The 14th annual meeting of the Association of VA Hematology/Oncology is set to begin near Chicago on Friday, September 28, 2018. The conference is expected to bring together hundreds of VA hematology and oncology care providers from across the US Department of Veterans Affairs (VA) and other federal health care systems. Helping VA health care providers increase access to clinical trials is expected to be a prominent theme of the meeting.

Subramanyeswara Rao Arekapudi, MD, MPH, FACP, of the VA Central California Health Care System (VACCHCS) will provide an update on an effort to improve clinicaltrials.gov search functionality. As reported earlier this year, through AVAHO, VACCHCS oncologists and a team at the Richmond VA Medical Center (VAMC) in Virginia are working with the National Institutes of Health to create a VA-specific cancer clinical trials’ filter at the website Clinicaltrials.gov.

Holly Carlson, RN, MSN, OCN, will also present on the development of a program in Des Moines, Iowa, to connect veterans with clinical trials at local and regional facilities. The program provides a framework for coordinating care between VA and non-VA oncology teams to ensure veterans can be included in open clinical trials without sacrificing their current care within the VA system.

According to Col (ret) Rick Starrs, CEO of the National Association of Veterans' Research and Education Foundations (NAVREF), these are just a few of the many efforts underway to help increase access to clinical trials for veterans with cancer. Starrs will also be delivering a keynote address at the conference on opportunities for veterans in clinical trials. Formed in 1992, NAVREF is a nonprofit organization of research and education foundations affiliated with VA medical centers that facilitate research and education. 

Starrs will discuss NAVREF’s role in playing a “matchmaking role” in connecting VA researchers and clinical trial sponsors. NAVREF also has helped the VA implement a $50 million agreement with the Prostate Cancer Foundation that expands clinical research for prostate cancer in the VA.  “Our main goal is to bring more clinical trials to veterans and VAMCs,” Starrs told Federal Practitioner.  According to Starrs, NAVREF has partnered with the AVAHO clinical research committee as well as other stakeholders throughout the VA to improve capabilities and increase “predictability” for research partners.

The 14th annual meeting of the Association of VA Hematology/Oncology is set to begin near Chicago on Friday, September 28, 2018. The conference is expected to bring together hundreds of VA hematology and oncology care providers from across the US Department of Veterans Affairs (VA) and other federal health care systems. Helping VA health care providers increase access to clinical trials is expected to be a prominent theme of the meeting.

Subramanyeswara Rao Arekapudi, MD, MPH, FACP, of the VA Central California Health Care System (VACCHCS) will provide an update on an effort to improve clinicaltrials.gov search functionality. As reported earlier this year, through AVAHO, VACCHCS oncologists and a team at the Richmond VA Medical Center (VAMC) in Virginia are working with the National Institutes of Health to create a VA-specific cancer clinical trials’ filter at the website Clinicaltrials.gov.

Holly Carlson, RN, MSN, OCN, will also present on the development of a program in Des Moines, Iowa, to connect veterans with clinical trials at local and regional facilities. The program provides a framework for coordinating care between VA and non-VA oncology teams to ensure veterans can be included in open clinical trials without sacrificing their current care within the VA system.

According to Col (ret) Rick Starrs, CEO of the National Association of Veterans' Research and Education Foundations (NAVREF), these are just a few of the many efforts underway to help increase access to clinical trials for veterans with cancer. Starrs will also be delivering a keynote address at the conference on opportunities for veterans in clinical trials. Formed in 1992, NAVREF is a nonprofit organization of research and education foundations affiliated with VA medical centers that facilitate research and education. 

Starrs will discuss NAVREF’s role in playing a “matchmaking role” in connecting VA researchers and clinical trial sponsors. NAVREF also has helped the VA implement a $50 million agreement with the Prostate Cancer Foundation that expands clinical research for prostate cancer in the VA.  “Our main goal is to bring more clinical trials to veterans and VAMCs,” Starrs told Federal Practitioner.  According to Starrs, NAVREF has partnered with the AVAHO clinical research committee as well as other stakeholders throughout the VA to improve capabilities and increase “predictability” for research partners.

The 14th annual meeting of the Association of VA Hematology/Oncology is set to begin near Chicago on Friday, September 28, 2018. The conference is expected to bring together hundreds of VA hematology and oncology care providers from across the US Department of Veterans Affairs (VA) and other federal health care systems. Helping VA health care providers increase access to clinical trials is expected to be a prominent theme of the meeting.

Subramanyeswara Rao Arekapudi, MD, MPH, FACP, of the VA Central California Health Care System (VACCHCS) will provide an update on an effort to improve clinicaltrials.gov search functionality. As reported earlier this year, through AVAHO, VACCHCS oncologists and a team at the Richmond VA Medical Center (VAMC) in Virginia are working with the National Institutes of Health to create a VA-specific cancer clinical trials’ filter at the website Clinicaltrials.gov.

Holly Carlson, RN, MSN, OCN, will also present on the development of a program in Des Moines, Iowa, to connect veterans with clinical trials at local and regional facilities. The program provides a framework for coordinating care between VA and non-VA oncology teams to ensure veterans can be included in open clinical trials without sacrificing their current care within the VA system.

According to Col (ret) Rick Starrs, CEO of the National Association of Veterans' Research and Education Foundations (NAVREF), these are just a few of the many efforts underway to help increase access to clinical trials for veterans with cancer. Starrs will also be delivering a keynote address at the conference on opportunities for veterans in clinical trials. Formed in 1992, NAVREF is a nonprofit organization of research and education foundations affiliated with VA medical centers that facilitate research and education. 

Starrs will discuss NAVREF’s role in playing a “matchmaking role” in connecting VA researchers and clinical trial sponsors. NAVREF also has helped the VA implement a $50 million agreement with the Prostate Cancer Foundation that expands clinical research for prostate cancer in the VA.  “Our main goal is to bring more clinical trials to veterans and VAMCs,” Starrs told Federal Practitioner.  According to Starrs, NAVREF has partnered with the AVAHO clinical research committee as well as other stakeholders throughout the VA to improve capabilities and increase “predictability” for research partners.

