overactive in chronic pain, and disrupting them might help modify pain perception, the investigators hypothesized. Therefore, they randomly assigned 65 adults with at least 3 months of abdominal pain related to chronic pancreatitis or abdominal surgery to receive oral placebo or THC tablets three times daily for 50-52 days. The 31 patients in the THC group received step-up dosing (3 mg per dose for 5 days, followed by 5 mg per dose for 5 days) followed by stable dosing at 8 mg. Both groups continued other prescribed analgesics as usual, including oxycontin, fentanyl, morphine, codeine, tramadol, paracetamol, anti-epileptics, and nonsteroidal anti-inflammatories. All but two study participants were white, 25 were male, and 24 were female.

At baseline, all patients reported pain of at least 3 on an 11-point visual analogue scale (VAS). By days 50-52, average VAS scores decreased by 1.6 points (40%) in the THC group and by 1.9 points (37%) in the placebo group (P = .9). Although a strong placebo effect is common in studies of visceral pain, that did not prevent pregabalin from significantly outperforming placebo in another similarly designed randomized clinical trial of patients from this study group with chronic pancreatitis, the investigators noted.

The THC and placebo groups also resembled each other on various secondary outcome measures, including patient global impression of change, pain catastrophizing, pain-related anxiety, measures of depression and generalized anxiety, and subjective impressions of alertness, mood, feeling “high,” drowsiness, and difficulties in controlling thoughts. The only exception was that the THC group showed a trend toward improvement on the Short Form 36, compared with the placebo group (P = .051).

Pharmacokinetic analysis showed good oral absorption of THC. Dizziness, somnolence, and headache were common in both groups, but were more frequent with THC than placebo, as was nausea, dry mouth, and visual impairment. There were no serious treatment-related adverse events, although seven patients stopped THC because they could not tolerate the maximum dose.

Some evidence suggests that the shift from acute to chronic pain entails a transition from nociceptive to cognitive, affective, and autonomic sensitization, the researchers noted. “Therefore, an agent targeting particular brain areas related to the cognitive emotional feature of chronic pain, such as THC, might be efficacious in our chronic pain population, but might be better measured by using affective outcomes of pain,” they concluded.

The trial was supported by a grant from the European Union, the European Fund for Regional Development, and the Province of Gelderland. The THC was provided by Echo Pharmaceuticals, Nijmegen, the Netherlands. The investigators reported having no conflicts of interest.

Seven weeks of treatment with delta-9-atetrahydrocannabinol (THC) did not improve chronic abdominal pain in a placebo-controlled trial of 65 adults.

Treatment “was safe and well tolerated,” but did not significantly reduce pain scores or secondary efficacy outcomes, Marjan de Vries, MSc, and her associates wrote in the July issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.09.147). Studies have not clearly shown that THC improves central pain sensitization, a key mechanism in chronic abdominal pain, they noted. Future studies of THC and central sensitization include quantitative sensory testing or electroencephalography, they added.

Source: American Gastroenterological Association

Treatment-refractory chronic abdominal pain is common after abdominal surgery or in chronic pancreatitis, wrote Ms. de Vries of Radboud University Medical Center, Nijmegen, the Netherlands. Affected patients tend to develop central sensitization, or hyper-responsive nociceptive central nervous system pathways. When this happens, pain no longer couples reliably with peripheral stimuli, and therapy targeting central nociceptive pathways is indicated. The main psychoactive compound of Cannabis sativa is THC, which interacts with CB1 receptors in the central nervous system, including in areas of the brain that help regulate emotions, such as the amygdala. Emotion-processing circuits are often overactive in chronic pain, and disrupting them might help modify pain perception, the investigators hypothesized. Therefore, they randomly assigned 65 adults with at least 3 months of abdominal pain related to chronic pancreatitis or abdominal surgery to receive oral placebo or THC tablets three times daily for 50-52 days. The 31 patients in the THC group received step-up dosing (3 mg per dose for 5 days, followed by 5 mg per dose for 5 days) followed by stable dosing at 8 mg. Both groups continued other prescribed analgesics as usual, including oxycontin, fentanyl, morphine, codeine, tramadol, paracetamol, anti-epileptics, and nonsteroidal anti-inflammatories. All but two study participants were white, 25 were male, and 24 were female.

At baseline, all patients reported pain of at least 3 on an 11-point visual analogue scale (VAS). By days 50-52, average VAS scores decreased by 1.6 points (40%) in the THC group and by 1.9 points (37%) in the placebo group (P = .9). Although a strong placebo effect is common in studies of visceral pain, that did not prevent pregabalin from significantly outperforming placebo in another similarly designed randomized clinical trial of patients from this study group with chronic pancreatitis, the investigators noted.

The THC and placebo groups also resembled each other on various secondary outcome measures, including patient global impression of change, pain catastrophizing, pain-related anxiety, measures of depression and generalized anxiety, and subjective impressions of alertness, mood, feeling “high,” drowsiness, and difficulties in controlling thoughts. The only exception was that the THC group showed a trend toward improvement on the Short Form 36, compared with the placebo group (P = .051).

Pharmacokinetic analysis showed good oral absorption of THC. Dizziness, somnolence, and headache were common in both groups, but were more frequent with THC than placebo, as was nausea, dry mouth, and visual impairment. There were no serious treatment-related adverse events, although seven patients stopped THC because they could not tolerate the maximum dose.

Some evidence suggests that the shift from acute to chronic pain entails a transition from nociceptive to cognitive, affective, and autonomic sensitization, the researchers noted. “Therefore, an agent targeting particular brain areas related to the cognitive emotional feature of chronic pain, such as THC, might be efficacious in our chronic pain population, but might be better measured by using affective outcomes of pain,” they concluded.

The trial was supported by a grant from the European Union, the European Fund for Regional Development, and the Province of Gelderland. The THC was provided by Echo Pharmaceuticals, Nijmegen, the Netherlands. The investigators reported having no conflicts of interest.

Seven weeks of treatment with delta-9-atetrahydrocannabinol (THC) did not improve chronic abdominal pain in a placebo-controlled trial of 65 adults.

Treatment “was safe and well tolerated,” but did not significantly reduce pain scores or secondary efficacy outcomes, Marjan de Vries, MSc, and her associates wrote in the July issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.09.147). Studies have not clearly shown that THC improves central pain sensitization, a key mechanism in chronic abdominal pain, they noted. Future studies of THC and central sensitization include quantitative sensory testing or electroencephalography, they added.

Source: American Gastroenterological Association

Treatment-refractory chronic abdominal pain is common after abdominal surgery or in chronic pancreatitis, wrote Ms. de Vries of Radboud University Medical Center, Nijmegen, the Netherlands. Affected patients tend to develop central sensitization, or hyper-responsive nociceptive central nervous system pathways. When this happens, pain no longer couples reliably with peripheral stimuli, and therapy targeting central nociceptive pathways is indicated. The main psychoactive compound of Cannabis sativa is THC, which interacts with CB1 receptors in the central nervous system, including in areas of the brain that help regulate emotions, such as the amygdala. Emotion-processing circuits are often overactive in chronic pain, and disrupting them might help modify pain perception, the investigators hypothesized. Therefore, they randomly assigned 65 adults with at least 3 months of abdominal pain related to chronic pancreatitis or abdominal surgery to receive oral placebo or THC tablets three times daily for 50-52 days. The 31 patients in the THC group received step-up dosing (3 mg per dose for 5 days, followed by 5 mg per dose for 5 days) followed by stable dosing at 8 mg. Both groups continued other prescribed analgesics as usual, including oxycontin, fentanyl, morphine, codeine, tramadol, paracetamol, anti-epileptics, and nonsteroidal anti-inflammatories. All but two study participants were white, 25 were male, and 24 were female.

