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Nerve growth factor therapy speeds gastric ulcer healing

Ulcers on NSAIDs
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Sat, 12/08/2018 - 15:18

Nerve growth factor (NGF) therapy in aging rats improves angiogenesis and speeds gastric ulcer healing, which suggests possible applications in human medicine, a recent study found.

Compared with young individuals, elderly people have significantly lower levels of NGF in gastric endothelial cells (GECs), a finding that is associated with impaired angiogenesis and delayed gastric ulcer healing.

“Our previous studies have shown that the gastric mucosa of aging individuals ... has increased susceptibility to injury and delayed healing owing to impaired angiogenesis, but the mechanisms are not fully elucidated,” wrote Amrita Ahluwalia, PhD, of Medical and Research Services at the Veterans Affairs Long Beach (Calif.) Healthcare System and her coauthors.

Mapping the drivers of angiogenesis in the gastric mucosa could lead to treatment options for elderly patients with injured or ulcerated gastric tissue. In prior trials (with rats), “treatment with VEGF [vascular endothelial growth factor] only partly reversed impaired angiogenesis in aging [GECs], indicating an essential role for other factor(s) in addition to VEGF,” the investigators wrote in the September issue of Cellular and Molecular Gastroenterology and Hepatology. They looked to NGF as another possible factor because recent studies had shown it could improve angiogenesis in the brain.

The present study measured NGF expression in rats and humans of varying ages, with NGF treatment and gene therapy performed in rats (in vitro and in vivo).

In vitro angiogenesis was 4.1-fold lower in GECs from aging rats (24 months of age) than it was in GECs from young rats (3 months of age; P less than .001). NGF protein and NGF mRNA levels were also significantly lower in aging GECs than they were with young GECs (NGF protein, 3.0-fold lower; NGF mRNA, 4.2-fold lower; P less than .001).

Treatment of aging rat GECs with exogenous NGF increased angiogenesis by 1.5-fold (P less than .001). Pretreatment with a PI3 kinase inhibitor or an mTOR inhibitor abolished this improvement, suggesting that the PI3 kinase/Akt and mTOR pathways are involved.

When NGF gene therapy was performed in aging GECs, NGF levels rose to the level of that in young GECs, with an accompanying restoration of angiogenesis (threefold increase; P less than .001). Proliferation of aging GECs also increased with gene therapy (P less than .001).

In vivo studies revealed that NGF expression and cell proliferation in aging rat gastric mucosa were lower than in younger rats. Of note, older rats treated with local NGF protein showed increased gastric mucosa angiogenesis and faster ulcer healing, compared with phosphate-buffered saline treatment.

Similar age-related NGF declines were found in humans. When gastric mucosa biopsies were collected from younger individuals (younger than 40 years old; n = 10) and compared with samples from an older population (at least 70 years old; n = 10), the investigators found that NGF expression was 5.5-fold lower in the older people (P less than .001).

“This clearly indicates human relevance of our experimental findings and also can explain impaired angiogenesis and delayed healing of injured gastric mucosa in aging individuals,” the investigators wrote.

“Aging gastropathy and its consequences are clinically critical issues,” the investigators noted, “especially because the aging U.S. population is growing rapidly and it is estimated that, by the year 2030, approximately 70 million Americans will be older than 65 years of age.” Gastric ulcers become more common with age, and individuals 70 years or older have an eightfold increased risk of associated complications, compared with people under 50 years.

The investigators noted that multiple growth factors likely play a role in stimulation of angiogenesis, including NGF, VEGF, epidermal growth factor, and basic fibroblast growth factor. “Further studies are necessary to investigate the role of other growth factors and cytokines in angiogenesis, [gastric ulcer] healing, and their impairment in aging,” the investigators concluded.

The study was funded by the Department of Veterans Affairs Biomedical Laboratory Research and Development Service. The authors declared no conflicts of interest.
 

SOURCE: Ahluwalia A et al. CMGH. 2018 May 17. doi: 10.1016/j.jcmgh.2018.05.003

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Although the incidence of gastric ulcers has been declining in the general population, hospitalization and mortality linked to gastric ulcers remains high in the elderly population. One of the major risk factors for gastric ulceration is the use of NSAIDs. It is estimated that 40% of individuals aged 65 years and older fill at least one prescription for an NSAID each year. Given that the elderly population (those aged 65 years and older) is anticipated to more than double by the year 2050, reaching 84 million, understanding the pathogenesis of gastric ulceration is increasingly relevant.

Dr. Amy Christine Engevik

This study described a new role for nerve growth factor (NGF) in promoting angiogenesis during gastric ulcer repair. The authors observed that aged rats exhibited low NGF levels in gastric endothelial cells that corresponded with impaired ulcer healing of the gastric mucosa following injury. Local NGF treatment to aged rats significantly increased angiogenesis and gastric regeneration. Consistent with their in vivo rat model, analysis of human gastric biopsy specimens showed that individuals more than 70 years of age had decreased expression of NGF in gastric endothelial cells, compared with individuals younger than 40 years.

Ahluwalia and colleagues are the first to demonstrate the role of NGF in aging gastropathy, and their work highlights a key mechanism of angiogenesis during gastric repair that may inform future therapeutic strategies.

Amy Christine Engevik, PhD, is a postdoctoral fellow in the division of surgical sciences at Vanderbilt University Medical Center, Nashville, Tenn. She has no conflicts of interest.

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Although the incidence of gastric ulcers has been declining in the general population, hospitalization and mortality linked to gastric ulcers remains high in the elderly population. One of the major risk factors for gastric ulceration is the use of NSAIDs. It is estimated that 40% of individuals aged 65 years and older fill at least one prescription for an NSAID each year. Given that the elderly population (those aged 65 years and older) is anticipated to more than double by the year 2050, reaching 84 million, understanding the pathogenesis of gastric ulceration is increasingly relevant.

Dr. Amy Christine Engevik

This study described a new role for nerve growth factor (NGF) in promoting angiogenesis during gastric ulcer repair. The authors observed that aged rats exhibited low NGF levels in gastric endothelial cells that corresponded with impaired ulcer healing of the gastric mucosa following injury. Local NGF treatment to aged rats significantly increased angiogenesis and gastric regeneration. Consistent with their in vivo rat model, analysis of human gastric biopsy specimens showed that individuals more than 70 years of age had decreased expression of NGF in gastric endothelial cells, compared with individuals younger than 40 years.

Ahluwalia and colleagues are the first to demonstrate the role of NGF in aging gastropathy, and their work highlights a key mechanism of angiogenesis during gastric repair that may inform future therapeutic strategies.

Amy Christine Engevik, PhD, is a postdoctoral fellow in the division of surgical sciences at Vanderbilt University Medical Center, Nashville, Tenn. She has no conflicts of interest.

Body

Although the incidence of gastric ulcers has been declining in the general population, hospitalization and mortality linked to gastric ulcers remains high in the elderly population. One of the major risk factors for gastric ulceration is the use of NSAIDs. It is estimated that 40% of individuals aged 65 years and older fill at least one prescription for an NSAID each year. Given that the elderly population (those aged 65 years and older) is anticipated to more than double by the year 2050, reaching 84 million, understanding the pathogenesis of gastric ulceration is increasingly relevant.

Dr. Amy Christine Engevik

This study described a new role for nerve growth factor (NGF) in promoting angiogenesis during gastric ulcer repair. The authors observed that aged rats exhibited low NGF levels in gastric endothelial cells that corresponded with impaired ulcer healing of the gastric mucosa following injury. Local NGF treatment to aged rats significantly increased angiogenesis and gastric regeneration. Consistent with their in vivo rat model, analysis of human gastric biopsy specimens showed that individuals more than 70 years of age had decreased expression of NGF in gastric endothelial cells, compared with individuals younger than 40 years.

Ahluwalia and colleagues are the first to demonstrate the role of NGF in aging gastropathy, and their work highlights a key mechanism of angiogenesis during gastric repair that may inform future therapeutic strategies.

Amy Christine Engevik, PhD, is a postdoctoral fellow in the division of surgical sciences at Vanderbilt University Medical Center, Nashville, Tenn. She has no conflicts of interest.

Title
Ulcers on NSAIDs
Ulcers on NSAIDs

Nerve growth factor (NGF) therapy in aging rats improves angiogenesis and speeds gastric ulcer healing, which suggests possible applications in human medicine, a recent study found.

Compared with young individuals, elderly people have significantly lower levels of NGF in gastric endothelial cells (GECs), a finding that is associated with impaired angiogenesis and delayed gastric ulcer healing.

“Our previous studies have shown that the gastric mucosa of aging individuals ... has increased susceptibility to injury and delayed healing owing to impaired angiogenesis, but the mechanisms are not fully elucidated,” wrote Amrita Ahluwalia, PhD, of Medical and Research Services at the Veterans Affairs Long Beach (Calif.) Healthcare System and her coauthors.

Mapping the drivers of angiogenesis in the gastric mucosa could lead to treatment options for elderly patients with injured or ulcerated gastric tissue. In prior trials (with rats), “treatment with VEGF [vascular endothelial growth factor] only partly reversed impaired angiogenesis in aging [GECs], indicating an essential role for other factor(s) in addition to VEGF,” the investigators wrote in the September issue of Cellular and Molecular Gastroenterology and Hepatology. They looked to NGF as another possible factor because recent studies had shown it could improve angiogenesis in the brain.

The present study measured NGF expression in rats and humans of varying ages, with NGF treatment and gene therapy performed in rats (in vitro and in vivo).

In vitro angiogenesis was 4.1-fold lower in GECs from aging rats (24 months of age) than it was in GECs from young rats (3 months of age; P less than .001). NGF protein and NGF mRNA levels were also significantly lower in aging GECs than they were with young GECs (NGF protein, 3.0-fold lower; NGF mRNA, 4.2-fold lower; P less than .001).

Treatment of aging rat GECs with exogenous NGF increased angiogenesis by 1.5-fold (P less than .001). Pretreatment with a PI3 kinase inhibitor or an mTOR inhibitor abolished this improvement, suggesting that the PI3 kinase/Akt and mTOR pathways are involved.

When NGF gene therapy was performed in aging GECs, NGF levels rose to the level of that in young GECs, with an accompanying restoration of angiogenesis (threefold increase; P less than .001). Proliferation of aging GECs also increased with gene therapy (P less than .001).

In vivo studies revealed that NGF expression and cell proliferation in aging rat gastric mucosa were lower than in younger rats. Of note, older rats treated with local NGF protein showed increased gastric mucosa angiogenesis and faster ulcer healing, compared with phosphate-buffered saline treatment.

Similar age-related NGF declines were found in humans. When gastric mucosa biopsies were collected from younger individuals (younger than 40 years old; n = 10) and compared with samples from an older population (at least 70 years old; n = 10), the investigators found that NGF expression was 5.5-fold lower in the older people (P less than .001).

“This clearly indicates human relevance of our experimental findings and also can explain impaired angiogenesis and delayed healing of injured gastric mucosa in aging individuals,” the investigators wrote.

“Aging gastropathy and its consequences are clinically critical issues,” the investigators noted, “especially because the aging U.S. population is growing rapidly and it is estimated that, by the year 2030, approximately 70 million Americans will be older than 65 years of age.” Gastric ulcers become more common with age, and individuals 70 years or older have an eightfold increased risk of associated complications, compared with people under 50 years.

The investigators noted that multiple growth factors likely play a role in stimulation of angiogenesis, including NGF, VEGF, epidermal growth factor, and basic fibroblast growth factor. “Further studies are necessary to investigate the role of other growth factors and cytokines in angiogenesis, [gastric ulcer] healing, and their impairment in aging,” the investigators concluded.

The study was funded by the Department of Veterans Affairs Biomedical Laboratory Research and Development Service. The authors declared no conflicts of interest.
 

SOURCE: Ahluwalia A et al. CMGH. 2018 May 17. doi: 10.1016/j.jcmgh.2018.05.003

Nerve growth factor (NGF) therapy in aging rats improves angiogenesis and speeds gastric ulcer healing, which suggests possible applications in human medicine, a recent study found.

Compared with young individuals, elderly people have significantly lower levels of NGF in gastric endothelial cells (GECs), a finding that is associated with impaired angiogenesis and delayed gastric ulcer healing.

“Our previous studies have shown that the gastric mucosa of aging individuals ... has increased susceptibility to injury and delayed healing owing to impaired angiogenesis, but the mechanisms are not fully elucidated,” wrote Amrita Ahluwalia, PhD, of Medical and Research Services at the Veterans Affairs Long Beach (Calif.) Healthcare System and her coauthors.

Mapping the drivers of angiogenesis in the gastric mucosa could lead to treatment options for elderly patients with injured or ulcerated gastric tissue. In prior trials (with rats), “treatment with VEGF [vascular endothelial growth factor] only partly reversed impaired angiogenesis in aging [GECs], indicating an essential role for other factor(s) in addition to VEGF,” the investigators wrote in the September issue of Cellular and Molecular Gastroenterology and Hepatology. They looked to NGF as another possible factor because recent studies had shown it could improve angiogenesis in the brain.

The present study measured NGF expression in rats and humans of varying ages, with NGF treatment and gene therapy performed in rats (in vitro and in vivo).

In vitro angiogenesis was 4.1-fold lower in GECs from aging rats (24 months of age) than it was in GECs from young rats (3 months of age; P less than .001). NGF protein and NGF mRNA levels were also significantly lower in aging GECs than they were with young GECs (NGF protein, 3.0-fold lower; NGF mRNA, 4.2-fold lower; P less than .001).

Treatment of aging rat GECs with exogenous NGF increased angiogenesis by 1.5-fold (P less than .001). Pretreatment with a PI3 kinase inhibitor or an mTOR inhibitor abolished this improvement, suggesting that the PI3 kinase/Akt and mTOR pathways are involved.

When NGF gene therapy was performed in aging GECs, NGF levels rose to the level of that in young GECs, with an accompanying restoration of angiogenesis (threefold increase; P less than .001). Proliferation of aging GECs also increased with gene therapy (P less than .001).

In vivo studies revealed that NGF expression and cell proliferation in aging rat gastric mucosa were lower than in younger rats. Of note, older rats treated with local NGF protein showed increased gastric mucosa angiogenesis and faster ulcer healing, compared with phosphate-buffered saline treatment.

Similar age-related NGF declines were found in humans. When gastric mucosa biopsies were collected from younger individuals (younger than 40 years old; n = 10) and compared with samples from an older population (at least 70 years old; n = 10), the investigators found that NGF expression was 5.5-fold lower in the older people (P less than .001).

“This clearly indicates human relevance of our experimental findings and also can explain impaired angiogenesis and delayed healing of injured gastric mucosa in aging individuals,” the investigators wrote.

“Aging gastropathy and its consequences are clinically critical issues,” the investigators noted, “especially because the aging U.S. population is growing rapidly and it is estimated that, by the year 2030, approximately 70 million Americans will be older than 65 years of age.” Gastric ulcers become more common with age, and individuals 70 years or older have an eightfold increased risk of associated complications, compared with people under 50 years.

The investigators noted that multiple growth factors likely play a role in stimulation of angiogenesis, including NGF, VEGF, epidermal growth factor, and basic fibroblast growth factor. “Further studies are necessary to investigate the role of other growth factors and cytokines in angiogenesis, [gastric ulcer] healing, and their impairment in aging,” the investigators concluded.

The study was funded by the Department of Veterans Affairs Biomedical Laboratory Research and Development Service. The authors declared no conflicts of interest.
 

SOURCE: Ahluwalia A et al. CMGH. 2018 May 17. doi: 10.1016/j.jcmgh.2018.05.003

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Key clinical point: Nerve growth factor (NGF) therapy in aging rats improves angiogenesis and speeds gastric ulcer (GU) healing, suggesting possible applications in human medicine.

Major finding: Compared with young individuals, elderly people have 5.5-fold lower NGF expression in their gastric mucosa.

Study details: A prospective study involving rats and humans, with NGF therapy performed in rats.

Disclosures: The study was funded by the Department of Veterans Affairs Biomedical Laboratory Research and Development Service. The authors declared no conflicts of interest.

Source: Ahluwalia et al. CMGH. 2018 May 17. doi: 10.1016/j.jcmgh.2018.05.003

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Study examines POEM learning curve

Sophisticated measurement technique evaluates individual learning curves
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Wed, 01/02/2019 - 10:13

Technical failures or adverse events complicated 4% of peroral endoscopic myotomies (POEMs) in a large single-center retrospective study.

Individual predictors of this composite negative outcome included case number, full-thickness myotomy, and procedure time, Zuqiang Liu, PhD, and his associates at Fudan University, Shanghai, China, wrote in the September issue of Clinical Gastroenterology and Hepatology.

