From the AGA Journals

Inflammatory bowel disease (IBD) does not seem to make patients any more likely to contract SARS-COV-2 or develop COVID-19, but a rapid review commissioned by the American Gastroenterological Association acknowledges that determination is based on limited evidence and IBD patients should nonetheless maintain remission to reduce their risk of relapse or hospitalization during the COVID-19 pandemic.

The AGA has published a clinical practice update based on that rapid review online in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.04.012).

Because of the widespread use of immunosuppressive or immune-modifying drugs, “It is understandable why patients with Crohn’s disease and ulcerative colitis have specific concerns and potential for increased risk of infection with SARS-CoV-2,” wrote David T. Rubin, MD, AGAF, of the University of Chicago and colleagues in the expert commentary.

They noted that, while association between GI symptoms and COVID-19 RNA in stool samples isn’t clear, given the reports of GI symptoms in COVID-19 patients – ranging from 10% (JAMA. 2020:323:1061-9) to half of patients (Am J Gastroenterol. 2020;115:766-73) – “the clinical implications of this are quite important.” In IBD patients, changes in digestive symptoms without accompanying fever or respiratory symptoms can be monitored for symptoms that could merit testing for the virus as well as “trigger additional treatment adjustments.”

In accordance with the IOIBD (International Organization for the Study of Inflammatory Bowel Disease) consensus, the update noted that IBD patients should continue going to infusion centers for therapies, provided that the centers use a COVID-19 screening protocol.

Patients with IBD who contract COVID-19 seem more likely to be hospitalized for one or the other disease, but that’s based on data from the international SECURE-IBD registry that had 164 patients as of the writing of the update. The update provides guidance for three scenarios for IBD patients during the pandemic:

• Patients not infected with SARS-CoV-2 should maintain their IBD therapies to sustain remission and avoid relapses. “Aside from the obvious negative consequences of a relapse, relapsing IBD will strain available medical resources, may require steroid therapy or necessitate hospitalization, outcomes that are all much worse than the known risks of existing IBD therapies,” Dr. Rubin and colleagues noted.
• Patients who are infected but have no symptoms of COVID-19 should have their dosing of prednisone adjusted to less than 20 mg/day or switched to budesonide; suspend thiopurines, methotrexate, and tofacitinib; and delay dosing of monoclonal antibodies (anti–tumor necrosis factor [anti-TNF] drugs, ustekinumab, or vedolizumab) for 2 weeks while their symptoms for COVID-19 are monitored. “Restarting therapy after 2 weeks if the patient has not developed manifestations of COVID-19 is reasonable,” wrote Dr. Rubin and colleagues. Emerging serial testing should indicate antibody status, but the effectiveness of stool testing for SARS-CoV-2 in these cases “remains to be seen.”
• In the patient with confirmed COVID-19, adjustment of IBD therapy “is appropriate, based on the understanding of the immune activity of the therapy and whether that therapy may worsen outcomes with COVID-19,” the update stated. Therapy adjustment should focus on reducing immune suppression during the active viral infection. Some studies are evaluating anticytokine-based therapies as COVID-19 treatments, so continued anti-TNF therapies might prevent acute respiratory distress syndrome and multiorgan failure, Dr. Rubin and colleagues wrote. “However, in the absence of those data, guidance is currently based on deciding whether to hold or to continue specific IBD therapies.”

The update considers most IBD therapies, specifically aminosalicylates, topical rectal therapy, dietary management, and antibiotics “safe and may be continued,” and oral budesonide can be continued if it’s needed for ongoing IBD control. However, corticosteroids “should be avoided and discontinued quickly.”

Likewise, during the acute stage of COVID-19, thiopurines, methotrexate, and tofacitinib should be discontinued, and anti-TNF drugs and ustekinumab should be stopped during viral illness. Holding vedolizumab during viral illness is also appropriate, according to the update, although the IOIBD group was uncertain if doing so was necessary.

If the IBD patient has digestive symptoms with COVID-19, ongoing supportive care of the COVID-19 is “reasonable,” but investigating the causes of the digestive symptoms “is critically important.” That should include ruling out enteric infections and confirming active inflammation with nonendoscopic testing. Endoscopy should be relegated to only urgent and emergent cases.

Management of IBD in COVID-19 patients also depends on disease severity. Safer therapies are indicated for mild disease, but withholding IBD therapy in moderate to severe cases may not be practical. “In this setting, the risks and benefits of escalating IBD therapy must be carefully weighed against the severity of the COVID-19,” Dr. Rubin and colleagues noted.

In hospitalized patients with severe COVID-19 and poor prognoses, “IBD therapy will likely take a back seat,” the update stated, although COVID-19 therapies should take the concomitant IBD into account. In patients with milder cases of COVID-19, IBD management should focus on acute manifestations, but intravenous steroid therapy shouldn’t exceed 3 days. The update urged providers to submit cases of IBD and confirmed COVID-19 to the SECURE-IBD registry at COVIDIBD.org.

Dr. Rubin disclosed financial relationships with AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene/Syneos, Gilead Sciences, Takeda, and many other pharmaceutical companies. Coauthors disclosed relationships with those companies and Medimmune, Novus Therapeutics, Osiris Therapeutics, RedHill Biopharma, Sanofi-Aventis, UCB Pharma, and multiple other pharmaceutical companies.

SOURCE: Rubin DT, et al. Gastroenterology. 2020:  doi: 10.1053/j.gastro.2020.04.012

Inflammatory bowel disease (IBD) does not seem to make patients any more likely to contract SARS-COV-2 or develop COVID-19, but a rapid review commissioned by the American Gastroenterological Association acknowledges that determination is based on limited evidence and IBD patients should nonetheless maintain remission to reduce their risk of relapse or hospitalization during the COVID-19 pandemic.

The AGA has published a clinical practice update based on that rapid review online in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.04.012).

Because of the widespread use of immunosuppressive or immune-modifying drugs, “It is understandable why patients with Crohn’s disease and ulcerative colitis have specific concerns and potential for increased risk of infection with SARS-CoV-2,” wrote David T. Rubin, MD, AGAF, of the University of Chicago and colleagues in the expert commentary.

They noted that, while association between GI symptoms and COVID-19 RNA in stool samples isn’t clear, given the reports of GI symptoms in COVID-19 patients – ranging from 10% (JAMA. 2020:323:1061-9) to half of patients (Am J Gastroenterol. 2020;115:766-73) – “the clinical implications of this are quite important.” In IBD patients, changes in digestive symptoms without accompanying fever or respiratory symptoms can be monitored for symptoms that could merit testing for the virus as well as “trigger additional treatment adjustments.”

In accordance with the IOIBD (International Organization for the Study of Inflammatory Bowel Disease) consensus, the update noted that IBD patients should continue going to infusion centers for therapies, provided that the centers use a COVID-19 screening protocol.

Patients with IBD who contract COVID-19 seem more likely to be hospitalized for one or the other disease, but that’s based on data from the international SECURE-IBD registry that had 164 patients as of the writing of the update. The update provides guidance for three scenarios for IBD patients during the pandemic:

• Patients not infected with SARS-CoV-2 should maintain their IBD therapies to sustain remission and avoid relapses. “Aside from the obvious negative consequences of a relapse, relapsing IBD will strain available medical resources, may require steroid therapy or necessitate hospitalization, outcomes that are all much worse than the known risks of existing IBD therapies,” Dr. Rubin and colleagues noted.
• Patients who are infected but have no symptoms of COVID-19 should have their dosing of prednisone adjusted to less than 20 mg/day or switched to budesonide; suspend thiopurines, methotrexate, and tofacitinib; and delay dosing of monoclonal antibodies (anti–tumor necrosis factor [anti-TNF] drugs, ustekinumab, or vedolizumab) for 2 weeks while their symptoms for COVID-19 are monitored. “Restarting therapy after 2 weeks if the patient has not developed manifestations of COVID-19 is reasonable,” wrote Dr. Rubin and colleagues. Emerging serial testing should indicate antibody status, but the effectiveness of stool testing for SARS-CoV-2 in these cases “remains to be seen.”
• In the patient with confirmed COVID-19, adjustment of IBD therapy “is appropriate, based on the understanding of the immune activity of the therapy and whether that therapy may worsen outcomes with COVID-19,” the update stated. Therapy adjustment should focus on reducing immune suppression during the active viral infection. Some studies are evaluating anticytokine-based therapies as COVID-19 treatments, so continued anti-TNF therapies might prevent acute respiratory distress syndrome and multiorgan failure, Dr. Rubin and colleagues wrote. “However, in the absence of those data, guidance is currently based on deciding whether to hold or to continue specific IBD therapies.”

The update considers most IBD therapies, specifically aminosalicylates, topical rectal therapy, dietary management, and antibiotics “safe and may be continued,” and oral budesonide can be continued if it’s needed for ongoing IBD control. However, corticosteroids “should be avoided and discontinued quickly.”

Likewise, during the acute stage of COVID-19, thiopurines, methotrexate, and tofacitinib should be discontinued, and anti-TNF drugs and ustekinumab should be stopped during viral illness. Holding vedolizumab during viral illness is also appropriate, according to the update, although the IOIBD group was uncertain if doing so was necessary.

If the IBD patient has digestive symptoms with COVID-19, ongoing supportive care of the COVID-19 is “reasonable,” but investigating the causes of the digestive symptoms “is critically important.” That should include ruling out enteric infections and confirming active inflammation with nonendoscopic testing. Endoscopy should be relegated to only urgent and emergent cases.

Management of IBD in COVID-19 patients also depends on disease severity. Safer therapies are indicated for mild disease, but withholding IBD therapy in moderate to severe cases may not be practical. “In this setting, the risks and benefits of escalating IBD therapy must be carefully weighed against the severity of the COVID-19,” Dr. Rubin and colleagues noted.

In hospitalized patients with severe COVID-19 and poor prognoses, “IBD therapy will likely take a back seat,” the update stated, although COVID-19 therapies should take the concomitant IBD into account. In patients with milder cases of COVID-19, IBD management should focus on acute manifestations, but intravenous steroid therapy shouldn’t exceed 3 days. The update urged providers to submit cases of IBD and confirmed COVID-19 to the SECURE-IBD registry at COVIDIBD.org.

Dr. Rubin disclosed financial relationships with AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene/Syneos, Gilead Sciences, Takeda, and many other pharmaceutical companies. Coauthors disclosed relationships with those companies and Medimmune, Novus Therapeutics, Osiris Therapeutics, RedHill Biopharma, Sanofi-Aventis, UCB Pharma, and multiple other pharmaceutical companies.

SOURCE: Rubin DT, et al. Gastroenterology. 2020:  doi: 10.1053/j.gastro.2020.04.012

Inflammatory bowel disease (IBD) does not seem to make patients any more likely to contract SARS-COV-2 or develop COVID-19, but a rapid review commissioned by the American Gastroenterological Association acknowledges that determination is based on limited evidence and IBD patients should nonetheless maintain remission to reduce their risk of relapse or hospitalization during the COVID-19 pandemic.

The AGA has published a clinical practice update based on that rapid review online in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.04.012).

Because of the widespread use of immunosuppressive or immune-modifying drugs, “It is understandable why patients with Crohn’s disease and ulcerative colitis have specific concerns and potential for increased risk of infection with SARS-CoV-2,” wrote David T. Rubin, MD, AGAF, of the University of Chicago and colleagues in the expert commentary.

They noted that, while association between GI symptoms and COVID-19 RNA in stool samples isn’t clear, given the reports of GI symptoms in COVID-19 patients – ranging from 10% (JAMA. 2020:323:1061-9) to half of patients (Am J Gastroenterol. 2020;115:766-73) – “the clinical implications of this are quite important.” In IBD patients, changes in digestive symptoms without accompanying fever or respiratory symptoms can be monitored for symptoms that could merit testing for the virus as well as “trigger additional treatment adjustments.”

In accordance with the IOIBD (International Organization for the Study of Inflammatory Bowel Disease) consensus, the update noted that IBD patients should continue going to infusion centers for therapies, provided that the centers use a COVID-19 screening protocol.

Patients with IBD who contract COVID-19 seem more likely to be hospitalized for one or the other disease, but that’s based on data from the international SECURE-IBD registry that had 164 patients as of the writing of the update. The update provides guidance for three scenarios for IBD patients during the pandemic:

• Patients not infected with SARS-CoV-2 should maintain their IBD therapies to sustain remission and avoid relapses. “Aside from the obvious negative consequences of a relapse, relapsing IBD will strain available medical resources, may require steroid therapy or necessitate hospitalization, outcomes that are all much worse than the known risks of existing IBD therapies,” Dr. Rubin and colleagues noted.
• Patients who are infected but have no symptoms of COVID-19 should have their dosing of prednisone adjusted to less than 20 mg/day or switched to budesonide; suspend thiopurines, methotrexate, and tofacitinib; and delay dosing of monoclonal antibodies (anti–tumor necrosis factor [anti-TNF] drugs, ustekinumab, or vedolizumab) for 2 weeks while their symptoms for COVID-19 are monitored. “Restarting therapy after 2 weeks if the patient has not developed manifestations of COVID-19 is reasonable,” wrote Dr. Rubin and colleagues. Emerging serial testing should indicate antibody status, but the effectiveness of stool testing for SARS-CoV-2 in these cases “remains to be seen.”
• In the patient with confirmed COVID-19, adjustment of IBD therapy “is appropriate, based on the understanding of the immune activity of the therapy and whether that therapy may worsen outcomes with COVID-19,” the update stated. Therapy adjustment should focus on reducing immune suppression during the active viral infection. Some studies are evaluating anticytokine-based therapies as COVID-19 treatments, so continued anti-TNF therapies might prevent acute respiratory distress syndrome and multiorgan failure, Dr. Rubin and colleagues wrote. “However, in the absence of those data, guidance is currently based on deciding whether to hold or to continue specific IBD therapies.”

The update considers most IBD therapies, specifically aminosalicylates, topical rectal therapy, dietary management, and antibiotics “safe and may be continued,” and oral budesonide can be continued if it’s needed for ongoing IBD control. However, corticosteroids “should be avoided and discontinued quickly.”

Likewise, during the acute stage of COVID-19, thiopurines, methotrexate, and tofacitinib should be discontinued, and anti-TNF drugs and ustekinumab should be stopped during viral illness. Holding vedolizumab during viral illness is also appropriate, according to the update, although the IOIBD group was uncertain if doing so was necessary.

If the IBD patient has digestive symptoms with COVID-19, ongoing supportive care of the COVID-19 is “reasonable,” but investigating the causes of the digestive symptoms “is critically important.” That should include ruling out enteric infections and confirming active inflammation with nonendoscopic testing. Endoscopy should be relegated to only urgent and emergent cases.

Management of IBD in COVID-19 patients also depends on disease severity. Safer therapies are indicated for mild disease, but withholding IBD therapy in moderate to severe cases may not be practical. “In this setting, the risks and benefits of escalating IBD therapy must be carefully weighed against the severity of the COVID-19,” Dr. Rubin and colleagues noted.

In hospitalized patients with severe COVID-19 and poor prognoses, “IBD therapy will likely take a back seat,” the update stated, although COVID-19 therapies should take the concomitant IBD into account. In patients with milder cases of COVID-19, IBD management should focus on acute manifestations, but intravenous steroid therapy shouldn’t exceed 3 days. The update urged providers to submit cases of IBD and confirmed COVID-19 to the SECURE-IBD registry at COVIDIBD.org.