At baseline, all patients reported pain of at least 3 on an 11-point visual analogue scale (VAS). By days 50-52, average VAS scores decreased by 1.6 points (40%) in the THC group and by 1.9 points (37%) in the placebo group (P = .9). Although a strong placebo effect is common in studies of visceral pain, that did not prevent pregabalin from significantly outperforming placebo in another similarly designed randomized clinical trial of patients from this study group with chronic pancreatitis, the investigators noted.

The THC and placebo groups also resembled each other on various secondary outcome measures, including patient global impression of change, pain catastrophizing, pain-related anxiety, measures of depression and generalized anxiety, and subjective impressions of alertness, mood, feeling “high,” drowsiness, and difficulties in controlling thoughts. The only exception was that the THC group showed a trend toward improvement on the Short Form 36, compared with the placebo group (P = .051).

Pharmacokinetic analysis showed good oral absorption of THC. Dizziness, somnolence, and headache were common in both groups, but were more frequent with THC than placebo, as was nausea, dry mouth, and visual impairment. There were no serious treatment-related adverse events, although seven patients stopped THC because they could not tolerate the maximum dose.

Some evidence suggests that the shift from acute to chronic pain entails a transition from nociceptive to cognitive, affective, and autonomic sensitization, the researchers noted. “Therefore, an agent targeting particular brain areas related to the cognitive emotional feature of chronic pain, such as THC, might be efficacious in our chronic pain population, but might be better measured by using affective outcomes of pain,” they concluded.

The trial was supported by a grant from the European Union, the European Fund for Regional Development, and the Province of Gelderland. The THC was provided by Echo Pharmaceuticals, Nijmegen, the Netherlands. The investigators reported having no conflicts of interest.

Patients with more than 10 colonic polyps, of which at least half were serrated, and their first-degree relatives had a risk of colorectal cancer similar to that of patients who met formal diagnostic criteria for serrated polyposis syndrome (SPS), according to a retrospective multicenter study published in the July issue of Gastroenterology (doi: 10.1053/j.gastro.2017.04.003).

Such patients “should be treated with the same follow-up procedures as those proposed for patients with SPS, and possibly the definition of SPS should be broadened to include this phenotype,” wrote Cecilia M. Egoavil, MD, Miriam Juárez, and their associates.

SPS increases the risk of colorectal cancer (CRC) and is considered a heritable disease, which mandates “strict surveillance” of first-degree relatives, the researchers noted. The World Health Organization defines SPS as having at least five histologically diagnosed serrated lesions proximal to the sigmoid colon, of which two are at least 10 mm in diameter, or serrated polyps proximal to the sigmoid colon and a first-degree relative with SPS, or more than 20 serrated polyps throughout the colon. This “arbitrary” definition is “somewhat restrictive, and possibly leads to underdiagnosis of this disease,” the researchers wrote. Patients with multiple serrated polyps who do not meet WHO SPS criteria might have a “phenotypically attenuated form of serrated polyposis.”

For the study, the researchers compared 53 patients meeting WHO SPS criteria with 145 patients who did not meet these criteria but had more than 10 polyps throughout the colon, of which at least 50% were serrated. For both groups, number of polyps was obtained by adding polyp counts from subsequent colonoscopies. The data source was EPIPOLIP, a multicenter study of patients recruited from 24 hospitals in Spain in 2008 and 2009. At baseline, all patients had more than 10 adenomatous or serrated colonic polyps but did not have familial adenomatous polyposis, Lynch syndrome, hamartomatous polyposis, inflammatory bowel disease, or only hyperplastic rectosigmoid polyps.

The prevalence of CRC was statistically similar between groups (P = .4). There were 12 (22.6%) cases among SPS patients (mean age at diagnosis, 50 years), and 41 (28.3%) cases (mean age, 59 years) among patients with multiple serrated polyps who did not meet SPS criteria. During a mean follow-up of 4.2 years, one (1.9%) SPS patient developed incident CRC, as did four (2.8%) patients with multiple serrated polyps without SPS. Thus, standardized incidence ratios were 0.51 (95% confidence interval, 0.01-2.82) and 0.74 (95% CI, 0.20-1.90), respectively (P = .7). Standardized incidence ratios for CRC also did not significantly differ between first-degree relatives of patients with SPS (3.28, 95% CI, 2.16-4.77) and those with multiple serrated polyps (2.79, 95% CI, 2.10-3.63; P = .5).

A Kaplan-Meier analysis confirmed that there were no differences in the incidence of CRC between groups during follow-up. The findings “confirm that a special surveillance strategy is needed for patients with multiple serrated polyps and their relatives, probably similar to the strategy currently recommended for SPS patients,” the researchers concluded. They arbitrarily defined the group with multiple serrated polyps, so they were not able to link CRC to a cutoff number or percentage of serrated polyps, they noted.

Funders included Instituto de Salud Carlos III, Fundación de Investigación Biomédica de la Comunidad Valenciana-Instituto de Investigación Sanitaria y Biomédica de Alicante, Asociación Española Contra el Cáncer, and Conselleria d’Educació de la Generalitat Valenciana. The investigators had no conflicts of interest.

Patients with more than 10 colonic polyps, of which at least half were serrated, and their first-degree relatives had a risk of colorectal cancer similar to that of patients who met formal diagnostic criteria for serrated polyposis syndrome (SPS), according to a retrospective multicenter study published in the July issue of Gastroenterology (doi: 10.1053/j.gastro.2017.04.003).

Such patients “should be treated with the same follow-up procedures as those proposed for patients with SPS, and possibly the definition of SPS should be broadened to include this phenotype,” wrote Cecilia M. Egoavil, MD, Miriam Juárez, and their associates.

SPS increases the risk of colorectal cancer (CRC) and is considered a heritable disease, which mandates “strict surveillance” of first-degree relatives, the researchers noted. The World Health Organization defines SPS as having at least five histologically diagnosed serrated lesions proximal to the sigmoid colon, of which two are at least 10 mm in diameter, or serrated polyps proximal to the sigmoid colon and a first-degree relative with SPS, or more than 20 serrated polyps throughout the colon. This “arbitrary” definition is “somewhat restrictive, and possibly leads to underdiagnosis of this disease,” the researchers wrote. Patients with multiple serrated polyps who do not meet WHO SPS criteria might have a “phenotypically attenuated form of serrated polyposis.”

For the study, the researchers compared 53 patients meeting WHO SPS criteria with 145 patients who did not meet these criteria but had more than 10 polyps throughout the colon, of which at least 50% were serrated. For both groups, number of polyps was obtained by adding polyp counts from subsequent colonoscopies. The data source was EPIPOLIP, a multicenter study of patients recruited from 24 hospitals in Spain in 2008 and 2009. At baseline, all patients had more than 10 adenomatous or serrated colonic polyps but did not have familial adenomatous polyposis, Lynch syndrome, hamartomatous polyposis, inflammatory bowel disease, or only hyperplastic rectosigmoid polyps.