After controlling for these risk factors, the composite rate of adverse events and technical failures dropped gradually after an endoscopist had performed his or her first 100 cases, according to the researchers. “Technical proficiency, demonstrated by plateauing of the procedure time, could be achieved after 70 cases,” they wrote. “The volume of cases required to manage challenging situations and prevent adverse events was thus higher than that needed for simple technical proficiency.” The experience of the training surgeon helped trainees gain technical proficiency faster, they added.

Peroral endoscopic myotomy (POEM) is minimally invasive and effectively treats spastic esophageal motility disorders. However, it is also a challenging procedure, and little is known about its learning curve. For the study, the researchers retrospectively reviewed technical failures and adverse events among 1,346 POEMs performed for achalasia at a single hospital in China between August 2010 and July 2015. They also assessed procedure time and a secondary composite outcome consisting of technical failure, adverse events, and clinical failure (further symptoms) for the first 192 cases performed by the original training surgeon.

There were 10 technical failures and 44 adverse events affecting a total of 54 patients (4%). Case number (P = .010), full-thickness myotomy (P = .002), and procedure time (P = .001) independently predicted this primary composite outcome. Adjusted cumulative sum analysis showed that the rate of this composite outcome decreased gradually after a surgeon had performed his or her first 100 cases. “The procedure time was high during the first few cases and decreased after endoscopists performed 70 cases,” indicating technical proficiency, the investigators wrote. The rate of the secondary composite outcome also fell gradually after the primary surgeon had performed between 90 and 100 cases.

For the first 192 cases performed by the lead surgeon, postprocedural follow-up time was typically 59 months, with a range of 3-71 months. Clinical failures occurred in 20 cases (10%). Rates of clinical failure were 6% at 1 year, 8% at 2 years, and 10% at 3 years.

This is the first study and the largest POEM database so far to assess the learning curve for this procedure by evaluating adverse events and clinical and technical failure, said the researchers. Previous studies consisted of small cases, usually of less than 100 patients each, they added. Such studies would inherently be biased because the smaller the caseload, the longer it might take for the learning curves of surgeons to plateau, they added.

Funders included the National Natural Science Foundation of China, the Major Project of Shanghai Municipal Science and Technology Committee, the Chen Guang Program of Shanghai Municipal Education Commission, and the Outstanding Young Doctor Training Project of Shanghai Municipal Commission of Health and Family Planning. The investigators reported having no relevant conflicts of interest.

SOURCE: Zuqiang L et al. Clin Gastroenterol Hepatol. 2017 Dec 5. doi: 10.1016/j.cgh.2017.11.048.

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Determining competency in endoscopic procedures has been a vexing challenge since the introduction of flexible endoscopy.  Traditionally, procedure volume has been used as a surrogate for technical competence. However, each endoscopist has their own learning curve. Furthermore, that curve is influenced by both the endoscopist and the characteristics of each patient. Thus, relying on procedure volume or length of time are likely inadequate markers of the true learning process. It has become more important to rely on more sophisticated measurements of competence, as illustrated in this study by Liu et al.

By using a large database of patients undergoing POEM, the authors applied risk-adjusted cumulative sum and moving averages (CUSUM) analysis to develop individual learning curves of six training endoscopists. The primary outcomes used to develop the curve were technical failure and adverse effects (likely the two outcomes patients are most concerned about). The analysis was adjusted for case complexity as well, reflecting that not all training episodes are the same. The results reveal that, although trainee endoscopists were able to perform POEM “quickly” by 70 cases, they did not achieve the more important primary outcomes of technical success and low adverse events until at least 100 procedures. This is akin to the difference between getting to the cecum quickly and having a high adenoma detection rate in colonoscopy.

Moving forward, using sophisticated measurement of individual endoscopists’ learning curves will allow maximal effectiveness of routine procedures such as colonoscopy.

Kal Patel, MD, is associate professor of medicine, Baylor College of Medicine, Houston. He has no conflicts of interest.

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Determining competency in endoscopic procedures has been a vexing challenge since the introduction of flexible endoscopy.  Traditionally, procedure volume has been used as a surrogate for technical competence. However, each endoscopist has their own learning curve. Furthermore, that curve is influenced by both the endoscopist and the characteristics of each patient. Thus, relying on procedure volume or length of time are likely inadequate markers of the true learning process. It has become more important to rely on more sophisticated measurements of competence, as illustrated in this study by Liu et al.

By using a large database of patients undergoing POEM, the authors applied risk-adjusted cumulative sum and moving averages (CUSUM) analysis to develop individual learning curves of six training endoscopists. The primary outcomes used to develop the curve were technical failure and adverse effects (likely the two outcomes patients are most concerned about). The analysis was adjusted for case complexity as well, reflecting that not all training episodes are the same. The results reveal that, although trainee endoscopists were able to perform POEM “quickly” by 70 cases, they did not achieve the more important primary outcomes of technical success and low adverse events until at least 100 procedures. This is akin to the difference between getting to the cecum quickly and having a high adenoma detection rate in colonoscopy.

Moving forward, using sophisticated measurement of individual endoscopists’ learning curves will allow maximal effectiveness of routine procedures such as colonoscopy.

Kal Patel, MD, is associate professor of medicine, Baylor College of Medicine, Houston. He has no conflicts of interest.

Body

Determining competency in endoscopic procedures has been a vexing challenge since the introduction of flexible endoscopy.  Traditionally, procedure volume has been used as a surrogate for technical competence. However, each endoscopist has their own learning curve. Furthermore, that curve is influenced by both the endoscopist and the characteristics of each patient. Thus, relying on procedure volume or length of time are likely inadequate markers of the true learning process. It has become more important to rely on more sophisticated measurements of competence, as illustrated in this study by Liu et al.

By using a large database of patients undergoing POEM, the authors applied risk-adjusted cumulative sum and moving averages (CUSUM) analysis to develop individual learning curves of six training endoscopists. The primary outcomes used to develop the curve were technical failure and adverse effects (likely the two outcomes patients are most concerned about). The analysis was adjusted for case complexity as well, reflecting that not all training episodes are the same. The results reveal that, although trainee endoscopists were able to perform POEM “quickly” by 70 cases, they did not achieve the more important primary outcomes of technical success and low adverse events until at least 100 procedures. This is akin to the difference between getting to the cecum quickly and having a high adenoma detection rate in colonoscopy.

Moving forward, using sophisticated measurement of individual endoscopists’ learning curves will allow maximal effectiveness of routine procedures such as colonoscopy.

Kal Patel, MD, is associate professor of medicine, Baylor College of Medicine, Houston. He has no conflicts of interest.

Title
Sophisticated measurement technique evaluates individual learning curves
Sophisticated measurement technique evaluates individual learning curves

Technical failures or adverse events complicated 4% of peroral endoscopic myotomies (POEMs) in a large single-center retrospective study.

Individual predictors of this composite negative outcome included case number, full-thickness myotomy, and procedure time, Zuqiang Liu, PhD, and his associates at Fudan University, Shanghai, China, wrote in the September issue of Clinical Gastroenterology and Hepatology.

After controlling for these risk factors, the composite rate of adverse events and technical failures dropped gradually after an endoscopist had performed his or her first 100 cases, according to the researchers. “Technical proficiency, demonstrated by plateauing of the procedure time, could be achieved after 70 cases,” they wrote. “The volume of cases required to manage challenging situations and prevent adverse events was thus higher than that needed for simple technical proficiency.” The experience of the training surgeon helped trainees gain technical proficiency faster, they added.

Peroral endoscopic myotomy (POEM) is minimally invasive and effectively treats spastic esophageal motility disorders. However, it is also a challenging procedure, and little is known about its learning curve. For the study, the researchers retrospectively reviewed technical failures and adverse events among 1,346 POEMs performed for achalasia at a single hospital in China between August 2010 and July 2015. They also assessed procedure time and a secondary composite outcome consisting of technical failure, adverse events, and clinical failure (further symptoms) for the first 192 cases performed by the original training surgeon.

There were 10 technical failures and 44 adverse events affecting a total of 54 patients (4%). Case number (P = .010), full-thickness myotomy (P = .002), and procedure time (P = .001) independently predicted this primary composite outcome. Adjusted cumulative sum analysis showed that the rate of this composite outcome decreased gradually after a surgeon had performed his or her first 100 cases. “The procedure time was high during the first few cases and decreased after endoscopists performed 70 cases,” indicating technical proficiency, the investigators wrote. The rate of the secondary composite outcome also fell gradually after the primary surgeon had performed between 90 and 100 cases.

For the first 192 cases performed by the lead surgeon, postprocedural follow-up time was typically 59 months, with a range of 3-71 months. Clinical failures occurred in 20 cases (10%). Rates of clinical failure were 6% at 1 year, 8% at 2 years, and 10% at 3 years.

This is the first study and the largest POEM database so far to assess the learning curve for this procedure by evaluating adverse events and clinical and technical failure, said the researchers. Previous studies consisted of small cases, usually of less than 100 patients each, they added. Such studies would inherently be biased because the smaller the caseload, the longer it might take for the learning curves of surgeons to plateau, they added.

Funders included the National Natural Science Foundation of China, the Major Project of Shanghai Municipal Science and Technology Committee, the Chen Guang Program of Shanghai Municipal Education Commission, and the Outstanding Young Doctor Training Project of Shanghai Municipal Commission of Health and Family Planning. The investigators reported having no relevant conflicts of interest.

SOURCE: Zuqiang L et al. Clin Gastroenterol Hepatol. 2017 Dec 5. doi: 10.1016/j.cgh.2017.11.048.

Technical failures or adverse events complicated 4% of peroral endoscopic myotomies (POEMs) in a large single-center retrospective study.

Individual predictors of this composite negative outcome included case number, full-thickness myotomy, and procedure time, Zuqiang Liu, PhD, and his associates at Fudan University, Shanghai, China, wrote in the September issue of Clinical Gastroenterology and Hepatology.

After controlling for these risk factors, the composite rate of adverse events and technical failures dropped gradually after an endoscopist had performed his or her first 100 cases, according to the researchers. “Technical proficiency, demonstrated by plateauing of the procedure time, could be achieved after 70 cases,” they wrote. “The volume of cases required to manage challenging situations and prevent adverse events was thus higher than that needed for simple technical proficiency.” The experience of the training surgeon helped trainees gain technical proficiency faster, they added.

Peroral endoscopic myotomy (POEM) is minimally invasive and effectively treats spastic esophageal motility disorders. However, it is also a challenging procedure, and little is known about its learning curve. For the study, the researchers retrospectively reviewed technical failures and adverse events among 1,346 POEMs performed for achalasia at a single hospital in China between August 2010 and July 2015. They also assessed procedure time and a secondary composite outcome consisting of technical failure, adverse events, and clinical failure (further symptoms) for the first 192 cases performed by the original training surgeon.

There were 10 technical failures and 44 adverse events affecting a total of 54 patients (4%). Case number (P = .010), full-thickness myotomy (P = .002), and procedure time (P = .001) independently predicted this primary composite outcome. Adjusted cumulative sum analysis showed that the rate of this composite outcome decreased gradually after a surgeon had performed his or her first 100 cases. “The procedure time was high during the first few cases and decreased after endoscopists performed 70 cases,” indicating technical proficiency, the investigators wrote. The rate of the secondary composite outcome also fell gradually after the primary surgeon had performed between 90 and 100 cases.

For the first 192 cases performed by the lead surgeon, postprocedural follow-up time was typically 59 months, with a range of 3-71 months. Clinical failures occurred in 20 cases (10%). Rates of clinical failure were 6% at 1 year, 8% at 2 years, and 10% at 3 years.

This is the first study and the largest POEM database so far to assess the learning curve for this procedure by evaluating adverse events and clinical and technical failure, said the researchers. Previous studies consisted of small cases, usually of less than 100 patients each, they added. Such studies would inherently be biased because the smaller the caseload, the longer it might take for the learning curves of surgeons to plateau, they added.

Funders included the National Natural Science Foundation of China, the Major Project of Shanghai Municipal Science and Technology Committee, the Chen Guang Program of Shanghai Municipal Education Commission, and the Outstanding Young Doctor Training Project of Shanghai Municipal Commission of Health and Family Planning. The investigators reported having no relevant conflicts of interest.

SOURCE: Zuqiang L et al. Clin Gastroenterol Hepatol. 2017 Dec 5. doi: 10.1016/j.cgh.2017.11.048.

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Key clinical point: One hundred cases was the typical learning curve for peroral endoscopic myotomy (POEM).

Major finding: The composite rate of technical failure or adverse events was 4%. An adjusted analysis showed that the rate of this negative composite outcome fell gradually after an endoscopist had performed his or her first 100 cases.

Study details: Single-center retrospective study of 1,346 patients undergoing POEM.

Disclosures: Funders included the National Natural Science Foundation of China, the Major Project of Shanghai Municipal Science and Technology Committee, the Chen Guang Program of Shanghai Municipal Education Commission, and the Outstanding Young Doctor Training Project of Shanghai Municipal Commission of Health and Family Planning. The investigators reported having no relevant conflicts of interest..

Source: Zuqiang L et al. Clin Gastroenterol Hepatol. 2017 Dec 5. doi: 10.1016/j.cgh.2017.11.048.

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Even modest alcohol use may worsen NAFLD

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Patients with nonalcoholic fatty liver disease who consumed modest quantities of alcohol had significantly less improvement in steatosis and significantly lower odds of resolution of nonalcoholic steatohepatitis, compared with nondrinkers, according to the results of a longitudinal cohort study published in the Clinical Gastroenterology and Hepatology.

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Modest drinkers also had significantly less improvement in their AST levels, compared with nondrinkers, said Veeral Ajmera, MD, of the University of California, San Diego, and his associates. “Importantly, our results suggest that cessation of alcohol use may mitigate these changes,” they wrote. Clinicians should consider the spectrum of nonalcoholic fatty liver disease (NAFLD), and especially nonalcoholic steatohepatitis (NASH), when making recommendations about alcohol use. “More advanced NAFLD severity may warrant counseling against [even] modest alcohol use.”

More than one in three adults in the United States has NAFLD and about two-thirds drink alcohol, almost always in moderation, the researchers noted. Modest alcohol use has been linked to decreased cardiovascular risk, which is particularly relevant because patients with NAFLD tend to have risk factors for cardiovascular disease. Results from at least two cross-sectional studies also suggest modest drinkers with NAFLD have less severe histology, including less NASH and fibrosis. However, modest drinkers tend to be more physically active, with lower body mass indices, higher physical activity levels, and less obesity, which are potential confounders. To better understand the effects of modest alcohol consumption on NAFLD, the researchers studied adults with NAFLD who participated in studies conducted by the multicenter NASH Clinical Research Network.

The 285 participants were typically aged in their late 40s, female, white, and obese, with an average body mass index of 34.7 kg/m2. In all, 168 participants (59%) reported consuming up to two drinks per day, while 41% abstained from alcohol use. During an average of 47 months between biopsies (standard deviation, 26 months), nondrinkers averaged a 0.49 reduction in steatosis grade, significantly more than that of modest drinkers (reduction, 0.30; P = .04). Nondrinkers also had a greater decrease in mean AST level (7 U/L), compared with drinkers (2 U/L; P = .04).

A total of 64% of patients were classified as having definite NASH, 19% had NAFLD without NASH, and 17% had borderline NASH. At baseline, 23% of patients did not have fibrosis, 32% had stage 1 fibrosis, 21% had stage 2, 21% had stage 3, and 3% had stage 4. Modest drinkers were more likely to be white and were less likely to be diagnosed with definitive NASH at baseline. After controlling for these potential confounders, modest drinkers had significantly lower odds of NASH resolution, compared with nondrinkers (adjusted odds ratio, 0.32; 95% confidence interval, 0.11-0.92; P = .04).

“[The] presence of NASH has consistently been shown to predict increased risk for fibrosis progression, and therefore, our finding of less NASH resolution among consistent modest drinkers is clinically relevant,” the investigators wrote. “Although we were unable to assess the association between modest alcohol consumption and cardiovascular risk, we did not see any significant changes in measured metabolic risk factors with known associations with cardiovascular disease including low-density lipoprotein and high-density lipoprotein cholesterol and insulin resistance.”

Funders of the study included the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Advancing Translational Sciences, the Advanced/Transplant Hepatology Fellowship, the American Association for the Study of Liver Diseases Foundation, and the Intramural Research Program of the National Institutes of Health.

SOURCE: Ajmera V et al. Clin Gastroenterol Hepatol. 2018 Mar 14. doi: 10.1016/j.cgh.2018.01.026.