Dr. Rubin disclosed financial relationships with AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene/Syneos, Gilead Sciences, Takeda, and many other pharmaceutical companies. Coauthors disclosed relationships with those companies and Medimmune, Novus Therapeutics, Osiris Therapeutics, RedHill Biopharma, Sanofi-Aventis, UCB Pharma, and multiple other pharmaceutical companies.

SOURCE: Rubin DT, et al. Gastroenterology. 2020:  doi: 10.1053/j.gastro.2020.04.012

Cancers of the gastrointestinal tract represented about one in four cancer cases in 2018 but more than one in three cancer-related deaths, underscoring the importance of preventive measures, according to an analysis of global cancer datasets that identified trends in five major GI cancer types – esophageal, stomach, colorectal, liver, and pancreatic – published in Gastroenterology.

“Although the incidence of some GI cancer types has decreased, this group of malignancies continues to pose major challenges to public health,” wrote Melina Arnold, PhD, of the International for Research on Cancer in Lyon, France, and colleagues. “Primary and secondary prevention measures are important for controlling these malignancies – most importantly, reducing consumption of tobacco and alcohol, obesity control, immunizing populations against hepatitis B virus infection, and screening for colorectal cancer.”

For example, the study found that the proportion of GI cancer deaths in Asia exceeds that of new cases, with the greatest disparity in China, while the opposite can be said of GI cancer trends in Europe and North America.

The study reported 4.8 million new cases of GI cancer and 3.4 million deaths worldwide in 2018. GI cancers accounted for 26% of the global cancer burden but 35% of cancer-related deaths. Incidence-to-death disparities were greatest for Africa, accounting for 4% of new cases and 5% of deaths; and Asia, with about 63% of new cases but 65% of deaths. The disparity was even wider in China, which accounted for 38% of worldwide cases but 41% of the deaths. Europe and North America, on the other hand, accounted for 26% of global cases but 23% of deaths. High death rates of these cancers are associated with late detection, Dr. Arnold and colleagues noted.

Regarding the five different types of GI cancer, the study reported the following:

• Esophageal cancer accounted for 572,000 new cases and 508,000 deaths in 2018, making it the sixth-most-deadly cancer worldwide. Rates in men are two to three times higher than in women. Eastern Asia has the highest rates, 12.2 per 100,000 person-years, followed by eastern Africa (8.3) and southern Africa (7.4). China alone accounts for 54% of the global burden. A large percentage of these cancers in developing countries are squamous cell carcinoma, the most common form of esophageal cancer globally, which has been linked to tobacco use, heavy alcohol consumption, opium intake, air pollution, and diet.
• Gastric cancer accounted for more than 1 million new cases and nearly 800,000 deaths in 2018. Again, the incidence is twice as high in men as in women, and eastern Asia has the highest rates of 22 per 100,000 vs. < 5 in Africa, North America, and northern Europe. Cardia gastric cancer (CGC), associated with obesity and gastroesophageal reflux disease, is more prevalent in Western countries, while noncardia gastric cancer (CG) is more prevalent in countries with higher rates of Helicobacter pylori infection. In the United States specifically, CGC is more common in non-Hispanic whites than other ethnic groups. Gastric cancer rates have been declining in recent years, although trends of CGC and cancer of the gastric corpus, which the study terms “a noncardia subsite,” among younger people “may lead to a deceleration or a reversal” of declining gastric cancer rates, stated Dr. Arnold and colleagues.
• Colorectal cancer remained the most commonly diagnosed GI cancer in 2018, accounting for 1.8 million cases and 881,000 deaths, which represents 1 in 10 cancer deaths. The highest incidence was found in Australia/New Zealand, the lowest in south and central Asia. Colorectal cancers are in “transition” from infection-related cancers to those related to “rapid societal and economic change.” Dr. Arnold and colleagues attributed these changes to higher dietary intake of fats, sugar, and animal-source foods and increases in sedentary behavior and obesity. Despite advances in cures for colorectal cancer, disparities continue, even in high-income countries, and screening programs have been limited, according to the study. Colorectal cancer will be “one of the main contributors” to the doubling of cancer rates in older adults by 2035.
• Liver cancer comprised 841,000 cases and 782,000 deaths in 2018, making it the sixth-most-diagnosed cancer but the fourth most deadly. “Transitioning countries” in eastern Asia, Micronesia, and northern Africa have the highest rates. In eastern Asia, hepatitis B infections and aflatoxins are the primary risk factors for hepatocellular carcinoma, while in Japan and Europe hepatitis C is the main cause for hepatocellular carcinoma. Decreases in both infections and aflatoxins may explain declines in liver cancer rates in those regions. Whereas in lower-risk areas, increasing liver cancer rates caused by more widespread obesity and diabetes may be offsetting declines in HBV and HCV rates.
• Pancreatic cancer was the 12th-most-common cancer but the seventh leading cause of cancer death, with 432,000 cases and 459,000 deaths in 2018. Wealthy countries have incidence and death rates three to four times higher than do less-developed countries, with rates highest in Europe, North America, and Australia/New Zealand. Because pancreatic cancer isn’t typically diagnosed until it is in the metastatic or locally advanced state, curative surgery isn’t feasible, Dr. Arnold and colleagues stated. Population aging and growth, along with advances in treating other types of cancers, mean that pancreatic cancer “has become or is set out to become one of the leading causes of cancer-related death in many countries,” Dr. Arnold and colleagues stated. They added that, in the European Union, pancreatic cancer is already the third-leading cause of cancer death after lung and colorectal cancer.

The findings, Dr. Arnold and colleagues wrote, underscore the shift of the cancer burden toward transitioning countries, “which are less equipped to manage this increasing burden.” In the United States, the rates of all five GI cancers in young adults (aged 25-49 years) have increased.

GI cancers, with the exception of colorectal cancers, also contribute disproportionately to cancer-related death rates, mostly because all but colorectal cancers are difficult to diagnose.

However, early detection and screening programs for gastric cancer in Japan and Korea, and esophageal cancer in China “have shown promising results,” Dr. Arnold and colleagues said. “Pancreatic cancer, on the other hand, is becoming a more important contributor to cancer-related mortality as a consequence of improved diagnosis and management of the historically most common forms of cancer death,” they wrote.

Prevention remains key, and lifestyle choices like smoking, alcohol intake, and physical activity are all drivers of GI cancer burden. “Primary and secondary prevention measures remain the most important tools to control this group of malignancies, particularly in light of their preventability and often dreadful prognosis,” Dr. Arnold and colleagues wrote.

Dr. Arnold and colleagues have no financial relationships to disclose.

SOURCE: Arnold M et al. Gastroenterology. 2020 Apr 2;S0016-5085(20)30452-2. doi: 10.1053/j.gastro.2020.02.068.

Cancers of the gastrointestinal tract represented about one in four cancer cases in 2018 but more than one in three cancer-related deaths, underscoring the importance of preventive measures, according to an analysis of global cancer datasets that identified trends in five major GI cancer types – esophageal, stomach, colorectal, liver, and pancreatic – published in Gastroenterology.

“Although the incidence of some GI cancer types has decreased, this group of malignancies continues to pose major challenges to public health,” wrote Melina Arnold, PhD, of the International for Research on Cancer in Lyon, France, and colleagues. “Primary and secondary prevention measures are important for controlling these malignancies – most importantly, reducing consumption of tobacco and alcohol, obesity control, immunizing populations against hepatitis B virus infection, and screening for colorectal cancer.”

For example, the study found that the proportion of GI cancer deaths in Asia exceeds that of new cases, with the greatest disparity in China, while the opposite can be said of GI cancer trends in Europe and North America.

The study reported 4.8 million new cases of GI cancer and 3.4 million deaths worldwide in 2018. GI cancers accounted for 26% of the global cancer burden but 35% of cancer-related deaths. Incidence-to-death disparities were greatest for Africa, accounting for 4% of new cases and 5% of deaths; and Asia, with about 63% of new cases but 65% of deaths. The disparity was even wider in China, which accounted for 38% of worldwide cases but 41% of the deaths. Europe and North America, on the other hand, accounted for 26% of global cases but 23% of deaths. High death rates of these cancers are associated with late detection, Dr. Arnold and colleagues noted.

Regarding the five different types of GI cancer, the study reported the following:

• Esophageal cancer accounted for 572,000 new cases and 508,000 deaths in 2018, making it the sixth-most-deadly cancer worldwide. Rates in men are two to three times higher than in women. Eastern Asia has the highest rates, 12.2 per 100,000 person-years, followed by eastern Africa (8.3) and southern Africa (7.4). China alone accounts for 54% of the global burden. A large percentage of these cancers in developing countries are squamous cell carcinoma, the most common form of esophageal cancer globally, which has been linked to tobacco use, heavy alcohol consumption, opium intake, air pollution, and diet.
• Gastric cancer accounted for more than 1 million new cases and nearly 800,000 deaths in 2018. Again, the incidence is twice as high in men as in women, and eastern Asia has the highest rates of 22 per 100,000 vs. < 5 in Africa, North America, and northern Europe. Cardia gastric cancer (CGC), associated with obesity and gastroesophageal reflux disease, is more prevalent in Western countries, while noncardia gastric cancer (CG) is more prevalent in countries with higher rates of Helicobacter pylori infection. In the United States specifically, CGC is more common in non-Hispanic whites than other ethnic groups. Gastric cancer rates have been declining in recent years, although trends of CGC and cancer of the gastric corpus, which the study terms “a noncardia subsite,” among younger people “may lead to a deceleration or a reversal” of declining gastric cancer rates, stated Dr. Arnold and colleagues.
• Colorectal cancer remained the most commonly diagnosed GI cancer in 2018, accounting for 1.8 million cases and 881,000 deaths, which represents 1 in 10 cancer deaths. The highest incidence was found in Australia/New Zealand, the lowest in south and central Asia. Colorectal cancers are in “transition” from infection-related cancers to those related to “rapid societal and economic change.” Dr. Arnold and colleagues attributed these changes to higher dietary intake of fats, sugar, and animal-source foods and increases in sedentary behavior and obesity. Despite advances in cures for colorectal cancer, disparities continue, even in high-income countries, and screening programs have been limited, according to the study. Colorectal cancer will be “one of the main contributors” to the doubling of cancer rates in older adults by 2035.
• Liver cancer comprised 841,000 cases and 782,000 deaths in 2018, making it the sixth-most-diagnosed cancer but the fourth most deadly. “Transitioning countries” in eastern Asia, Micronesia, and northern Africa have the highest rates. In eastern Asia, hepatitis B infections and aflatoxins are the primary risk factors for hepatocellular carcinoma, while in Japan and Europe hepatitis C is the main cause for hepatocellular carcinoma. Decreases in both infections and aflatoxins may explain declines in liver cancer rates in those regions. Whereas in lower-risk areas, increasing liver cancer rates caused by more widespread obesity and diabetes may be offsetting declines in HBV and HCV rates.
• Pancreatic cancer was the 12th-most-common cancer but the seventh leading cause of cancer death, with 432,000 cases and 459,000 deaths in 2018. Wealthy countries have incidence and death rates three to four times higher than do less-developed countries, with rates highest in Europe, North America, and Australia/New Zealand. Because pancreatic cancer isn’t typically diagnosed until it is in the metastatic or locally advanced state, curative surgery isn’t feasible, Dr. Arnold and colleagues stated. Population aging and growth, along with advances in treating other types of cancers, mean that pancreatic cancer “has become or is set out to become one of the leading causes of cancer-related death in many countries,” Dr. Arnold and colleagues stated. They added that, in the European Union, pancreatic cancer is already the third-leading cause of cancer death after lung and colorectal cancer.

The findings, Dr. Arnold and colleagues wrote, underscore the shift of the cancer burden toward transitioning countries, “which are less equipped to manage this increasing burden.” In the United States, the rates of all five GI cancers in young adults (aged 25-49 years) have increased.

GI cancers, with the exception of colorectal cancers, also contribute disproportionately to cancer-related death rates, mostly because all but colorectal cancers are difficult to diagnose.

However, early detection and screening programs for gastric cancer in Japan and Korea, and esophageal cancer in China “have shown promising results,” Dr. Arnold and colleagues said. “Pancreatic cancer, on the other hand, is becoming a more important contributor to cancer-related mortality as a consequence of improved diagnosis and management of the historically most common forms of cancer death,” they wrote.

Prevention remains key, and lifestyle choices like smoking, alcohol intake, and physical activity are all drivers of GI cancer burden. “Primary and secondary prevention measures remain the most important tools to control this group of malignancies, particularly in light of their preventability and often dreadful prognosis,” Dr. Arnold and colleagues wrote.

Dr. Arnold and colleagues have no financial relationships to disclose.

SOURCE: Arnold M et al. Gastroenterology. 2020 Apr 2;S0016-5085(20)30452-2. doi: 10.1053/j.gastro.2020.02.068.

Cancers of the gastrointestinal tract represented about one in four cancer cases in 2018 but more than one in three cancer-related deaths, underscoring the importance of preventive measures, according to an analysis of global cancer datasets that identified trends in five major GI cancer types – esophageal, stomach, colorectal, liver, and pancreatic – published in Gastroenterology.

“Although the incidence of some GI cancer types has decreased, this group of malignancies continues to pose major challenges to public health,” wrote Melina Arnold, PhD, of the International for Research on Cancer in Lyon, France, and colleagues. “Primary and secondary prevention measures are important for controlling these malignancies – most importantly, reducing consumption of tobacco and alcohol, obesity control, immunizing populations against hepatitis B virus infection, and screening for colorectal cancer.”

For example, the study found that the proportion of GI cancer deaths in Asia exceeds that of new cases, with the greatest disparity in China, while the opposite can be said of GI cancer trends in Europe and North America.

The study reported 4.8 million new cases of GI cancer and 3.4 million deaths worldwide in 2018. GI cancers accounted for 26% of the global cancer burden but 35% of cancer-related deaths. Incidence-to-death disparities were greatest for Africa, accounting for 4% of new cases and 5% of deaths; and Asia, with about 63% of new cases but 65% of deaths. The disparity was even wider in China, which accounted for 38% of worldwide cases but 41% of the deaths. Europe and North America, on the other hand, accounted for 26% of global cases but 23% of deaths. High death rates of these cancers are associated with late detection, Dr. Arnold and colleagues noted.