Photo by Rhoda Baer

New research suggests race, clinical trial participation, and treatment duration may influence the risk of relapse in adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL).

The study showed that AYAs with ALL were significantly more likely to relapse than pediatric ALL patients.

Among AYAs, the risk of on-therapy relapse was higher for non-white patients and those who did not participate in clinical trials. The risk of relapse after therapy was higher for AYAs with a shorter treatment duration.

Julie A. Wolfson, MD, of University of Alabama at Birmingham, and her colleagues reported these findings in Cancer Epidemiology, Biomarkers & Prevention.

The researchers conducted this study to investigate why AYAs with ALL have not experienced the same improvement in survival rates as pediatric patients with ALL.

“Patients diagnosed between the ages of 15 and 39 simply have not seen the same improvement as those in other age groups,” Dr. Wolfson said. “In this study, we examined factors related to health care delivery and treatment to increase our understanding of why they experience poorer outcomes.”

The researchers retrospectively studied ALL patients diagnosed between ages 1 and 39 and treated at a single center between 1990 and 2010.

Ninety-one patients were children (ages 1 to 14), and 93 were AYAs (ages 15 to 39).

The researchers assessed variables including demographics, insurance status, participation in clinical trials, duration of treatment, and whether the patients had been treated with pediatric-inspired or adult-inspired regimens. Using Kaplan-Meier survival analysis, the researchers calculated the risk of relapse.

Results

As previous research indicated, children with ALL had superior relapse-free survival compared to AYAs.

The 5-year relapse-free survival rate was 74% in children, 29% in younger AYAs (ages 15 to 21), and 32% in older AYAs (ages 22-39). The difference between children and AYAs was statistically significant (P<0.0001), but the difference between younger and older AYAs was not (P=0.6).

Forty-eight percent of AYAs relapsed while on therapy, compared with 17% of children (P<0.001).

In a multivariable analysis adjusted for clinical prognosticators, health care delivery, and treatment, the risk of on-therapy relapse was more than 10 times higher among AYAs than children (hazard ratio [HR], 10.5; P=0.004).

Among AYAs, the strongest predictors of on-therapy relapse were race and enrollment in clinical trials.

Non-white patients were more than twice as likely to relapse as white patients (HR, 2.2; P=0.05), and patients who were not enrolled in clinical trials were more than twice as likely to relapse as trial participants (HR, 2.6, P=0.04).

Dr. Wolfson said this finding adds to evidence suggesting AYA patients should be encouraged to participate in clinical trials.

“It is possible that patients sometimes benefit from being enrolled on a clinical trial not only because the therapy itself is providing a benefit, but also because it is a protocolized, regulated approach that requires patients to stay on course and not take breaks,” she said.

After the completion of therapy, 47% of AYAs suffered a relapse, compared to 13% of children (P<0.0001).

In a multivariable analysis, the risk of relapse after therapy was more than seven times higher among AYAs than children (HR, 7.7; P<0.001).

Among AYAs who relapsed after therapy, the most significant factor associated with relapse was the duration of treatment.

For each additional month of consolidation therapy, there was a 20% lower risk of relapse (HR, 0.8; P=0.03). And for each additional month of maintenance, there was a 30% lower risk of relapse (HR, 0.7; P<0.001).

Dr. Wolfson noted that a range of factors may affect the duration of treatment. For example, the AYA population is more likely to be uninsured or underinsured, which can make them more likely to stop treatment or miss appointments.

Finally, Dr. Wolfson acknowledged that this study had limitations, primarily its single-institution approach and its limited sample size.

This study was funded by the National Institutes of Health, the St. Baldrick’s Scholar Career Development Award, and the Concern Foundation. The authors declared no conflicts of interest.

Photo by Rhoda Baer

New research suggests race, clinical trial participation, and treatment duration may influence the risk of relapse in adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL).

The study showed that AYAs with ALL were significantly more likely to relapse than pediatric ALL patients.

Among AYAs, the risk of on-therapy relapse was higher for non-white patients and those who did not participate in clinical trials. The risk of relapse after therapy was higher for AYAs with a shorter treatment duration.

Julie A. Wolfson, MD, of University of Alabama at Birmingham, and her colleagues reported these findings in Cancer Epidemiology, Biomarkers & Prevention.

The researchers conducted this study to investigate why AYAs with ALL have not experienced the same improvement in survival rates as pediatric patients with ALL.

“Patients diagnosed between the ages of 15 and 39 simply have not seen the same improvement as those in other age groups,” Dr. Wolfson said. “In this study, we examined factors related to health care delivery and treatment to increase our understanding of why they experience poorer outcomes.”

The researchers retrospectively studied ALL patients diagnosed between ages 1 and 39 and treated at a single center between 1990 and 2010.

Ninety-one patients were children (ages 1 to 14), and 93 were AYAs (ages 15 to 39).

The researchers assessed variables including demographics, insurance status, participation in clinical trials, duration of treatment, and whether the patients had been treated with pediatric-inspired or adult-inspired regimens. Using Kaplan-Meier survival analysis, the researchers calculated the risk of relapse.

Results

As previous research indicated, children with ALL had superior relapse-free survival compared to AYAs.

The 5-year relapse-free survival rate was 74% in children, 29% in younger AYAs (ages 15 to 21), and 32% in older AYAs (ages 22-39). The difference between children and AYAs was statistically significant (P<0.0001), but the difference between younger and older AYAs was not (P=0.6).

Forty-eight percent of AYAs relapsed while on therapy, compared with 17% of children (P<0.001).

In a multivariable analysis adjusted for clinical prognosticators, health care delivery, and treatment, the risk of on-therapy relapse was more than 10 times higher among AYAs than children (hazard ratio [HR], 10.5; P=0.004).

Among AYAs, the strongest predictors of on-therapy relapse were race and enrollment in clinical trials.