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Patients with nonalcoholic fatty liver disease who consumed modest quantities of alcohol had significantly less improvement in steatosis and significantly lower odds of resolution of nonalcoholic steatohepatitis, compared with nondrinkers, according to the results of a longitudinal cohort study published in the Clinical Gastroenterology and Hepatology.

Kirby Hamilton/iStockphoto

Modest drinkers also had significantly less improvement in their AST levels, compared with nondrinkers, said Veeral Ajmera, MD, of the University of California, San Diego, and his associates. “Importantly, our results suggest that cessation of alcohol use may mitigate these changes,” they wrote. Clinicians should consider the spectrum of nonalcoholic fatty liver disease (NAFLD), and especially nonalcoholic steatohepatitis (NASH), when making recommendations about alcohol use. “More advanced NAFLD severity may warrant counseling against [even] modest alcohol use.”

More than one in three adults in the United States has NAFLD and about two-thirds drink alcohol, almost always in moderation, the researchers noted. Modest alcohol use has been linked to decreased cardiovascular risk, which is particularly relevant because patients with NAFLD tend to have risk factors for cardiovascular disease. Results from at least two cross-sectional studies also suggest modest drinkers with NAFLD have less severe histology, including less NASH and fibrosis. However, modest drinkers tend to be more physically active, with lower body mass indices, higher physical activity levels, and less obesity, which are potential confounders. To better understand the effects of modest alcohol consumption on NAFLD, the researchers studied adults with NAFLD who participated in studies conducted by the multicenter NASH Clinical Research Network.

The 285 participants were typically aged in their late 40s, female, white, and obese, with an average body mass index of 34.7 kg/m2. In all, 168 participants (59%) reported consuming up to two drinks per day, while 41% abstained from alcohol use. During an average of 47 months between biopsies (standard deviation, 26 months), nondrinkers averaged a 0.49 reduction in steatosis grade, significantly more than that of modest drinkers (reduction, 0.30; P = .04). Nondrinkers also had a greater decrease in mean AST level (7 U/L), compared with drinkers (2 U/L; P = .04).

A total of 64% of patients were classified as having definite NASH, 19% had NAFLD without NASH, and 17% had borderline NASH. At baseline, 23% of patients did not have fibrosis, 32% had stage 1 fibrosis, 21% had stage 2, 21% had stage 3, and 3% had stage 4. Modest drinkers were more likely to be white and were less likely to be diagnosed with definitive NASH at baseline. After controlling for these potential confounders, modest drinkers had significantly lower odds of NASH resolution, compared with nondrinkers (adjusted odds ratio, 0.32; 95% confidence interval, 0.11-0.92; P = .04).

“[The] presence of NASH has consistently been shown to predict increased risk for fibrosis progression, and therefore, our finding of less NASH resolution among consistent modest drinkers is clinically relevant,” the investigators wrote. “Although we were unable to assess the association between modest alcohol consumption and cardiovascular risk, we did not see any significant changes in measured metabolic risk factors with known associations with cardiovascular disease including low-density lipoprotein and high-density lipoprotein cholesterol and insulin resistance.”

Funders of the study included the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Advancing Translational Sciences, the Advanced/Transplant Hepatology Fellowship, the American Association for the Study of Liver Diseases Foundation, and the Intramural Research Program of the National Institutes of Health.

SOURCE: Ajmera V et al. Clin Gastroenterol Hepatol. 2018 Mar 14. doi: 10.1016/j.cgh.2018.01.026.

 

Patients with nonalcoholic fatty liver disease who consumed modest quantities of alcohol had significantly less improvement in steatosis and significantly lower odds of resolution of nonalcoholic steatohepatitis, compared with nondrinkers, according to the results of a longitudinal cohort study published in the Clinical Gastroenterology and Hepatology.

Kirby Hamilton/iStockphoto

Modest drinkers also had significantly less improvement in their AST levels, compared with nondrinkers, said Veeral Ajmera, MD, of the University of California, San Diego, and his associates. “Importantly, our results suggest that cessation of alcohol use may mitigate these changes,” they wrote. Clinicians should consider the spectrum of nonalcoholic fatty liver disease (NAFLD), and especially nonalcoholic steatohepatitis (NASH), when making recommendations about alcohol use. “More advanced NAFLD severity may warrant counseling against [even] modest alcohol use.”

More than one in three adults in the United States has NAFLD and about two-thirds drink alcohol, almost always in moderation, the researchers noted. Modest alcohol use has been linked to decreased cardiovascular risk, which is particularly relevant because patients with NAFLD tend to have risk factors for cardiovascular disease. Results from at least two cross-sectional studies also suggest modest drinkers with NAFLD have less severe histology, including less NASH and fibrosis. However, modest drinkers tend to be more physically active, with lower body mass indices, higher physical activity levels, and less obesity, which are potential confounders. To better understand the effects of modest alcohol consumption on NAFLD, the researchers studied adults with NAFLD who participated in studies conducted by the multicenter NASH Clinical Research Network.

The 285 participants were typically aged in their late 40s, female, white, and obese, with an average body mass index of 34.7 kg/m2. In all, 168 participants (59%) reported consuming up to two drinks per day, while 41% abstained from alcohol use. During an average of 47 months between biopsies (standard deviation, 26 months), nondrinkers averaged a 0.49 reduction in steatosis grade, significantly more than that of modest drinkers (reduction, 0.30; P = .04). Nondrinkers also had a greater decrease in mean AST level (7 U/L), compared with drinkers (2 U/L; P = .04).

A total of 64% of patients were classified as having definite NASH, 19% had NAFLD without NASH, and 17% had borderline NASH. At baseline, 23% of patients did not have fibrosis, 32% had stage 1 fibrosis, 21% had stage 2, 21% had stage 3, and 3% had stage 4. Modest drinkers were more likely to be white and were less likely to be diagnosed with definitive NASH at baseline. After controlling for these potential confounders, modest drinkers had significantly lower odds of NASH resolution, compared with nondrinkers (adjusted odds ratio, 0.32; 95% confidence interval, 0.11-0.92; P = .04).

“[The] presence of NASH has consistently been shown to predict increased risk for fibrosis progression, and therefore, our finding of less NASH resolution among consistent modest drinkers is clinically relevant,” the investigators wrote. “Although we were unable to assess the association between modest alcohol consumption and cardiovascular risk, we did not see any significant changes in measured metabolic risk factors with known associations with cardiovascular disease including low-density lipoprotein and high-density lipoprotein cholesterol and insulin resistance.”

Funders of the study included the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Advancing Translational Sciences, the Advanced/Transplant Hepatology Fellowship, the American Association for the Study of Liver Diseases Foundation, and the Intramural Research Program of the National Institutes of Health.

SOURCE: Ajmera V et al. Clin Gastroenterol Hepatol. 2018 Mar 14. doi: 10.1016/j.cgh.2018.01.026.

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Key clinical point: Consider counseling patients with more advanced nonalcoholic fatty liver disease to avoid alcohol.

Major finding: Compared with nondrinkers, patients who reported modest alcohol use had significantly less improvement in steatosis and significantly lower odds of resolution of nonalcoholic steatohepatitis (P = .04 for both comparisons).

Study details: A longitudinal cohort study of 285 adults with nonalcoholic fatty liver disease with paired biopsy specimens obtained an average of 4 years apart.

Disclosures: Funders of the study included the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Advancing Translational Sciences, the Advanced/Transplant Hepatology Fellowship, the American Association for the Study of Liver Diseases Foundation, and the Intramural Research Program of the National Institutes of Health.

Source: Ajmera V et al. Clin Gastroenterol Hepatol. 2018 Mar 14. doi: 10.1016/j.cgh.2018.01.026.

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Pancreatic surveillance identified resectable cancers

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Long-term pancreatic surveillance of high-risk patients identified cancers while they were still resectable, and 85% of such patients remained alive 3 years after diagnosis, researchers reported.

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“Among individuals undergoing pancreatic surveillance, specific detectable lesions with worrisome features predicted neoplastic progression. The short-term outcomes of patients with screening-detected PDACs [pancreatic ductal adenocarcinomas] improved,” wrote Marcia Irene Canto, MD, MHS, of the Johns Hopkins University, Baltimore, together with her associates in the September issue of Gastroenterology.

The lifetime risk of PDAC is about 1.5%, the researchers noted. Consequently, the U.S. Preventive Services Task Force does not recommend pancreatic surveillance at a population level. However, pancreatic screening is being evaluated for individuals who are at significantly elevated risk of PDAC, including those with at least two first-degree relatives with PDAC or who have germline mutations in BRCA1, BRCA2, PALB2, PRSS1 (hereditary pancreatitis), CDKN2A, MLH1, MSH2, MSH6, PMS2 (Lynch syndrome), or STK11 (Peutz-Jeghers syndrome).

For the study, Dr. Canto and her associates analyzed data from 354 such high-risk individuals enrolled in the CAPS (Cancer of the Pancreas Screening) cohort studies, which were conducted at tertiary care academic centers during 1998-2014. All participants underwent endoscopic ultrasound at baseline, followed by surveillance with endoscopic ultrasound, magnetic resonance imaging, computed tomography, or some combination of these modalities. Patients who developed pancreatic cancer or high-grade dysplasia were offered surgery.

In all, 68 patients (19%) developed pancreatic lesions with worrisome features, such as solid masses, multiple cysts, mural nodules, thickened or enhancing walls, cysts exceeding 3 cm in size or that grew more than 4 mm annually, a greater than 5-mm dilation of the main pancreatic duct, or an abrupt change in duct caliber. The lesions developed over a median of 13.1 months (interquartile range, 0.2-52 months).

A total of 7% of patients had neoplastic progression, including 14 cases of PDAC and 10 cases of high-grade dysplasia. Median times from baseline to detection of PDAC were 4.8 years overall (IQR, 1.6-6.9 years), 1.7 years (IQR, 0.5-4.4 years) among patients aged at least 60 years at baseline, and 5.2 years among younger patients (IQR, 0.4-8 years). Patients developed PDAC at a median of 67 years old.

Among 10 PDACs detected by surveillance, 9 were resectable. Three patients subsequently died of PDAC, while one patient died of complications of gastric cancer surgery. However, 85% of patients survived for at least 3 years after surgical resection of PDAC. The remaining four cases of PDAC were detected outside surveillance or after patients stopped surveillance.

The 10 cases of high-grade dysplasia consisted of intraductal papillary mucinous neoplasm with high-grade dysplasia or high-grade pancreatic intraepithelial neoplasia. Patients whose PDAC or high-grade dysplasia was detected by surveillance survived a median of 5.3 years, while patients whose surveillance was late or stopped and who subsequently developed neoplasia survived a median of only 1.4 years after diagnosis (P less than .0001).

Funders included the Pancreatic Cancer Action Network, Lustgarten Foundation for Pancreatic Cancer Research, the John and Peter Hooven Memorial Endowment, Hugh and Rachel Victor, and ChiRhoClin. Dr. Canto had no disclosures. Three coinvestigators disclosed royalties for licensing of PALB2 as a pancreatic cancer susceptibility gene.

SOURCE: Canto MI et al. Gastroenterology. 2018 May 24. doi: 10.1053/j.gastro.2018.05.035

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Long-term pancreatic surveillance of high-risk patients identified cancers while they were still resectable, and 85% of such patients remained alive 3 years after diagnosis, researchers reported.

iStock/ThinkStock

“Among individuals undergoing pancreatic surveillance, specific detectable lesions with worrisome features predicted neoplastic progression. The short-term outcomes of patients with screening-detected PDACs [pancreatic ductal adenocarcinomas] improved,” wrote Marcia Irene Canto, MD, MHS, of the Johns Hopkins University, Baltimore, together with her associates in the September issue of Gastroenterology.

The lifetime risk of PDAC is about 1.5%, the researchers noted. Consequently, the U.S. Preventive Services Task Force does not recommend pancreatic surveillance at a population level. However, pancreatic screening is being evaluated for individuals who are at significantly elevated risk of PDAC, including those with at least two first-degree relatives with PDAC or who have germline mutations in BRCA1, BRCA2, PALB2, PRSS1 (hereditary pancreatitis), CDKN2A, MLH1, MSH2, MSH6, PMS2 (Lynch syndrome), or STK11 (Peutz-Jeghers syndrome).

For the study, Dr. Canto and her associates analyzed data from 354 such high-risk individuals enrolled in the CAPS (Cancer of the Pancreas Screening) cohort studies, which were conducted at tertiary care academic centers during 1998-2014. All participants underwent endoscopic ultrasound at baseline, followed by surveillance with endoscopic ultrasound, magnetic resonance imaging, computed tomography, or some combination of these modalities. Patients who developed pancreatic cancer or high-grade dysplasia were offered surgery.

In all, 68 patients (19%) developed pancreatic lesions with worrisome features, such as solid masses, multiple cysts, mural nodules, thickened or enhancing walls, cysts exceeding 3 cm in size or that grew more than 4 mm annually, a greater than 5-mm dilation of the main pancreatic duct, or an abrupt change in duct caliber. The lesions developed over a median of 13.1 months (interquartile range, 0.2-52 months).

A total of 7% of patients had neoplastic progression, including 14 cases of PDAC and 10 cases of high-grade dysplasia. Median times from baseline to detection of PDAC were 4.8 years overall (IQR, 1.6-6.9 years), 1.7 years (IQR, 0.5-4.4 years) among patients aged at least 60 years at baseline, and 5.2 years among younger patients (IQR, 0.4-8 years). Patients developed PDAC at a median of 67 years old.

Among 10 PDACs detected by surveillance, 9 were resectable. Three patients subsequently died of PDAC, while one patient died of complications of gastric cancer surgery. However, 85% of patients survived for at least 3 years after surgical resection of PDAC. The remaining four cases of PDAC were detected outside surveillance or after patients stopped surveillance.

The 10 cases of high-grade dysplasia consisted of intraductal papillary mucinous neoplasm with high-grade dysplasia or high-grade pancreatic intraepithelial neoplasia. Patients whose PDAC or high-grade dysplasia was detected by surveillance survived a median of 5.3 years, while patients whose surveillance was late or stopped and who subsequently developed neoplasia survived a median of only 1.4 years after diagnosis (P less than .0001).

Funders included the Pancreatic Cancer Action Network, Lustgarten Foundation for Pancreatic Cancer Research, the John and Peter Hooven Memorial Endowment, Hugh and Rachel Victor, and ChiRhoClin. Dr. Canto had no disclosures. Three coinvestigators disclosed royalties for licensing of PALB2 as a pancreatic cancer susceptibility gene.

SOURCE: Canto MI et al. Gastroenterology. 2018 May 24. doi: 10.1053/j.gastro.2018.05.035

 

Long-term pancreatic surveillance of high-risk patients identified cancers while they were still resectable, and 85% of such patients remained alive 3 years after diagnosis, researchers reported.

iStock/ThinkStock

“Among individuals undergoing pancreatic surveillance, specific detectable lesions with worrisome features predicted neoplastic progression. The short-term outcomes of patients with screening-detected PDACs [pancreatic ductal adenocarcinomas] improved,” wrote Marcia Irene Canto, MD, MHS, of the Johns Hopkins University, Baltimore, together with her associates in the September issue of Gastroenterology.

The lifetime risk of PDAC is about 1.5%, the researchers noted. Consequently, the U.S. Preventive Services Task Force does not recommend pancreatic surveillance at a population level. However, pancreatic screening is being evaluated for individuals who are at significantly elevated risk of PDAC, including those with at least two first-degree relatives with PDAC or who have germline mutations in BRCA1, BRCA2, PALB2, PRSS1 (hereditary pancreatitis), CDKN2A, MLH1, MSH2, MSH6, PMS2 (Lynch syndrome), or STK11 (Peutz-Jeghers syndrome).

For the study, Dr. Canto and her associates analyzed data from 354 such high-risk individuals enrolled in the CAPS (Cancer of the Pancreas Screening) cohort studies, which were conducted at tertiary care academic centers during 1998-2014. All participants underwent endoscopic ultrasound at baseline, followed by surveillance with endoscopic ultrasound, magnetic resonance imaging, computed tomography, or some combination of these modalities. Patients who developed pancreatic cancer or high-grade dysplasia were offered surgery.

In all, 68 patients (19%) developed pancreatic lesions with worrisome features, such as solid masses, multiple cysts, mural nodules, thickened or enhancing walls, cysts exceeding 3 cm in size or that grew more than 4 mm annually, a greater than 5-mm dilation of the main pancreatic duct, or an abrupt change in duct caliber. The lesions developed over a median of 13.1 months (interquartile range, 0.2-52 months).