The prevalence of CRC was statistically similar between groups (P = .4). There were 12 (22.6%) cases among SPS patients (mean age at diagnosis, 50 years), and 41 (28.3%) cases (mean age, 59 years) among patients with multiple serrated polyps who did not meet SPS criteria. During a mean follow-up of 4.2 years, one (1.9%) SPS patient developed incident CRC, as did four (2.8%) patients with multiple serrated polyps without SPS. Thus, standardized incidence ratios were 0.51 (95% confidence interval, 0.01-2.82) and 0.74 (95% CI, 0.20-1.90), respectively (P = .7). Standardized incidence ratios for CRC also did not significantly differ between first-degree relatives of patients with SPS (3.28, 95% CI, 2.16-4.77) and those with multiple serrated polyps (2.79, 95% CI, 2.10-3.63; P = .5).

A Kaplan-Meier analysis confirmed that there were no differences in the incidence of CRC between groups during follow-up. The findings “confirm that a special surveillance strategy is needed for patients with multiple serrated polyps and their relatives, probably similar to the strategy currently recommended for SPS patients,” the researchers concluded. They arbitrarily defined the group with multiple serrated polyps, so they were not able to link CRC to a cutoff number or percentage of serrated polyps, they noted.

Funders included Instituto de Salud Carlos III, Fundación de Investigación Biomédica de la Comunidad Valenciana-Instituto de Investigación Sanitaria y Biomédica de Alicante, Asociación Española Contra el Cáncer, and Conselleria d’Educació de la Generalitat Valenciana. The investigators had no conflicts of interest.

Patients with more than 10 colonic polyps, of which at least half were serrated, and their first-degree relatives had a risk of colorectal cancer similar to that of patients who met formal diagnostic criteria for serrated polyposis syndrome (SPS), according to a retrospective multicenter study published in the July issue of Gastroenterology (doi: 10.1053/j.gastro.2017.04.003).

Such patients “should be treated with the same follow-up procedures as those proposed for patients with SPS, and possibly the definition of SPS should be broadened to include this phenotype,” wrote Cecilia M. Egoavil, MD, Miriam Juárez, and their associates.

SPS increases the risk of colorectal cancer (CRC) and is considered a heritable disease, which mandates “strict surveillance” of first-degree relatives, the researchers noted. The World Health Organization defines SPS as having at least five histologically diagnosed serrated lesions proximal to the sigmoid colon, of which two are at least 10 mm in diameter, or serrated polyps proximal to the sigmoid colon and a first-degree relative with SPS, or more than 20 serrated polyps throughout the colon. This “arbitrary” definition is “somewhat restrictive, and possibly leads to underdiagnosis of this disease,” the researchers wrote. Patients with multiple serrated polyps who do not meet WHO SPS criteria might have a “phenotypically attenuated form of serrated polyposis.”

For the study, the researchers compared 53 patients meeting WHO SPS criteria with 145 patients who did not meet these criteria but had more than 10 polyps throughout the colon, of which at least 50% were serrated. For both groups, number of polyps was obtained by adding polyp counts from subsequent colonoscopies. The data source was EPIPOLIP, a multicenter study of patients recruited from 24 hospitals in Spain in 2008 and 2009. At baseline, all patients had more than 10 adenomatous or serrated colonic polyps but did not have familial adenomatous polyposis, Lynch syndrome, hamartomatous polyposis, inflammatory bowel disease, or only hyperplastic rectosigmoid polyps.

The prevalence of CRC was statistically similar between groups (P = .4). There were 12 (22.6%) cases among SPS patients (mean age at diagnosis, 50 years), and 41 (28.3%) cases (mean age, 59 years) among patients with multiple serrated polyps who did not meet SPS criteria. During a mean follow-up of 4.2 years, one (1.9%) SPS patient developed incident CRC, as did four (2.8%) patients with multiple serrated polyps without SPS. Thus, standardized incidence ratios were 0.51 (95% confidence interval, 0.01-2.82) and 0.74 (95% CI, 0.20-1.90), respectively (P = .7). Standardized incidence ratios for CRC also did not significantly differ between first-degree relatives of patients with SPS (3.28, 95% CI, 2.16-4.77) and those with multiple serrated polyps (2.79, 95% CI, 2.10-3.63; P = .5).

A Kaplan-Meier analysis confirmed that there were no differences in the incidence of CRC between groups during follow-up. The findings “confirm that a special surveillance strategy is needed for patients with multiple serrated polyps and their relatives, probably similar to the strategy currently recommended for SPS patients,” the researchers concluded. They arbitrarily defined the group with multiple serrated polyps, so they were not able to link CRC to a cutoff number or percentage of serrated polyps, they noted.

Funders included Instituto de Salud Carlos III, Fundación de Investigación Biomédica de la Comunidad Valenciana-Instituto de Investigación Sanitaria y Biomédica de Alicante, Asociación Española Contra el Cáncer, and Conselleria d’Educació de la Generalitat Valenciana. The investigators had no conflicts of interest.

About one in five patients with chronic hepatitis B virus (HBV) infection had persistently elevated alanine aminotransferase (ALT) levels despite long-term treatment with tenofovir disoproxil fumarate, according to data from two phase III trials reported in the July issue of Clinical Gastroenterology and Hepatology (2017. doi: 10.1016/j.cgh.2017.01.032).

“Both host and viral factors, particularly hepatic steatosis and hepatitis B e antigen [HBeAg] seropositivity, are important contributors to this phenomenon,” Ira M. Jacobson, MD, of Mount Sinai Beth Israel Medical Center, New York, wrote with his associates. “Although serum ALT may indicate significant liver injury, this association is inconsistent, suggesting that relying on serum ALT alone is not sufficient to gauge either the extent of liver injury or the impact of antiviral therapy.”

Long-term treatment with newer antivirals such as tenofovir disoproxil fumarate (TDF) achieves complete viral suppression and improves liver histology in most cases of HBV infection. Transaminase levels are used to track long-term clinical response but sometimes remain elevated in the face of complete virologic response and regression of fibrosis. To explore predictors of this outcome, the researchers analyzed data from 471 chronic HBV patients receiving TDF 300 mg once daily for 5 years as part of two ongoing phase III trials (NCT00117676 and NCT00116805). At baseline, about 25% of patients were cirrhotic (Ishak fibrosis score greater than or equal to 5) and none had decompensated cirrhosis. A central laboratory analyzed ALT levels, which were up to 10 times the upper limit of normal in both HBeAg-positive and -negative patients and were at least twice the upper limit of normal in all HBeAg-positive patients.

After 5 years of TDF, ALT levels remained elevated in 87 (18%) of patients. Patients with at least 5% (grade 1) steatosis at baseline were significantly more likely to have persistent ALT elevation than were those with less or no steatosis (odds ratio, 2.2; 95% confidence interval, 1.03-4.9; P = .04). At least grade 1 steatosis at year 5 also was associated with persistent ALT elevation (OR, 3.4; 95% CI, 1.6-7.4; P =.002). Other significant correlates included HBeAg seropositivity (OR, 3.3; 95% CI, 1.7-6.6; P less than .001) and age 40 years or younger (OR, 2.1; 95% CI, 1.01-4.3; P = .046). Strikingly, half of HBeAg-positive patients with steatosis at baseline had elevated ALT at year 5, said the investigators.

Because many patients whose ALT values fall within commercial laboratory reference ranges have chronic active necroinflammation or fibrogenesis, the researchers performed a sensitivity analysis of patients who achieved a stricter definition of ALT normalization of no more than 30 U/L for men and 19 U/L for women that has been previously recommended (Ann Intern Med. 2002;137:1-10). In this analysis, 47% of patients had persistently elevated ALT despite effective virologic suppression, and the only significant predictor of persistent ALT elevation was grade 1 or more steatosis at year 5 (OR, 6.2; 95% CI, 2.3-16.4; P less than .001). Younger age and HBeAg positivity plus age were no longer significant.