Non-white patients were more than twice as likely to relapse as white patients (HR, 2.2; P=0.05), and patients who were not enrolled in clinical trials were more than twice as likely to relapse as trial participants (HR, 2.6, P=0.04).

Dr. Wolfson said this finding adds to evidence suggesting AYA patients should be encouraged to participate in clinical trials.

“It is possible that patients sometimes benefit from being enrolled on a clinical trial not only because the therapy itself is providing a benefit, but also because it is a protocolized, regulated approach that requires patients to stay on course and not take breaks,” she said.

After the completion of therapy, 47% of AYAs suffered a relapse, compared to 13% of children (P<0.0001).

In a multivariable analysis, the risk of relapse after therapy was more than seven times higher among AYAs than children (HR, 7.7; P<0.001).

Among AYAs who relapsed after therapy, the most significant factor associated with relapse was the duration of treatment.

For each additional month of consolidation therapy, there was a 20% lower risk of relapse (HR, 0.8; P=0.03). And for each additional month of maintenance, there was a 30% lower risk of relapse (HR, 0.7; P<0.001).

Dr. Wolfson noted that a range of factors may affect the duration of treatment. For example, the AYA population is more likely to be uninsured or underinsured, which can make them more likely to stop treatment or miss appointments.

Finally, Dr. Wolfson acknowledged that this study had limitations, primarily its single-institution approach and its limited sample size.

This study was funded by the National Institutes of Health, the St. Baldrick’s Scholar Career Development Award, and the Concern Foundation. The authors declared no conflicts of interest.

Photo by Rhoda Baer

New research suggests race, clinical trial participation, and treatment duration may influence the risk of relapse in adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL).

The study showed that AYAs with ALL were significantly more likely to relapse than pediatric ALL patients.

Among AYAs, the risk of on-therapy relapse was higher for non-white patients and those who did not participate in clinical trials. The risk of relapse after therapy was higher for AYAs with a shorter treatment duration.

Julie A. Wolfson, MD, of University of Alabama at Birmingham, and her colleagues reported these findings in Cancer Epidemiology, Biomarkers & Prevention.

The researchers conducted this study to investigate why AYAs with ALL have not experienced the same improvement in survival rates as pediatric patients with ALL.

“Patients diagnosed between the ages of 15 and 39 simply have not seen the same improvement as those in other age groups,” Dr. Wolfson said. “In this study, we examined factors related to health care delivery and treatment to increase our understanding of why they experience poorer outcomes.”

The researchers retrospectively studied ALL patients diagnosed between ages 1 and 39 and treated at a single center between 1990 and 2010.

Ninety-one patients were children (ages 1 to 14), and 93 were AYAs (ages 15 to 39).

The researchers assessed variables including demographics, insurance status, participation in clinical trials, duration of treatment, and whether the patients had been treated with pediatric-inspired or adult-inspired regimens. Using Kaplan-Meier survival analysis, the researchers calculated the risk of relapse.

Results

As previous research indicated, children with ALL had superior relapse-free survival compared to AYAs.

The 5-year relapse-free survival rate was 74% in children, 29% in younger AYAs (ages 15 to 21), and 32% in older AYAs (ages 22-39). The difference between children and AYAs was statistically significant (P<0.0001), but the difference between younger and older AYAs was not (P=0.6).

Forty-eight percent of AYAs relapsed while on therapy, compared with 17% of children (P<0.001).

In a multivariable analysis adjusted for clinical prognosticators, health care delivery, and treatment, the risk of on-therapy relapse was more than 10 times higher among AYAs than children (hazard ratio [HR], 10.5; P=0.004).

Among AYAs, the strongest predictors of on-therapy relapse were race and enrollment in clinical trials.

Non-white patients were more than twice as likely to relapse as white patients (HR, 2.2; P=0.05), and patients who were not enrolled in clinical trials were more than twice as likely to relapse as trial participants (HR, 2.6, P=0.04).

Dr. Wolfson said this finding adds to evidence suggesting AYA patients should be encouraged to participate in clinical trials.

“It is possible that patients sometimes benefit from being enrolled on a clinical trial not only because the therapy itself is providing a benefit, but also because it is a protocolized, regulated approach that requires patients to stay on course and not take breaks,” she said.

After the completion of therapy, 47% of AYAs suffered a relapse, compared to 13% of children (P<0.0001).

In a multivariable analysis, the risk of relapse after therapy was more than seven times higher among AYAs than children (HR, 7.7; P<0.001).

Among AYAs who relapsed after therapy, the most significant factor associated with relapse was the duration of treatment.

For each additional month of consolidation therapy, there was a 20% lower risk of relapse (HR, 0.8; P=0.03). And for each additional month of maintenance, there was a 30% lower risk of relapse (HR, 0.7; P<0.001).

Dr. Wolfson noted that a range of factors may affect the duration of treatment. For example, the AYA population is more likely to be uninsured or underinsured, which can make them more likely to stop treatment or miss appointments.

Finally, Dr. Wolfson acknowledged that this study had limitations, primarily its single-institution approach and its limited sample size.

This study was funded by the National Institutes of Health, the St. Baldrick’s Scholar Career Development Award, and the Concern Foundation. The authors declared no conflicts of interest.

Universitair Medisch Centrum

Immediate compression therapy provides a “clear benefit” for patients with deep vein thrombosis (DVT), according to the senior author of a study published in Blood.

In this prospective study, patients who started compression therapy within the first 24 hours of DVT diagnosis were 20% less likely to develop residual vein occlusion (RVO) than patients who did not start compression therapy in the acute phase.

Furthermore, patients who did not develop RVO were 8% less likely to have post-thrombotic syndrome (PTS) than patients with RVO.

“We found little reason for those treating DVT not to use compression therapy as a prevention measure against future complications,” said study author Arina J. ten Cate-Hoek, MD, PhD, of Maastricht University in the Netherlands.

“Although the use of compression stockings after DVT is routine across much of Europe, it is less common in the United States, where guidelines emphasize compression primarily for patients who complain of ongoing symptoms.”