Regarding the five different types of GI cancer, the study reported the following:

• Esophageal cancer accounted for 572,000 new cases and 508,000 deaths in 2018, making it the sixth-most-deadly cancer worldwide. Rates in men are two to three times higher than in women. Eastern Asia has the highest rates, 12.2 per 100,000 person-years, followed by eastern Africa (8.3) and southern Africa (7.4). China alone accounts for 54% of the global burden. A large percentage of these cancers in developing countries are squamous cell carcinoma, the most common form of esophageal cancer globally, which has been linked to tobacco use, heavy alcohol consumption, opium intake, air pollution, and diet.
• Gastric cancer accounted for more than 1 million new cases and nearly 800,000 deaths in 2018. Again, the incidence is twice as high in men as in women, and eastern Asia has the highest rates of 22 per 100,000 vs. < 5 in Africa, North America, and northern Europe. Cardia gastric cancer (CGC), associated with obesity and gastroesophageal reflux disease, is more prevalent in Western countries, while noncardia gastric cancer (CG) is more prevalent in countries with higher rates of Helicobacter pylori infection. In the United States specifically, CGC is more common in non-Hispanic whites than other ethnic groups. Gastric cancer rates have been declining in recent years, although trends of CGC and cancer of the gastric corpus, which the study terms “a noncardia subsite,” among younger people “may lead to a deceleration or a reversal” of declining gastric cancer rates, stated Dr. Arnold and colleagues.
• Colorectal cancer remained the most commonly diagnosed GI cancer in 2018, accounting for 1.8 million cases and 881,000 deaths, which represents 1 in 10 cancer deaths. The highest incidence was found in Australia/New Zealand, the lowest in south and central Asia. Colorectal cancers are in “transition” from infection-related cancers to those related to “rapid societal and economic change.” Dr. Arnold and colleagues attributed these changes to higher dietary intake of fats, sugar, and animal-source foods and increases in sedentary behavior and obesity. Despite advances in cures for colorectal cancer, disparities continue, even in high-income countries, and screening programs have been limited, according to the study. Colorectal cancer will be “one of the main contributors” to the doubling of cancer rates in older adults by 2035.
• Liver cancer comprised 841,000 cases and 782,000 deaths in 2018, making it the sixth-most-diagnosed cancer but the fourth most deadly. “Transitioning countries” in eastern Asia, Micronesia, and northern Africa have the highest rates. In eastern Asia, hepatitis B infections and aflatoxins are the primary risk factors for hepatocellular carcinoma, while in Japan and Europe hepatitis C is the main cause for hepatocellular carcinoma. Decreases in both infections and aflatoxins may explain declines in liver cancer rates in those regions. Whereas in lower-risk areas, increasing liver cancer rates caused by more widespread obesity and diabetes may be offsetting declines in HBV and HCV rates.
• Pancreatic cancer was the 12th-most-common cancer but the seventh leading cause of cancer death, with 432,000 cases and 459,000 deaths in 2018. Wealthy countries have incidence and death rates three to four times higher than do less-developed countries, with rates highest in Europe, North America, and Australia/New Zealand. Because pancreatic cancer isn’t typically diagnosed until it is in the metastatic or locally advanced state, curative surgery isn’t feasible, Dr. Arnold and colleagues stated. Population aging and growth, along with advances in treating other types of cancers, mean that pancreatic cancer “has become or is set out to become one of the leading causes of cancer-related death in many countries,” Dr. Arnold and colleagues stated. They added that, in the European Union, pancreatic cancer is already the third-leading cause of cancer death after lung and colorectal cancer.

The findings, Dr. Arnold and colleagues wrote, underscore the shift of the cancer burden toward transitioning countries, “which are less equipped to manage this increasing burden.” In the United States, the rates of all five GI cancers in young adults (aged 25-49 years) have increased.

GI cancers, with the exception of colorectal cancers, also contribute disproportionately to cancer-related death rates, mostly because all but colorectal cancers are difficult to diagnose.

However, early detection and screening programs for gastric cancer in Japan and Korea, and esophageal cancer in China “have shown promising results,” Dr. Arnold and colleagues said. “Pancreatic cancer, on the other hand, is becoming a more important contributor to cancer-related mortality as a consequence of improved diagnosis and management of the historically most common forms of cancer death,” they wrote.

Prevention remains key, and lifestyle choices like smoking, alcohol intake, and physical activity are all drivers of GI cancer burden. “Primary and secondary prevention measures remain the most important tools to control this group of malignancies, particularly in light of their preventability and often dreadful prognosis,” Dr. Arnold and colleagues wrote.

Dr. Arnold and colleagues have no financial relationships to disclose.

SOURCE: Arnold M et al. Gastroenterology. 2020 Apr 2;S0016-5085(20)30452-2. doi: 10.1053/j.gastro.2020.02.068.

Individuals at high risk for pancreatic cancer should at least be considered for screening for the disease, states a new clinical practice update from the American Gastroenterological Association that further defines what constitutes high risk for pancreatic cancer, when and how screenings should occur, and the role of genetic testing and counseling (Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.088).

Individuals who have a first-degree relative with two or more genetically related relatives with pancreatic cancer should be considered for screening, as should people with Peutz-Jeghers syndrome, a CDKN2A gene mutation, one or more first-degree relatives with pancreatic cancer with Lynch syndrome and mutations in the BRCA1, BRCA2, PALB2, and ATM genes, the clinical update stated. Screening in high-risk individuals should begin at age 50, but some groups should start having screening earlier: age 40 in carriers of the CKDN2A and PRSS1 mutations with hereditary pancreatitis; and age 35 in those with Peutz-Jeghers syndrome.

“Studies to date have demonstrated variability regarding definitions of high-risk groups and the age at which screening should be initiated,” wrote Harry R. Aslanian, MD, AGAF, of Yale New Haven (Conn.) Hospital, and coauthors. “The genetic basis of much of the inherited susceptibility to pancreas cancer remains unexplained (in approximately 90% of cases) and familial history is important in risk stratification.”

Genetic testing and counseling should be considered for any familial pancreas cancer relative – that is, a person with two or more first-degree relatives with pancreas cancer that’s outside the definition of other hereditary cancers. “A positive germline mutation is associated with an increased risk of neoplastic progression and may also lead to screening for other relevant associated cancers,” wrote Dr. Aslanian and coauthors.

The screening itself should consist of MRI and endoscopic ultrasonography (EUS) in combination, the clinical practice update states. It defines detectable targets as stage 1 pancreatic ductal adenocarcinoma and high-risk neoplasms such as intraductal papillary mucinous neoplasms with high-grade dysplasia and some enlarged pancreatic intraepithelial neoplasms.

High-risk patients having screening should also be enrolled in a registry and referred to a pancreas center of excellence.

The update suggests screening every 12 months when the baseline screening is negative for any suspect lesions, with shorter intervals for EUS when suspected lesions are found: 6-12 months for low-risk lesions; 3-6 months for intermediate lesions; and 3 months for high-risk lesions if the patient hasn’t had surgery to remove the lesions.

Regarding management of positive screening results, a multidisciplinary team should confer with the individual and family to determine therapy. If surgery is indicated, it should be done at a high-volume center.

The update also provides guidance for two scenarios when patients shouldn’t undergo screening: those at average risk; and those at high-risk more likely to die from another cause. Of course, the physician should review the limitations and risk of screening with patients beforehand.

Dr. Aslanian and coauthors noted that a number of areas require further study, including defining the highest-risk groups and refining screening tests with high sensitivity and specificity to detect high-grade precursors, along with more data on risks of precursor lesions themselves.

They also acknowledged the need for more study into the effectiveness of pancreatic cancer screening, although a randomized clinical trial comparing screening vs. no screening “might be challenging to conduct given implementation of clinical screening as standard of care in some practices.” Blood tests for pancreatic cancer screening in high-risk patients also need more study, they stated.

The authors did not report any funding sources or conflicts of interest.

SOURCE: Aslanian HR et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.088.

Individuals at high risk for pancreatic cancer should at least be considered for screening for the disease, states a new clinical practice update from the American Gastroenterological Association that further defines what constitutes high risk for pancreatic cancer, when and how screenings should occur, and the role of genetic testing and counseling (Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.088).

Individuals who have a first-degree relative with two or more genetically related relatives with pancreatic cancer should be considered for screening, as should people with Peutz-Jeghers syndrome, a CDKN2A gene mutation, one or more first-degree relatives with pancreatic cancer with Lynch syndrome and mutations in the BRCA1, BRCA2, PALB2, and ATM genes, the clinical update stated. Screening in high-risk individuals should begin at age 50, but some groups should start having screening earlier: age 40 in carriers of the CKDN2A and PRSS1 mutations with hereditary pancreatitis; and age 35 in those with Peutz-Jeghers syndrome.

“Studies to date have demonstrated variability regarding definitions of high-risk groups and the age at which screening should be initiated,” wrote Harry R. Aslanian, MD, AGAF, of Yale New Haven (Conn.) Hospital, and coauthors. “The genetic basis of much of the inherited susceptibility to pancreas cancer remains unexplained (in approximately 90% of cases) and familial history is important in risk stratification.”

Genetic testing and counseling should be considered for any familial pancreas cancer relative – that is, a person with two or more first-degree relatives with pancreas cancer that’s outside the definition of other hereditary cancers. “A positive germline mutation is associated with an increased risk of neoplastic progression and may also lead to screening for other relevant associated cancers,” wrote Dr. Aslanian and coauthors.

The screening itself should consist of MRI and endoscopic ultrasonography (EUS) in combination, the clinical practice update states. It defines detectable targets as stage 1 pancreatic ductal adenocarcinoma and high-risk neoplasms such as intraductal papillary mucinous neoplasms with high-grade dysplasia and some enlarged pancreatic intraepithelial neoplasms.

High-risk patients having screening should also be enrolled in a registry and referred to a pancreas center of excellence.

The update suggests screening every 12 months when the baseline screening is negative for any suspect lesions, with shorter intervals for EUS when suspected lesions are found: 6-12 months for low-risk lesions; 3-6 months for intermediate lesions; and 3 months for high-risk lesions if the patient hasn’t had surgery to remove the lesions.

Regarding management of positive screening results, a multidisciplinary team should confer with the individual and family to determine therapy. If surgery is indicated, it should be done at a high-volume center.

The update also provides guidance for two scenarios when patients shouldn’t undergo screening: those at average risk; and those at high-risk more likely to die from another cause. Of course, the physician should review the limitations and risk of screening with patients beforehand.

Dr. Aslanian and coauthors noted that a number of areas require further study, including defining the highest-risk groups and refining screening tests with high sensitivity and specificity to detect high-grade precursors, along with more data on risks of precursor lesions themselves.

They also acknowledged the need for more study into the effectiveness of pancreatic cancer screening, although a randomized clinical trial comparing screening vs. no screening “might be challenging to conduct given implementation of clinical screening as standard of care in some practices.” Blood tests for pancreatic cancer screening in high-risk patients also need more study, they stated.

The authors did not report any funding sources or conflicts of interest.

SOURCE: Aslanian HR et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.088.

Individuals at high risk for pancreatic cancer should at least be considered for screening for the disease, states a new clinical practice update from the American Gastroenterological Association that further defines what constitutes high risk for pancreatic cancer, when and how screenings should occur, and the role of genetic testing and counseling (Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.088).

Individuals who have a first-degree relative with two or more genetically related relatives with pancreatic cancer should be considered for screening, as should people with Peutz-Jeghers syndrome, a CDKN2A gene mutation, one or more first-degree relatives with pancreatic cancer with Lynch syndrome and mutations in the BRCA1, BRCA2, PALB2, and ATM genes, the clinical update stated. Screening in high-risk individuals should begin at age 50, but some groups should start having screening earlier: age 40 in carriers of the CKDN2A and PRSS1 mutations with hereditary pancreatitis; and age 35 in those with Peutz-Jeghers syndrome.

“Studies to date have demonstrated variability regarding definitions of high-risk groups and the age at which screening should be initiated,” wrote Harry R. Aslanian, MD, AGAF, of Yale New Haven (Conn.) Hospital, and coauthors. “The genetic basis of much of the inherited susceptibility to pancreas cancer remains unexplained (in approximately 90% of cases) and familial history is important in risk stratification.”

Genetic testing and counseling should be considered for any familial pancreas cancer relative – that is, a person with two or more first-degree relatives with pancreas cancer that’s outside the definition of other hereditary cancers. “A positive germline mutation is associated with an increased risk of neoplastic progression and may also lead to screening for other relevant associated cancers,” wrote Dr. Aslanian and coauthors.

The screening itself should consist of MRI and endoscopic ultrasonography (EUS) in combination, the clinical practice update states. It defines detectable targets as stage 1 pancreatic ductal adenocarcinoma and high-risk neoplasms such as intraductal papillary mucinous neoplasms with high-grade dysplasia and some enlarged pancreatic intraepithelial neoplasms.

High-risk patients having screening should also be enrolled in a registry and referred to a pancreas center of excellence.

The update suggests screening every 12 months when the baseline screening is negative for any suspect lesions, with shorter intervals for EUS when suspected lesions are found: 6-12 months for low-risk lesions; 3-6 months for intermediate lesions; and 3 months for high-risk lesions if the patient hasn’t had surgery to remove the lesions.

Regarding management of positive screening results, a multidisciplinary team should confer with the individual and family to determine therapy. If surgery is indicated, it should be done at a high-volume center.

The update also provides guidance for two scenarios when patients shouldn’t undergo screening: those at average risk; and those at high-risk more likely to die from another cause. Of course, the physician should review the limitations and risk of screening with patients beforehand.

Dr. Aslanian and coauthors noted that a number of areas require further study, including defining the highest-risk groups and refining screening tests with high sensitivity and specificity to detect high-grade precursors, along with more data on risks of precursor lesions themselves.

They also acknowledged the need for more study into the effectiveness of pancreatic cancer screening, although a randomized clinical trial comparing screening vs. no screening “might be challenging to conduct given implementation of clinical screening as standard of care in some practices.” Blood tests for pancreatic cancer screening in high-risk patients also need more study, they stated.

The authors did not report any funding sources or conflicts of interest.

SOURCE: Aslanian HR et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.088.

For patients with inflammatory bowel disease (IBD) who develop coronavirus disease of 2019 (COVID-19), corticosteroid use may significantly increase risk of severe disease, according to data from more than 500 patients.

Use of sulfasalazine or 5-aminosalicylates (5-ASAs) also increased risk of severe COVID-19, albeit to a lesser degree, reported co-lead authors Erica J. Brenner, MD, of University of North Carolina Children’s Hospital, Chapel Hill, and Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues.

In contrast, tumor necrosis factor (TNF) blockers were not an independent risk factor for severe COVID-19.

“As TNF antagonists are the most commonly prescribed biologic therapy for patients with IBD, these initial findings should be reassuring to the large number of patients receiving TNF antagonist therapy and support their continued use during this current pandemic,” the investigators wrote in Gastroenterology.

These conclusions were drawn from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) database, a large registry actively collecting data from clinicians around the world.

In the present analysis, which involved 525 patients from 33 countries, the investigators searched for independent risk factors for severe COVID-19. Various factors were tested through multivariable regression, including age, comorbidities, usage of specific medications, and more.

The primary outcome was defined by a composite of hospitalization, ventilator use, or death, while secondary outcomes included a composite of hospitalization or death, as well as death alone.

The analysis revealed that patients receiving corticosteroids had an adjusted odds ratio of 6.87 (95% confidence interval, 2.30-20.51) for severe COVID-19, with increased risks also detected for both secondary outcomes. In contrast, TNF antagonist use was not significantly associated with the primary outcome; in fact, a possible protective effect was detected for hospitalization or death (aOR, 0.60; 95% CI, 0.38-0.96).

The investigators noted that the above findings aligned with extensive literature concerning infectious complications with corticosteroid use and “more recent commentary” surrounding TNF antagonists. Similarly, increased age and the presence of at least two comorbidities were each independently associated with increased risk of severe COVID-19, both of which are correlations that have been previously described.