Hepatic steatosis is common overall and in chronic HBV infection and often leads to increased serum transaminases, the researchers noted. Although past work has linked a PNPLA3 single nucleotide polymorphism to obesity, metabolic syndrome, and hepatic steatosis, the presence of this single nucleotide polymorphism was not significant in their study, possibly because many patients lacked genotype data, they added. “Larger longitudinal studies are warranted to further explore this factor and its potential effect on the biochemical response to antiviral treatment in [chronic HBV] patients,” they concluded.

Gilead Sciences sponsored the study. Dr. Jacobson disclosed consultancy, honoraria, and research ties to Gilead and several other pharmaceutical companies.

About one in five patients with chronic hepatitis B virus (HBV) infection had persistently elevated alanine aminotransferase (ALT) levels despite long-term treatment with tenofovir disoproxil fumarate, according to data from two phase III trials reported in the July issue of Clinical Gastroenterology and Hepatology (2017. doi: 10.1016/j.cgh.2017.01.032).

“Both host and viral factors, particularly hepatic steatosis and hepatitis B e antigen [HBeAg] seropositivity, are important contributors to this phenomenon,” Ira M. Jacobson, MD, of Mount Sinai Beth Israel Medical Center, New York, wrote with his associates. “Although serum ALT may indicate significant liver injury, this association is inconsistent, suggesting that relying on serum ALT alone is not sufficient to gauge either the extent of liver injury or the impact of antiviral therapy.”

Long-term treatment with newer antivirals such as tenofovir disoproxil fumarate (TDF) achieves complete viral suppression and improves liver histology in most cases of HBV infection. Transaminase levels are used to track long-term clinical response but sometimes remain elevated in the face of complete virologic response and regression of fibrosis. To explore predictors of this outcome, the researchers analyzed data from 471 chronic HBV patients receiving TDF 300 mg once daily for 5 years as part of two ongoing phase III trials (NCT00117676 and NCT00116805). At baseline, about 25% of patients were cirrhotic (Ishak fibrosis score greater than or equal to 5) and none had decompensated cirrhosis. A central laboratory analyzed ALT levels, which were up to 10 times the upper limit of normal in both HBeAg-positive and -negative patients and were at least twice the upper limit of normal in all HBeAg-positive patients.

After 5 years of TDF, ALT levels remained elevated in 87 (18%) of patients. Patients with at least 5% (grade 1) steatosis at baseline were significantly more likely to have persistent ALT elevation than were those with less or no steatosis (odds ratio, 2.2; 95% confidence interval, 1.03-4.9; P = .04). At least grade 1 steatosis at year 5 also was associated with persistent ALT elevation (OR, 3.4; 95% CI, 1.6-7.4; P =.002). Other significant correlates included HBeAg seropositivity (OR, 3.3; 95% CI, 1.7-6.6; P less than .001) and age 40 years or younger (OR, 2.1; 95% CI, 1.01-4.3; P = .046). Strikingly, half of HBeAg-positive patients with steatosis at baseline had elevated ALT at year 5, said the investigators.

Because many patients whose ALT values fall within commercial laboratory reference ranges have chronic active necroinflammation or fibrogenesis, the researchers performed a sensitivity analysis of patients who achieved a stricter definition of ALT normalization of no more than 30 U/L for men and 19 U/L for women that has been previously recommended (Ann Intern Med. 2002;137:1-10). In this analysis, 47% of patients had persistently elevated ALT despite effective virologic suppression, and the only significant predictor of persistent ALT elevation was grade 1 or more steatosis at year 5 (OR, 6.2; 95% CI, 2.3-16.4; P less than .001). Younger age and HBeAg positivity plus age were no longer significant.

Hepatic steatosis is common overall and in chronic HBV infection and often leads to increased serum transaminases, the researchers noted. Although past work has linked a PNPLA3 single nucleotide polymorphism to obesity, metabolic syndrome, and hepatic steatosis, the presence of this single nucleotide polymorphism was not significant in their study, possibly because many patients lacked genotype data, they added. “Larger longitudinal studies are warranted to further explore this factor and its potential effect on the biochemical response to antiviral treatment in [chronic HBV] patients,” they concluded.

Gilead Sciences sponsored the study. Dr. Jacobson disclosed consultancy, honoraria, and research ties to Gilead and several other pharmaceutical companies.

About one in five patients with chronic hepatitis B virus (HBV) infection had persistently elevated alanine aminotransferase (ALT) levels despite long-term treatment with tenofovir disoproxil fumarate, according to data from two phase III trials reported in the July issue of Clinical Gastroenterology and Hepatology (2017. doi: 10.1016/j.cgh.2017.01.032).

“Both host and viral factors, particularly hepatic steatosis and hepatitis B e antigen [HBeAg] seropositivity, are important contributors to this phenomenon,” Ira M. Jacobson, MD, of Mount Sinai Beth Israel Medical Center, New York, wrote with his associates. “Although serum ALT may indicate significant liver injury, this association is inconsistent, suggesting that relying on serum ALT alone is not sufficient to gauge either the extent of liver injury or the impact of antiviral therapy.”

Long-term treatment with newer antivirals such as tenofovir disoproxil fumarate (TDF) achieves complete viral suppression and improves liver histology in most cases of HBV infection. Transaminase levels are used to track long-term clinical response but sometimes remain elevated in the face of complete virologic response and regression of fibrosis. To explore predictors of this outcome, the researchers analyzed data from 471 chronic HBV patients receiving TDF 300 mg once daily for 5 years as part of two ongoing phase III trials (NCT00117676 and NCT00116805). At baseline, about 25% of patients were cirrhotic (Ishak fibrosis score greater than or equal to 5) and none had decompensated cirrhosis. A central laboratory analyzed ALT levels, which were up to 10 times the upper limit of normal in both HBeAg-positive and -negative patients and were at least twice the upper limit of normal in all HBeAg-positive patients.

After 5 years of TDF, ALT levels remained elevated in 87 (18%) of patients. Patients with at least 5% (grade 1) steatosis at baseline were significantly more likely to have persistent ALT elevation than were those with less or no steatosis (odds ratio, 2.2; 95% confidence interval, 1.03-4.9; P = .04). At least grade 1 steatosis at year 5 also was associated with persistent ALT elevation (OR, 3.4; 95% CI, 1.6-7.4; P =.002). Other significant correlates included HBeAg seropositivity (OR, 3.3; 95% CI, 1.7-6.6; P less than .001) and age 40 years or younger (OR, 2.1; 95% CI, 1.01-4.3; P = .046). Strikingly, half of HBeAg-positive patients with steatosis at baseline had elevated ALT at year 5, said the investigators.

Because many patients whose ALT values fall within commercial laboratory reference ranges have chronic active necroinflammation or fibrogenesis, the researchers performed a sensitivity analysis of patients who achieved a stricter definition of ALT normalization of no more than 30 U/L for men and 19 U/L for women that has been previously recommended (Ann Intern Med. 2002;137:1-10). In this analysis, 47% of patients had persistently elevated ALT despite effective virologic suppression, and the only significant predictor of persistent ALT elevation was grade 1 or more steatosis at year 5 (OR, 6.2; 95% CI, 2.3-16.4; P less than .001). Younger age and HBeAg positivity plus age were no longer significant.