Dr. ten Cate-Hoek and her colleagues studied 592 adults with DVT who were treated in 10 centers across the Netherlands.

All patients were treated with anticoagulants, largely vitamin K antagonists (80.6%) but also direct oral anticoagulants (3.0%), investigational anticoagulants (11.1%), and low-molecular-weight heparin (4.4%).

Within 24 hours of DVT diagnosis, most patients received compression therapy (pressure 35 mmHg) with either multilayer compression bandaging (62.3%) or compression hosiery (25.5%). A minority of patients did not receive compression in the acute phase (12.2%).

The average time from DVT diagnosis to RVO assessment was 5.3 months.

The incidence of RVO was significantly lower in patients who received immediate compression than in those who did not—46.3% and 66.7%, respectively (odds ratio [OR], 0.46; P=0.005).

In addition, PTS was more common among patients with RVO.

At 6 months, the incidence of PTS was 55.7% among patients with RVO and 44.3% among patients without RVO (OR, 0.66; P=0.029). At 24 months, the incidence of PTS was 54.0% and 46.0%, respectively (OR, 0.65; P=0.013).

The researchers said there was no significant association between RVO and recurrent DVT or pulmonary embolism.

Among the 30 patients with DVT recurrence, 60% had RVO and 40% did not (OR, 0.82; P=0.263).

Among the 19 patients who had recurrent pulmonary embolism, 52.6% had RVO and 47.7% did not (OR, 0.95; P=0.805).

Dr. ten Cate-Hoek noted that compression therapy is thought to improve blood flow by reducing the diameter of veins so that blood is pushed through them more forcefully, which helps to clear clot material.

“I think we can infer from our findings that this improved blood flow certainly helps prevent complications like residual vein occlusion and post-thrombotic syndrome after DVT,” she said.

“Given these outcomes, and that compression stockings are fairly easy to self-administer, relatively inexpensive, and minimally intrusive, compression therapy offers a clear benefit for all patients with DVT.”

Universitair Medisch Centrum

Immediate compression therapy provides a “clear benefit” for patients with deep vein thrombosis (DVT), according to the senior author of a study published in Blood.

In this prospective study, patients who started compression therapy within the first 24 hours of DVT diagnosis were 20% less likely to develop residual vein occlusion (RVO) than patients who did not start compression therapy in the acute phase.

Furthermore, patients who did not develop RVO were 8% less likely to have post-thrombotic syndrome (PTS) than patients with RVO.

“We found little reason for those treating DVT not to use compression therapy as a prevention measure against future complications,” said study author Arina J. ten Cate-Hoek, MD, PhD, of Maastricht University in the Netherlands.

“Although the use of compression stockings after DVT is routine across much of Europe, it is less common in the United States, where guidelines emphasize compression primarily for patients who complain of ongoing symptoms.”

Dr. ten Cate-Hoek and her colleagues studied 592 adults with DVT who were treated in 10 centers across the Netherlands.

All patients were treated with anticoagulants, largely vitamin K antagonists (80.6%) but also direct oral anticoagulants (3.0%), investigational anticoagulants (11.1%), and low-molecular-weight heparin (4.4%).

Within 24 hours of DVT diagnosis, most patients received compression therapy (pressure 35 mmHg) with either multilayer compression bandaging (62.3%) or compression hosiery (25.5%). A minority of patients did not receive compression in the acute phase (12.2%).

The average time from DVT diagnosis to RVO assessment was 5.3 months.

The incidence of RVO was significantly lower in patients who received immediate compression than in those who did not—46.3% and 66.7%, respectively (odds ratio [OR], 0.46; P=0.005).

In addition, PTS was more common among patients with RVO.

At 6 months, the incidence of PTS was 55.7% among patients with RVO and 44.3% among patients without RVO (OR, 0.66; P=0.029). At 24 months, the incidence of PTS was 54.0% and 46.0%, respectively (OR, 0.65; P=0.013).

The researchers said there was no significant association between RVO and recurrent DVT or pulmonary embolism.

Among the 30 patients with DVT recurrence, 60% had RVO and 40% did not (OR, 0.82; P=0.263).

Among the 19 patients who had recurrent pulmonary embolism, 52.6% had RVO and 47.7% did not (OR, 0.95; P=0.805).

Dr. ten Cate-Hoek noted that compression therapy is thought to improve blood flow by reducing the diameter of veins so that blood is pushed through them more forcefully, which helps to clear clot material.

“I think we can infer from our findings that this improved blood flow certainly helps prevent complications like residual vein occlusion and post-thrombotic syndrome after DVT,” she said.

“Given these outcomes, and that compression stockings are fairly easy to self-administer, relatively inexpensive, and minimally intrusive, compression therapy offers a clear benefit for all patients with DVT.”

Universitair Medisch Centrum

Immediate compression therapy provides a “clear benefit” for patients with deep vein thrombosis (DVT), according to the senior author of a study published in Blood.

In this prospective study, patients who started compression therapy within the first 24 hours of DVT diagnosis were 20% less likely to develop residual vein occlusion (RVO) than patients who did not start compression therapy in the acute phase.

Furthermore, patients who did not develop RVO were 8% less likely to have post-thrombotic syndrome (PTS) than patients with RVO.

“We found little reason for those treating DVT not to use compression therapy as a prevention measure against future complications,” said study author Arina J. ten Cate-Hoek, MD, PhD, of Maastricht University in the Netherlands.

“Although the use of compression stockings after DVT is routine across much of Europe, it is less common in the United States, where guidelines emphasize compression primarily for patients who complain of ongoing symptoms.”

Dr. ten Cate-Hoek and her colleagues studied 592 adults with DVT who were treated in 10 centers across the Netherlands.

All patients were treated with anticoagulants, largely vitamin K antagonists (80.6%) but also direct oral anticoagulants (3.0%), investigational anticoagulants (11.1%), and low-molecular-weight heparin (4.4%).