But the threefold increased risk of severe COVID-19 associated with use of sulfasalazine or 5-ASAs (aOR, 3.14; 95% CI, 1.28-7.71) was a “surprising” finding, the investigators noted.

“In a direct comparison, we observed that 5-ASA/sulfasalazine–treated patients fared worse than those treated with TNF inhibitors,” the investigators wrote. “Although we cannot exclude unmeasured confounding, further exploration of biological mechanisms is warranted.”

David T. Rubin, MD, AGAF, of the University of Chicago agreed that the finding deserves further investigation, particularly since sulfasalazine and 5-ASAs represent the second most commonly prescribed medication class for IBD.

“The risk with 5-ASAs is of interest but not well explained by what we know about the safety or the mechanism of these therapies,” Dr. Rubin said. “Clearly, more work is needed.”

The risks associated with corticosteroids were particularly concerning, Dr. Rubin said, because 10%-20% of patients with IBD may be taking corticosteroids at any given time.

“Steroids are still the number one prescribed therapy for Crohn’s and colitis,” he said.

Still, Dr. Rubin advised against abrupt changes to drug regimens, especially if they are effectively controlling IBD.

“Patients should stay on their existing therapies and stay in remission,” Dr. Rubin said. “If you stop your therapies … you are more likely to relapse. When you relapse, you’re more likely to need steroids as a rescue therapy … or end up in the hospital, and those are not places we want you to be.”

Despite the risks associated with steroids and sulfasalazine/5-ASAs, Dr. Rubin had an optimistic take on the study, calling the findings “very reassuring” because they support continued usage of TNF inhibitors and other biologic agents during the pandemic. He also noted that the SECURE-IBD registry, which he has contributed to, represents “an extraordinary effort” from around the world.

“[This is] an unprecedented collaboration across a scale and timeframe that has really never been seen before in our field, and I would hazard a guess that it’s probably never been seen in most other fields right now,” he said.

Clinicians seeking more information about managing patients with IBD during the COVID-19 pandemic can find guidance in the recent AGA practice update, of which Dr. Rubin was the lead author. Clinicians who would like to contribute to the SECURE-IBD registry may do so at covidibd.org. The registry now includes more than 1,000 patients.

The study was funded by Clinical and Translational Science Award grants through Dr. Ungaro. The investigators disclosed relationships with Takeda, Janssen, Pfizer, and others. Dr. Rubin disclosed relationships with Gilead, Eli Lilly, Shire, and others.

Check out the AGA COVID-19 Resource Library for new clinical guidance, education, research and physician resources, including recent guidance on how to treat patients with IBD during the pandemic, at www.gastro.org/covid.

SOURCE: Brenner EJ et al. Gastroenterology. 2020 May 18. doi: 10.1053/j.gastro.2020.05.032.

For patients with inflammatory bowel disease (IBD) who develop coronavirus disease of 2019 (COVID-19), corticosteroid use may significantly increase risk of severe disease, according to data from more than 500 patients.

Use of sulfasalazine or 5-aminosalicylates (5-ASAs) also increased risk of severe COVID-19, albeit to a lesser degree, reported co-lead authors Erica J. Brenner, MD, of University of North Carolina Children’s Hospital, Chapel Hill, and Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues.

In contrast, tumor necrosis factor (TNF) blockers were not an independent risk factor for severe COVID-19.

“As TNF antagonists are the most commonly prescribed biologic therapy for patients with IBD, these initial findings should be reassuring to the large number of patients receiving TNF antagonist therapy and support their continued use during this current pandemic,” the investigators wrote in Gastroenterology.

These conclusions were drawn from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) database, a large registry actively collecting data from clinicians around the world.

In the present analysis, which involved 525 patients from 33 countries, the investigators searched for independent risk factors for severe COVID-19. Various factors were tested through multivariable regression, including age, comorbidities, usage of specific medications, and more.

The primary outcome was defined by a composite of hospitalization, ventilator use, or death, while secondary outcomes included a composite of hospitalization or death, as well as death alone.

The analysis revealed that patients receiving corticosteroids had an adjusted odds ratio of 6.87 (95% confidence interval, 2.30-20.51) for severe COVID-19, with increased risks also detected for both secondary outcomes. In contrast, TNF antagonist use was not significantly associated with the primary outcome; in fact, a possible protective effect was detected for hospitalization or death (aOR, 0.60; 95% CI, 0.38-0.96).

The investigators noted that the above findings aligned with extensive literature concerning infectious complications with corticosteroid use and “more recent commentary” surrounding TNF antagonists. Similarly, increased age and the presence of at least two comorbidities were each independently associated with increased risk of severe COVID-19, both of which are correlations that have been previously described.

But the threefold increased risk of severe COVID-19 associated with use of sulfasalazine or 5-ASAs (aOR, 3.14; 95% CI, 1.28-7.71) was a “surprising” finding, the investigators noted.

“In a direct comparison, we observed that 5-ASA/sulfasalazine–treated patients fared worse than those treated with TNF inhibitors,” the investigators wrote. “Although we cannot exclude unmeasured confounding, further exploration of biological mechanisms is warranted.”

David T. Rubin, MD, AGAF, of the University of Chicago agreed that the finding deserves further investigation, particularly since sulfasalazine and 5-ASAs represent the second most commonly prescribed medication class for IBD.

“The risk with 5-ASAs is of interest but not well explained by what we know about the safety or the mechanism of these therapies,” Dr. Rubin said. “Clearly, more work is needed.”

The risks associated with corticosteroids were particularly concerning, Dr. Rubin said, because 10%-20% of patients with IBD may be taking corticosteroids at any given time.

“Steroids are still the number one prescribed therapy for Crohn’s and colitis,” he said.

Still, Dr. Rubin advised against abrupt changes to drug regimens, especially if they are effectively controlling IBD.

“Patients should stay on their existing therapies and stay in remission,” Dr. Rubin said. “If you stop your therapies … you are more likely to relapse. When you relapse, you’re more likely to need steroids as a rescue therapy … or end up in the hospital, and those are not places we want you to be.”

Despite the risks associated with steroids and sulfasalazine/5-ASAs, Dr. Rubin had an optimistic take on the study, calling the findings “very reassuring” because they support continued usage of TNF inhibitors and other biologic agents during the pandemic. He also noted that the SECURE-IBD registry, which he has contributed to, represents “an extraordinary effort” from around the world.

“[This is] an unprecedented collaboration across a scale and timeframe that has really never been seen before in our field, and I would hazard a guess that it’s probably never been seen in most other fields right now,” he said.

Clinicians seeking more information about managing patients with IBD during the COVID-19 pandemic can find guidance in the recent AGA practice update, of which Dr. Rubin was the lead author. Clinicians who would like to contribute to the SECURE-IBD registry may do so at covidibd.org. The registry now includes more than 1,000 patients.

The study was funded by Clinical and Translational Science Award grants through Dr. Ungaro. The investigators disclosed relationships with Takeda, Janssen, Pfizer, and others. Dr. Rubin disclosed relationships with Gilead, Eli Lilly, Shire, and others.

Check out the AGA COVID-19 Resource Library for new clinical guidance, education, research and physician resources, including recent guidance on how to treat patients with IBD during the pandemic, at www.gastro.org/covid.

SOURCE: Brenner EJ et al. Gastroenterology. 2020 May 18. doi: 10.1053/j.gastro.2020.05.032.

For patients with inflammatory bowel disease (IBD) who develop coronavirus disease of 2019 (COVID-19), corticosteroid use may significantly increase risk of severe disease, according to data from more than 500 patients.

Use of sulfasalazine or 5-aminosalicylates (5-ASAs) also increased risk of severe COVID-19, albeit to a lesser degree, reported co-lead authors Erica J. Brenner, MD, of University of North Carolina Children’s Hospital, Chapel Hill, and Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues.

In contrast, tumor necrosis factor (TNF) blockers were not an independent risk factor for severe COVID-19.

“As TNF antagonists are the most commonly prescribed biologic therapy for patients with IBD, these initial findings should be reassuring to the large number of patients receiving TNF antagonist therapy and support their continued use during this current pandemic,” the investigators wrote in Gastroenterology.

These conclusions were drawn from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) database, a large registry actively collecting data from clinicians around the world.

In the present analysis, which involved 525 patients from 33 countries, the investigators searched for independent risk factors for severe COVID-19. Various factors were tested through multivariable regression, including age, comorbidities, usage of specific medications, and more.

The primary outcome was defined by a composite of hospitalization, ventilator use, or death, while secondary outcomes included a composite of hospitalization or death, as well as death alone.

The analysis revealed that patients receiving corticosteroids had an adjusted odds ratio of 6.87 (95% confidence interval, 2.30-20.51) for severe COVID-19, with increased risks also detected for both secondary outcomes. In contrast, TNF antagonist use was not significantly associated with the primary outcome; in fact, a possible protective effect was detected for hospitalization or death (aOR, 0.60; 95% CI, 0.38-0.96).

The investigators noted that the above findings aligned with extensive literature concerning infectious complications with corticosteroid use and “more recent commentary” surrounding TNF antagonists. Similarly, increased age and the presence of at least two comorbidities were each independently associated with increased risk of severe COVID-19, both of which are correlations that have been previously described.

But the threefold increased risk of severe COVID-19 associated with use of sulfasalazine or 5-ASAs (aOR, 3.14; 95% CI, 1.28-7.71) was a “surprising” finding, the investigators noted.

“In a direct comparison, we observed that 5-ASA/sulfasalazine–treated patients fared worse than those treated with TNF inhibitors,” the investigators wrote. “Although we cannot exclude unmeasured confounding, further exploration of biological mechanisms is warranted.”

David T. Rubin, MD, AGAF, of the University of Chicago agreed that the finding deserves further investigation, particularly since sulfasalazine and 5-ASAs represent the second most commonly prescribed medication class for IBD.

“The risk with 5-ASAs is of interest but not well explained by what we know about the safety or the mechanism of these therapies,” Dr. Rubin said. “Clearly, more work is needed.”

The risks associated with corticosteroids were particularly concerning, Dr. Rubin said, because 10%-20% of patients with IBD may be taking corticosteroids at any given time.

“Steroids are still the number one prescribed therapy for Crohn’s and colitis,” he said.

Still, Dr. Rubin advised against abrupt changes to drug regimens, especially if they are effectively controlling IBD.

“Patients should stay on their existing therapies and stay in remission,” Dr. Rubin said. “If you stop your therapies … you are more likely to relapse. When you relapse, you’re more likely to need steroids as a rescue therapy … or end up in the hospital, and those are not places we want you to be.”

Despite the risks associated with steroids and sulfasalazine/5-ASAs, Dr. Rubin had an optimistic take on the study, calling the findings “very reassuring” because they support continued usage of TNF inhibitors and other biologic agents during the pandemic. He also noted that the SECURE-IBD registry, which he has contributed to, represents “an extraordinary effort” from around the world.

“[This is] an unprecedented collaboration across a scale and timeframe that has really never been seen before in our field, and I would hazard a guess that it’s probably never been seen in most other fields right now,” he said.

Clinicians seeking more information about managing patients with IBD during the COVID-19 pandemic can find guidance in the recent AGA practice update, of which Dr. Rubin was the lead author. Clinicians who would like to contribute to the SECURE-IBD registry may do so at covidibd.org. The registry now includes more than 1,000 patients.

The study was funded by Clinical and Translational Science Award grants through Dr. Ungaro. The investigators disclosed relationships with Takeda, Janssen, Pfizer, and others. Dr. Rubin disclosed relationships with Gilead, Eli Lilly, Shire, and others.

Check out the AGA COVID-19 Resource Library for new clinical guidance, education, research and physician resources, including recent guidance on how to treat patients with IBD during the pandemic, at www.gastro.org/covid.

SOURCE: Brenner EJ et al. Gastroenterology. 2020 May 18. doi: 10.1053/j.gastro.2020.05.032.

Gastrointestinal symptoms affected 26% of hospital employees hospitalized with presumptive COVID-19 infection, according to the results of a study from Wuhan, China.

Among nonmedical personnel in the study (median age, 62 years), 63% of those with GI symptoms were female (P = .03), wrote Zili Zhou of Huazhong University of Science and Technology, Wuhan, China, and associates. Gastrointestinal symptoms correlated significantly with lower hemoglobin levels, increased levels of inflammatory markers, and poorer liver function, but not with clinical complications or mortality, they noted. However, “most patients were still hospitalized at the time of [manuscript] submission, [which made it] difficult to further assess the correlation between GI symptoms and clinical outcomes,” they wrote in Gastroenterology.

Reverse transcriptase polymerase chain reaction has detected COVID-19 in patients’ stool, and COVID-19’s primary receptor for cellular entry, the angiotensin converting enzyme 2 (ACE2) receptor, “is highly expressed not only in lung AT2 cells but also in absorptive enterocytes in the ileum and colon,” the investigators wrote. They compared laboratory and clinical findings among 254 adults with and without GI symptoms who were admitted to Wuhan’s main hospital with presumptive COVID-19 pneumonia between December 20, 2019, and February 9, 2020. All patients were employed by the hospital.

Gastrointestinal symptoms affected 26% of patients and most commonly included diarrhea (18%), nausea (8%), vomiting (6%), and abdominal pain (2%), the researchers reported. Arrhythmias and shock were rare, affecting less than 0.5% of patients. A total of 16 patients (6%) died.

The 161 nonmedical staff in the study were older and, therefore, were evaluated separately from medical staff (respective medians, 36 and 62 years; interquartile ranges, 31-41 years and 49-69 years). Among nonmedical staff, GI symptoms correlated with significantly lower hemoglobin levels (117 g/L [range, 106-127] vs. 133 g/L [range, 114-141], P = .03), and significantly higher levels of C-reactive protein (7.3 mg [range, 2.9-6.6] vs. 3.8 mg (1.8-5.8), P = .021) and alanine aminotransferase (64.1 U/L [range, 51.2-64.4] vs. 46.6 U/L [range, 31.9-61.2]; P = .049). Gastrointestinal symptoms also correlated significantly with fatigue, sore throat, and dizziness. Although the nonmedical cohort included five more males than females, females made up nearly two-thirds (63%) of individuals with GI symptoms (P = .03).

Although 25% of medical staff in the study had GI symptoms, GI symptoms did not correlate with other symptoms or with laboratory findings. This might be because “most of the infected medical staff were younger nurses without comorbidities,” the investigators wrote. “In addition, there [was] less delay from the onset of symptoms to hospital admission.”

For the overall cohort, the most prevalent symptoms were fever (84%), fatigue (52%), productive cough (42%), dry cough (42%), and myalgia (34%). Although these symptoms are typical of COVID-19 infection, most patients were not tested for the virus, “which will inevitably lead to several patients without [COVID-19 pneumonia] being included,” the investigators noted.

The National Nature Science Foundation of China provided funding. The investigators reported having no relevant conflicts of interest.

SOURCE: Zhou Z et al. Gastroenterology. 2020 Mar 18. doi: 10.1053/j.gastro.2020.03.020.

Gastrointestinal symptoms affected 26% of hospital employees hospitalized with presumptive COVID-19 infection, according to the results of a study from Wuhan, China.