Hepatic steatosis is common overall and in chronic HBV infection and often leads to increased serum transaminases, the researchers noted. Although past work has linked a PNPLA3 single nucleotide polymorphism to obesity, metabolic syndrome, and hepatic steatosis, the presence of this single nucleotide polymorphism was not significant in their study, possibly because many patients lacked genotype data, they added. “Larger longitudinal studies are warranted to further explore this factor and its potential effect on the biochemical response to antiviral treatment in [chronic HBV] patients,” they concluded.

Gilead Sciences sponsored the study. Dr. Jacobson disclosed consultancy, honoraria, and research ties to Gilead and several other pharmaceutical companies.

An improved annual adenoma detection rate was associated with a significantly decreased risk of interval colorectal cancer (ICRC) and subsequent death in a national prospective cohort study published in the July issue of Gastroenterology (doi: 10.1053/j.gastro.2017.04.006).

Eraxion/Thinkstock

Source: American Gastroenterological Association

This is the first study to show a significant inverse relationship between an improved annual adenoma detection rate (ADR) and ICRC or subsequent death, Michal F. Kaminski MD, PhD, of the Institute of Oncology, Warsaw, wrote with his associates.

The rates of these outcomes were lowest when endoscopists achieved and maintained ADRs above 24.6%, which supports the currently recommended performance target of 25% for a mixed male-female population, they reported (Am J Gastroenterol. 2015;110:72-90).

This study included 294 endoscopists and 146,860 individuals who underwent screening colonoscopy as part of a national cancer prevention program in Poland between 2004 and 2008. Endoscopists received annual feedback based on quality benchmarks to spur improvements in colonoscopy performance, and all participated for at least 2 years. For each endoscopist, investigators categorized annual ADRs based on quintiles for the entire data set. “Improved ADR” was defined as keeping annual ADR within the highest quintile (above 24.6%) or as increasing annual ADR by at least one quintile, compared with baseline.

Based on this definition, 219 endoscopists (75%) improved their ADR during a median of 5.8 years of follow-up (interquartile range, 5-7.2 years). In all, 168 interval CRCs were diagnosed, of which 44 cases led to death. After age, sex, and family history of colorectal cancer were controlled for, patients whose endoscopists improved their ADRs were significantly less likely to develop (adjusted hazard ratio, 0.6; 95% confidence interval, 0.5-0.9; P = .006) or to die of interval CRC (95% CI, 0.3-0.95; P = .04) than were patients whose endoscopists did not improve their ADRs.

Maintaining ADR in the highest quintile (above 24.6%) throughout follow-up led to an even lower risk of interval CRC (HR, 0.3; 95% CI, 0.1-0.6; P = .003) and death (HR, 0.2; 95% CI, 0.1-0.6; P = .003), the researchers reported. In absolute numbers, that translated to a decrease from 25.3 interval CRCs per 100,000 person-years of follow-up to 7.1 cases when endoscopists eventually reached the highest ADR quintile or to 4.5 cases when they were in the highest quintile throughout follow-up. Rates of colonic perforation remained stable even though most endoscopists upped their ADRs.

Together, these findings “prove the causal relationship between endoscopists’ ADRs and the likelihood of being diagnosed with, or dying from, interval CRC,” the investigators concluded. The national cancer registry in Poland is thought to miss about 10% of cases, but the rate of missing cases was not thought to change over time, they noted. However, they also lacked data on colonoscope withdrawal times, and had no control group to definitively show that feedback based on benchmarking was responsible for improved ADRs.

Funders included the Foundation of Polish Science, the Innovative Economy Operational Programme, the Polish Foundation of Gastroenterology, the Polish Ministry of Health, and the Polish Ministry of Science and Higher Education. The investigators reported having no relevant conflicts of interest.

An improved annual adenoma detection rate was associated with a significantly decreased risk of interval colorectal cancer (ICRC) and subsequent death in a national prospective cohort study published in the July issue of Gastroenterology (doi: 10.1053/j.gastro.2017.04.006).

Eraxion/Thinkstock

Source: American Gastroenterological Association

This is the first study to show a significant inverse relationship between an improved annual adenoma detection rate (ADR) and ICRC or subsequent death, Michal F. Kaminski MD, PhD, of the Institute of Oncology, Warsaw, wrote with his associates.

The rates of these outcomes were lowest when endoscopists achieved and maintained ADRs above 24.6%, which supports the currently recommended performance target of 25% for a mixed male-female population, they reported (Am J Gastroenterol. 2015;110:72-90).

This study included 294 endoscopists and 146,860 individuals who underwent screening colonoscopy as part of a national cancer prevention program in Poland between 2004 and 2008. Endoscopists received annual feedback based on quality benchmarks to spur improvements in colonoscopy performance, and all participated for at least 2 years. For each endoscopist, investigators categorized annual ADRs based on quintiles for the entire data set. “Improved ADR” was defined as keeping annual ADR within the highest quintile (above 24.6%) or as increasing annual ADR by at least one quintile, compared with baseline.

Based on this definition, 219 endoscopists (75%) improved their ADR during a median of 5.8 years of follow-up (interquartile range, 5-7.2 years). In all, 168 interval CRCs were diagnosed, of which 44 cases led to death. After age, sex, and family history of colorectal cancer were controlled for, patients whose endoscopists improved their ADRs were significantly less likely to develop (adjusted hazard ratio, 0.6; 95% confidence interval, 0.5-0.9; P = .006) or to die of interval CRC (95% CI, 0.3-0.95; P = .04) than were patients whose endoscopists did not improve their ADRs.

Maintaining ADR in the highest quintile (above 24.6%) throughout follow-up led to an even lower risk of interval CRC (HR, 0.3; 95% CI, 0.1-0.6; P = .003) and death (HR, 0.2; 95% CI, 0.1-0.6; P = .003), the researchers reported. In absolute numbers, that translated to a decrease from 25.3 interval CRCs per 100,000 person-years of follow-up to 7.1 cases when endoscopists eventually reached the highest ADR quintile or to 4.5 cases when they were in the highest quintile throughout follow-up. Rates of colonic perforation remained stable even though most endoscopists upped their ADRs.

Together, these findings “prove the causal relationship between endoscopists’ ADRs and the likelihood of being diagnosed with, or dying from, interval CRC,” the investigators concluded. The national cancer registry in Poland is thought to miss about 10% of cases, but the rate of missing cases was not thought to change over time, they noted. However, they also lacked data on colonoscope withdrawal times, and had no control group to definitively show that feedback based on benchmarking was responsible for improved ADRs.

Funders included the Foundation of Polish Science, the Innovative Economy Operational Programme, the Polish Foundation of Gastroenterology, the Polish Ministry of Health, and the Polish Ministry of Science and Higher Education. The investigators reported having no relevant conflicts of interest.

An improved annual adenoma detection rate was associated with a significantly decreased risk of interval colorectal cancer (ICRC) and subsequent death in a national prospective cohort study published in the July issue of Gastroenterology (doi: 10.1053/j.gastro.2017.04.006).

Eraxion/Thinkstock

Source: American Gastroenterological Association

This is the first study to show a significant inverse relationship between an improved annual adenoma detection rate (ADR) and ICRC or subsequent death, Michal F. Kaminski MD, PhD, of the Institute of Oncology, Warsaw, wrote with his associates.

The rates of these outcomes were lowest when endoscopists achieved and maintained ADRs above 24.6%, which supports the currently recommended performance target of 25% for a mixed male-female population, they reported (Am J Gastroenterol. 2015;110:72-90).