Within 24 hours of DVT diagnosis, most patients received compression therapy (pressure 35 mmHg) with either multilayer compression bandaging (62.3%) or compression hosiery (25.5%). A minority of patients did not receive compression in the acute phase (12.2%).

The average time from DVT diagnosis to RVO assessment was 5.3 months.

The incidence of RVO was significantly lower in patients who received immediate compression than in those who did not—46.3% and 66.7%, respectively (odds ratio [OR], 0.46; P=0.005).

In addition, PTS was more common among patients with RVO.

At 6 months, the incidence of PTS was 55.7% among patients with RVO and 44.3% among patients without RVO (OR, 0.66; P=0.029). At 24 months, the incidence of PTS was 54.0% and 46.0%, respectively (OR, 0.65; P=0.013).

The researchers said there was no significant association between RVO and recurrent DVT or pulmonary embolism.

Among the 30 patients with DVT recurrence, 60% had RVO and 40% did not (OR, 0.82; P=0.263).

Among the 19 patients who had recurrent pulmonary embolism, 52.6% had RVO and 47.7% did not (OR, 0.95; P=0.805).

Dr. ten Cate-Hoek noted that compression therapy is thought to improve blood flow by reducing the diameter of veins so that blood is pushed through them more forcefully, which helps to clear clot material.

“I think we can infer from our findings that this improved blood flow certainly helps prevent complications like residual vein occlusion and post-thrombotic syndrome after DVT,” she said.

“Given these outcomes, and that compression stockings are fairly easy to self-administer, relatively inexpensive, and minimally intrusive, compression therapy offers a clear benefit for all patients with DVT.”

Photo by Chad McNeeley

The U.S. Food and Drug Administration (FDA) has granted orphan designation to PLX-R18 for the treatment of graft failure and incomplete hematopoietic recovery following hematopoietic stem cell transplant (HSCT).

PLX-R18 consists of placenta-derived, mesenchymal-like adherent stromal cells that are designed to be administered to patients without the need for tissue or genetic matching.

PLX-R18 cells release a combination of therapeutic proteins in response to a damaged or poorly functioning hematopoietic system.

PLX-R18 is currently being evaluated for the treatment of insufficient hematopoietic recovery following HSCT in an ongoing, phase 1 trial (NCT03002519).

The trial is designed to evaluate the safety of intramuscular injections of PLX-R18 cells in 24 subjects with incomplete hematopoietic recovery persisting for at least 4 months after HSCT, with a 12-month follow-up period.

The primary endpoint is safety. Exploratory endpoints include changes in platelet and hemoglobin levels, changes in transfusion frequency, a shift from transfusion dependence to transfusion independence, changes in quality of life, and changes in the serum immunological parameters.

PLX-R18 is being developed by Pluristem Therapeutics, Inc. PLX-R18 also has orphan designation for the treatment of acute radiation syndrome.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the United States.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Photo by Chad McNeeley

The U.S. Food and Drug Administration (FDA) has granted orphan designation to PLX-R18 for the treatment of graft failure and incomplete hematopoietic recovery following hematopoietic stem cell transplant (HSCT).

PLX-R18 consists of placenta-derived, mesenchymal-like adherent stromal cells that are designed to be administered to patients without the need for tissue or genetic matching.

PLX-R18 cells release a combination of therapeutic proteins in response to a damaged or poorly functioning hematopoietic system.

PLX-R18 is currently being evaluated for the treatment of insufficient hematopoietic recovery following HSCT in an ongoing, phase 1 trial (NCT03002519).

The trial is designed to evaluate the safety of intramuscular injections of PLX-R18 cells in 24 subjects with incomplete hematopoietic recovery persisting for at least 4 months after HSCT, with a 12-month follow-up period.

The primary endpoint is safety. Exploratory endpoints include changes in platelet and hemoglobin levels, changes in transfusion frequency, a shift from transfusion dependence to transfusion independence, changes in quality of life, and changes in the serum immunological parameters.

PLX-R18 is being developed by Pluristem Therapeutics, Inc. PLX-R18 also has orphan designation for the treatment of acute radiation syndrome.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the United States.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Photo by Chad McNeeley

The U.S. Food and Drug Administration (FDA) has granted orphan designation to PLX-R18 for the treatment of graft failure and incomplete hematopoietic recovery following hematopoietic stem cell transplant (HSCT).

PLX-R18 consists of placenta-derived, mesenchymal-like adherent stromal cells that are designed to be administered to patients without the need for tissue or genetic matching.

PLX-R18 cells release a combination of therapeutic proteins in response to a damaged or poorly functioning hematopoietic system.

PLX-R18 is currently being evaluated for the treatment of insufficient hematopoietic recovery following HSCT in an ongoing, phase 1 trial (NCT03002519).

The trial is designed to evaluate the safety of intramuscular injections of PLX-R18 cells in 24 subjects with incomplete hematopoietic recovery persisting for at least 4 months after HSCT, with a 12-month follow-up period.

The primary endpoint is safety. Exploratory endpoints include changes in platelet and hemoglobin levels, changes in transfusion frequency, a shift from transfusion dependence to transfusion independence, changes in quality of life, and changes in the serum immunological parameters.

PLX-R18 is being developed by Pluristem Therapeutics, Inc. PLX-R18 also has orphan designation for the treatment of acute radiation syndrome.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the United States.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

The lesion on this 12-year-old girl’s trunk has been present since birth, growing slowly as she has. Recently, an abrasion sustained during a basketball game caused the lesion to become swollen and tender. It has since returned to its original size and nontender state, but the change in appearance raised enough concern to prompt dermatologic consultation.

The child is otherwise healthy and reports having had very few sunburns, tanning easily (though seldom).

EXAMINATION
The lesion—an oval, nevoid, hair-bearing, uniformly brown plaque with a mammilated surface—is located on the right lower anterior abdominal wall and measures just short of 3 cm x 2 cm. It bears no sign of the recent trauma. The margins are clearly defined, and the lesion is nontender on palpation. No increased warmth is detected.

Overall, the patient’s type III skin has little, if any, evidence of excessive sun exposure.