Among nonmedical personnel in the study (median age, 62 years), 63% of those with GI symptoms were female (P = .03), wrote Zili Zhou of Huazhong University of Science and Technology, Wuhan, China, and associates. Gastrointestinal symptoms correlated significantly with lower hemoglobin levels, increased levels of inflammatory markers, and poorer liver function, but not with clinical complications or mortality, they noted. However, “most patients were still hospitalized at the time of [manuscript] submission, [which made it] difficult to further assess the correlation between GI symptoms and clinical outcomes,” they wrote in Gastroenterology.

Reverse transcriptase polymerase chain reaction has detected COVID-19 in patients’ stool, and COVID-19’s primary receptor for cellular entry, the angiotensin converting enzyme 2 (ACE2) receptor, “is highly expressed not only in lung AT2 cells but also in absorptive enterocytes in the ileum and colon,” the investigators wrote. They compared laboratory and clinical findings among 254 adults with and without GI symptoms who were admitted to Wuhan’s main hospital with presumptive COVID-19 pneumonia between December 20, 2019, and February 9, 2020. All patients were employed by the hospital.

Gastrointestinal symptoms affected 26% of patients and most commonly included diarrhea (18%), nausea (8%), vomiting (6%), and abdominal pain (2%), the researchers reported. Arrhythmias and shock were rare, affecting less than 0.5% of patients. A total of 16 patients (6%) died.

The 161 nonmedical staff in the study were older and, therefore, were evaluated separately from medical staff (respective medians, 36 and 62 years; interquartile ranges, 31-41 years and 49-69 years). Among nonmedical staff, GI symptoms correlated with significantly lower hemoglobin levels (117 g/L [range, 106-127] vs. 133 g/L [range, 114-141], P = .03), and significantly higher levels of C-reactive protein (7.3 mg [range, 2.9-6.6] vs. 3.8 mg (1.8-5.8), P = .021) and alanine aminotransferase (64.1 U/L [range, 51.2-64.4] vs. 46.6 U/L [range, 31.9-61.2]; P = .049). Gastrointestinal symptoms also correlated significantly with fatigue, sore throat, and dizziness. Although the nonmedical cohort included five more males than females, females made up nearly two-thirds (63%) of individuals with GI symptoms (P = .03).

Although 25% of medical staff in the study had GI symptoms, GI symptoms did not correlate with other symptoms or with laboratory findings. This might be because “most of the infected medical staff were younger nurses without comorbidities,” the investigators wrote. “In addition, there [was] less delay from the onset of symptoms to hospital admission.”

For the overall cohort, the most prevalent symptoms were fever (84%), fatigue (52%), productive cough (42%), dry cough (42%), and myalgia (34%). Although these symptoms are typical of COVID-19 infection, most patients were not tested for the virus, “which will inevitably lead to several patients without [COVID-19 pneumonia] being included,” the investigators noted.

The National Nature Science Foundation of China provided funding. The investigators reported having no relevant conflicts of interest.

SOURCE: Zhou Z et al. Gastroenterology. 2020 Mar 18. doi: 10.1053/j.gastro.2020.03.020.

Gastrointestinal symptoms affected 26% of hospital employees hospitalized with presumptive COVID-19 infection, according to the results of a study from Wuhan, China.

Among nonmedical personnel in the study (median age, 62 years), 63% of those with GI symptoms were female (P = .03), wrote Zili Zhou of Huazhong University of Science and Technology, Wuhan, China, and associates. Gastrointestinal symptoms correlated significantly with lower hemoglobin levels, increased levels of inflammatory markers, and poorer liver function, but not with clinical complications or mortality, they noted. However, “most patients were still hospitalized at the time of [manuscript] submission, [which made it] difficult to further assess the correlation between GI symptoms and clinical outcomes,” they wrote in Gastroenterology.

Reverse transcriptase polymerase chain reaction has detected COVID-19 in patients’ stool, and COVID-19’s primary receptor for cellular entry, the angiotensin converting enzyme 2 (ACE2) receptor, “is highly expressed not only in lung AT2 cells but also in absorptive enterocytes in the ileum and colon,” the investigators wrote. They compared laboratory and clinical findings among 254 adults with and without GI symptoms who were admitted to Wuhan’s main hospital with presumptive COVID-19 pneumonia between December 20, 2019, and February 9, 2020. All patients were employed by the hospital.

Gastrointestinal symptoms affected 26% of patients and most commonly included diarrhea (18%), nausea (8%), vomiting (6%), and abdominal pain (2%), the researchers reported. Arrhythmias and shock were rare, affecting less than 0.5% of patients. A total of 16 patients (6%) died.

The 161 nonmedical staff in the study were older and, therefore, were evaluated separately from medical staff (respective medians, 36 and 62 years; interquartile ranges, 31-41 years and 49-69 years). Among nonmedical staff, GI symptoms correlated with significantly lower hemoglobin levels (117 g/L [range, 106-127] vs. 133 g/L [range, 114-141], P = .03), and significantly higher levels of C-reactive protein (7.3 mg [range, 2.9-6.6] vs. 3.8 mg (1.8-5.8), P = .021) and alanine aminotransferase (64.1 U/L [range, 51.2-64.4] vs. 46.6 U/L [range, 31.9-61.2]; P = .049). Gastrointestinal symptoms also correlated significantly with fatigue, sore throat, and dizziness. Although the nonmedical cohort included five more males than females, females made up nearly two-thirds (63%) of individuals with GI symptoms (P = .03).

Although 25% of medical staff in the study had GI symptoms, GI symptoms did not correlate with other symptoms or with laboratory findings. This might be because “most of the infected medical staff were younger nurses without comorbidities,” the investigators wrote. “In addition, there [was] less delay from the onset of symptoms to hospital admission.”

For the overall cohort, the most prevalent symptoms were fever (84%), fatigue (52%), productive cough (42%), dry cough (42%), and myalgia (34%). Although these symptoms are typical of COVID-19 infection, most patients were not tested for the virus, “which will inevitably lead to several patients without [COVID-19 pneumonia] being included,” the investigators noted.

The National Nature Science Foundation of China provided funding. The investigators reported having no relevant conflicts of interest.

SOURCE: Zhou Z et al. Gastroenterology. 2020 Mar 18. doi: 10.1053/j.gastro.2020.03.020.

Recognizing the presence of functional heartburn is vital to prevent unnecessary acid-suppressive therapy and invasive antireflux treatments, which are ineffective and “might even lead to harm,” cautions a new clinical practice update from the American Gastroenterological Association.

Proton pump inhibitors (PPIs) “have no therapeutic value in functional heartburn,” unless patients also have gastroesophageal reflux disease (GERD), Ronnie Fass, MD, of MetroHealth System in Cleveland, and coauthors wrote in Gastroenterology. If clinical work-up finds no clear evidence of GERD, “an attempt to discontinue PPI therapy is warranted,” they added. Likewise, antireflux surgery and endoscopic treatments for GERD “have no therapeutic benefit in functional heartburn and should not be recommended.” However, histamine₂ receptor antagonists (H₂RAs) “may have an independent benefit in functional heartburn from an esophageal pain modulatory effect.”

Heartburn consists of burning or discomfort that radiates retrosternally from the epigastrium. Patients may report reflux, regurgitation, chest pain or discomfort, fullness, water brash, belching, or a sour and bitter taste in the mouth. Functional heartburn is heartburn that persists after at least 3 months of maximal (double-dose) PPIs taken before meals. Confirming functional heartburn requires high-resolution manometry to rule out major esophageal motor disorders, esophageal endoscopy with biopsy to rule out structural abnormalities and mucosal disorders (e.g., erosive esophagitis, Barrett’s esophagus, and eosinophilic esophagitis), and either pH monitoring while off PPI therapy or pH-impedance monitoring on therapy if patients have proven GERD. According to the clinical practice update, pH studies should document physiological acid exposure in the distal esophagus that is unlinked to symptoms (i.e., both a negative symptom index and a negative symptom association probability).

Functional heartburn resembles GERD, but symptoms are unrelated to acid exposure. Balloon distension studies indicate that patients with functional heartburn experience both esophageal and rectal hypersensitivity. Anxiety and mood disorders also are highly prevalent, and patients “will likely not improve unless esophageal perception and underlying affective disorders are adequately managed,” Dr. Fass and coauthors emphasized.

In keeping with this approach, limited evidence from clinical trials supports the first-line use of neuromodulator therapies, including selective serotonin reuptake inhibitors, tricyclic antidepressants, the serotonin 4 receptor antagonist tegaserod, and H₂RAs (e.g., cimetidine, famotidine, nizatidine). The only SSRI studied thus far in functional heartburn is fluoxetine. In a placebo-controlled trial of patients with normal endoscopy and heartburn that had not responded to once-daily PPI therapy, 6 weeks of fluoxetine (20 mg daily) significantly outperformed double-dose omeprazole (P < .001) for the primary endpoint of heartburn-free days. “This superior therapeutic effect of fluoxetine was seen only in the subset of patients with a normal pH test,” the experts noted.

In another placebo-controlled trial, the neuromodulator tegaserod (a serotonin 5-HT₄ receptor partial agonist) significantly improved tolerance of esophageal pressure during balloon distension and significantly decreased heartburn, regurgitation, and associated distress among patients with functional heartburn. Melatonin, which “also has a pain modulatory effect in the gastrointestinal tract,” significantly improved symptom-related quality of life, compared with nortriptyline and placebo in a randomized, three-arm trial. The patients on melatonin received a 6-mg dose at bedtime for 3 months.

Acupuncture and hypnotherapy also have shown benefit in small studies of functional heartburn patients and may be appropriate as monotherapy or adjunctive treatment, according to the clinical practice update. In a small randomized study, 10 acupuncture sessions delivered over 4 weeks significantly improved daytime and nighttime heartburn and acid regurgitation scores, compared with double-dose PPI. “Mean general health score was significantly improved only in those receiving acupuncture,” the experts noted. Hypnotherapy, the only psychological intervention to have been studied in functional heartburn, was associated with significant improvements in symptoms, visceral anxiety, and quality of life in an uncontrolled study of nine patients.

Although the overall prevalence of functional heartburn is unclear, it has been detected in 21%-39% of PPI-refractory patients evaluated with pH-impedance monitoring, Dr. Fass and associates wrote. Because functional heartburn and GERD can co-occur, some patients with functional heartburn may develop long-term complications of GERD, such as Barrett’s esophagus or peptic stricture. However, the experts noted, “this is anticipated to be rare, and the vast majority of patients with functional heartburn will have compromised quality of life, rather than organic complications over time.

Dr. Fass reported receiving consulting, research, and speaking fees from Ironwood, Takeda, and Salix, among other pharmaceutical companies; Dr. Zerbib received consulting fees from Reckitt Benckiser; and Dr. Gyawali received teaching and consulting fees from Medtronic, Diversatek, and Ironwood.

SOURCE: Fass R et al. Gastroenterology. 2020 Feb 1. doi: 10.1053/j.gastro.2020.01.034.

This story was updated on 6/11/2020.

Recognizing the presence of functional heartburn is vital to prevent unnecessary acid-suppressive therapy and invasive antireflux treatments, which are ineffective and “might even lead to harm,” cautions a new clinical practice update from the American Gastroenterological Association.

Proton pump inhibitors (PPIs) “have no therapeutic value in functional heartburn,” unless patients also have gastroesophageal reflux disease (GERD), Ronnie Fass, MD, of MetroHealth System in Cleveland, and coauthors wrote in Gastroenterology. If clinical work-up finds no clear evidence of GERD, “an attempt to discontinue PPI therapy is warranted,” they added. Likewise, antireflux surgery and endoscopic treatments for GERD “have no therapeutic benefit in functional heartburn and should not be recommended.” However, histamine₂ receptor antagonists (H₂RAs) “may have an independent benefit in functional heartburn from an esophageal pain modulatory effect.”

Heartburn consists of burning or discomfort that radiates retrosternally from the epigastrium. Patients may report reflux, regurgitation, chest pain or discomfort, fullness, water brash, belching, or a sour and bitter taste in the mouth. Functional heartburn is heartburn that persists after at least 3 months of maximal (double-dose) PPIs taken before meals. Confirming functional heartburn requires high-resolution manometry to rule out major esophageal motor disorders, esophageal endoscopy with biopsy to rule out structural abnormalities and mucosal disorders (e.g., erosive esophagitis, Barrett’s esophagus, and eosinophilic esophagitis), and either pH monitoring while off PPI therapy or pH-impedance monitoring on therapy if patients have proven GERD. According to the clinical practice update, pH studies should document physiological acid exposure in the distal esophagus that is unlinked to symptoms (i.e., both a negative symptom index and a negative symptom association probability).

Functional heartburn resembles GERD, but symptoms are unrelated to acid exposure. Balloon distension studies indicate that patients with functional heartburn experience both esophageal and rectal hypersensitivity. Anxiety and mood disorders also are highly prevalent, and patients “will likely not improve unless esophageal perception and underlying affective disorders are adequately managed,” Dr. Fass and coauthors emphasized.

In keeping with this approach, limited evidence from clinical trials supports the first-line use of neuromodulator therapies, including selective serotonin reuptake inhibitors, tricyclic antidepressants, the serotonin 4 receptor antagonist tegaserod, and H₂RAs (e.g., cimetidine, famotidine, nizatidine). The only SSRI studied thus far in functional heartburn is fluoxetine. In a placebo-controlled trial of patients with normal endoscopy and heartburn that had not responded to once-daily PPI therapy, 6 weeks of fluoxetine (20 mg daily) significantly outperformed double-dose omeprazole (P < .001) for the primary endpoint of heartburn-free days. “This superior therapeutic effect of fluoxetine was seen only in the subset of patients with a normal pH test,” the experts noted.

In another placebo-controlled trial, the neuromodulator tegaserod (a serotonin 5-HT₄ receptor partial agonist) significantly improved tolerance of esophageal pressure during balloon distension and significantly decreased heartburn, regurgitation, and associated distress among patients with functional heartburn. Melatonin, which “also has a pain modulatory effect in the gastrointestinal tract,” significantly improved symptom-related quality of life, compared with nortriptyline and placebo in a randomized, three-arm trial. The patients on melatonin received a 6-mg dose at bedtime for 3 months.

Acupuncture and hypnotherapy also have shown benefit in small studies of functional heartburn patients and may be appropriate as monotherapy or adjunctive treatment, according to the clinical practice update. In a small randomized study, 10 acupuncture sessions delivered over 4 weeks significantly improved daytime and nighttime heartburn and acid regurgitation scores, compared with double-dose PPI. “Mean general health score was significantly improved only in those receiving acupuncture,” the experts noted. Hypnotherapy, the only psychological intervention to have been studied in functional heartburn, was associated with significant improvements in symptoms, visceral anxiety, and quality of life in an uncontrolled study of nine patients.

Although the overall prevalence of functional heartburn is unclear, it has been detected in 21%-39% of PPI-refractory patients evaluated with pH-impedance monitoring, Dr. Fass and associates wrote. Because functional heartburn and GERD can co-occur, some patients with functional heartburn may develop long-term complications of GERD, such as Barrett’s esophagus or peptic stricture. However, the experts noted, “this is anticipated to be rare, and the vast majority of patients with functional heartburn will have compromised quality of life, rather than organic complications over time.