A total of 7% of patients had neoplastic progression, including 14 cases of PDAC and 10 cases of high-grade dysplasia. Median times from baseline to detection of PDAC were 4.8 years overall (IQR, 1.6-6.9 years), 1.7 years (IQR, 0.5-4.4 years) among patients aged at least 60 years at baseline, and 5.2 years among younger patients (IQR, 0.4-8 years). Patients developed PDAC at a median of 67 years old.

Among 10 PDACs detected by surveillance, 9 were resectable. Three patients subsequently died of PDAC, while one patient died of complications of gastric cancer surgery. However, 85% of patients survived for at least 3 years after surgical resection of PDAC. The remaining four cases of PDAC were detected outside surveillance or after patients stopped surveillance.

The 10 cases of high-grade dysplasia consisted of intraductal papillary mucinous neoplasm with high-grade dysplasia or high-grade pancreatic intraepithelial neoplasia. Patients whose PDAC or high-grade dysplasia was detected by surveillance survived a median of 5.3 years, while patients whose surveillance was late or stopped and who subsequently developed neoplasia survived a median of only 1.4 years after diagnosis (P less than .0001).

Funders included the Pancreatic Cancer Action Network, Lustgarten Foundation for Pancreatic Cancer Research, the John and Peter Hooven Memorial Endowment, Hugh and Rachel Victor, and ChiRhoClin. Dr. Canto had no disclosures. Three coinvestigators disclosed royalties for licensing of PALB2 as a pancreatic cancer susceptibility gene.

SOURCE: Canto MI et al. Gastroenterology. 2018 May 24. doi: 10.1053/j.gastro.2018.05.035

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Key clinical point: Pancreatic surveillance of high-risk individuals identified neoplasias when they were still resectable.

Major finding: Nine of ten tumors detected by surveillance were resectable, and 85% of patients remained alive 3 years after surgery, versus 25% of patients who were diagnosed after stopping or delaying surveillance (P less than .001).

Study details: Prospective cohort study of 354 high-risk individuals with 16 years of follow-up.

Disclosures: Funders included the Pancreatic Cancer Action Network, Lustgarten Foundation for Pancreatic Cancer Research, the John and Peter Hooven Memorial Endowment, Hugh and Rachel Victor, and ChiRhoClin. Dr. Canto had no disclosures. Three coinvestigators disclosed royalties for licensing of PALB2 as a pancreatic cancer susceptibility gene.

Source: Canto MI et al. Gastroenterology. 2018 May 24. doi: 10.1053/j.gastro.2018.05.035.

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Avatrombopag cut procedure-related transfusions in patients with thrombocytopenia, chronic liver disease

Avatrombopaq looks good with some caveats
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Once-daily treatment with the oral second-generation thrombopoietin agonist avatrombopag (Doptelet) significantly reduced the need for platelet transfusion and rescue therapy for up to 7 days after patients with chronic liver disease and thrombocytopenia underwent scheduled procedures, according to the results of two international, randomized, double-blind, phase III, placebo-controlled trials reported in the September issue of Gastroenterology.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

In the ADAPT-1 trial, 66% of patients in the 60-mg arm met this primary endpoint, as did 88% of patients who received 40 mg for less severe thrombocytopenia, versus 23% and 38% of the placebo arms, respectively (P less than .001 for each comparison). In the ADAPT-2 trial, 69% of the 60-mg group met the primary endpoint, as did 88% of the 40-mg group, versus 35% and 33% of the respective placebo groups (P less than .001 for each comparison).

These results led the Food and Drug Administration to approve avatrombopag in May 2018 under its priority review process. The novel therapy “may be a safe and effective alternative to platelet transfusions” that could simplify the clinical management of patients with chronic liver disease and thrombocytopenia, Norah Terrault, MD, MPH, and her associates wrote in Gastroenterology.

The ADAPT-1 study included 231 patients, while ADAPT-2 included 204 patients. In each trial, patients were randomized on a 2:1 basis to receive oral avatrombopag or placebo once daily for 5 consecutive days. Patients in the intervention arms received 60 mg avatrombopag if their baseline platelet count was less than 40 x 109 per liter, and 40 mg if their baseline platelet count was 40-50 x 109 per liter. Procedures were scheduled for 10-13 days after treatment initiation.

“Platelet counts increased by [treatment] day 4, peaked at days 10-13, and then returned to baseline levels by day 35,” the researchers reported. Among ADAPT-1 patients with low baseline counts, 69% of avatrombopag recipients reached a prespecified target of at least 50 x 109 platelets per liter on their procedure day, versus 4% of placebo recipients (P less than .0001). Corresponding proportions in ADAPT-2 were 67% and 7%, respectively (P less than .0001). Among patients with higher baseline counts, 88% and 20% achieved the target, respectively, in ADAPT-1 (P less than .0001), as did 93% versus 39%, respectively, in ADAPT-2 (P less than .0001).

Avatrombopag and placebo produced similar rates of treatment-emergent adverse events. These most often consisted of abdominal pain, dyspepsia, nausea, pyrexia, dizziness, and headache. Only three avatrombopag patients developed platelet counts above 200 x 109 per liter, and they all remained asymptomatic, the investigators said.

Dova Pharmaceuticals makes avatrombopag and funded medical writing support. Dr. Terrault and three coinvestigators disclosed ties to AbbVie, Allergan, Bristol-Myers Squibb, Eisai, Gilead, Merck, and other pharmaceutical companies. One coinvestigator is chief medical officer of Dova, helped analyze the data and write the manuscript, and gave final approval of the submitted version.

SOURCE: Terrault N et al. Gastroenterology. 2018 May 17. doi: 10.1053/j.gastro.2018.05.025.

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Thrombocytopenia in cirrhosis is frequent and multifactorial and includes sequestration in the spleen, reduced liver-derived thrombopoietin, bone marrow toxicity, and autoimmunity towards platelets. Severe thrombocytopenia (less than 50/nL) is rare in cirrhotic patients, but when it occurs may prevent required procedures from being performed or require platelet transfusions, which are associated with significant risks.

Dr. Hans L. Tillmann

Previous attempts to increase platelets in cirrhotic patients with thrombopoietin agonists were halted because of increased frequency of portal vein thrombosis and hepatic decompensation. 
Now avatrombopag has been specifically licensed with a 5-day regimen to increase platelets prior to elective interventions in severely thrombocytopenic (less than 50/nL) patients with chronic liver disease with a seemingly better safety profile than earlier treatments and good efficacy. The patient groups studied in the licensing trial had slightly milder but not significantly different liver disease, compared with those in the eltrombopag studies. The key difference was a pretreatment requirement of a portal vein flow of more than 10 cm/sec prior to enrollment, which likely reduced the risk of portal vein thrombosis. It is important that providers ready to use avatrombopag are aware of this. 

Importantly, no data are currently available for patients with a Model for End-Stage Liver Disease score greater than 24, and very limited data are available for patients with Child B and Child C cirrhosis. 

Given this limitation, careful judgment will be needed; a pretreatment portal vein flow may be advisable, though not a label requirement.

An observational study, NCT03554759, in patients with chronic liver disease and thrombocytopenia is ongoing and will further confirm the likely safety of avatrombopag.
 
Hans L. Tillmann, MD, is a clinical associate professor, East Carolina University, Greenville, and staff physician, Greenville (N.C.) VA Health Care Center. He has no relevant conflicts of interest.

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Thrombocytopenia in cirrhosis is frequent and multifactorial and includes sequestration in the spleen, reduced liver-derived thrombopoietin, bone marrow toxicity, and autoimmunity towards platelets. Severe thrombocytopenia (less than 50/nL) is rare in cirrhotic patients, but when it occurs may prevent required procedures from being performed or require platelet transfusions, which are associated with significant risks.

Dr. Hans L. Tillmann

Previous attempts to increase platelets in cirrhotic patients with thrombopoietin agonists were halted because of increased frequency of portal vein thrombosis and hepatic decompensation. 
Now avatrombopag has been specifically licensed with a 5-day regimen to increase platelets prior to elective interventions in severely thrombocytopenic (less than 50/nL) patients with chronic liver disease with a seemingly better safety profile than earlier treatments and good efficacy. The patient groups studied in the licensing trial had slightly milder but not significantly different liver disease, compared with those in the eltrombopag studies. The key difference was a pretreatment requirement of a portal vein flow of more than 10 cm/sec prior to enrollment, which likely reduced the risk of portal vein thrombosis. It is important that providers ready to use avatrombopag are aware of this. 

Importantly, no data are currently available for patients with a Model for End-Stage Liver Disease score greater than 24, and very limited data are available for patients with Child B and Child C cirrhosis. 

Given this limitation, careful judgment will be needed; a pretreatment portal vein flow may be advisable, though not a label requirement.

An observational study, NCT03554759, in patients with chronic liver disease and thrombocytopenia is ongoing and will further confirm the likely safety of avatrombopag.
 
Hans L. Tillmann, MD, is a clinical associate professor, East Carolina University, Greenville, and staff physician, Greenville (N.C.) VA Health Care Center. He has no relevant conflicts of interest.

Body

Thrombocytopenia in cirrhosis is frequent and multifactorial and includes sequestration in the spleen, reduced liver-derived thrombopoietin, bone marrow toxicity, and autoimmunity towards platelets. Severe thrombocytopenia (less than 50/nL) is rare in cirrhotic patients, but when it occurs may prevent required procedures from being performed or require platelet transfusions, which are associated with significant risks.

Dr. Hans L. Tillmann

Previous attempts to increase platelets in cirrhotic patients with thrombopoietin agonists were halted because of increased frequency of portal vein thrombosis and hepatic decompensation. 
Now avatrombopag has been specifically licensed with a 5-day regimen to increase platelets prior to elective interventions in severely thrombocytopenic (less than 50/nL) patients with chronic liver disease with a seemingly better safety profile than earlier treatments and good efficacy. The patient groups studied in the licensing trial had slightly milder but not significantly different liver disease, compared with those in the eltrombopag studies. The key difference was a pretreatment requirement of a portal vein flow of more than 10 cm/sec prior to enrollment, which likely reduced the risk of portal vein thrombosis. It is important that providers ready to use avatrombopag are aware of this. 

Importantly, no data are currently available for patients with a Model for End-Stage Liver Disease score greater than 24, and very limited data are available for patients with Child B and Child C cirrhosis. 

Given this limitation, careful judgment will be needed; a pretreatment portal vein flow may be advisable, though not a label requirement.

An observational study, NCT03554759, in patients with chronic liver disease and thrombocytopenia is ongoing and will further confirm the likely safety of avatrombopag.
 
Hans L. Tillmann, MD, is a clinical associate professor, East Carolina University, Greenville, and staff physician, Greenville (N.C.) VA Health Care Center. He has no relevant conflicts of interest.

Title
Avatrombopaq looks good with some caveats
Avatrombopaq looks good with some caveats

Once-daily treatment with the oral second-generation thrombopoietin agonist avatrombopag (Doptelet) significantly reduced the need for platelet transfusion and rescue therapy for up to 7 days after patients with chronic liver disease and thrombocytopenia underwent scheduled procedures, according to the results of two international, randomized, double-blind, phase III, placebo-controlled trials reported in the September issue of Gastroenterology.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

In the ADAPT-1 trial, 66% of patients in the 60-mg arm met this primary endpoint, as did 88% of patients who received 40 mg for less severe thrombocytopenia, versus 23% and 38% of the placebo arms, respectively (P less than .001 for each comparison). In the ADAPT-2 trial, 69% of the 60-mg group met the primary endpoint, as did 88% of the 40-mg group, versus 35% and 33% of the respective placebo groups (P less than .001 for each comparison).

These results led the Food and Drug Administration to approve avatrombopag in May 2018 under its priority review process. The novel therapy “may be a safe and effective alternative to platelet transfusions” that could simplify the clinical management of patients with chronic liver disease and thrombocytopenia, Norah Terrault, MD, MPH, and her associates wrote in Gastroenterology.

The ADAPT-1 study included 231 patients, while ADAPT-2 included 204 patients. In each trial, patients were randomized on a 2:1 basis to receive oral avatrombopag or placebo once daily for 5 consecutive days. Patients in the intervention arms received 60 mg avatrombopag if their baseline platelet count was less than 40 x 109 per liter, and 40 mg if their baseline platelet count was 40-50 x 109 per liter. Procedures were scheduled for 10-13 days after treatment initiation.

“Platelet counts increased by [treatment] day 4, peaked at days 10-13, and then returned to baseline levels by day 35,” the researchers reported. Among ADAPT-1 patients with low baseline counts, 69% of avatrombopag recipients reached a prespecified target of at least 50 x 109 platelets per liter on their procedure day, versus 4% of placebo recipients (P less than .0001). Corresponding proportions in ADAPT-2 were 67% and 7%, respectively (P less than .0001). Among patients with higher baseline counts, 88% and 20% achieved the target, respectively, in ADAPT-1 (P less than .0001), as did 93% versus 39%, respectively, in ADAPT-2 (P less than .0001).

Avatrombopag and placebo produced similar rates of treatment-emergent adverse events. These most often consisted of abdominal pain, dyspepsia, nausea, pyrexia, dizziness, and headache. Only three avatrombopag patients developed platelet counts above 200 x 109 per liter, and they all remained asymptomatic, the investigators said.

Dova Pharmaceuticals makes avatrombopag and funded medical writing support. Dr. Terrault and three coinvestigators disclosed ties to AbbVie, Allergan, Bristol-Myers Squibb, Eisai, Gilead, Merck, and other pharmaceutical companies. One coinvestigator is chief medical officer of Dova, helped analyze the data and write the manuscript, and gave final approval of the submitted version.

SOURCE: Terrault N et al. Gastroenterology. 2018 May 17. doi: 10.1053/j.gastro.2018.05.025.

Once-daily treatment with the oral second-generation thrombopoietin agonist avatrombopag (Doptelet) significantly reduced the need for platelet transfusion and rescue therapy for up to 7 days after patients with chronic liver disease and thrombocytopenia underwent scheduled procedures, according to the results of two international, randomized, double-blind, phase III, placebo-controlled trials reported in the September issue of Gastroenterology.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

In the ADAPT-1 trial, 66% of patients in the 60-mg arm met this primary endpoint, as did 88% of patients who received 40 mg for less severe thrombocytopenia, versus 23% and 38% of the placebo arms, respectively (P less than .001 for each comparison). In the ADAPT-2 trial, 69% of the 60-mg group met the primary endpoint, as did 88% of the 40-mg group, versus 35% and 33% of the respective placebo groups (P less than .001 for each comparison).

These results led the Food and Drug Administration to approve avatrombopag in May 2018 under its priority review process. The novel therapy “may be a safe and effective alternative to platelet transfusions” that could simplify the clinical management of patients with chronic liver disease and thrombocytopenia, Norah Terrault, MD, MPH, and her associates wrote in Gastroenterology.

The ADAPT-1 study included 231 patients, while ADAPT-2 included 204 patients. In each trial, patients were randomized on a 2:1 basis to receive oral avatrombopag or placebo once daily for 5 consecutive days. Patients in the intervention arms received 60 mg avatrombopag if their baseline platelet count was less than 40 x 109 per liter, and 40 mg if their baseline platelet count was 40-50 x 109 per liter. Procedures were scheduled for 10-13 days after treatment initiation.

“Platelet counts increased by [treatment] day 4, peaked at days 10-13, and then returned to baseline levels by day 35,” the researchers reported. Among ADAPT-1 patients with low baseline counts, 69% of avatrombopag recipients reached a prespecified target of at least 50 x 109 platelets per liter on their procedure day, versus 4% of placebo recipients (P less than .0001). Corresponding proportions in ADAPT-2 were 67% and 7%, respectively (P less than .0001). Among patients with higher baseline counts, 88% and 20% achieved the target, respectively, in ADAPT-1 (P less than .0001), as did 93% versus 39%, respectively, in ADAPT-2 (P less than .0001).

Avatrombopag and placebo produced similar rates of treatment-emergent adverse events. These most often consisted of abdominal pain, dyspepsia, nausea, pyrexia, dizziness, and headache. Only three avatrombopag patients developed platelet counts above 200 x 109 per liter, and they all remained asymptomatic, the investigators said.

Dova Pharmaceuticals makes avatrombopag and funded medical writing support. Dr. Terrault and three coinvestigators disclosed ties to AbbVie, Allergan, Bristol-Myers Squibb, Eisai, Gilead, Merck, and other pharmaceutical companies. One coinvestigator is chief medical officer of Dova, helped analyze the data and write the manuscript, and gave final approval of the submitted version.

SOURCE: Terrault N et al. Gastroenterology. 2018 May 17. doi: 10.1053/j.gastro.2018.05.025.

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Key clinical point: Once-daily treatment with oral avatrombopag significantly reduced the need for platelet transfusion and rescue therapy for up to 7 days after patients with chronic liver disease and thrombocytopenia underwent scheduled procedures.