What is the diagnosis?

DISCUSSION
Congenital melanocytic nevi (CMNs) affect about 1% of newborns, appearing within months after birth. There is no unanimity in opinion regarding their origin, although they appear to be hereditary in some cases.

About 50% of CMNs occur on the trunk and 15% on the head or neck; the rest are scattered about on the extremities. The distinctive morphologic appearance of the lesion helps to distinguish it from other items in the differential, such as warts or cancer.

Only rarely do CMNs raise concern for malignant potential. (Trauma cannot cause a benign lesion to undergo malignant transformation.) So-called “giant” CMNs (> 20 cm) appear to be associated with the greatest risk, though the incidence of melanoma in children younger than 9 is only about 0.7 cases per million. Of particular concern are “bathing trunk” CMNs, which occasionally cover more than half of the body; affected patients need special attention from pediatric dermatologists who have the appropriate experience.

Neither “small” (< 2 cm) nor “medium” CMNs (> 2 cm, < 20 cm) are particularly worrisome in terms of malignancy. But depending on the location and original size, CMNs can become the object of unwanted attention or ridicule from peers—a little 1-cm lesion on an infant’s neck can grow four to six times its original size by puberty. And at that point, excision becomes much more problematic due to the likelihood of scarring.

Therefore, many experts advise excising some lesions early on, while the lesion and resulting scar are small—and before the child has a chance to develop any anxiety over it. If not excised, CMNs simply need to be watched for change (size, uniformity of color, and border).

TAKE-HOME LEARNING POINTS

• Congenital melanocytic nevi (CMNs) < 20 cm in diameter are generally quite safe but can grow much larger—often becoming a source of ridicule.
• Depending on the size, location, and appearance of the lesion, excision is justifiable before it has a chance to grow and become problematic.
• Children younger than 10 almost never develop melanoma (the rate is 0.7 cases per million)—and even when they do, it is almost never related to malignant transformation of a CMN.
• Trauma cannot cause a benign lesion to undergo malignant transformation.

The lesion on this 12-year-old girl’s trunk has been present since birth, growing slowly as she has. Recently, an abrasion sustained during a basketball game caused the lesion to become swollen and tender. It has since returned to its original size and nontender state, but the change in appearance raised enough concern to prompt dermatologic consultation.

The child is otherwise healthy and reports having had very few sunburns, tanning easily (though seldom).

EXAMINATION
The lesion—an oval, nevoid, hair-bearing, uniformly brown plaque with a mammilated surface—is located on the right lower anterior abdominal wall and measures just short of 3 cm x 2 cm. It bears no sign of the recent trauma. The margins are clearly defined, and the lesion is nontender on palpation. No increased warmth is detected.

Overall, the patient’s type III skin has little, if any, evidence of excessive sun exposure.

What is the diagnosis?

DISCUSSION
Congenital melanocytic nevi (CMNs) affect about 1% of newborns, appearing within months after birth. There is no unanimity in opinion regarding their origin, although they appear to be hereditary in some cases.

About 50% of CMNs occur on the trunk and 15% on the head or neck; the rest are scattered about on the extremities. The distinctive morphologic appearance of the lesion helps to distinguish it from other items in the differential, such as warts or cancer.

Only rarely do CMNs raise concern for malignant potential. (Trauma cannot cause a benign lesion to undergo malignant transformation.) So-called “giant” CMNs (> 20 cm) appear to be associated with the greatest risk, though the incidence of melanoma in children younger than 9 is only about 0.7 cases per million. Of particular concern are “bathing trunk” CMNs, which occasionally cover more than half of the body; affected patients need special attention from pediatric dermatologists who have the appropriate experience.

Neither “small” (< 2 cm) nor “medium” CMNs (> 2 cm, < 20 cm) are particularly worrisome in terms of malignancy. But depending on the location and original size, CMNs can become the object of unwanted attention or ridicule from peers—a little 1-cm lesion on an infant’s neck can grow four to six times its original size by puberty. And at that point, excision becomes much more problematic due to the likelihood of scarring.

Therefore, many experts advise excising some lesions early on, while the lesion and resulting scar are small—and before the child has a chance to develop any anxiety over it. If not excised, CMNs simply need to be watched for change (size, uniformity of color, and border).

TAKE-HOME LEARNING POINTS

• Congenital melanocytic nevi (CMNs) < 20 cm in diameter are generally quite safe but can grow much larger—often becoming a source of ridicule.
• Depending on the size, location, and appearance of the lesion, excision is justifiable before it has a chance to grow and become problematic.
• Children younger than 10 almost never develop melanoma (the rate is 0.7 cases per million)—and even when they do, it is almost never related to malignant transformation of a CMN.
• Trauma cannot cause a benign lesion to undergo malignant transformation.

The lesion on this 12-year-old girl’s trunk has been present since birth, growing slowly as she has. Recently, an abrasion sustained during a basketball game caused the lesion to become swollen and tender. It has since returned to its original size and nontender state, but the change in appearance raised enough concern to prompt dermatologic consultation.

The child is otherwise healthy and reports having had very few sunburns, tanning easily (though seldom).

EXAMINATION
The lesion—an oval, nevoid, hair-bearing, uniformly brown plaque with a mammilated surface—is located on the right lower anterior abdominal wall and measures just short of 3 cm x 2 cm. It bears no sign of the recent trauma. The margins are clearly defined, and the lesion is nontender on palpation. No increased warmth is detected.

Overall, the patient’s type III skin has little, if any, evidence of excessive sun exposure.

What is the diagnosis?

DISCUSSION
Congenital melanocytic nevi (CMNs) affect about 1% of newborns, appearing within months after birth. There is no unanimity in opinion regarding their origin, although they appear to be hereditary in some cases.

About 50% of CMNs occur on the trunk and 15% on the head or neck; the rest are scattered about on the extremities. The distinctive morphologic appearance of the lesion helps to distinguish it from other items in the differential, such as warts or cancer.