Dr. Fass reported receiving consulting, research, and speaking fees from Ironwood, Takeda, and Salix, among other pharmaceutical companies; Dr. Zerbib received consulting fees from Reckitt Benckiser; and Dr. Gyawali received teaching and consulting fees from Medtronic, Diversatek, and Ironwood.

SOURCE: Fass R et al. Gastroenterology. 2020 Feb 1. doi: 10.1053/j.gastro.2020.01.034.

This story was updated on 6/11/2020.

Recognizing the presence of functional heartburn is vital to prevent unnecessary acid-suppressive therapy and invasive antireflux treatments, which are ineffective and “might even lead to harm,” cautions a new clinical practice update from the American Gastroenterological Association.

Proton pump inhibitors (PPIs) “have no therapeutic value in functional heartburn,” unless patients also have gastroesophageal reflux disease (GERD), Ronnie Fass, MD, of MetroHealth System in Cleveland, and coauthors wrote in Gastroenterology. If clinical work-up finds no clear evidence of GERD, “an attempt to discontinue PPI therapy is warranted,” they added. Likewise, antireflux surgery and endoscopic treatments for GERD “have no therapeutic benefit in functional heartburn and should not be recommended.” However, histamine₂ receptor antagonists (H₂RAs) “may have an independent benefit in functional heartburn from an esophageal pain modulatory effect.”

Heartburn consists of burning or discomfort that radiates retrosternally from the epigastrium. Patients may report reflux, regurgitation, chest pain or discomfort, fullness, water brash, belching, or a sour and bitter taste in the mouth. Functional heartburn is heartburn that persists after at least 3 months of maximal (double-dose) PPIs taken before meals. Confirming functional heartburn requires high-resolution manometry to rule out major esophageal motor disorders, esophageal endoscopy with biopsy to rule out structural abnormalities and mucosal disorders (e.g., erosive esophagitis, Barrett’s esophagus, and eosinophilic esophagitis), and either pH monitoring while off PPI therapy or pH-impedance monitoring on therapy if patients have proven GERD. According to the clinical practice update, pH studies should document physiological acid exposure in the distal esophagus that is unlinked to symptoms (i.e., both a negative symptom index and a negative symptom association probability).

Functional heartburn resembles GERD, but symptoms are unrelated to acid exposure. Balloon distension studies indicate that patients with functional heartburn experience both esophageal and rectal hypersensitivity. Anxiety and mood disorders also are highly prevalent, and patients “will likely not improve unless esophageal perception and underlying affective disorders are adequately managed,” Dr. Fass and coauthors emphasized.

In keeping with this approach, limited evidence from clinical trials supports the first-line use of neuromodulator therapies, including selective serotonin reuptake inhibitors, tricyclic antidepressants, the serotonin 4 receptor antagonist tegaserod, and H₂RAs (e.g., cimetidine, famotidine, nizatidine). The only SSRI studied thus far in functional heartburn is fluoxetine. In a placebo-controlled trial of patients with normal endoscopy and heartburn that had not responded to once-daily PPI therapy, 6 weeks of fluoxetine (20 mg daily) significantly outperformed double-dose omeprazole (P < .001) for the primary endpoint of heartburn-free days. “This superior therapeutic effect of fluoxetine was seen only in the subset of patients with a normal pH test,” the experts noted.

In another placebo-controlled trial, the neuromodulator tegaserod (a serotonin 5-HT₄ receptor partial agonist) significantly improved tolerance of esophageal pressure during balloon distension and significantly decreased heartburn, regurgitation, and associated distress among patients with functional heartburn. Melatonin, which “also has a pain modulatory effect in the gastrointestinal tract,” significantly improved symptom-related quality of life, compared with nortriptyline and placebo in a randomized, three-arm trial. The patients on melatonin received a 6-mg dose at bedtime for 3 months.

Acupuncture and hypnotherapy also have shown benefit in small studies of functional heartburn patients and may be appropriate as monotherapy or adjunctive treatment, according to the clinical practice update. In a small randomized study, 10 acupuncture sessions delivered over 4 weeks significantly improved daytime and nighttime heartburn and acid regurgitation scores, compared with double-dose PPI. “Mean general health score was significantly improved only in those receiving acupuncture,” the experts noted. Hypnotherapy, the only psychological intervention to have been studied in functional heartburn, was associated with significant improvements in symptoms, visceral anxiety, and quality of life in an uncontrolled study of nine patients.

Although the overall prevalence of functional heartburn is unclear, it has been detected in 21%-39% of PPI-refractory patients evaluated with pH-impedance monitoring, Dr. Fass and associates wrote. Because functional heartburn and GERD can co-occur, some patients with functional heartburn may develop long-term complications of GERD, such as Barrett’s esophagus or peptic stricture. However, the experts noted, “this is anticipated to be rare, and the vast majority of patients with functional heartburn will have compromised quality of life, rather than organic complications over time.

Dr. Fass reported receiving consulting, research, and speaking fees from Ironwood, Takeda, and Salix, among other pharmaceutical companies; Dr. Zerbib received consulting fees from Reckitt Benckiser; and Dr. Gyawali received teaching and consulting fees from Medtronic, Diversatek, and Ironwood.

SOURCE: Fass R et al. Gastroenterology. 2020 Feb 1. doi: 10.1053/j.gastro.2020.01.034.

This story was updated on 6/11/2020.

For patients with chronic hepatitis B virus (HBV) infection, triple-combination therapy with tenofovir disoproxil fumarate, pegylated interferon alfa-2a (TDF-pegIFN), and either of two investigational nucleic acid polymers was tolerable and led to long-term functional cures in an open-label phase 2 trial.

The addition of either REP 2139 or REP 2165 to backbone TDF-pegIFN therapy produced functional cures in 39% of patients without lessening HBV DNA control or exacerbating treatment-induced neutropenia or thrombocytopenia, said Michel Bazinet, MD, of Replicor in Montreal and his associates. “Increases in levels of transaminases were significantly more frequent (P < .001 vs. controls) and greater (P = .002 vs. controls) in the nucleic acid polymer groups but did not produce symptoms, correlated with [an] initial decrease in hepatitis B surface antigen [HBsAg], and normalized during therapy and follow-up,” the investigators wrote in Gastroenterology.

Nucleic acid polymers (NAPs) suppress the assembly and secretion of HBV subviral particles. NAP monotherapy is active against HBV but usually does not provide long-term virologic control. In a small study, adding pegIFN or thymosin alpha-1 to an investigational NAP achieved functional control (HBsAg positive, HBV DNA ≤ 2000 IU/mL, and normal alanine aminotransferase levels) in eight of nine patients.

Building on these findings, two triple-combination NAP regimens were evaluated in 40 noncirrhotic HB envelope antigen–negative adults with chronic HBV infection. After 24 weeks of TDF monotherapy, participants were randomly assigned to either 48 weeks of REP 2139 or REP 2165 plus backbone therapy with TDF and pegIFN, or 24 weeks of backbone therapy followed by 48 weeks of triple-combination treatment. Patients were then followed without treatment for 24-48 weeks.

Backbone TDF-pegIFN therapy produced no HBsAg seroconversions, and HBsAg levels dropped by more than 1 log10 IU/mL in only three patients. In contrast, triple-combination NAP therapy produced undetectable HBsAg and HBsAg seroconversions (up to 233,055 mIU/mL) for 60% of patients. Among 36 patients followed for 24-48 weeks after completing treatment, 78% maintained virologic control and 39% showed functional cures (HBsAg < 0.05 IU/mL, undetectable HBV DNA, and normal ALT). “Additional follow-up is planned to confirm the long-term stability of [these] outcomes,” the researchers said.

Both NAPs were formulated with chelated magnesium to improve their tolerability. Although 95% of patients experienced transaminase flares, these “self-resolved or declined during continuing NAP therapy and normalized in 32 of 34 (94%) of participants completing 48 weeks of follow-up,” the researchers said. In keeping with prior studies, transaminase flares were associated with early declines in HBsAg but not with altered liver function or liver disease symptoms.

The study was conducted at three sites in Maldova. Most participants were men with HBV genotype D infection. “During follow-up, viral rebound occurred in participants [in whom] HBsAg was still detectable at the end of 48 weeks of combination therapy (≥ 57.9 IU/mL), who did not complete therapy, or [for whom] HBsAg clearance occurred very late in therapy,” the researchers wrote. Thus, “persistent exposure to pegIFN while HBsAg is cleared may be important for the establishment of virologic control and functional cure.” They recommended evaluating NAP plus nucleos(t)ide analogue (NUC) therapy to assess response in the absence of pegIFN. Such studies should enroll “NUC-experienced participants with well-controlled HBV DNA.”

Replicor provided funding. Dr. Bazinet and the senior investigator reported that they are employees and shareholders of Replicor and have invented patents that Replicor holds. One coinvestigator reported compensation from Replicor to his institution. The remaining 11 coinvestigators reported having no relevant disclosures.
 

SOURCE: Bazinet M et al. Gastroenterology. 2020 Mar 5. doi: 0.1053/j.gastro.2020.02.058.

For patients with chronic hepatitis B virus (HBV) infection, triple-combination therapy with tenofovir disoproxil fumarate, pegylated interferon alfa-2a (TDF-pegIFN), and either of two investigational nucleic acid polymers was tolerable and led to long-term functional cures in an open-label phase 2 trial.

The addition of either REP 2139 or REP 2165 to backbone TDF-pegIFN therapy produced functional cures in 39% of patients without lessening HBV DNA control or exacerbating treatment-induced neutropenia or thrombocytopenia, said Michel Bazinet, MD, of Replicor in Montreal and his associates. “Increases in levels of transaminases were significantly more frequent (P < .001 vs. controls) and greater (P = .002 vs. controls) in the nucleic acid polymer groups but did not produce symptoms, correlated with [an] initial decrease in hepatitis B surface antigen [HBsAg], and normalized during therapy and follow-up,” the investigators wrote in Gastroenterology.

Nucleic acid polymers (NAPs) suppress the assembly and secretion of HBV subviral particles. NAP monotherapy is active against HBV but usually does not provide long-term virologic control. In a small study, adding pegIFN or thymosin alpha-1 to an investigational NAP achieved functional control (HBsAg positive, HBV DNA ≤ 2000 IU/mL, and normal alanine aminotransferase levels) in eight of nine patients.

Building on these findings, two triple-combination NAP regimens were evaluated in 40 noncirrhotic HB envelope antigen–negative adults with chronic HBV infection. After 24 weeks of TDF monotherapy, participants were randomly assigned to either 48 weeks of REP 2139 or REP 2165 plus backbone therapy with TDF and pegIFN, or 24 weeks of backbone therapy followed by 48 weeks of triple-combination treatment. Patients were then followed without treatment for 24-48 weeks.

Backbone TDF-pegIFN therapy produced no HBsAg seroconversions, and HBsAg levels dropped by more than 1 log10 IU/mL in only three patients. In contrast, triple-combination NAP therapy produced undetectable HBsAg and HBsAg seroconversions (up to 233,055 mIU/mL) for 60% of patients. Among 36 patients followed for 24-48 weeks after completing treatment, 78% maintained virologic control and 39% showed functional cures (HBsAg < 0.05 IU/mL, undetectable HBV DNA, and normal ALT). “Additional follow-up is planned to confirm the long-term stability of [these] outcomes,” the researchers said.

Both NAPs were formulated with chelated magnesium to improve their tolerability. Although 95% of patients experienced transaminase flares, these “self-resolved or declined during continuing NAP therapy and normalized in 32 of 34 (94%) of participants completing 48 weeks of follow-up,” the researchers said. In keeping with prior studies, transaminase flares were associated with early declines in HBsAg but not with altered liver function or liver disease symptoms.

The study was conducted at three sites in Maldova. Most participants were men with HBV genotype D infection. “During follow-up, viral rebound occurred in participants [in whom] HBsAg was still detectable at the end of 48 weeks of combination therapy (≥ 57.9 IU/mL), who did not complete therapy, or [for whom] HBsAg clearance occurred very late in therapy,” the researchers wrote. Thus, “persistent exposure to pegIFN while HBsAg is cleared may be important for the establishment of virologic control and functional cure.” They recommended evaluating NAP plus nucleos(t)ide analogue (NUC) therapy to assess response in the absence of pegIFN. Such studies should enroll “NUC-experienced participants with well-controlled HBV DNA.”

Replicor provided funding. Dr. Bazinet and the senior investigator reported that they are employees and shareholders of Replicor and have invented patents that Replicor holds. One coinvestigator reported compensation from Replicor to his institution. The remaining 11 coinvestigators reported having no relevant disclosures.
 

SOURCE: Bazinet M et al. Gastroenterology. 2020 Mar 5. doi: 0.1053/j.gastro.2020.02.058.

For patients with chronic hepatitis B virus (HBV) infection, triple-combination therapy with tenofovir disoproxil fumarate, pegylated interferon alfa-2a (TDF-pegIFN), and either of two investigational nucleic acid polymers was tolerable and led to long-term functional cures in an open-label phase 2 trial.

The addition of either REP 2139 or REP 2165 to backbone TDF-pegIFN therapy produced functional cures in 39% of patients without lessening HBV DNA control or exacerbating treatment-induced neutropenia or thrombocytopenia, said Michel Bazinet, MD, of Replicor in Montreal and his associates. “Increases in levels of transaminases were significantly more frequent (P < .001 vs. controls) and greater (P = .002 vs. controls) in the nucleic acid polymer groups but did not produce symptoms, correlated with [an] initial decrease in hepatitis B surface antigen [HBsAg], and normalized during therapy and follow-up,” the investigators wrote in Gastroenterology.

Nucleic acid polymers (NAPs) suppress the assembly and secretion of HBV subviral particles. NAP monotherapy is active against HBV but usually does not provide long-term virologic control. In a small study, adding pegIFN or thymosin alpha-1 to an investigational NAP achieved functional control (HBsAg positive, HBV DNA ≤ 2000 IU/mL, and normal alanine aminotransferase levels) in eight of nine patients.

Building on these findings, two triple-combination NAP regimens were evaluated in 40 noncirrhotic HB envelope antigen–negative adults with chronic HBV infection. After 24 weeks of TDF monotherapy, participants were randomly assigned to either 48 weeks of REP 2139 or REP 2165 plus backbone therapy with TDF and pegIFN, or 24 weeks of backbone therapy followed by 48 weeks of triple-combination treatment. Patients were then followed without treatment for 24-48 weeks.

Backbone TDF-pegIFN therapy produced no HBsAg seroconversions, and HBsAg levels dropped by more than 1 log10 IU/mL in only three patients. In contrast, triple-combination NAP therapy produced undetectable HBsAg and HBsAg seroconversions (up to 233,055 mIU/mL) for 60% of patients. Among 36 patients followed for 24-48 weeks after completing treatment, 78% maintained virologic control and 39% showed functional cures (HBsAg < 0.05 IU/mL, undetectable HBV DNA, and normal ALT). “Additional follow-up is planned to confirm the long-term stability of [these] outcomes,” the researchers said.