This study included 294 endoscopists and 146,860 individuals who underwent screening colonoscopy as part of a national cancer prevention program in Poland between 2004 and 2008. Endoscopists received annual feedback based on quality benchmarks to spur improvements in colonoscopy performance, and all participated for at least 2 years. For each endoscopist, investigators categorized annual ADRs based on quintiles for the entire data set. “Improved ADR” was defined as keeping annual ADR within the highest quintile (above 24.6%) or as increasing annual ADR by at least one quintile, compared with baseline.

Based on this definition, 219 endoscopists (75%) improved their ADR during a median of 5.8 years of follow-up (interquartile range, 5-7.2 years). In all, 168 interval CRCs were diagnosed, of which 44 cases led to death. After age, sex, and family history of colorectal cancer were controlled for, patients whose endoscopists improved their ADRs were significantly less likely to develop (adjusted hazard ratio, 0.6; 95% confidence interval, 0.5-0.9; P = .006) or to die of interval CRC (95% CI, 0.3-0.95; P = .04) than were patients whose endoscopists did not improve their ADRs.

Maintaining ADR in the highest quintile (above 24.6%) throughout follow-up led to an even lower risk of interval CRC (HR, 0.3; 95% CI, 0.1-0.6; P = .003) and death (HR, 0.2; 95% CI, 0.1-0.6; P = .003), the researchers reported. In absolute numbers, that translated to a decrease from 25.3 interval CRCs per 100,000 person-years of follow-up to 7.1 cases when endoscopists eventually reached the highest ADR quintile or to 4.5 cases when they were in the highest quintile throughout follow-up. Rates of colonic perforation remained stable even though most endoscopists upped their ADRs.

Together, these findings “prove the causal relationship between endoscopists’ ADRs and the likelihood of being diagnosed with, or dying from, interval CRC,” the investigators concluded. The national cancer registry in Poland is thought to miss about 10% of cases, but the rate of missing cases was not thought to change over time, they noted. However, they also lacked data on colonoscope withdrawal times, and had no control group to definitively show that feedback based on benchmarking was responsible for improved ADRs.

Funders included the Foundation of Polish Science, the Innovative Economy Operational Programme, the Polish Foundation of Gastroenterology, the Polish Ministry of Health, and the Polish Ministry of Science and Higher Education. The investigators reported having no relevant conflicts of interest.

Starting probiotics within 2 days of the first antibiotic dose could cut the risk of Clostridium difficile infection among hospitalized adults by more than 50%, according to the results of a systemic review and metaregression analysis.

The protective effect waned when patients delayed starting probiotics, reported Nicole T. Shen, MD, of Cornell University, New York, and her associates. The study appears in Gastroenterology (doi: 10.1053/j.gastro.2017.02.003). “Given the magnitude of benefit and the low cost of probiotics, the decision is likely to be highly cost effective,” they added.

Systematic reviews support the use of probiotics for preventing Clostridium difficile infection (CDI), but guidelines do not reflect these findings. To help guide clinical practice, the reviewers searched MEDLINE, EMBASE, the International Journal of Probiotics and Prebiotics, and the Cochrane Library databases for randomized controlled trials of probiotics and CDI among hospitalized adults taking antibiotics. This search yielded 19 published studies of 6,261 patients. Two reviewers separately extracted data from these studies and examined quality of evidence and risk of bias.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

A total of 54 patients in the probiotic cohort (1.6%) developed CDI, compared with 115 controls (3.9%), a statistically significant difference (P less than .001). In ­regression analysis, the probiotic group was about 58% less likely to develop CDI than controls (hazard ratio, 0.42; 95% confidence interval, 0.30-0.57; P less than .001). Importantly, probiotics were significantly effective against CDI only when started within 2 days of antibiotic initiation (relative risk, 0.32; 95% CI, 0.22-0.48), not when started within 3-7 days (RR, 0.70, 95% CI, 0.40-1.23). The difference between these estimated risk ratios was statistically significant (P = .02).

In 18 of the 19 studies, patients received probiotics within 3 days of starting antibiotics, while patients in the remaining study could start probiotics any time within 7 days of antibiotic initiation. “Not only was [this] study unusual with respect to probiotic timing, it was also much larger than all other studies, and its results were statistically insignificant,” the reviewers wrote. Metaregression analyses of all studies and of all but the outlier study linked delaying probiotics with a decrease in efficacy against CDI, with P values of .04 and .09, respectively. Those findings “suggest that the decrement in efficacy with delay in starting probiotics is not sensitive to inclusion of a single large ‘outlier’ study,” the reviewers emphasized. “In fact, inclusion only dampens the magnitude of the decrement in efficacy, although it is still clinically important and statistically significant.”

The trials included 12 probiotic formulas containing Lactobacillus, Saccharomyces, Bifidobacterium, and Streptococcus, either alone or in combination. Probiotics were not associated with adverse effects in the trials. Quality of evidence was generally high, but seven trials had missing data on the primary outcome. Furthermore, two studies lacked a placebo group, and lead authors of two studies disclosed ties to the probiotic manufacturers that provided funding.

One reviewer received fellowship support from the Louis and Rachel Rudin Foundation. None had conflicts of interest.

Starting probiotics within 2 days of the first antibiotic dose could cut the risk of Clostridium difficile infection among hospitalized adults by more than 50%, according to the results of a systemic review and metaregression analysis.

The protective effect waned when patients delayed starting probiotics, reported Nicole T. Shen, MD, of Cornell University, New York, and her associates. The study appears in Gastroenterology (doi: 10.1053/j.gastro.2017.02.003). “Given the magnitude of benefit and the low cost of probiotics, the decision is likely to be highly cost effective,” they added.

Systematic reviews support the use of probiotics for preventing Clostridium difficile infection (CDI), but guidelines do not reflect these findings. To help guide clinical practice, the reviewers searched MEDLINE, EMBASE, the International Journal of Probiotics and Prebiotics, and the Cochrane Library databases for randomized controlled trials of probiotics and CDI among hospitalized adults taking antibiotics. This search yielded 19 published studies of 6,261 patients. Two reviewers separately extracted data from these studies and examined quality of evidence and risk of bias.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

A total of 54 patients in the probiotic cohort (1.6%) developed CDI, compared with 115 controls (3.9%), a statistically significant difference (P less than .001). In ­regression analysis, the probiotic group was about 58% less likely to develop CDI than controls (hazard ratio, 0.42; 95% confidence interval, 0.30-0.57; P less than .001). Importantly, probiotics were significantly effective against CDI only when started within 2 days of antibiotic initiation (relative risk, 0.32; 95% CI, 0.22-0.48), not when started within 3-7 days (RR, 0.70, 95% CI, 0.40-1.23). The difference between these estimated risk ratios was statistically significant (P = .02).

In 18 of the 19 studies, patients received probiotics within 3 days of starting antibiotics, while patients in the remaining study could start probiotics any time within 7 days of antibiotic initiation. “Not only was [this] study unusual with respect to probiotic timing, it was also much larger than all other studies, and its results were statistically insignificant,” the reviewers wrote. Metaregression analyses of all studies and of all but the outlier study linked delaying probiotics with a decrease in efficacy against CDI, with P values of .04 and .09, respectively. Those findings “suggest that the decrement in efficacy with delay in starting probiotics is not sensitive to inclusion of a single large ‘outlier’ study,” the reviewers emphasized. “In fact, inclusion only dampens the magnitude of the decrement in efficacy, although it is still clinically important and statistically significant.”