Major finding: In the ADAPT-1 trial, 66% of patients in the 60-mg arm met this primary endpoint, as did 88% of patients who received 40 mg for less severe thrombocytopenia versus 23% and 38% of the placebo arms, respectively (P less than .001 for each comparison). In the ADAPT-2 trial, 69% of the 60-mg group met the primary endpoint, as did 88% of the 40-mg group versus 35% and 33% of the respective placebo groups (P less than .001 for each comparison).

Study details: ADAPT-1 and ADAPT-2, international, randomized, double-blind, placebo-controlled, phase III trials.

Disclosures: Dova Pharmaceuticals makes avatrombopag and funded medical writing support. Dr. Terrault and three coinvestigators disclosed ties to AbbVie, Allergan, BMS, Eisai, Gilead, Merck, and other pharmaceutical companies. One coinvestigator is chief medical officer of Dova, helped analyze the data and write the manuscript, and gave final approval of the submitted version.

Source: Terrault N et al. Gastroenterology. 2018 May 17. doi: 10.1053/j.gastro.2018.05.025.

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AGA Clinical Practice Update: Tumor seeding with endoscopic procedures

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Certain endoscopic procedures carry the risk of tumor seeding. In prior studies, these rates were 0.005% to 0.009% for patients undergoing percutaneous abdominal biopsy, 1.6% for percutaneous radiofrequency ablation of hepatocellular carcinoma, and 2.7% for needle biopsy of hepatocellular carcinoma. When placing percutaneous endoscopic gastrostomy tubes, the “pull-through” technique is most common but “should be avoided in all patients with oropharyngeal or esophageal cancer,” the clinical practice update states. The authors cite multiple studies linking the pull-through technique to metastasis.

Clinicians also should avoid fine needle aspiration (FNA) of primary hilar cholangiocarcinomas, especially in patients who are surgical or transplant candidates, wrote Ferga C. Gleeson, MB, BCh, and her associates, MD Anderson Cancer Center, Houston. The report is in the September issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2018.05.014).

For patients with suspected pancreatic cancer, the clinical practice update recommends endoscopic ultrasound (EUS)–guided FNA “in any site within the gland when a confirmatory diagnosis of cancer would alter patient management.” The authors also emphasize promptly closing iatrogenic perforations during endoscopic mucosal resection and endoscopic submucosal dissection and practicing nonexposure techniques during endoscopic resection of subepithelial lesions.

For patients with cholangiocarcinoma, primary tumor FNA is controversial because it can be the sole means of cancer diagnosis but also significantly increases the risk of peritoneal metastasis, especially in the setting of larger tumor size, thicker needles, multiple passes, high-grade tumors, and scanty normal tissue along the needle tract, the experts note. Because FNA “may render a patient with cholangiocarcinoma ineligible for entry into a liver transplantation protocol,” it is “best to avoid” or at least discuss with a transplant hepatologist, they add.

However, EUS is appropriate when evaluating suspicious lymphadenopathy in liver transplantation candidates with cholangiocarcinoma, they note. This is because imaging techniques have inadequate sensitivity and a positive EUS result would preclude unnecessary neoadjuvant chemoradiation and staging laparotomy. If FNA is negative, patients do require staging laparotomy to verify the absence of nodal disease before transplantation, according to the clinical practice update.

Endoscopic mucosal and submucosal resection are valuable treatment options for esophageal, gastric, and colonic dysplasia and early carcinoma, but they also can lead to unintended gastrointestinal perforation. In past studies, rates of iatrogenic perforation were 1% when patients underwent endoscopic mucosal resection and 5% when they underwent submucosal resection. For patients with any stage of gastric cancer, an accidental perforation can seed the peritoneum with cancer cells from the contents of the stomach. Contact with a primary tumor also can cause shedding of tumor cells that can enter the peritoneal cavity through a perforation. Although most of these cases do not have clinically significant outcomes, perforations need to be promptly closed and should be avoided, if at all possible, during endoscopic full-thickness resections, the experts wrote.

They recommend using nonexposure techniques while resecting subepithelial tumors and call for more safety studies of endoscopic submucosal dissection of malignancies and endoscopic full-thickness resection of subepithelial lesions. “These studies should focus on individual reports or case series of peritoneal or mediastinal examination during surgery following failed resection of these lesions,” the authors concluded.

Dr. Gleeson and her associates disclosed no funding sources and reported having no conflicts of interest.

SOURCE: Gleeson FC et al. Clin Gastroenterol Hepatol. 2018 May 17. doi: 10.1016/j.cgh.2018.05.014.

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Certain endoscopic procedures carry the risk of tumor seeding. In prior studies, these rates were 0.005% to 0.009% for patients undergoing percutaneous abdominal biopsy, 1.6% for percutaneous radiofrequency ablation of hepatocellular carcinoma, and 2.7% for needle biopsy of hepatocellular carcinoma. When placing percutaneous endoscopic gastrostomy tubes, the “pull-through” technique is most common but “should be avoided in all patients with oropharyngeal or esophageal cancer,” the clinical practice update states. The authors cite multiple studies linking the pull-through technique to metastasis.

Clinicians also should avoid fine needle aspiration (FNA) of primary hilar cholangiocarcinomas, especially in patients who are surgical or transplant candidates, wrote Ferga C. Gleeson, MB, BCh, and her associates, MD Anderson Cancer Center, Houston. The report is in the September issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2018.05.014).

For patients with suspected pancreatic cancer, the clinical practice update recommends endoscopic ultrasound (EUS)–guided FNA “in any site within the gland when a confirmatory diagnosis of cancer would alter patient management.” The authors also emphasize promptly closing iatrogenic perforations during endoscopic mucosal resection and endoscopic submucosal dissection and practicing nonexposure techniques during endoscopic resection of subepithelial lesions.

For patients with cholangiocarcinoma, primary tumor FNA is controversial because it can be the sole means of cancer diagnosis but also significantly increases the risk of peritoneal metastasis, especially in the setting of larger tumor size, thicker needles, multiple passes, high-grade tumors, and scanty normal tissue along the needle tract, the experts note. Because FNA “may render a patient with cholangiocarcinoma ineligible for entry into a liver transplantation protocol,” it is “best to avoid” or at least discuss with a transplant hepatologist, they add.

However, EUS is appropriate when evaluating suspicious lymphadenopathy in liver transplantation candidates with cholangiocarcinoma, they note. This is because imaging techniques have inadequate sensitivity and a positive EUS result would preclude unnecessary neoadjuvant chemoradiation and staging laparotomy. If FNA is negative, patients do require staging laparotomy to verify the absence of nodal disease before transplantation, according to the clinical practice update.

Endoscopic mucosal and submucosal resection are valuable treatment options for esophageal, gastric, and colonic dysplasia and early carcinoma, but they also can lead to unintended gastrointestinal perforation. In past studies, rates of iatrogenic perforation were 1% when patients underwent endoscopic mucosal resection and 5% when they underwent submucosal resection. For patients with any stage of gastric cancer, an accidental perforation can seed the peritoneum with cancer cells from the contents of the stomach. Contact with a primary tumor also can cause shedding of tumor cells that can enter the peritoneal cavity through a perforation. Although most of these cases do not have clinically significant outcomes, perforations need to be promptly closed and should be avoided, if at all possible, during endoscopic full-thickness resections, the experts wrote.

They recommend using nonexposure techniques while resecting subepithelial tumors and call for more safety studies of endoscopic submucosal dissection of malignancies and endoscopic full-thickness resection of subepithelial lesions. “These studies should focus on individual reports or case series of peritoneal or mediastinal examination during surgery following failed resection of these lesions,” the authors concluded.

Dr. Gleeson and her associates disclosed no funding sources and reported having no conflicts of interest.

SOURCE: Gleeson FC et al. Clin Gastroenterol Hepatol. 2018 May 17. doi: 10.1016/j.cgh.2018.05.014.

Certain endoscopic procedures carry the risk of tumor seeding. In prior studies, these rates were 0.005% to 0.009% for patients undergoing percutaneous abdominal biopsy, 1.6% for percutaneous radiofrequency ablation of hepatocellular carcinoma, and 2.7% for needle biopsy of hepatocellular carcinoma. When placing percutaneous endoscopic gastrostomy tubes, the “pull-through” technique is most common but “should be avoided in all patients with oropharyngeal or esophageal cancer,” the clinical practice update states. The authors cite multiple studies linking the pull-through technique to metastasis.

Clinicians also should avoid fine needle aspiration (FNA) of primary hilar cholangiocarcinomas, especially in patients who are surgical or transplant candidates, wrote Ferga C. Gleeson, MB, BCh, and her associates, MD Anderson Cancer Center, Houston. The report is in the September issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2018.05.014).

For patients with suspected pancreatic cancer, the clinical practice update recommends endoscopic ultrasound (EUS)–guided FNA “in any site within the gland when a confirmatory diagnosis of cancer would alter patient management.” The authors also emphasize promptly closing iatrogenic perforations during endoscopic mucosal resection and endoscopic submucosal dissection and practicing nonexposure techniques during endoscopic resection of subepithelial lesions.

For patients with cholangiocarcinoma, primary tumor FNA is controversial because it can be the sole means of cancer diagnosis but also significantly increases the risk of peritoneal metastasis, especially in the setting of larger tumor size, thicker needles, multiple passes, high-grade tumors, and scanty normal tissue along the needle tract, the experts note. Because FNA “may render a patient with cholangiocarcinoma ineligible for entry into a liver transplantation protocol,” it is “best to avoid” or at least discuss with a transplant hepatologist, they add.

However, EUS is appropriate when evaluating suspicious lymphadenopathy in liver transplantation candidates with cholangiocarcinoma, they note. This is because imaging techniques have inadequate sensitivity and a positive EUS result would preclude unnecessary neoadjuvant chemoradiation and staging laparotomy. If FNA is negative, patients do require staging laparotomy to verify the absence of nodal disease before transplantation, according to the clinical practice update.

Endoscopic mucosal and submucosal resection are valuable treatment options for esophageal, gastric, and colonic dysplasia and early carcinoma, but they also can lead to unintended gastrointestinal perforation. In past studies, rates of iatrogenic perforation were 1% when patients underwent endoscopic mucosal resection and 5% when they underwent submucosal resection. For patients with any stage of gastric cancer, an accidental perforation can seed the peritoneum with cancer cells from the contents of the stomach. Contact with a primary tumor also can cause shedding of tumor cells that can enter the peritoneal cavity through a perforation. Although most of these cases do not have clinically significant outcomes, perforations need to be promptly closed and should be avoided, if at all possible, during endoscopic full-thickness resections, the experts wrote.

They recommend using nonexposure techniques while resecting subepithelial tumors and call for more safety studies of endoscopic submucosal dissection of malignancies and endoscopic full-thickness resection of subepithelial lesions. “These studies should focus on individual reports or case series of peritoneal or mediastinal examination during surgery following failed resection of these lesions,” the authors concluded.

Dr. Gleeson and her associates disclosed no funding sources and reported having no conflicts of interest.

SOURCE: Gleeson FC et al. Clin Gastroenterol Hepatol. 2018 May 17. doi: 10.1016/j.cgh.2018.05.014.

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Endoscopic screening tied to significantly lower risk of death from gastric cancer

Surveillance identifies more cancers earlier
Article Type
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Wed, 05/26/2021 - 13:49

Endoscopic screening was associated with an approximately 40% reduction in risk of death from gastric cancer in a systematic review and meta-analysis of studies from Asian countries.

The study is the first systematic review and meta-analysis of gastric cancer mortality and incidence after endoscopic screening, wrote Xing Zhang, MD, of the China Academy of Chinese Medical Sciences in Beijing with his associates. “Population-based prospective cohort studies are warranted to confirm our findings,” the reviewers wrote in the August issue of Gastroenterology.

In general, the rates of gastric cancer and related mortality in East Asian countries are significantly higher than global averages. As a result, countries in this region have implemented a variety of national and opportunistic screening programs that vary from country to country. Japan, for example, has a national screening program based on photofluorography. “Although data are inconsistent, most studies have shown a 40%-60% decrease in the mortality of gastric cancer in those who have been screened using photofluorography,” the reviewers noted. When findings are positive, follow-up endoscopy is recommended. However, debates persist about whether population-level endoscopy significantly improves hard endpoints in gastric cancer, such as incidence and mortality.

To help clarify the population-level benefits of endoscopic screening, Dr. Zhang and his associates searched PubMed and EMBASE; they identified six cohort studies and four nested case-control studies that included approximately 342,000 adults from Asia who did not have baseline gastric cancer but did undergo surveillance endoscopy at least once. Studies of both mass and opportunistic screening were included. Each study included a comparator; reported incidence, mortality, or both; and was published by March 8, 2018.

Endoscopic screening was tied to a 40% reduction in the relative risk of death from gastric cancer (risk ratio, 0.60; 95% confidence interval, 0.49-0.73). There also was a slight trend toward increased incidence of gastric cancer, which was not statistically significant (RR, 1.14; 95% CI, 0.93-1.40). However, only two studies examined the incidence of gastric cancer, so this outcome “should be interpreted with caution,” the reviewers wrote. Endoscopic screening also was associated with a significantly lower risk of death from gastric cancer, compared with radiographic screening (RR, 0.33; 95% CI, 0.12-0.91).

Endoscopic screening did not significantly reduce mortality, compared with expected deaths (RR, 0.67; 95% CI, 0.38-1.16), the reviewers reported. This might be because the reviewers included an outlier study conducted in Linqu County, China, which has some of the highest rates of gastric cancer death in the world, they noted. Endoscopic surveillance did not reduce mortality in the Linqu County study, but screenings were spaced by 4.5 years, which was probably too long to show an effect, especially in a high-risk region, they added. The study in Linqu County accounted for most of the heterogeneity among studies, and removing it from the pooled analysis produced a “slightly more pronounced reduction in gastric cancer mortality,” with an RR of 0.56, they noted.

Funders included the National Natural Science Foundation and the National Twelfth Five-Year Plan for Science and Technology Support Program of China. The reviewers reported having no relevant conflicts of interest.

SOURCE: Zhang X, et al. Gastroenterology. 2018 Apr 30. doi: 10.1053/j.gastro.2018.04.026.

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Gastric cancer remains the third most common cause of cancer death worldwide, although incidence and mortality rates have been declining for several years. For populations in eastern Asia – a region that carries the unenviable tag of having the highest gastric cancer mortality rates in the world – finding ways to reduce the burden of this disease remains a key priority. 
New findings reported by Zhang and his colleagues have highlighted a strong evidence base for one mode of gastric cancer control in eastern Asia. The systematic review team demonstrated a significant 40% reduction in the risk of death from gastric cancer when screening was conducted in general populations. The magnitude of this benefit likely reflects the appropriateness of screening in such high-incidence areas, although this finding might not necessarily be extrapolated to other regions. 

The authors cautioned that screening did not reduce gastric cancer incidence, although only two studies were included. However, reduced incidence is often not an aim of screening programs; indeed, to detect more gastric cancers at an earlier stage can be an intentional outcome. 

The observed benefits might be somewhat attributed to lead time bias (whereby individuals are diagnosed at a younger age than they would have presented symptomatically but still die at the same age) or length time bias (detecting only the slower-growing biological tumors). Further refinement of optimal screening intervals is also required. Nevertheless, public health policy makers in Japan and Korea, where national screening programs already exist, should be reassured by these review findings.   

Helen Coleman, PhD, BSc(Hons), is a senior lecturer and lead of the Cancer Epidemiology Research Group at the Centre for Public Health and Centre for Cancer Research and Cell Biology at Queen’s University Belfast. She has no conflicts of interest.

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Gastric cancer remains the third most common cause of cancer death worldwide, although incidence and mortality rates have been declining for several years. For populations in eastern Asia – a region that carries the unenviable tag of having the highest gastric cancer mortality rates in the world – finding ways to reduce the burden of this disease remains a key priority. 
New findings reported by Zhang and his colleagues have highlighted a strong evidence base for one mode of gastric cancer control in eastern Asia. The systematic review team demonstrated a significant 40% reduction in the risk of death from gastric cancer when screening was conducted in general populations. The magnitude of this benefit likely reflects the appropriateness of screening in such high-incidence areas, although this finding might not necessarily be extrapolated to other regions. 

The authors cautioned that screening did not reduce gastric cancer incidence, although only two studies were included. However, reduced incidence is often not an aim of screening programs; indeed, to detect more gastric cancers at an earlier stage can be an intentional outcome. 