Both NAPs were formulated with chelated magnesium to improve their tolerability. Although 95% of patients experienced transaminase flares, these “self-resolved or declined during continuing NAP therapy and normalized in 32 of 34 (94%) of participants completing 48 weeks of follow-up,” the researchers said. In keeping with prior studies, transaminase flares were associated with early declines in HBsAg but not with altered liver function or liver disease symptoms.

The study was conducted at three sites in Maldova. Most participants were men with HBV genotype D infection. “During follow-up, viral rebound occurred in participants [in whom] HBsAg was still detectable at the end of 48 weeks of combination therapy (≥ 57.9 IU/mL), who did not complete therapy, or [for whom] HBsAg clearance occurred very late in therapy,” the researchers wrote. Thus, “persistent exposure to pegIFN while HBsAg is cleared may be important for the establishment of virologic control and functional cure.” They recommended evaluating NAP plus nucleos(t)ide analogue (NUC) therapy to assess response in the absence of pegIFN. Such studies should enroll “NUC-experienced participants with well-controlled HBV DNA.”

Replicor provided funding. Dr. Bazinet and the senior investigator reported that they are employees and shareholders of Replicor and have invented patents that Replicor holds. One coinvestigator reported compensation from Replicor to his institution. The remaining 11 coinvestigators reported having no relevant disclosures.
 

SOURCE: Bazinet M et al. Gastroenterology. 2020 Mar 5. doi: 0.1053/j.gastro.2020.02.058.

Total underwater colonoscopy can surmount challenges with insertion, simplify endoscopic mucosal resection, and lessen pain and the need for sedation, according to a “Here and Now: Clinical Practice” article published in Clinical Gastroenterology and Hepatology.

At the same time, total underwater colonoscopy has not been shown to significantly affect adenoma miss rates, requires a longer insertion and overall procedure time, and cannot be performed without adequate bowel preparation, wrote Joseph C. Anderson, MD, of the Department of Veterans Affairs Medical Center in White River Junction, Vt., and the Geisel School of Medicine at Dartmouth, Hanover, N.H.

He noted that total underwater colonoscopy is not the same as water immersion or water exchange, both of which involve infusing water while inserting the colonoscope and then distending the colon with carbon dioxide to visualize the mucosa during withdrawal. During total underwater colonoscopy, insertion, examination, and resection all are carried out with the lumen filled with water. Air is suctioned out, and the air valve is kept off.

This approach can surmount problems with insertion stemming from either severe angulation (often of the sigmoid colon), or redundant colon (excessive looping) that does not respond to abdominal pressure, colonoscope stiffening, or a change in position, Dr. Anderson noted. He explained that, unlike air, water does not maximally distend the lumen and therefore does not exacerbate angulation. “When I am in the ascending colon and cannot reach the cecum, I turn off the air valve, aspirate all gas, infuse water, and complete the insertion underwater,” he said. “Another advantage of water in patients with angulated sigmoid colons is that its use could prevent [the] excessive use of air and potential barotrauma of the cecum, even when using carbon dioxide.”

The use of water can aid endoscopic mucosal resection (EMR) because polyps tend to float into view (including from hard-to-visualize areas, such as folds) and into the snare, he said. “Because water has a magnifying property, underwater EMR may allow for easier delineation of the polyp’s border, also facilitating complete removal.”

Nonetheless, it remains unclear whether the use of total underwater colonoscopy significantly affects adenoma detection rates. In a recent study, Dr. Anderson and his coinvestiators randomly assigned 121 patients to undergo either colonoscopy with carbon dioxide insufflation, followed by total underwater colonoscopy, or the same examinations in the reverse sequence (Anderson KC et al. Gastrointest Endosc. 2019;89:591-8). Adenoma miss rates were statistically similar between groups. Although water decreases green mucus and residual stool and suspends “unsuctionable” particles (e.g. seeds) into the cecal lumen, where colonoscopists can better see past them, water also increases the production of white mucus, which can be difficult to remove during withdrawal, Dr. Anderson said.

He cited meta-analyses in which colonoscopies performed with water, without sedation or with minimal sedation, were associated with less pain and a higher likelihood of performing a complete examination than when only air was used. “I find this [approach] particularly useful in older, thinner patients, especially women,” Dr. Anderson said. “In addition, in patients with multiple comorbidities, cecal intubation often can be achieved safely with minimal sedation.”

Dr. Anderson reported having no relevant conflicts of interest.

SOURCE: Anderson JC. Clin Gastroenterol Hepatol. 2020 Feb 25. doi: 10.1016/j.cgh.2020.02.042.

Total underwater colonoscopy can surmount challenges with insertion, simplify endoscopic mucosal resection, and lessen pain and the need for sedation, according to a “Here and Now: Clinical Practice” article published in Clinical Gastroenterology and Hepatology.

At the same time, total underwater colonoscopy has not been shown to significantly affect adenoma miss rates, requires a longer insertion and overall procedure time, and cannot be performed without adequate bowel preparation, wrote Joseph C. Anderson, MD, of the Department of Veterans Affairs Medical Center in White River Junction, Vt., and the Geisel School of Medicine at Dartmouth, Hanover, N.H.

He noted that total underwater colonoscopy is not the same as water immersion or water exchange, both of which involve infusing water while inserting the colonoscope and then distending the colon with carbon dioxide to visualize the mucosa during withdrawal. During total underwater colonoscopy, insertion, examination, and resection all are carried out with the lumen filled with water. Air is suctioned out, and the air valve is kept off.

This approach can surmount problems with insertion stemming from either severe angulation (often of the sigmoid colon), or redundant colon (excessive looping) that does not respond to abdominal pressure, colonoscope stiffening, or a change in position, Dr. Anderson noted. He explained that, unlike air, water does not maximally distend the lumen and therefore does not exacerbate angulation. “When I am in the ascending colon and cannot reach the cecum, I turn off the air valve, aspirate all gas, infuse water, and complete the insertion underwater,” he said. “Another advantage of water in patients with angulated sigmoid colons is that its use could prevent [the] excessive use of air and potential barotrauma of the cecum, even when using carbon dioxide.”

The use of water can aid endoscopic mucosal resection (EMR) because polyps tend to float into view (including from hard-to-visualize areas, such as folds) and into the snare, he said. “Because water has a magnifying property, underwater EMR may allow for easier delineation of the polyp’s border, also facilitating complete removal.”

Nonetheless, it remains unclear whether the use of total underwater colonoscopy significantly affects adenoma detection rates. In a recent study, Dr. Anderson and his coinvestiators randomly assigned 121 patients to undergo either colonoscopy with carbon dioxide insufflation, followed by total underwater colonoscopy, or the same examinations in the reverse sequence (Anderson KC et al. Gastrointest Endosc. 2019;89:591-8). Adenoma miss rates were statistically similar between groups. Although water decreases green mucus and residual stool and suspends “unsuctionable” particles (e.g. seeds) into the cecal lumen, where colonoscopists can better see past them, water also increases the production of white mucus, which can be difficult to remove during withdrawal, Dr. Anderson said.

He cited meta-analyses in which colonoscopies performed with water, without sedation or with minimal sedation, were associated with less pain and a higher likelihood of performing a complete examination than when only air was used. “I find this [approach] particularly useful in older, thinner patients, especially women,” Dr. Anderson said. “In addition, in patients with multiple comorbidities, cecal intubation often can be achieved safely with minimal sedation.”

Dr. Anderson reported having no relevant conflicts of interest.

SOURCE: Anderson JC. Clin Gastroenterol Hepatol. 2020 Feb 25. doi: 10.1016/j.cgh.2020.02.042.

Total underwater colonoscopy can surmount challenges with insertion, simplify endoscopic mucosal resection, and lessen pain and the need for sedation, according to a “Here and Now: Clinical Practice” article published in Clinical Gastroenterology and Hepatology.

At the same time, total underwater colonoscopy has not been shown to significantly affect adenoma miss rates, requires a longer insertion and overall procedure time, and cannot be performed without adequate bowel preparation, wrote Joseph C. Anderson, MD, of the Department of Veterans Affairs Medical Center in White River Junction, Vt., and the Geisel School of Medicine at Dartmouth, Hanover, N.H.

He noted that total underwater colonoscopy is not the same as water immersion or water exchange, both of which involve infusing water while inserting the colonoscope and then distending the colon with carbon dioxide to visualize the mucosa during withdrawal. During total underwater colonoscopy, insertion, examination, and resection all are carried out with the lumen filled with water. Air is suctioned out, and the air valve is kept off.

This approach can surmount problems with insertion stemming from either severe angulation (often of the sigmoid colon), or redundant colon (excessive looping) that does not respond to abdominal pressure, colonoscope stiffening, or a change in position, Dr. Anderson noted. He explained that, unlike air, water does not maximally distend the lumen and therefore does not exacerbate angulation. “When I am in the ascending colon and cannot reach the cecum, I turn off the air valve, aspirate all gas, infuse water, and complete the insertion underwater,” he said. “Another advantage of water in patients with angulated sigmoid colons is that its use could prevent [the] excessive use of air and potential barotrauma of the cecum, even when using carbon dioxide.”

The use of water can aid endoscopic mucosal resection (EMR) because polyps tend to float into view (including from hard-to-visualize areas, such as folds) and into the snare, he said. “Because water has a magnifying property, underwater EMR may allow for easier delineation of the polyp’s border, also facilitating complete removal.”

Nonetheless, it remains unclear whether the use of total underwater colonoscopy significantly affects adenoma detection rates. In a recent study, Dr. Anderson and his coinvestiators randomly assigned 121 patients to undergo either colonoscopy with carbon dioxide insufflation, followed by total underwater colonoscopy, or the same examinations in the reverse sequence (Anderson KC et al. Gastrointest Endosc. 2019;89:591-8). Adenoma miss rates were statistically similar between groups. Although water decreases green mucus and residual stool and suspends “unsuctionable” particles (e.g. seeds) into the cecal lumen, where colonoscopists can better see past them, water also increases the production of white mucus, which can be difficult to remove during withdrawal, Dr. Anderson said.

He cited meta-analyses in which colonoscopies performed with water, without sedation or with minimal sedation, were associated with less pain and a higher likelihood of performing a complete examination than when only air was used. “I find this [approach] particularly useful in older, thinner patients, especially women,” Dr. Anderson said. “In addition, in patients with multiple comorbidities, cecal intubation often can be achieved safely with minimal sedation.”

Dr. Anderson reported having no relevant conflicts of interest.

SOURCE: Anderson JC. Clin Gastroenterol Hepatol. 2020 Feb 25. doi: 10.1016/j.cgh.2020.02.042.

The health care costs of patients with nonalcoholic fatty liver disease (NAFLD) were nearly twice that of matched population controls, according to the results of a longitudinal cohort study.

Patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) were hospitalized an average of 0.27 times per year versus 0.16 times for controls (P < .001), for an annual incremental cost of $635, reported Hannes Hagström, MD, PhD, of Karolinska University Hospital in Stockholm. Patients with NAFLD also made significantly more outpatient care visits than controls (P < .001), he said. “Patients with advanced fibrosis [had] the highest costs, suggesting that reducing fibrosis progression is important to reduce future health care costs” among patients with NASH, Dr. Hagström and his associates wrote in Clinical Gastroenterology and Hepatology.

The retrospective longitudinal cohort study included all 646 patients diagnosed with biopsy-confirmed NAFLD at two hospitals in Sweden between 1971 and 2019. Patients with other liver diseases were excluded, as were heavy drinkers: men who drank more than 30 g of alcohol (just under four units) daily and women who drank more than 20 g daily. Each patient with NAFLD was matched with 10 population controls matched by age, sex, and county of residence.

Over a mean of 19.9 years of follow-up (range, 0-40 years), patients with NASH were hospitalized a total of 3,478 times, an average of 5.4 hospitalizations per patient. Controls were hospitalized an average of 3.2 times during the same time period (P < .001 vs. NASH patients). “This corresponded to a higher incremental cost in NAFLD patients of $635 per year (95% confidence interval, $407-$864; P < .001),” the researchers reported.

Between 2001 and 2009, patients with NAFLD averaged 5.4 more outpatient visits than controls (P < .001), with annual averages of 1.46 versus 0.86 visits (P < .001). Consequently, patient with NASH incurred $255 more per year in annual outpatient care costs. Liver disease accounted for 6% of outpatient care costs among NASH patients versus 0.2% of costs among controls.

“Cumulative costs in the [fibrosis stage 3 and 4] subgroup were relatively matched with the control population until around year 4 after biopsy, when costs diverged,” the researchers said. “This could possibly be an effect of the larger F3 population developing cirrhosis and increasing costs due to decompensation events.”

They noted that the rising prevalence of NAFLD will further burden health care budgets. “Costs [among patients with NASH] were higher in conjunction with liver biopsy, which is why using noninvasive diagnostic methods (e.g., transient elastography) is likely to reduce total costs,” they added. Of note, although patients with NAFLD also incurred somewhat more per year in prescription costs, the difference was not statistically significant.

The study was supported by Stockholm City Council, the Bengt Ihre Foundation, the County Council of Östergötland, and Gilead. The researchers reported having no conflicts of interest.

SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.10.023.

The health care costs of patients with nonalcoholic fatty liver disease (NAFLD) were nearly twice that of matched population controls, according to the results of a longitudinal cohort study.

Patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) were hospitalized an average of 0.27 times per year versus 0.16 times for controls (P < .001), for an annual incremental cost of $635, reported Hannes Hagström, MD, PhD, of Karolinska University Hospital in Stockholm. Patients with NAFLD also made significantly more outpatient care visits than controls (P < .001), he said. “Patients with advanced fibrosis [had] the highest costs, suggesting that reducing fibrosis progression is important to reduce future health care costs” among patients with NASH, Dr. Hagström and his associates wrote in Clinical Gastroenterology and Hepatology.

The retrospective longitudinal cohort study included all 646 patients diagnosed with biopsy-confirmed NAFLD at two hospitals in Sweden between 1971 and 2019. Patients with other liver diseases were excluded, as were heavy drinkers: men who drank more than 30 g of alcohol (just under four units) daily and women who drank more than 20 g daily. Each patient with NAFLD was matched with 10 population controls matched by age, sex, and county of residence.

Over a mean of 19.9 years of follow-up (range, 0-40 years), patients with NASH were hospitalized a total of 3,478 times, an average of 5.4 hospitalizations per patient. Controls were hospitalized an average of 3.2 times during the same time period (P < .001 vs. NASH patients). “This corresponded to a higher incremental cost in NAFLD patients of $635 per year (95% confidence interval, $407-$864; P < .001),” the researchers reported.

Between 2001 and 2009, patients with NAFLD averaged 5.4 more outpatient visits than controls (P < .001), with annual averages of 1.46 versus 0.86 visits (P < .001). Consequently, patient with NASH incurred $255 more per year in annual outpatient care costs. Liver disease accounted for 6% of outpatient care costs among NASH patients versus 0.2% of costs among controls.

“Cumulative costs in the [fibrosis stage 3 and 4] subgroup were relatively matched with the control population until around year 4 after biopsy, when costs diverged,” the researchers said. “This could possibly be an effect of the larger F3 population developing cirrhosis and increasing costs due to decompensation events.”

They noted that the rising prevalence of NAFLD will further burden health care budgets. “Costs [among patients with NASH] were higher in conjunction with liver biopsy, which is why using noninvasive diagnostic methods (e.g., transient elastography) is likely to reduce total costs,” they added. Of note, although patients with NAFLD also incurred somewhat more per year in prescription costs, the difference was not statistically significant.