The trials included 12 probiotic formulas containing Lactobacillus, Saccharomyces, Bifidobacterium, and Streptococcus, either alone or in combination. Probiotics were not associated with adverse effects in the trials. Quality of evidence was generally high, but seven trials had missing data on the primary outcome. Furthermore, two studies lacked a placebo group, and lead authors of two studies disclosed ties to the probiotic manufacturers that provided funding.

One reviewer received fellowship support from the Louis and Rachel Rudin Foundation. None had conflicts of interest.

Starting probiotics within 2 days of the first antibiotic dose could cut the risk of Clostridium difficile infection among hospitalized adults by more than 50%, according to the results of a systemic review and metaregression analysis.

The protective effect waned when patients delayed starting probiotics, reported Nicole T. Shen, MD, of Cornell University, New York, and her associates. The study appears in Gastroenterology (doi: 10.1053/j.gastro.2017.02.003). “Given the magnitude of benefit and the low cost of probiotics, the decision is likely to be highly cost effective,” they added.

Systematic reviews support the use of probiotics for preventing Clostridium difficile infection (CDI), but guidelines do not reflect these findings. To help guide clinical practice, the reviewers searched MEDLINE, EMBASE, the International Journal of Probiotics and Prebiotics, and the Cochrane Library databases for randomized controlled trials of probiotics and CDI among hospitalized adults taking antibiotics. This search yielded 19 published studies of 6,261 patients. Two reviewers separately extracted data from these studies and examined quality of evidence and risk of bias.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

A total of 54 patients in the probiotic cohort (1.6%) developed CDI, compared with 115 controls (3.9%), a statistically significant difference (P less than .001). In ­regression analysis, the probiotic group was about 58% less likely to develop CDI than controls (hazard ratio, 0.42; 95% confidence interval, 0.30-0.57; P less than .001). Importantly, probiotics were significantly effective against CDI only when started within 2 days of antibiotic initiation (relative risk, 0.32; 95% CI, 0.22-0.48), not when started within 3-7 days (RR, 0.70, 95% CI, 0.40-1.23). The difference between these estimated risk ratios was statistically significant (P = .02).

In 18 of the 19 studies, patients received probiotics within 3 days of starting antibiotics, while patients in the remaining study could start probiotics any time within 7 days of antibiotic initiation. “Not only was [this] study unusual with respect to probiotic timing, it was also much larger than all other studies, and its results were statistically insignificant,” the reviewers wrote. Metaregression analyses of all studies and of all but the outlier study linked delaying probiotics with a decrease in efficacy against CDI, with P values of .04 and .09, respectively. Those findings “suggest that the decrement in efficacy with delay in starting probiotics is not sensitive to inclusion of a single large ‘outlier’ study,” the reviewers emphasized. “In fact, inclusion only dampens the magnitude of the decrement in efficacy, although it is still clinically important and statistically significant.”

The trials included 12 probiotic formulas containing Lactobacillus, Saccharomyces, Bifidobacterium, and Streptococcus, either alone or in combination. Probiotics were not associated with adverse effects in the trials. Quality of evidence was generally high, but seven trials had missing data on the primary outcome. Furthermore, two studies lacked a placebo group, and lead authors of two studies disclosed ties to the probiotic manufacturers that provided funding.

One reviewer received fellowship support from the Louis and Rachel Rudin Foundation. None had conflicts of interest.

Living more than 150 miles from a liver transplant center was associated with a higher risk of mortality among patients with chronic liver failure, regardless of etiology, transplantation status, or whether patients had decompensated cirrhosis or hepatocellular carcinoma, according to a first-in-kind, population-based study reported in the June issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.02.023).

The findings underscore the need for accessible, specialized liver care irrespective of whether patients with chronic liver failure (CLF) are destined for transplantation, David S. Goldberg, MD, of the University of Pennsylvania, Philadelphia, wrote with his associates. The associations “do not provide cause and effect,” but underscore the need to consider “the broader impact of transplant-related policies that could decrease transplant volumes and threaten closures of smaller liver transplant centers that serve geographically isolated populations in the Southeast and Midwest,” they added.

Living more than 150 miles from a liver transplant center was associated with a higher risk of mortality among patients with chronic liver failure, regardless of etiology, transplantation status, or whether patients had decompensated cirrhosis or hepatocellular carcinoma, according to a first-in-kind, population-based study reported in the June issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.02.023).

The findings underscore the need for accessible, specialized liver care irrespective of whether patients with chronic liver failure (CLF) are destined for transplantation, David S. Goldberg, MD, of the University of Pennsylvania, Philadelphia, wrote with his associates. The associations “do not provide cause and effect,” but underscore the need to consider “the broader impact of transplant-related policies that could decrease transplant volumes and threaten closures of smaller liver transplant centers that serve geographically isolated populations in the Southeast and Midwest,” they added.

Living more than 150 miles from a liver transplant center was associated with a higher risk of mortality among patients with chronic liver failure, regardless of etiology, transplantation status, or whether patients had decompensated cirrhosis or hepatocellular carcinoma, according to a first-in-kind, population-based study reported in the June issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.02.023).

The findings underscore the need for accessible, specialized liver care irrespective of whether patients with chronic liver failure (CLF) are destined for transplantation, David S. Goldberg, MD, of the University of Pennsylvania, Philadelphia, wrote with his associates. The associations “do not provide cause and effect,” but underscore the need to consider “the broader impact of transplant-related policies that could decrease transplant volumes and threaten closures of smaller liver transplant centers that serve geographically isolated populations in the Southeast and Midwest,” they added.

Patients with at least five biopsies showing nondysplastic Barrett’s esophagus were statistically as likely to progress to high-grade dysplasia or esophageal adenocarcinoma as patients with a single such biopsy, according to a multicenter prospective registry study reported in the June issue of Clinical Gastroenterology and Hepatology (doi: org/10.1016/j.cgh.2017.02.019).

The findings, which contradict those from another recent multicenter cohort study (Gastroenterology. 2013;145[3]:548-53), highlight the need for more studies before lengthening the time between surveillance biopsies in patients with nondysplastic Barrett’s esophagus, Rajesh Krishnamoorthi, MD, of Mayo Clinic in Rochester, Minn., wrote with his associates.

Barrett’s esophagus is the strongest predictor of esophageal adenocarcinoma, but studies have reported mixed results as to whether the risk of this cancer increases over time or wanes with consecutive biopsies that indicate nondysplasia, the researchers noted. Therefore, they studied the prospective, multicenter Mayo Clinic Esophageal Adenocarcinoma and Barrett’s Esophagus registry, excluding patients who progressed to adenocarcinoma within 12 months, had missing data, or had no follow-up biopsies. This approach left 480 subjects for analysis. Patients averaged 63 years of age, 78% were male, the mean length of Barrett’s esophagus was 5.7 cm, and the average time between biopsies was 1.8 years, with a standard deviation of 1.3 years.

A total of 16 patients progressed to high-grade dysplasia or esophageal adenocarcinoma over 1,832 patient-years of follow-up, for an overall annual risk of progression of 0.87%. Two patients progressed to esophageal adenocarcinoma (annual risk, 0.11%; 95% confidence interval, 0.03% to 0.44%), while 14 patients progressed to high-grade dysplasia (annual risk, 0.76%; 95% CI, 0.45% to 1.29%). Eight patients progressed to one of these two outcomes after a single nondysplastic biopsy, three progressed after two such biopsies, three progressed after three such biopsies, none progressed after four such biopsies, and two progressed after five such biopsies. Statistically, patients with at least five consecutive nondysplastic biopsies were no less likely to progress than were patients with only one nondysplastic biopsy (hazard ratio, 0.48; 95% CI, 0.07 to 1.92; P = .32). Hazard ratios for the other groups ranged between 0.0 and 0.85, with no significant difference in estimated risk between groups (P = .68) after controlling for age, sex, and length of Barrett’s esophagus.