Only rarely do CMNs raise concern for malignant potential. (Trauma cannot cause a benign lesion to undergo malignant transformation.) So-called “giant” CMNs (> 20 cm) appear to be associated with the greatest risk, though the incidence of melanoma in children younger than 9 is only about 0.7 cases per million. Of particular concern are “bathing trunk” CMNs, which occasionally cover more than half of the body; affected patients need special attention from pediatric dermatologists who have the appropriate experience.

Neither “small” (< 2 cm) nor “medium” CMNs (> 2 cm, < 20 cm) are particularly worrisome in terms of malignancy. But depending on the location and original size, CMNs can become the object of unwanted attention or ridicule from peers—a little 1-cm lesion on an infant’s neck can grow four to six times its original size by puberty. And at that point, excision becomes much more problematic due to the likelihood of scarring.

Therefore, many experts advise excising some lesions early on, while the lesion and resulting scar are small—and before the child has a chance to develop any anxiety over it. If not excised, CMNs simply need to be watched for change (size, uniformity of color, and border).

TAKE-HOME LEARNING POINTS

• Congenital melanocytic nevi (CMNs) < 20 cm in diameter are generally quite safe but can grow much larger—often becoming a source of ridicule.
• Depending on the size, location, and appearance of the lesion, excision is justifiable before it has a chance to grow and become problematic.
• Children younger than 10 almost never develop melanoma (the rate is 0.7 cases per million)—and even when they do, it is almost never related to malignant transformation of a CMN.
• Trauma cannot cause a benign lesion to undergo malignant transformation.

The FP noted a horn-like growth on the patient's face with some scaling around it. He recommended a shave biopsy. His differential diagnosis included actinic keratosis and Bowen’s disease (also known as squamous cell carcinoma in situ).

A biopsy was performed with a DermaBlade using a shave technique deep enough to get the base of the horn and a good sampling of the abnormal-looking tissue. (See the Watch & Learn video on “Shave biopsy.”) The pathology report revealed a cutaneous horn in a squamous cell carcinoma in situ.

The patient was referred to Dermatology for further treatment. Options included treatment with topical 5-fluorouracil (over weeks to months), standard excision, or Mohs surgery.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Cutaneous horn. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:985-988.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP noted a horn-like growth on the patient's face with some scaling around it. He recommended a shave biopsy. His differential diagnosis included actinic keratosis and Bowen’s disease (also known as squamous cell carcinoma in situ).

A biopsy was performed with a DermaBlade using a shave technique deep enough to get the base of the horn and a good sampling of the abnormal-looking tissue. (See the Watch & Learn video on “Shave biopsy.”) The pathology report revealed a cutaneous horn in a squamous cell carcinoma in situ.

The patient was referred to Dermatology for further treatment. Options included treatment with topical 5-fluorouracil (over weeks to months), standard excision, or Mohs surgery.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Cutaneous horn. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:985-988.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP noted a horn-like growth on the patient's face with some scaling around it. He recommended a shave biopsy. His differential diagnosis included actinic keratosis and Bowen’s disease (also known as squamous cell carcinoma in situ).

A biopsy was performed with a DermaBlade using a shave technique deep enough to get the base of the horn and a good sampling of the abnormal-looking tissue. (See the Watch & Learn video on “Shave biopsy.”) The pathology report revealed a cutaneous horn in a squamous cell carcinoma in situ.

The patient was referred to Dermatology for further treatment. Options included treatment with topical 5-fluorouracil (over weeks to months), standard excision, or Mohs surgery.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Cutaneous horn. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:985-988.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The American Cancer Society’s recent recommendation to lower the age of first screening for colorectal cancer to 45 years does not reflect clear knowledge of risks versus benefits, experts wrote in a recent commentary.

“In the big picture, [the question of whether to start screening at 45 versus 50 years] seems relatively unimportant compared with using individual patient risk for advanced neoplasia in practical, feasible models” that are geared toward adherence, efficiency, and cost-efficacy, wrote Thomas F. Imperiale, MD, of Indiana University, Indianapolis, and his associates. The commentary is in the October issue of Clinical Gastroenterology and Hepatology.

Tailoring age of first screening on an individual level, based on other risk factors and patient preferences, might improve uptake and benefit-risk ratios, balance, they argued.

Rates of colorectal cancer in persons under age 50 years rose by about 22% between 2000 and 2013. However, estimates for the most recent birth cohorts have wide confidence intervals, “indicating imprecision and uncertainty that this trend will continue,” the experts wrote. Furthermore, the absolute risk of colorectal cancer among individuals younger than 50 years has risen only slightly, from 5.9 cases per 100,000 population to 7.2 cases per 100,000 population. “[This] small increase in incidence may represent a true increase or could be due to increased use of colonoscopy in general, and specifically, for diagnosis or high-risk screening of first-degree relatives of persons with colorectal cancer,” the experts wrote.

Implementing the new recommendation could detect earlier-stage (curable) colorectal cancer “in a youthful and productive age group that may be sandwiched between raising children and caring for aging parents,” they continued. Earlier detection could reduce mortality and reduce the costs of treating a disease that often exceeds $100,000 per person annually.

However, the recommendation was based on a modeling study that assumed 100% adherence. In reality, uptake among 45- to 49-year-olds might be 15%-20%, and “who actually shows up for screening could make or break this recommendation,” the experts said. If younger individuals who underwent screening tended to have few risk factors for colorectal cancer, then the new recommendation would lead to many false positives and unnecessary colonoscopies, with the associated fallout of emotional harm and wasted health care resources, they added.

Population-level studies have identified age as the strongest predictor of colorectal cancer, but age “does not perform as well” at patient level, the experts said. They emphasized the role of other risk factors, such as male sex, having a first-degree relative with colorectal cancer, high body mass index, metabolic syndrome, cigarette smoking, diet, adherence to screening, and use of aspirin, nonsteroidal anti-inflammatory drugs, and hormone therapy. “The goal for providers and health systems is to determine whether and how to change screening practice and policy, and how to incorporate this new recommendation into practice, a necessarily complex process that requires knowing patient risk, patient preferences, and the long-term balance of benefits and burdens,” they concluded (Clin Gastroenterol Hepatol. 2018 Aug 13. doi: 10.1016/j.cgh.2018.08.023).