The study was supported by Stockholm City Council, the Bengt Ihre Foundation, the County Council of Östergötland, and Gilead. The researchers reported having no conflicts of interest.

SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.10.023.

The health care costs of patients with nonalcoholic fatty liver disease (NAFLD) were nearly twice that of matched population controls, according to the results of a longitudinal cohort study.

Patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) were hospitalized an average of 0.27 times per year versus 0.16 times for controls (P < .001), for an annual incremental cost of $635, reported Hannes Hagström, MD, PhD, of Karolinska University Hospital in Stockholm. Patients with NAFLD also made significantly more outpatient care visits than controls (P < .001), he said. “Patients with advanced fibrosis [had] the highest costs, suggesting that reducing fibrosis progression is important to reduce future health care costs” among patients with NASH, Dr. Hagström and his associates wrote in Clinical Gastroenterology and Hepatology.

The retrospective longitudinal cohort study included all 646 patients diagnosed with biopsy-confirmed NAFLD at two hospitals in Sweden between 1971 and 2019. Patients with other liver diseases were excluded, as were heavy drinkers: men who drank more than 30 g of alcohol (just under four units) daily and women who drank more than 20 g daily. Each patient with NAFLD was matched with 10 population controls matched by age, sex, and county of residence.

Over a mean of 19.9 years of follow-up (range, 0-40 years), patients with NASH were hospitalized a total of 3,478 times, an average of 5.4 hospitalizations per patient. Controls were hospitalized an average of 3.2 times during the same time period (P < .001 vs. NASH patients). “This corresponded to a higher incremental cost in NAFLD patients of $635 per year (95% confidence interval, $407-$864; P < .001),” the researchers reported.

Between 2001 and 2009, patients with NAFLD averaged 5.4 more outpatient visits than controls (P < .001), with annual averages of 1.46 versus 0.86 visits (P < .001). Consequently, patient with NASH incurred $255 more per year in annual outpatient care costs. Liver disease accounted for 6% of outpatient care costs among NASH patients versus 0.2% of costs among controls.

“Cumulative costs in the [fibrosis stage 3 and 4] subgroup were relatively matched with the control population until around year 4 after biopsy, when costs diverged,” the researchers said. “This could possibly be an effect of the larger F3 population developing cirrhosis and increasing costs due to decompensation events.”

They noted that the rising prevalence of NAFLD will further burden health care budgets. “Costs [among patients with NASH] were higher in conjunction with liver biopsy, which is why using noninvasive diagnostic methods (e.g., transient elastography) is likely to reduce total costs,” they added. Of note, although patients with NAFLD also incurred somewhat more per year in prescription costs, the difference was not statistically significant.

The study was supported by Stockholm City Council, the Bengt Ihre Foundation, the County Council of Östergötland, and Gilead. The researchers reported having no conflicts of interest.

SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.10.023.

Patients with eosinophilic esophagitis should receive topical steroids instead of oral steroids or no treatment, according to new recommendations from the American Gastroenterological Association and the Joint Task Force on Allergy-Immunology Practice Parameters.

In a pooled analysis of eight double-blind clinical trials, monotherapy with topical budesonide or topical fluticasone was about 61% more likely than placebo to produce histologic remissions in patients with eosinophilic esophagitis (relative risk of failure to achieve remission, 0.39; 95% confidence interval, 0.26-0.58), wrote Ikuo Hirano, MD, of Northwestern University, Chicago. Although these trials differed methodologically, the results were robust enough to warrant a strong recommendation for topical steroids, wrote Dr. Hirano and coauthors of the guidelines, published in Gastroenterology (doi: 10.1053/j.gastro.2020.02.038). “[T]he same inhaled steroid agents are considered very safe for use in children and adults with asthma and are routinely used in [its] primary management,” they noted.

All other recommendations in the guidelines are graded as conditional, reflecting a lack of high-quality supporting evidence. For example, one only study to date has compared topical and oral steroids for patients with eosinophilic esophagitis. In this pediatric trial, children benefited similarly from fluticasone (two puffs four times daily) and oral prednisone (1 mg/kg twice daily), but prednisone caused side effects (weight gain and cushingoid appearance) in 40% of patients, while topical steroids caused oral candidiasis (thrush) in only 15% of patients. Similarities between pediatric and adult eosinophilic esophagitis support the use of topical versus oral steroids in both groups, the guidelines conclude.

Eosinophilic esophagitis tends to be chronic and can progress to recurrent dysphagia, esophageal impactions, and stricture if left untreated. For this reason, the guidelines call for remitted patients to stay on topical steroids as maintenance therapy despite “very low confidence in the estimated benefits of [any type of] long-term therapy.” In a very small trial, 1 year of low-dose budesonide maintenance therapy (0.25 mg twice daily) outperformed placebo, but only 36% of patients maintained less than 5 eosinophils per high power field. Other studies have produced mixed results. Pending more data, the guidelines call maintenance treatment with topical steroids, proton pump inhibitors, and elimination diets “reasonable options” that comprise “a preference-sensitive area of management.”

Dietary interventions for eosinophilic esophagitis include the elemental diet (amino acid–based formulas), the empiric six-food elimination diet, and eliminating foods based on allergy testing. The guidelines cite moderate-quality evidence for the elemental diet, which induced histologic remissions (less than than 15 eosinophils per high power field) in nearly 94% of patients in six single-arm observational studies (in contrast, the rate of histologic failure with placebo is nearly 87%). However, patients may struggle to adhere to both the elemental diet and the six-food elimination diet, which has less supporting evidence. Hence, patients “may reasonably decline” these treatment options and “may prefer alternative medical or dietary therapies” to a diet exclusively based on food allergens, tests for which are potentially inaccurate, the guidelines state.

Esophageal dilation is recommended for patients with stricture based on a systematic review in which 87% of patients improved with this therapy. However, dilation “does not address the esophageal inflammation associated with eosinophilic esophagitis,” and the “assumption that no clinical improvement would occur if dilation was not performed likely overestimates [its] treatment benefit, given the reported symptom-placebo response noted in controlled trials,” according to the guidelines. Moreover, the evidence for dilation “was considered low quality due to the retrospective, single-arm design of all but one of the reports, and the lack of a standard definition for what constitutes clinical improvement.”

Anti-IgE therapy is not recommended – it failed to improve symptoms or esophageal eosinophilia in the only trial conducted to date. Because of a lack of evidence, the guidelines state that patients should receive only montelukast, cromolyn sodium, immunomodulators, anti–tumor necrosis factor (anti-TNF) therapies, or therapies targeting interleukin (IL)-5, IL-13, or IL-4 in the context of a clinical trial.

Eosinophilic esophagitis is triggered by exposure to food antigens and often overlaps with other atopic conditions, such as asthma, eczema, and allergic rhinitis. It has no approved treatments in the United States, although in 2018, the European Medicines Agency approved a budesonide tablet formulation.

The guideline authors disclosed no conflicts of interest.

SOURCE: Hirano I et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.02.038.

Patients with eosinophilic esophagitis should receive topical steroids instead of oral steroids or no treatment, according to new recommendations from the American Gastroenterological Association and the Joint Task Force on Allergy-Immunology Practice Parameters.

In a pooled analysis of eight double-blind clinical trials, monotherapy with topical budesonide or topical fluticasone was about 61% more likely than placebo to produce histologic remissions in patients with eosinophilic esophagitis (relative risk of failure to achieve remission, 0.39; 95% confidence interval, 0.26-0.58), wrote Ikuo Hirano, MD, of Northwestern University, Chicago. Although these trials differed methodologically, the results were robust enough to warrant a strong recommendation for topical steroids, wrote Dr. Hirano and coauthors of the guidelines, published in Gastroenterology (doi: 10.1053/j.gastro.2020.02.038). “[T]he same inhaled steroid agents are considered very safe for use in children and adults with asthma and are routinely used in [its] primary management,” they noted.

All other recommendations in the guidelines are graded as conditional, reflecting a lack of high-quality supporting evidence. For example, one only study to date has compared topical and oral steroids for patients with eosinophilic esophagitis. In this pediatric trial, children benefited similarly from fluticasone (two puffs four times daily) and oral prednisone (1 mg/kg twice daily), but prednisone caused side effects (weight gain and cushingoid appearance) in 40% of patients, while topical steroids caused oral candidiasis (thrush) in only 15% of patients. Similarities between pediatric and adult eosinophilic esophagitis support the use of topical versus oral steroids in both groups, the guidelines conclude.

Eosinophilic esophagitis tends to be chronic and can progress to recurrent dysphagia, esophageal impactions, and stricture if left untreated. For this reason, the guidelines call for remitted patients to stay on topical steroids as maintenance therapy despite “very low confidence in the estimated benefits of [any type of] long-term therapy.” In a very small trial, 1 year of low-dose budesonide maintenance therapy (0.25 mg twice daily) outperformed placebo, but only 36% of patients maintained less than 5 eosinophils per high power field. Other studies have produced mixed results. Pending more data, the guidelines call maintenance treatment with topical steroids, proton pump inhibitors, and elimination diets “reasonable options” that comprise “a preference-sensitive area of management.”

Dietary interventions for eosinophilic esophagitis include the elemental diet (amino acid–based formulas), the empiric six-food elimination diet, and eliminating foods based on allergy testing. The guidelines cite moderate-quality evidence for the elemental diet, which induced histologic remissions (less than than 15 eosinophils per high power field) in nearly 94% of patients in six single-arm observational studies (in contrast, the rate of histologic failure with placebo is nearly 87%). However, patients may struggle to adhere to both the elemental diet and the six-food elimination diet, which has less supporting evidence. Hence, patients “may reasonably decline” these treatment options and “may prefer alternative medical or dietary therapies” to a diet exclusively based on food allergens, tests for which are potentially inaccurate, the guidelines state.

Esophageal dilation is recommended for patients with stricture based on a systematic review in which 87% of patients improved with this therapy. However, dilation “does not address the esophageal inflammation associated with eosinophilic esophagitis,” and the “assumption that no clinical improvement would occur if dilation was not performed likely overestimates [its] treatment benefit, given the reported symptom-placebo response noted in controlled trials,” according to the guidelines. Moreover, the evidence for dilation “was considered low quality due to the retrospective, single-arm design of all but one of the reports, and the lack of a standard definition for what constitutes clinical improvement.”

Anti-IgE therapy is not recommended – it failed to improve symptoms or esophageal eosinophilia in the only trial conducted to date. Because of a lack of evidence, the guidelines state that patients should receive only montelukast, cromolyn sodium, immunomodulators, anti–tumor necrosis factor (anti-TNF) therapies, or therapies targeting interleukin (IL)-5, IL-13, or IL-4 in the context of a clinical trial.

Eosinophilic esophagitis is triggered by exposure to food antigens and often overlaps with other atopic conditions, such as asthma, eczema, and allergic rhinitis. It has no approved treatments in the United States, although in 2018, the European Medicines Agency approved a budesonide tablet formulation.

The guideline authors disclosed no conflicts of interest.

SOURCE: Hirano I et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.02.038.

Patients with eosinophilic esophagitis should receive topical steroids instead of oral steroids or no treatment, according to new recommendations from the American Gastroenterological Association and the Joint Task Force on Allergy-Immunology Practice Parameters.

In a pooled analysis of eight double-blind clinical trials, monotherapy with topical budesonide or topical fluticasone was about 61% more likely than placebo to produce histologic remissions in patients with eosinophilic esophagitis (relative risk of failure to achieve remission, 0.39; 95% confidence interval, 0.26-0.58), wrote Ikuo Hirano, MD, of Northwestern University, Chicago. Although these trials differed methodologically, the results were robust enough to warrant a strong recommendation for topical steroids, wrote Dr. Hirano and coauthors of the guidelines, published in Gastroenterology (doi: 10.1053/j.gastro.2020.02.038). “[T]he same inhaled steroid agents are considered very safe for use in children and adults with asthma and are routinely used in [its] primary management,” they noted.

All other recommendations in the guidelines are graded as conditional, reflecting a lack of high-quality supporting evidence. For example, one only study to date has compared topical and oral steroids for patients with eosinophilic esophagitis. In this pediatric trial, children benefited similarly from fluticasone (two puffs four times daily) and oral prednisone (1 mg/kg twice daily), but prednisone caused side effects (weight gain and cushingoid appearance) in 40% of patients, while topical steroids caused oral candidiasis (thrush) in only 15% of patients. Similarities between pediatric and adult eosinophilic esophagitis support the use of topical versus oral steroids in both groups, the guidelines conclude.

Eosinophilic esophagitis tends to be chronic and can progress to recurrent dysphagia, esophageal impactions, and stricture if left untreated. For this reason, the guidelines call for remitted patients to stay on topical steroids as maintenance therapy despite “very low confidence in the estimated benefits of [any type of] long-term therapy.” In a very small trial, 1 year of low-dose budesonide maintenance therapy (0.25 mg twice daily) outperformed placebo, but only 36% of patients maintained less than 5 eosinophils per high power field. Other studies have produced mixed results. Pending more data, the guidelines call maintenance treatment with topical steroids, proton pump inhibitors, and elimination diets “reasonable options” that comprise “a preference-sensitive area of management.”

Dietary interventions for eosinophilic esophagitis include the elemental diet (amino acid–based formulas), the empiric six-food elimination diet, and eliminating foods based on allergy testing. The guidelines cite moderate-quality evidence for the elemental diet, which induced histologic remissions (less than than 15 eosinophils per high power field) in nearly 94% of patients in six single-arm observational studies (in contrast, the rate of histologic failure with placebo is nearly 87%). However, patients may struggle to adhere to both the elemental diet and the six-food elimination diet, which has less supporting evidence. Hence, patients “may reasonably decline” these treatment options and “may prefer alternative medical or dietary therapies” to a diet exclusively based on food allergens, tests for which are potentially inaccurate, the guidelines state.

Esophageal dilation is recommended for patients with stricture based on a systematic review in which 87% of patients improved with this therapy. However, dilation “does not address the esophageal inflammation associated with eosinophilic esophagitis,” and the “assumption that no clinical improvement would occur if dilation was not performed likely overestimates [its] treatment benefit, given the reported symptom-placebo response noted in controlled trials,” according to the guidelines. Moreover, the evidence for dilation “was considered low quality due to the retrospective, single-arm design of all but one of the reports, and the lack of a standard definition for what constitutes clinical improvement.”

Anti-IgE therapy is not recommended – it failed to improve symptoms or esophageal eosinophilia in the only trial conducted to date. Because of a lack of evidence, the guidelines state that patients should receive only montelukast, cromolyn sodium, immunomodulators, anti–tumor necrosis factor (anti-TNF) therapies, or therapies targeting interleukin (IL)-5, IL-13, or IL-4 in the context of a clinical trial.

Eosinophilic esophagitis is triggered by exposure to food antigens and often overlaps with other atopic conditions, such as asthma, eczema, and allergic rhinitis. It has no approved treatments in the United States, although in 2018, the European Medicines Agency approved a budesonide tablet formulation.

The guideline authors disclosed no conflicts of interest.

SOURCE: Hirano I et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.02.038.