The observed benefits might be somewhat attributed to lead time bias (whereby individuals are diagnosed at a younger age than they would have presented symptomatically but still die at the same age) or length time bias (detecting only the slower-growing biological tumors). Further refinement of optimal screening intervals is also required. Nevertheless, public health policy makers in Japan and Korea, where national screening programs already exist, should be reassured by these review findings.   

Helen Coleman, PhD, BSc(Hons), is a senior lecturer and lead of the Cancer Epidemiology Research Group at the Centre for Public Health and Centre for Cancer Research and Cell Biology at Queen’s University Belfast. She has no conflicts of interest.

Body

Gastric cancer remains the third most common cause of cancer death worldwide, although incidence and mortality rates have been declining for several years. For populations in eastern Asia – a region that carries the unenviable tag of having the highest gastric cancer mortality rates in the world – finding ways to reduce the burden of this disease remains a key priority. 
New findings reported by Zhang and his colleagues have highlighted a strong evidence base for one mode of gastric cancer control in eastern Asia. The systematic review team demonstrated a significant 40% reduction in the risk of death from gastric cancer when screening was conducted in general populations. The magnitude of this benefit likely reflects the appropriateness of screening in such high-incidence areas, although this finding might not necessarily be extrapolated to other regions. 

The authors cautioned that screening did not reduce gastric cancer incidence, although only two studies were included. However, reduced incidence is often not an aim of screening programs; indeed, to detect more gastric cancers at an earlier stage can be an intentional outcome. 

The observed benefits might be somewhat attributed to lead time bias (whereby individuals are diagnosed at a younger age than they would have presented symptomatically but still die at the same age) or length time bias (detecting only the slower-growing biological tumors). Further refinement of optimal screening intervals is also required. Nevertheless, public health policy makers in Japan and Korea, where national screening programs already exist, should be reassured by these review findings.   

Helen Coleman, PhD, BSc(Hons), is a senior lecturer and lead of the Cancer Epidemiology Research Group at the Centre for Public Health and Centre for Cancer Research and Cell Biology at Queen’s University Belfast. She has no conflicts of interest.

Title
Surveillance identifies more cancers earlier
Surveillance identifies more cancers earlier

Endoscopic screening was associated with an approximately 40% reduction in risk of death from gastric cancer in a systematic review and meta-analysis of studies from Asian countries.

The study is the first systematic review and meta-analysis of gastric cancer mortality and incidence after endoscopic screening, wrote Xing Zhang, MD, of the China Academy of Chinese Medical Sciences in Beijing with his associates. “Population-based prospective cohort studies are warranted to confirm our findings,” the reviewers wrote in the August issue of Gastroenterology.

In general, the rates of gastric cancer and related mortality in East Asian countries are significantly higher than global averages. As a result, countries in this region have implemented a variety of national and opportunistic screening programs that vary from country to country. Japan, for example, has a national screening program based on photofluorography. “Although data are inconsistent, most studies have shown a 40%-60% decrease in the mortality of gastric cancer in those who have been screened using photofluorography,” the reviewers noted. When findings are positive, follow-up endoscopy is recommended. However, debates persist about whether population-level endoscopy significantly improves hard endpoints in gastric cancer, such as incidence and mortality.

To help clarify the population-level benefits of endoscopic screening, Dr. Zhang and his associates searched PubMed and EMBASE; they identified six cohort studies and four nested case-control studies that included approximately 342,000 adults from Asia who did not have baseline gastric cancer but did undergo surveillance endoscopy at least once. Studies of both mass and opportunistic screening were included. Each study included a comparator; reported incidence, mortality, or both; and was published by March 8, 2018.

Endoscopic screening was tied to a 40% reduction in the relative risk of death from gastric cancer (risk ratio, 0.60; 95% confidence interval, 0.49-0.73). There also was a slight trend toward increased incidence of gastric cancer, which was not statistically significant (RR, 1.14; 95% CI, 0.93-1.40). However, only two studies examined the incidence of gastric cancer, so this outcome “should be interpreted with caution,” the reviewers wrote. Endoscopic screening also was associated with a significantly lower risk of death from gastric cancer, compared with radiographic screening (RR, 0.33; 95% CI, 0.12-0.91).

Endoscopic screening did not significantly reduce mortality, compared with expected deaths (RR, 0.67; 95% CI, 0.38-1.16), the reviewers reported. This might be because the reviewers included an outlier study conducted in Linqu County, China, which has some of the highest rates of gastric cancer death in the world, they noted. Endoscopic surveillance did not reduce mortality in the Linqu County study, but screenings were spaced by 4.5 years, which was probably too long to show an effect, especially in a high-risk region, they added. The study in Linqu County accounted for most of the heterogeneity among studies, and removing it from the pooled analysis produced a “slightly more pronounced reduction in gastric cancer mortality,” with an RR of 0.56, they noted.

Funders included the National Natural Science Foundation and the National Twelfth Five-Year Plan for Science and Technology Support Program of China. The reviewers reported having no relevant conflicts of interest.

SOURCE: Zhang X, et al. Gastroenterology. 2018 Apr 30. doi: 10.1053/j.gastro.2018.04.026.

Endoscopic screening was associated with an approximately 40% reduction in risk of death from gastric cancer in a systematic review and meta-analysis of studies from Asian countries.

The study is the first systematic review and meta-analysis of gastric cancer mortality and incidence after endoscopic screening, wrote Xing Zhang, MD, of the China Academy of Chinese Medical Sciences in Beijing with his associates. “Population-based prospective cohort studies are warranted to confirm our findings,” the reviewers wrote in the August issue of Gastroenterology.

In general, the rates of gastric cancer and related mortality in East Asian countries are significantly higher than global averages. As a result, countries in this region have implemented a variety of national and opportunistic screening programs that vary from country to country. Japan, for example, has a national screening program based on photofluorography. “Although data are inconsistent, most studies have shown a 40%-60% decrease in the mortality of gastric cancer in those who have been screened using photofluorography,” the reviewers noted. When findings are positive, follow-up endoscopy is recommended. However, debates persist about whether population-level endoscopy significantly improves hard endpoints in gastric cancer, such as incidence and mortality.

To help clarify the population-level benefits of endoscopic screening, Dr. Zhang and his associates searched PubMed and EMBASE; they identified six cohort studies and four nested case-control studies that included approximately 342,000 adults from Asia who did not have baseline gastric cancer but did undergo surveillance endoscopy at least once. Studies of both mass and opportunistic screening were included. Each study included a comparator; reported incidence, mortality, or both; and was published by March 8, 2018.

Endoscopic screening was tied to a 40% reduction in the relative risk of death from gastric cancer (risk ratio, 0.60; 95% confidence interval, 0.49-0.73). There also was a slight trend toward increased incidence of gastric cancer, which was not statistically significant (RR, 1.14; 95% CI, 0.93-1.40). However, only two studies examined the incidence of gastric cancer, so this outcome “should be interpreted with caution,” the reviewers wrote. Endoscopic screening also was associated with a significantly lower risk of death from gastric cancer, compared with radiographic screening (RR, 0.33; 95% CI, 0.12-0.91).

Endoscopic screening did not significantly reduce mortality, compared with expected deaths (RR, 0.67; 95% CI, 0.38-1.16), the reviewers reported. This might be because the reviewers included an outlier study conducted in Linqu County, China, which has some of the highest rates of gastric cancer death in the world, they noted. Endoscopic surveillance did not reduce mortality in the Linqu County study, but screenings were spaced by 4.5 years, which was probably too long to show an effect, especially in a high-risk region, they added. The study in Linqu County accounted for most of the heterogeneity among studies, and removing it from the pooled analysis produced a “slightly more pronounced reduction in gastric cancer mortality,” with an RR of 0.56, they noted.

Funders included the National Natural Science Foundation and the National Twelfth Five-Year Plan for Science and Technology Support Program of China. The reviewers reported having no relevant conflicts of interest.

SOURCE: Zhang X, et al. Gastroenterology. 2018 Apr 30. doi: 10.1053/j.gastro.2018.04.026.

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Key clinical point: Endoscopic screening was associated with a significant decrease in risk of death from gastric cancer.

Major finding: Compared with no screening, the reduction in risk was 40% (risk ratio, 0.60; 95% confidence interval, 0.49-0.73).

Study details: Systematic review and meta-analysis of six cohort studies and four nested case-control studies of approximately 342,000 adults.

Disclosures: Funders included the National Natural Science Foundation and the National Twelfth Five-Year Plan for Science and Technology Support Program of China. The reviewers reported having no relevant conflicts of interest.

Source: Zhang X et al. Gastroenterology. 2018 Apr 30. doi: 10.1053/j.gastro.2018.04.026.

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Fine-needle aspirate, biopsy found equivalent in randomized trial

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For patients with pancreatic masses, infiltrated lymph nodes, or submucosal tumors, endoscopic ultrasound-guided fine-needle aspirate and fine-needle biopsy produced a comparable diagnostic yield with a similar number of needle passes, according to the results of a multicenter, randomized clinical trial.

Diagnostic yields were 91% for fine-needle aspirate versus 89% for fine-needle biopsy, with a median of one needle pass needed to obtain a diagnostic sample for each technique, reported Satish Nagula, MD, of the Icahn School of Medicine at Mount Sinai, New York, and his associates. The findings were published in the August issue of Clinical Gastroenterology and Hepatology.

Previously, two small, single-center randomized trials yielded conflicting data on whether fine-needle biopsy produces better diagnostic yield than fine-needle aspirate, the investigators noted. The results of four other studies indicated that the two techniques performed similarly. However, “many of these trials had study designs that did not allow for realistic comparisons of needle performance,” they noted. For example, the studies only analyzed the results of the first needle pass or only included specimens with visible core tissue.

The current study included six tertiary care centers that perform high volumes of endoscopic ultrasound. In all, 135 patients were randomly assigned to undergo fine-needle aspirate or fine-needle biopsy. When rapid on-site cytologic evaluation was used, the clinicians made consecutive needle passes until they considered the specimen adequate. Most lesions (77%) were masses, but 17% were lymph nodes, and 7% were submucosal tumors, the researchers said. The endoscopists used a curvilinear array echoendoscope (GF-UC140P or GF-UCT140; Olympus America, Central Valley, Penn.). They performed fine-needle aspirate or biopsy by using either a 22-gauge or 25-gauge needle at their own discretion.

The final diagnosis was malignancy for 70% of lesions, reactive lymphadenopathy for 11% of lesions, and spindle cell tumors in 9% of cases, the investigators said. Diagnostic yield was similar whether or not rapid on-site cytologic evaluation was used. Fine-needle aspiration detected cancer with a sensitivity of 90% and a specificity of 100%. Fine-needle biopsy had a sensitivity of 89% and a specificity of 100%. Adverse events were uncommon (1%), but one patient was hospitalized with pancreatitis for 2 days after undergoing fine-needle biopsy of a pancreatic body lesion.

The researchers noted several study limitations. “Ideally, each patient would undergo both fine-needle aspirate and fine-needle biopsy, allowing each as their own internal control,” they wrote. “It was considered too expensive to use two different needles in this unfunded study.” There also was no central pathology review, which they called “fiscally not feasible.”

There were no funding sources, and the investigators reported having no relevant conflicts of interest.SOURCE: Nagula S et al. Clin Gastroenterol Hepatol. 2017 Jun 14. doi: 10.1016/j.cgh.2017.06.013.

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For patients with pancreatic masses, infiltrated lymph nodes, or submucosal tumors, endoscopic ultrasound-guided fine-needle aspirate and fine-needle biopsy produced a comparable diagnostic yield with a similar number of needle passes, according to the results of a multicenter, randomized clinical trial.

Diagnostic yields were 91% for fine-needle aspirate versus 89% for fine-needle biopsy, with a median of one needle pass needed to obtain a diagnostic sample for each technique, reported Satish Nagula, MD, of the Icahn School of Medicine at Mount Sinai, New York, and his associates. The findings were published in the August issue of Clinical Gastroenterology and Hepatology.

Previously, two small, single-center randomized trials yielded conflicting data on whether fine-needle biopsy produces better diagnostic yield than fine-needle aspirate, the investigators noted. The results of four other studies indicated that the two techniques performed similarly. However, “many of these trials had study designs that did not allow for realistic comparisons of needle performance,” they noted. For example, the studies only analyzed the results of the first needle pass or only included specimens with visible core tissue.

The current study included six tertiary care centers that perform high volumes of endoscopic ultrasound. In all, 135 patients were randomly assigned to undergo fine-needle aspirate or fine-needle biopsy. When rapid on-site cytologic evaluation was used, the clinicians made consecutive needle passes until they considered the specimen adequate. Most lesions (77%) were masses, but 17% were lymph nodes, and 7% were submucosal tumors, the researchers said. The endoscopists used a curvilinear array echoendoscope (GF-UC140P or GF-UCT140; Olympus America, Central Valley, Penn.). They performed fine-needle aspirate or biopsy by using either a 22-gauge or 25-gauge needle at their own discretion.

The final diagnosis was malignancy for 70% of lesions, reactive lymphadenopathy for 11% of lesions, and spindle cell tumors in 9% of cases, the investigators said. Diagnostic yield was similar whether or not rapid on-site cytologic evaluation was used. Fine-needle aspiration detected cancer with a sensitivity of 90% and a specificity of 100%. Fine-needle biopsy had a sensitivity of 89% and a specificity of 100%. Adverse events were uncommon (1%), but one patient was hospitalized with pancreatitis for 2 days after undergoing fine-needle biopsy of a pancreatic body lesion.

The researchers noted several study limitations. “Ideally, each patient would undergo both fine-needle aspirate and fine-needle biopsy, allowing each as their own internal control,” they wrote. “It was considered too expensive to use two different needles in this unfunded study.” There also was no central pathology review, which they called “fiscally not feasible.”

There were no funding sources, and the investigators reported having no relevant conflicts of interest.SOURCE: Nagula S et al. Clin Gastroenterol Hepatol. 2017 Jun 14. doi: 10.1016/j.cgh.2017.06.013.

 

For patients with pancreatic masses, infiltrated lymph nodes, or submucosal tumors, endoscopic ultrasound-guided fine-needle aspirate and fine-needle biopsy produced a comparable diagnostic yield with a similar number of needle passes, according to the results of a multicenter, randomized clinical trial.

Diagnostic yields were 91% for fine-needle aspirate versus 89% for fine-needle biopsy, with a median of one needle pass needed to obtain a diagnostic sample for each technique, reported Satish Nagula, MD, of the Icahn School of Medicine at Mount Sinai, New York, and his associates. The findings were published in the August issue of Clinical Gastroenterology and Hepatology.

Previously, two small, single-center randomized trials yielded conflicting data on whether fine-needle biopsy produces better diagnostic yield than fine-needle aspirate, the investigators noted. The results of four other studies indicated that the two techniques performed similarly. However, “many of these trials had study designs that did not allow for realistic comparisons of needle performance,” they noted. For example, the studies only analyzed the results of the first needle pass or only included specimens with visible core tissue.

The current study included six tertiary care centers that perform high volumes of endoscopic ultrasound. In all, 135 patients were randomly assigned to undergo fine-needle aspirate or fine-needle biopsy. When rapid on-site cytologic evaluation was used, the clinicians made consecutive needle passes until they considered the specimen adequate. Most lesions (77%) were masses, but 17% were lymph nodes, and 7% were submucosal tumors, the researchers said. The endoscopists used a curvilinear array echoendoscope (GF-UC140P or GF-UCT140; Olympus America, Central Valley, Penn.). They performed fine-needle aspirate or biopsy by using either a 22-gauge or 25-gauge needle at their own discretion.

The final diagnosis was malignancy for 70% of lesions, reactive lymphadenopathy for 11% of lesions, and spindle cell tumors in 9% of cases, the investigators said. Diagnostic yield was similar whether or not rapid on-site cytologic evaluation was used. Fine-needle aspiration detected cancer with a sensitivity of 90% and a specificity of 100%. Fine-needle biopsy had a sensitivity of 89% and a specificity of 100%. Adverse events were uncommon (1%), but one patient was hospitalized with pancreatitis for 2 days after undergoing fine-needle biopsy of a pancreatic body lesion.

The researchers noted several study limitations. “Ideally, each patient would undergo both fine-needle aspirate and fine-needle biopsy, allowing each as their own internal control,” they wrote. “It was considered too expensive to use two different needles in this unfunded study.” There also was no central pathology review, which they called “fiscally not feasible.”

There were no funding sources, and the investigators reported having no relevant conflicts of interest.SOURCE: Nagula S et al. Clin Gastroenterol Hepatol. 2017 Jun 14. doi: 10.1016/j.cgh.2017.06.013.

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Key clinical point: Endoscopic ultrasound-guided final-needle aspirate and fine-needle biopsy performed similarly in solid lesions.