The previous multicenter cohort study linked persistently nondysplastic Barrett’s esophagus with a lower rate of progression to esophageal adenocarcinoma, and, based on those findings, the authors suggested lengthening intervals between biopsy surveillance or even stopping surveillance, Dr. Krishnamoorthi and his associates noted. However, that study did not have mutually exclusive groups. “Additional data are required before increasing the interval between surveillance endoscopies based on persistence of nondysplastic Barrett’s esophagus,” they concluded.

The study lacked misclassification bias given long-segment Barrett’s esophagus, and specialized gastrointestinal pathologists interpreted all histology specimens, the researchers noted. “The small number of progressors is a potential limitation, reducing power to assess associations,” they added.

The investigators did not report funding sources. They reported having no conflicts of interest.

Patients with at least five biopsies showing nondysplastic Barrett’s esophagus were statistically as likely to progress to high-grade dysplasia or esophageal adenocarcinoma as patients with a single such biopsy, according to a multicenter prospective registry study reported in the June issue of Clinical Gastroenterology and Hepatology (doi: org/10.1016/j.cgh.2017.02.019).

The findings, which contradict those from another recent multicenter cohort study (Gastroenterology. 2013;145[3]:548-53), highlight the need for more studies before lengthening the time between surveillance biopsies in patients with nondysplastic Barrett’s esophagus, Rajesh Krishnamoorthi, MD, of Mayo Clinic in Rochester, Minn., wrote with his associates.

Barrett’s esophagus is the strongest predictor of esophageal adenocarcinoma, but studies have reported mixed results as to whether the risk of this cancer increases over time or wanes with consecutive biopsies that indicate nondysplasia, the researchers noted. Therefore, they studied the prospective, multicenter Mayo Clinic Esophageal Adenocarcinoma and Barrett’s Esophagus registry, excluding patients who progressed to adenocarcinoma within 12 months, had missing data, or had no follow-up biopsies. This approach left 480 subjects for analysis. Patients averaged 63 years of age, 78% were male, the mean length of Barrett’s esophagus was 5.7 cm, and the average time between biopsies was 1.8 years, with a standard deviation of 1.3 years.

A total of 16 patients progressed to high-grade dysplasia or esophageal adenocarcinoma over 1,832 patient-years of follow-up, for an overall annual risk of progression of 0.87%. Two patients progressed to esophageal adenocarcinoma (annual risk, 0.11%; 95% confidence interval, 0.03% to 0.44%), while 14 patients progressed to high-grade dysplasia (annual risk, 0.76%; 95% CI, 0.45% to 1.29%). Eight patients progressed to one of these two outcomes after a single nondysplastic biopsy, three progressed after two such biopsies, three progressed after three such biopsies, none progressed after four such biopsies, and two progressed after five such biopsies. Statistically, patients with at least five consecutive nondysplastic biopsies were no less likely to progress than were patients with only one nondysplastic biopsy (hazard ratio, 0.48; 95% CI, 0.07 to 1.92; P = .32). Hazard ratios for the other groups ranged between 0.0 and 0.85, with no significant difference in estimated risk between groups (P = .68) after controlling for age, sex, and length of Barrett’s esophagus.

The previous multicenter cohort study linked persistently nondysplastic Barrett’s esophagus with a lower rate of progression to esophageal adenocarcinoma, and, based on those findings, the authors suggested lengthening intervals between biopsy surveillance or even stopping surveillance, Dr. Krishnamoorthi and his associates noted. However, that study did not have mutually exclusive groups. “Additional data are required before increasing the interval between surveillance endoscopies based on persistence of nondysplastic Barrett’s esophagus,” they concluded.

The study lacked misclassification bias given long-segment Barrett’s esophagus, and specialized gastrointestinal pathologists interpreted all histology specimens, the researchers noted. “The small number of progressors is a potential limitation, reducing power to assess associations,” they added.

The investigators did not report funding sources. They reported having no conflicts of interest.

Patients with at least five biopsies showing nondysplastic Barrett’s esophagus were statistically as likely to progress to high-grade dysplasia or esophageal adenocarcinoma as patients with a single such biopsy, according to a multicenter prospective registry study reported in the June issue of Clinical Gastroenterology and Hepatology (doi: org/10.1016/j.cgh.2017.02.019).

The findings, which contradict those from another recent multicenter cohort study (Gastroenterology. 2013;145[3]:548-53), highlight the need for more studies before lengthening the time between surveillance biopsies in patients with nondysplastic Barrett’s esophagus, Rajesh Krishnamoorthi, MD, of Mayo Clinic in Rochester, Minn., wrote with his associates.

Barrett’s esophagus is the strongest predictor of esophageal adenocarcinoma, but studies have reported mixed results as to whether the risk of this cancer increases over time or wanes with consecutive biopsies that indicate nondysplasia, the researchers noted. Therefore, they studied the prospective, multicenter Mayo Clinic Esophageal Adenocarcinoma and Barrett’s Esophagus registry, excluding patients who progressed to adenocarcinoma within 12 months, had missing data, or had no follow-up biopsies. This approach left 480 subjects for analysis. Patients averaged 63 years of age, 78% were male, the mean length of Barrett’s esophagus was 5.7 cm, and the average time between biopsies was 1.8 years, with a standard deviation of 1.3 years.

A total of 16 patients progressed to high-grade dysplasia or esophageal adenocarcinoma over 1,832 patient-years of follow-up, for an overall annual risk of progression of 0.87%. Two patients progressed to esophageal adenocarcinoma (annual risk, 0.11%; 95% confidence interval, 0.03% to 0.44%), while 14 patients progressed to high-grade dysplasia (annual risk, 0.76%; 95% CI, 0.45% to 1.29%). Eight patients progressed to one of these two outcomes after a single nondysplastic biopsy, three progressed after two such biopsies, three progressed after three such biopsies, none progressed after four such biopsies, and two progressed after five such biopsies. Statistically, patients with at least five consecutive nondysplastic biopsies were no less likely to progress than were patients with only one nondysplastic biopsy (hazard ratio, 0.48; 95% CI, 0.07 to 1.92; P = .32). Hazard ratios for the other groups ranged between 0.0 and 0.85, with no significant difference in estimated risk between groups (P = .68) after controlling for age, sex, and length of Barrett’s esophagus.

The previous multicenter cohort study linked persistently nondysplastic Barrett’s esophagus with a lower rate of progression to esophageal adenocarcinoma, and, based on those findings, the authors suggested lengthening intervals between biopsy surveillance or even stopping surveillance, Dr. Krishnamoorthi and his associates noted. However, that study did not have mutually exclusive groups. “Additional data are required before increasing the interval between surveillance endoscopies based on persistence of nondysplastic Barrett’s esophagus,” they concluded.

The study lacked misclassification bias given long-segment Barrett’s esophagus, and specialized gastrointestinal pathologists interpreted all histology specimens, the researchers noted. “The small number of progressors is a potential limitation, reducing power to assess associations,” they added.

The investigators did not report funding sources. They reported having no conflicts of interest.