Major finding: Diagnostic yields were 91% for fine-needle aspirate and 89% for fine-needle biopsy, with a median of one needle pass needed to obtain a diagnostic sample for each technique.

Study details: Multicenter randomized study of 135 patients.

Disclosures: The study was not funded, and the investigators reported having no relevant conflicts of interest.

Source: Nagula S et al. Clin Gastroenterol Hepatol. 2017 Jun 14. doi: 10.1016/j.cgh.2017.06.013.

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Who are the 'high-need, high-cost' patients?

Help these patients without hospitalization
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Among patients hospitalized with gastrointestinal and liver diseases, a clearly identifiable subset uses significantly more health care resources, which incurs significantly greater costs, according to the results of a national database analysis published in the August issue of Clinical Gastroenterology and Hepatology.

Compared with otherwise similar inpatients, these “high-need, high-cost” individuals are significantly more likely to be enrolled in Medicare or Medicaid, to have lower income, to initially be admitted to a large, rural hospital, to have multiple comorbidities, to be obese, or to be hospitalized for infection, said Nghia Nguyen, MD, and his associates. “[A] small fraction of high-need, high-cost patients contribute disproportionately to hospitalization costs,” they wrote. “Population health management directed toward these patients would facilitate high-value care.”

Gastrointestinal and liver diseases incur more than $100 billion in health care expenses annually in the United States, of which more than 60% is related to inpatient care, the researchers noted. However, few studies have comprehensively evaluated the annual burden and costs of hospitalization in patients with chronic gastrointestinal and liver diseases. Therefore, using the Nationwide Readmissions Database, the investigators studied patients with inflammatory bowel disease (IBD), chronic liver disease, functional gastrointestinal disorders, gastrointestinal hemorrhage, or pancreatic diseases who were hospitalized at least once during the first 6 months of 2013. All patients were diagnosed with IBD, chronic liver diseases, functional gastrointestinal disorders, gastrointestinal hemorrhage, or pancreatic diseases and followed for at least 6 months. The researchers stratified hospital days and costs and characterized the subset of patients who fell into the highest decile of days spent in the hospital per month.

The most common reason for hospitalization was chronic liver disease (nearly 377,000 patients), followed by functional gastrointestinal disorders (more than 351,000 patients), gastrointestinal hemorrhage (nearly 191,000 patients), pancreatic diseases (more than 98,000 patients), and IBD (more than 47,000 patients). Patients spent a median of 6-7 days in the hospital per year, with an interquartile range of 3-14 days. Compared with patients in the lowest decile for annual hospital stay (median, 0.13-0.14 days per month), patients in the highest decile spent a median of 3.7-5.1 days in the hospital per month. In this high-cost, high-need subset of patients, the costs of each hospitalization ranged from $7,438 per month to $11,425 per month, and they were typically hospitalized once every 2 months.

“Gastrointestinal diseases, infections, and cardiopulmonary causes were leading reasons for hospitalization of these patients,” the researchers wrote. “At a patient level, modifiable risk factors may include tackling the obesity epidemic and mental health issues and minimizing risk of iatrogenic or health care–associated infections, whereas at a health system level, interventions may include better access to care and connectivity between rural and specialty hospitals.”

Funders included the American College of Gastroenterology, the Crohn’s and Colitis Foundation, and the National Institutes of Health. Senior author Siddharth Singh disclosed unrelated grant funding from Pifzer and AbbVie. The other investigators reported having no conflicts of interest.

SOURCE: Nguyen NH et al. Clin Gastroenterol Hepatol. 2018 Feb 20. doi: 10.1016/j.cgh.2018.02.015.

Body

 

Understanding the reasons underlying variations in health care utilization is central to any plan to reduce costs at the population level. To this end, Nguyen et al. provide crucial data for the patients for whom we care as gastroenterologists. Studying a longitudinal database of hospitalizations in 2013, the authors provide comprehensive demographic data for the top decile of inpatient health care utilizers (defined by hospital-days/month) with inflammatory bowel disease, chronic liver disease, functional gastrointestinal disorders, gastrointestinal hemorrhage, and pancreatic diseases. Although constrained by the limits of administrative data and the lack of outpatient/pharmaceutical data linkage, these findings are strengthened by their consistency across conditions. Indeed, despite the heterogeneous disorders surveyed, a remarkably consistent high-need/high-cost "phenotype" emerges: publicly insured, low-income, rural, obese but malnourished, and beset by infections and the complications of diabetes.

Dr. Elliot Tapper
   

What are the next steps?  

When a minority of the patients are responsible for a substantial portion of the costs (i.e., the 80/20 rule), one strategy for cost containment is "hot-spotting." Hot-spotting is a two-step process: Identify high-need, high-cost patients, and then deploy interventions tailored to their needs. Nguyen and colleague's work is a landmark for the first step. However, before these findings may be translated into policy or intervention, we need granular data to explain these associations and suggest clear action items. Solutions will likely be multifactorial including early, intensified care for obesity and diabetes (before end-stage complications arise), novel care delivery methods for gastroenterology specialty care in rural hospitals, and intensified outpatient resources for high-need patients in order to coordinate alternatives to hospitalization.
 
Elliot B. Tapper, MD, is assistant professor, division of gastroenterology and hepatology, University of Michigan, Ann Arbor. He reports consulting for Novartis and receiving unrestricted research grants from Valeant and Gilead, all unrelated to this work.

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Understanding the reasons underlying variations in health care utilization is central to any plan to reduce costs at the population level. To this end, Nguyen et al. provide crucial data for the patients for whom we care as gastroenterologists. Studying a longitudinal database of hospitalizations in 2013, the authors provide comprehensive demographic data for the top decile of inpatient health care utilizers (defined by hospital-days/month) with inflammatory bowel disease, chronic liver disease, functional gastrointestinal disorders, gastrointestinal hemorrhage, and pancreatic diseases. Although constrained by the limits of administrative data and the lack of outpatient/pharmaceutical data linkage, these findings are strengthened by their consistency across conditions. Indeed, despite the heterogeneous disorders surveyed, a remarkably consistent high-need/high-cost "phenotype" emerges: publicly insured, low-income, rural, obese but malnourished, and beset by infections and the complications of diabetes.

Dr. Elliot Tapper
   

What are the next steps?  

When a minority of the patients are responsible for a substantial portion of the costs (i.e., the 80/20 rule), one strategy for cost containment is "hot-spotting." Hot-spotting is a two-step process: Identify high-need, high-cost patients, and then deploy interventions tailored to their needs. Nguyen and colleague's work is a landmark for the first step. However, before these findings may be translated into policy or intervention, we need granular data to explain these associations and suggest clear action items. Solutions will likely be multifactorial including early, intensified care for obesity and diabetes (before end-stage complications arise), novel care delivery methods for gastroenterology specialty care in rural hospitals, and intensified outpatient resources for high-need patients in order to coordinate alternatives to hospitalization.
 
Elliot B. Tapper, MD, is assistant professor, division of gastroenterology and hepatology, University of Michigan, Ann Arbor. He reports consulting for Novartis and receiving unrestricted research grants from Valeant and Gilead, all unrelated to this work.

Body

 

Understanding the reasons underlying variations in health care utilization is central to any plan to reduce costs at the population level. To this end, Nguyen et al. provide crucial data for the patients for whom we care as gastroenterologists. Studying a longitudinal database of hospitalizations in 2013, the authors provide comprehensive demographic data for the top decile of inpatient health care utilizers (defined by hospital-days/month) with inflammatory bowel disease, chronic liver disease, functional gastrointestinal disorders, gastrointestinal hemorrhage, and pancreatic diseases. Although constrained by the limits of administrative data and the lack of outpatient/pharmaceutical data linkage, these findings are strengthened by their consistency across conditions. Indeed, despite the heterogeneous disorders surveyed, a remarkably consistent high-need/high-cost "phenotype" emerges: publicly insured, low-income, rural, obese but malnourished, and beset by infections and the complications of diabetes.

Dr. Elliot Tapper
   

What are the next steps?  

When a minority of the patients are responsible for a substantial portion of the costs (i.e., the 80/20 rule), one strategy for cost containment is "hot-spotting." Hot-spotting is a two-step process: Identify high-need, high-cost patients, and then deploy interventions tailored to their needs. Nguyen and colleague's work is a landmark for the first step. However, before these findings may be translated into policy or intervention, we need granular data to explain these associations and suggest clear action items. Solutions will likely be multifactorial including early, intensified care for obesity and diabetes (before end-stage complications arise), novel care delivery methods for gastroenterology specialty care in rural hospitals, and intensified outpatient resources for high-need patients in order to coordinate alternatives to hospitalization.
 
Elliot B. Tapper, MD, is assistant professor, division of gastroenterology and hepatology, University of Michigan, Ann Arbor. He reports consulting for Novartis and receiving unrestricted research grants from Valeant and Gilead, all unrelated to this work.

Title
Help these patients without hospitalization
Help these patients without hospitalization

Among patients hospitalized with gastrointestinal and liver diseases, a clearly identifiable subset uses significantly more health care resources, which incurs significantly greater costs, according to the results of a national database analysis published in the August issue of Clinical Gastroenterology and Hepatology.

Compared with otherwise similar inpatients, these “high-need, high-cost” individuals are significantly more likely to be enrolled in Medicare or Medicaid, to have lower income, to initially be admitted to a large, rural hospital, to have multiple comorbidities, to be obese, or to be hospitalized for infection, said Nghia Nguyen, MD, and his associates. “[A] small fraction of high-need, high-cost patients contribute disproportionately to hospitalization costs,” they wrote. “Population health management directed toward these patients would facilitate high-value care.”

Gastrointestinal and liver diseases incur more than $100 billion in health care expenses annually in the United States, of which more than 60% is related to inpatient care, the researchers noted. However, few studies have comprehensively evaluated the annual burden and costs of hospitalization in patients with chronic gastrointestinal and liver diseases. Therefore, using the Nationwide Readmissions Database, the investigators studied patients with inflammatory bowel disease (IBD), chronic liver disease, functional gastrointestinal disorders, gastrointestinal hemorrhage, or pancreatic diseases who were hospitalized at least once during the first 6 months of 2013. All patients were diagnosed with IBD, chronic liver diseases, functional gastrointestinal disorders, gastrointestinal hemorrhage, or pancreatic diseases and followed for at least 6 months. The researchers stratified hospital days and costs and characterized the subset of patients who fell into the highest decile of days spent in the hospital per month.

The most common reason for hospitalization was chronic liver disease (nearly 377,000 patients), followed by functional gastrointestinal disorders (more than 351,000 patients), gastrointestinal hemorrhage (nearly 191,000 patients), pancreatic diseases (more than 98,000 patients), and IBD (more than 47,000 patients). Patients spent a median of 6-7 days in the hospital per year, with an interquartile range of 3-14 days. Compared with patients in the lowest decile for annual hospital stay (median, 0.13-0.14 days per month), patients in the highest decile spent a median of 3.7-5.1 days in the hospital per month. In this high-cost, high-need subset of patients, the costs of each hospitalization ranged from $7,438 per month to $11,425 per month, and they were typically hospitalized once every 2 months.

“Gastrointestinal diseases, infections, and cardiopulmonary causes were leading reasons for hospitalization of these patients,” the researchers wrote. “At a patient level, modifiable risk factors may include tackling the obesity epidemic and mental health issues and minimizing risk of iatrogenic or health care–associated infections, whereas at a health system level, interventions may include better access to care and connectivity between rural and specialty hospitals.”

Funders included the American College of Gastroenterology, the Crohn’s and Colitis Foundation, and the National Institutes of Health. Senior author Siddharth Singh disclosed unrelated grant funding from Pifzer and AbbVie. The other investigators reported having no conflicts of interest.

SOURCE: Nguyen NH et al. Clin Gastroenterol Hepatol. 2018 Feb 20. doi: 10.1016/j.cgh.2018.02.015.

Among patients hospitalized with gastrointestinal and liver diseases, a clearly identifiable subset uses significantly more health care resources, which incurs significantly greater costs, according to the results of a national database analysis published in the August issue of Clinical Gastroenterology and Hepatology.

Compared with otherwise similar inpatients, these “high-need, high-cost” individuals are significantly more likely to be enrolled in Medicare or Medicaid, to have lower income, to initially be admitted to a large, rural hospital, to have multiple comorbidities, to be obese, or to be hospitalized for infection, said Nghia Nguyen, MD, and his associates. “[A] small fraction of high-need, high-cost patients contribute disproportionately to hospitalization costs,” they wrote. “Population health management directed toward these patients would facilitate high-value care.”

Gastrointestinal and liver diseases incur more than $100 billion in health care expenses annually in the United States, of which more than 60% is related to inpatient care, the researchers noted. However, few studies have comprehensively evaluated the annual burden and costs of hospitalization in patients with chronic gastrointestinal and liver diseases. Therefore, using the Nationwide Readmissions Database, the investigators studied patients with inflammatory bowel disease (IBD), chronic liver disease, functional gastrointestinal disorders, gastrointestinal hemorrhage, or pancreatic diseases who were hospitalized at least once during the first 6 months of 2013. All patients were diagnosed with IBD, chronic liver diseases, functional gastrointestinal disorders, gastrointestinal hemorrhage, or pancreatic diseases and followed for at least 6 months. The researchers stratified hospital days and costs and characterized the subset of patients who fell into the highest decile of days spent in the hospital per month.

The most common reason for hospitalization was chronic liver disease (nearly 377,000 patients), followed by functional gastrointestinal disorders (more than 351,000 patients), gastrointestinal hemorrhage (nearly 191,000 patients), pancreatic diseases (more than 98,000 patients), and IBD (more than 47,000 patients). Patients spent a median of 6-7 days in the hospital per year, with an interquartile range of 3-14 days. Compared with patients in the lowest decile for annual hospital stay (median, 0.13-0.14 days per month), patients in the highest decile spent a median of 3.7-5.1 days in the hospital per month. In this high-cost, high-need subset of patients, the costs of each hospitalization ranged from $7,438 per month to $11,425 per month, and they were typically hospitalized once every 2 months.

“Gastrointestinal diseases, infections, and cardiopulmonary causes were leading reasons for hospitalization of these patients,” the researchers wrote. “At a patient level, modifiable risk factors may include tackling the obesity epidemic and mental health issues and minimizing risk of iatrogenic or health care–associated infections, whereas at a health system level, interventions may include better access to care and connectivity between rural and specialty hospitals.”

Funders included the American College of Gastroenterology, the Crohn’s and Colitis Foundation, and the National Institutes of Health. Senior author Siddharth Singh disclosed unrelated grant funding from Pifzer and AbbVie. The other investigators reported having no conflicts of interest.

SOURCE: Nguyen NH et al. Clin Gastroenterol Hepatol. 2018 Feb 20. doi: 10.1016/j.cgh.2018.02.015.

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Key clinical point: For patients with gastrointestinal or liver disease, significant predictors of high need and cost during hospitalization included Medicare or Medicaid insurance, lower income, first hospitalization in a large rural hospital, high comorbidity burden, obesity, and hospitalization for infection.

Major finding: Patients in the highest decile spent a median of 3.7-4.1 days in the hospital per month for all causes. Gastrointestinal disease, infections, and cardiopulmonary morbidity were the most common reasons for hospitalization.

Study details: Analysis of patients with inflammatory bowel disease, chronic liver disease, functional gastrointestinal disorders, gastrointestinal hemorrhage, or pancreatic diseases hospitalized at least once during 2013.

Disclosures: Funders included the American College of Gastroenterology, the Crohn’s and Colitis Foundation, and the National Institutes of Health. Senior author Siddharth Singh disclosed unrelated grant funding from Pifzer and AbbVie. The other investigators reported having no conflicts of interest.

Source: Nguyen NH et al. Clin Gastroenterol Hepatol. 2018 Feb 20. doi: 10.1016/j.cgh.2018.02.015.

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AGA Clinical Practice Update: Statins are safe, effective, and important for most patients with liver disease and dyslipidemia

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Lipid-lowering agents are safe and effective in patients with most liver diseases and should be used when indicated to reduce the risk of cardiovascular disease.

The medications are only contraindicated in patients with decompensated cirrhosis and statin-induced liver injury, Elizabeth Speliotes, MD, PhD, MPH, and her colleagues wrote in an expert review published in Clinical Gastroenterology and Hepatology. In these patients, statin treatment can compound liver damage and should be avoided, wrote Dr. Speliotes and her coauthors.

Dr. Elizabeth Speliotes

Because the liver plays a central role in cholesterol production, many clinicians shy away from treating hyperlipidemia in patients with liver disease. But studies consistently show that lipid-lowering drugs improve dyslipidemia in these patients, which significantly improves both high- and low-density lipoproteins and thereby reduces the long-term risk of cardiovascular disease, the authors wrote.

“Furthermore, the liver plays a role in the metabolism of many drugs, including those that are used to treat dyslipidemia,” wrote Dr. Speliotes of the University of Michigan, Ann Arbor. “It is not surprising, therefore, that many practitioners are hesitant to prescribe medicines to treat dyslipidemia in the setting of liver disease.”

Cholesterol targets described in the 2013 American College of Cardiology/American Heart Association guidelines can safely be applied to patients with liver disease. “The guidelines recommend that adults with cardiovascular disease or LDL of 190 mg/dL or higher be treated with high-intensity statins with the goal of reducing LDL levels by 50%,” they said. Patients whose LDL is 189 mg/dL or lower will benefit from moderate-intensity statins, with a target of a 30%-50% decrease in LDL.

The authors described best practice advice for dyslipidemia treatment in six liver diseases: drug-induced liver injury (DILI), nonalcoholic fatty liver disease (NAFLD), viral hepatitis B and C (HBV and HCV), primary biliary cholangitis (PBC), cirrhosis, and posttransplant dyslipidemia.
 

DILI

DILI is characterized by elevations of threefold or more in serum alanine aminotransferase (ALT) or aspartate aminotransferase and at least a doubling of total serum bilirubin with no other identifiable cause of these aberrations except the suspect drug. Statins rarely cause a DILI (1 in 100,000 patients), but can cause transient, benign ALT elevations. Statins should be discontinued if ALT or aspartate aminotransferase levels exceed a tripling of the upper limit of normal with concomitant bilirubin elevations. They should not be prescribed to patients with acute liver failure or decompensated liver disease, but otherwise they are safe for most patients with liver disease.

NAFLD

Many patients with NAFLD also have dyslipidemia. All NAFLD patients have an increased risk of cardiovascular disease, although NAFLD and nonalcoholic steatohepatitis are not traditional cardiovascular risk factors. Nevertheless, statins and the accompanying improvement in dyslipidemia have been shown to decrease cardiovascular mortality in these patients. The IDEAL study, for example, showed that moderate statin treatment with 80 mg atorvastatin was associated with a 44% decreased risk in secondary cardiovascular events. Other studies show similar results.

NAFLD patients with elevated LDL may benefit from ezetimibe as primary or add-on therapy. However, none of the drugs used to treat dyslipidemia will improve NAFLD or nonalcoholic steatohepatitis histology.
 

 

 

Viral hepatitis

Hepatitis C virus

Patients with HCV infection often experience decreased serum LDL and total cholesterol. However, these are virally mediated and don’t confer cardiovascular protection. In fact, HCV infections are associated with an increased risk of myocardial infarction. If the patient spontaneously clears the virus, lipids may rebound, so levels should be regularly monitored even if the patient does not need statin therapy.

Hepatitis B virus

HBV also interacts with lipid metabolism and can lead to hyperlipidemia. The American College of Cardiology/American Heart Association guidelines for cardiovascular risk assessment and statin therapy apply to these patients. Statins are safe in patients with either HCV or HBV, who tolerate them well.

PBC

PBC is a chronic autoimmune inflammatory cholestatic disease that is associated with dyslipidemia. These patients exhibit increased serum triglyceride and HDL levels that vary according to PBC stage. About 10% have a significant risk of cardiovascular disease. PBC patients with compensated liver disease can safely tolerate statin treatment, but the drugs should not be given to PBC patients with decompensated liver disease.

Obeticholic acid (OCA) is sometimes used as second-line therapy for PBC; it affects genes that regulate bile acid synthesis, transport, and action. However, the POISE study showed that, while OCA improved PBC symptoms, it was associated with an increase in LDL and total cholesterol and a decrease in HDL. No follow-up studies have determined cardiovascular implications of that change, but OCA should be avoided in patients with active cardiovascular disease or with cardiovascular risk factors.
 

Cirrhosis

Recent work suggests that patients with cirrhosis may face a higher risk of coronary artery disease than was previously thought, although that risk varies widely according to the etiology of the cirrhosis.

Statins are safe and effective in patients with Child-Pugh class A cirrhosis; there are few data on their safety in patients with decompensated cirrhosis. Some guidance for these patients exists in the 2014 recommendations of the Liver Expert Panel, which advised against statin use in patients with Child-Pugh class B or C cirrhosis.

There’s some evidence that statins reduce portal pressure and may reduce the risk of decompensation in patients whose cirrhosis is caused by HCV or HBV infections, but they should not be used for this purpose.
 

Posttransplant dyslipidemia

After liver transplant, more than 60% of patients will develop dyslipidemia; these patients often have obesity or diabetes.

Statins are safe for patients with liver transplant. Concomitant use of calcineurin inhibitors and statins that are metabolized by cytochrome P450 may increase the risk of statin-associated myopathy. Pravastatin and fluvastatin are preferable, because they are metabolized by cytochrome P450 34A.



Neither Dr. Speliotes nor her coauthors had any financial disclosures.

SOURCE: Speliotes EK et al. Clin Gastroenterol Hepatol. 2018 Apr 21. doi: 10.1016/j.cgh.2018.04.023.

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Lipid-lowering agents are safe and effective in patients with most liver diseases and should be used when indicated to reduce the risk of cardiovascular disease.

The medications are only contraindicated in patients with decompensated cirrhosis and statin-induced liver injury, Elizabeth Speliotes, MD, PhD, MPH, and her colleagues wrote in an expert review published in Clinical Gastroenterology and Hepatology. In these patients, statin treatment can compound liver damage and should be avoided, wrote Dr. Speliotes and her coauthors.

Dr. Elizabeth Speliotes

Because the liver plays a central role in cholesterol production, many clinicians shy away from treating hyperlipidemia in patients with liver disease. But studies consistently show that lipid-lowering drugs improve dyslipidemia in these patients, which significantly improves both high- and low-density lipoproteins and thereby reduces the long-term risk of cardiovascular disease, the authors wrote.

“Furthermore, the liver plays a role in the metabolism of many drugs, including those that are used to treat dyslipidemia,” wrote Dr. Speliotes of the University of Michigan, Ann Arbor. “It is not surprising, therefore, that many practitioners are hesitant to prescribe medicines to treat dyslipidemia in the setting of liver disease.”

Cholesterol targets described in the 2013 American College of Cardiology/American Heart Association guidelines can safely be applied to patients with liver disease. “The guidelines recommend that adults with cardiovascular disease or LDL of 190 mg/dL or higher be treated with high-intensity statins with the goal of reducing LDL levels by 50%,” they said. Patients whose LDL is 189 mg/dL or lower will benefit from moderate-intensity statins, with a target of a 30%-50% decrease in LDL.

The authors described best practice advice for dyslipidemia treatment in six liver diseases: drug-induced liver injury (DILI), nonalcoholic fatty liver disease (NAFLD), viral hepatitis B and C (HBV and HCV), primary biliary cholangitis (PBC), cirrhosis, and posttransplant dyslipidemia.
 

DILI

DILI is characterized by elevations of threefold or more in serum alanine aminotransferase (ALT) or aspartate aminotransferase and at least a doubling of total serum bilirubin with no other identifiable cause of these aberrations except the suspect drug. Statins rarely cause a DILI (1 in 100,000 patients), but can cause transient, benign ALT elevations. Statins should be discontinued if ALT or aspartate aminotransferase levels exceed a tripling of the upper limit of normal with concomitant bilirubin elevations. They should not be prescribed to patients with acute liver failure or decompensated liver disease, but otherwise they are safe for most patients with liver disease.

NAFLD

Many patients with NAFLD also have dyslipidemia. All NAFLD patients have an increased risk of cardiovascular disease, although NAFLD and nonalcoholic steatohepatitis are not traditional cardiovascular risk factors. Nevertheless, statins and the accompanying improvement in dyslipidemia have been shown to decrease cardiovascular mortality in these patients. The IDEAL study, for example, showed that moderate statin treatment with 80 mg atorvastatin was associated with a 44% decreased risk in secondary cardiovascular events. Other studies show similar results.

NAFLD patients with elevated LDL may benefit from ezetimibe as primary or add-on therapy. However, none of the drugs used to treat dyslipidemia will improve NAFLD or nonalcoholic steatohepatitis histology.
 

 

 

Viral hepatitis

Hepatitis C virus

Patients with HCV infection often experience decreased serum LDL and total cholesterol. However, these are virally mediated and don’t confer cardiovascular protection. In fact, HCV infections are associated with an increased risk of myocardial infarction. If the patient spontaneously clears the virus, lipids may rebound, so levels should be regularly monitored even if the patient does not need statin therapy.

Hepatitis B virus

HBV also interacts with lipid metabolism and can lead to hyperlipidemia. The American College of Cardiology/American Heart Association guidelines for cardiovascular risk assessment and statin therapy apply to these patients. Statins are safe in patients with either HCV or HBV, who tolerate them well.

PBC

PBC is a chronic autoimmune inflammatory cholestatic disease that is associated with dyslipidemia. These patients exhibit increased serum triglyceride and HDL levels that vary according to PBC stage. About 10% have a significant risk of cardiovascular disease. PBC patients with compensated liver disease can safely tolerate statin treatment, but the drugs should not be given to PBC patients with decompensated liver disease.

Obeticholic acid (OCA) is sometimes used as second-line therapy for PBC; it affects genes that regulate bile acid synthesis, transport, and action. However, the POISE study showed that, while OCA improved PBC symptoms, it was associated with an increase in LDL and total cholesterol and a decrease in HDL. No follow-up studies have determined cardiovascular implications of that change, but OCA should be avoided in patients with active cardiovascular disease or with cardiovascular risk factors.
 

Cirrhosis

Recent work suggests that patients with cirrhosis may face a higher risk of coronary artery disease than was previously thought, although that risk varies widely according to the etiology of the cirrhosis.

Statins are safe and effective in patients with Child-Pugh class A cirrhosis; there are few data on their safety in patients with decompensated cirrhosis. Some guidance for these patients exists in the 2014 recommendations of the Liver Expert Panel, which advised against statin use in patients with Child-Pugh class B or C cirrhosis.

There’s some evidence that statins reduce portal pressure and may reduce the risk of decompensation in patients whose cirrhosis is caused by HCV or HBV infections, but they should not be used for this purpose.
 

Posttransplant dyslipidemia

After liver transplant, more than 60% of patients will develop dyslipidemia; these patients often have obesity or diabetes.

Statins are safe for patients with liver transplant. Concomitant use of calcineurin inhibitors and statins that are metabolized by cytochrome P450 may increase the risk of statin-associated myopathy. Pravastatin and fluvastatin are preferable, because they are metabolized by cytochrome P450 34A.



Neither Dr. Speliotes nor her coauthors had any financial disclosures.

SOURCE: Speliotes EK et al. Clin Gastroenterol Hepatol. 2018 Apr 21. doi: 10.1016/j.cgh.2018.04.023.

 

Lipid-lowering agents are safe and effective in patients with most liver diseases and should be used when indicated to reduce the risk of cardiovascular disease.

The medications are only contraindicated in patients with decompensated cirrhosis and statin-induced liver injury, Elizabeth Speliotes, MD, PhD, MPH, and her colleagues wrote in an expert review published in Clinical Gastroenterology and Hepatology. In these patients, statin treatment can compound liver damage and should be avoided, wrote Dr. Speliotes and her coauthors.

Dr. Elizabeth Speliotes

Because the liver plays a central role in cholesterol production, many clinicians shy away from treating hyperlipidemia in patients with liver disease. But studies consistently show that lipid-lowering drugs improve dyslipidemia in these patients, which significantly improves both high- and low-density lipoproteins and thereby reduces the long-term risk of cardiovascular disease, the authors wrote.

“Furthermore, the liver plays a role in the metabolism of many drugs, including those that are used to treat dyslipidemia,” wrote Dr. Speliotes of the University of Michigan, Ann Arbor. “It is not surprising, therefore, that many practitioners are hesitant to prescribe medicines to treat dyslipidemia in the setting of liver disease.”

Cholesterol targets described in the 2013 American College of Cardiology/American Heart Association guidelines can safely be applied to patients with liver disease. “The guidelines recommend that adults with cardiovascular disease or LDL of 190 mg/dL or higher be treated with high-intensity statins with the goal of reducing LDL levels by 50%,” they said. Patients whose LDL is 189 mg/dL or lower will benefit from moderate-intensity statins, with a target of a 30%-50% decrease in LDL.

The authors described best practice advice for dyslipidemia treatment in six liver diseases: drug-induced liver injury (DILI), nonalcoholic fatty liver disease (NAFLD), viral hepatitis B and C (HBV and HCV), primary biliary cholangitis (PBC), cirrhosis, and posttransplant dyslipidemia.
 

DILI

DILI is characterized by elevations of threefold or more in serum alanine aminotransferase (ALT) or aspartate aminotransferase and at least a doubling of total serum bilirubin with no other identifiable cause of these aberrations except the suspect drug. Statins rarely cause a DILI (1 in 100,000 patients), but can cause transient, benign ALT elevations. Statins should be discontinued if ALT or aspartate aminotransferase levels exceed a tripling of the upper limit of normal with concomitant bilirubin elevations. They should not be prescribed to patients with acute liver failure or decompensated liver disease, but otherwise they are safe for most patients with liver disease.

NAFLD

Many patients with NAFLD also have dyslipidemia. All NAFLD patients have an increased risk of cardiovascular disease, although NAFLD and nonalcoholic steatohepatitis are not traditional cardiovascular risk factors. Nevertheless, statins and the accompanying improvement in dyslipidemia have been shown to decrease cardiovascular mortality in these patients. The IDEAL study, for example, showed that moderate statin treatment with 80 mg atorvastatin was associated with a 44% decreased risk in secondary cardiovascular events. Other studies show similar results.

NAFLD patients with elevated LDL may benefit from ezetimibe as primary or add-on therapy. However, none of the drugs used to treat dyslipidemia will improve NAFLD or nonalcoholic steatohepatitis histology.
 

 

 

Viral hepatitis

Hepatitis C virus

Patients with HCV infection often experience decreased serum LDL and total cholesterol. However, these are virally mediated and don’t confer cardiovascular protection. In fact, HCV infections are associated with an increased risk of myocardial infarction. If the patient spontaneously clears the virus, lipids may rebound, so levels should be regularly monitored even if the patient does not need statin therapy.

Hepatitis B virus

HBV also interacts with lipid metabolism and can lead to hyperlipidemia. The American College of Cardiology/American Heart Association guidelines for cardiovascular risk assessment and statin therapy apply to these patients. Statins are safe in patients with either HCV or HBV, who tolerate them well.

PBC

PBC is a chronic autoimmune inflammatory cholestatic disease that is associated with dyslipidemia. These patients exhibit increased serum triglyceride and HDL levels that vary according to PBC stage. About 10% have a significant risk of cardiovascular disease. PBC patients with compensated liver disease can safely tolerate statin treatment, but the drugs should not be given to PBC patients with decompensated liver disease.

Obeticholic acid (OCA) is sometimes used as second-line therapy for PBC; it affects genes that regulate bile acid synthesis, transport, and action. However, the POISE study showed that, while OCA improved PBC symptoms, it was associated with an increase in LDL and total cholesterol and a decrease in HDL. No follow-up studies have determined cardiovascular implications of that change, but OCA should be avoided in patients with active cardiovascular disease or with cardiovascular risk factors.
 

Cirrhosis

Recent work suggests that patients with cirrhosis may face a higher risk of coronary artery disease than was previously thought, although that risk varies widely according to the etiology of the cirrhosis.

Statins are safe and effective in patients with Child-Pugh class A cirrhosis; there are few data on their safety in patients with decompensated cirrhosis. Some guidance for these patients exists in the 2014 recommendations of the Liver Expert Panel, which advised against statin use in patients with Child-Pugh class B or C cirrhosis.

There’s some evidence that statins reduce portal pressure and may reduce the risk of decompensation in patients whose cirrhosis is caused by HCV or HBV infections, but they should not be used for this purpose.
 

Posttransplant dyslipidemia

After liver transplant, more than 60% of patients will develop dyslipidemia; these patients often have obesity or diabetes.

Statins are safe for patients with liver transplant. Concomitant use of calcineurin inhibitors and statins that are metabolized by cytochrome P450 may increase the risk of statin-associated myopathy. Pravastatin and fluvastatin are preferable, because they are metabolized by cytochrome P450 34A.



Neither Dr. Speliotes nor her coauthors had any financial disclosures.

SOURCE: Speliotes EK et al. Clin Gastroenterol Hepatol. 2018 Apr 21. doi: 10.1016/j.cgh.2018.04.023.

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