Dr. Imperiale and coauthor Charles J. Kahi, MD, MS, had no disclosures. Coauthor Douglas K. Rex, MD, disclosed ties to Aries Pharmaceutical, Cosmo Pharmaceuticals, Boston Scientific, Sebela, Medtronic, EndoAid Ltd, Olympus, Paion, Braintree, and Medivators. He also chairs the U.S. Multi-Society Task Force on Colorectal Cancer.

* This story was updated on 10/16/2018.

The American Cancer Society’s recent recommendation to lower the age of first screening for colorectal cancer to 45 years does not reflect clear knowledge of risks versus benefits, experts wrote in a recent commentary.

“In the big picture, [the question of whether to start screening at 45 versus 50 years] seems relatively unimportant compared with using individual patient risk for advanced neoplasia in practical, feasible models” that are geared toward adherence, efficiency, and cost-efficacy, wrote Thomas F. Imperiale, MD, of Indiana University, Indianapolis, and his associates. The commentary is in the October issue of Clinical Gastroenterology and Hepatology.

Tailoring age of first screening on an individual level, based on other risk factors and patient preferences, might improve uptake and benefit-risk ratios, balance, they argued.

Rates of colorectal cancer in persons under age 50 years rose by about 22% between 2000 and 2013. However, estimates for the most recent birth cohorts have wide confidence intervals, “indicating imprecision and uncertainty that this trend will continue,” the experts wrote. Furthermore, the absolute risk of colorectal cancer among individuals younger than 50 years has risen only slightly, from 5.9 cases per 100,000 population to 7.2 cases per 100,000 population. “[This] small increase in incidence may represent a true increase or could be due to increased use of colonoscopy in general, and specifically, for diagnosis or high-risk screening of first-degree relatives of persons with colorectal cancer,” the experts wrote.

Implementing the new recommendation could detect earlier-stage (curable) colorectal cancer “in a youthful and productive age group that may be sandwiched between raising children and caring for aging parents,” they continued. Earlier detection could reduce mortality and reduce the costs of treating a disease that often exceeds $100,000 per person annually.

However, the recommendation was based on a modeling study that assumed 100% adherence. In reality, uptake among 45- to 49-year-olds might be 15%-20%, and “who actually shows up for screening could make or break this recommendation,” the experts said. If younger individuals who underwent screening tended to have few risk factors for colorectal cancer, then the new recommendation would lead to many false positives and unnecessary colonoscopies, with the associated fallout of emotional harm and wasted health care resources, they added.

Population-level studies have identified age as the strongest predictor of colorectal cancer, but age “does not perform as well” at patient level, the experts said. They emphasized the role of other risk factors, such as male sex, having a first-degree relative with colorectal cancer, high body mass index, metabolic syndrome, cigarette smoking, diet, adherence to screening, and use of aspirin, nonsteroidal anti-inflammatory drugs, and hormone therapy. “The goal for providers and health systems is to determine whether and how to change screening practice and policy, and how to incorporate this new recommendation into practice, a necessarily complex process that requires knowing patient risk, patient preferences, and the long-term balance of benefits and burdens,” they concluded (Clin Gastroenterol Hepatol. 2018 Aug 13. doi: 10.1016/j.cgh.2018.08.023).

Dr. Imperiale and coauthor Charles J. Kahi, MD, MS, had no disclosures. Coauthor Douglas K. Rex, MD, disclosed ties to Aries Pharmaceutical, Cosmo Pharmaceuticals, Boston Scientific, Sebela, Medtronic, EndoAid Ltd, Olympus, Paion, Braintree, and Medivators. He also chairs the U.S. Multi-Society Task Force on Colorectal Cancer.

* This story was updated on 10/16/2018.

The American Cancer Society’s recent recommendation to lower the age of first screening for colorectal cancer to 45 years does not reflect clear knowledge of risks versus benefits, experts wrote in a recent commentary.

“In the big picture, [the question of whether to start screening at 45 versus 50 years] seems relatively unimportant compared with using individual patient risk for advanced neoplasia in practical, feasible models” that are geared toward adherence, efficiency, and cost-efficacy, wrote Thomas F. Imperiale, MD, of Indiana University, Indianapolis, and his associates. The commentary is in the October issue of Clinical Gastroenterology and Hepatology.

Tailoring age of first screening on an individual level, based on other risk factors and patient preferences, might improve uptake and benefit-risk ratios, balance, they argued.

Rates of colorectal cancer in persons under age 50 years rose by about 22% between 2000 and 2013. However, estimates for the most recent birth cohorts have wide confidence intervals, “indicating imprecision and uncertainty that this trend will continue,” the experts wrote. Furthermore, the absolute risk of colorectal cancer among individuals younger than 50 years has risen only slightly, from 5.9 cases per 100,000 population to 7.2 cases per 100,000 population. “[This] small increase in incidence may represent a true increase or could be due to increased use of colonoscopy in general, and specifically, for diagnosis or high-risk screening of first-degree relatives of persons with colorectal cancer,” the experts wrote.

Implementing the new recommendation could detect earlier-stage (curable) colorectal cancer “in a youthful and productive age group that may be sandwiched between raising children and caring for aging parents,” they continued. Earlier detection could reduce mortality and reduce the costs of treating a disease that often exceeds $100,000 per person annually.

However, the recommendation was based on a modeling study that assumed 100% adherence. In reality, uptake among 45- to 49-year-olds might be 15%-20%, and “who actually shows up for screening could make or break this recommendation,” the experts said. If younger individuals who underwent screening tended to have few risk factors for colorectal cancer, then the new recommendation would lead to many false positives and unnecessary colonoscopies, with the associated fallout of emotional harm and wasted health care resources, they added.

Population-level studies have identified age as the strongest predictor of colorectal cancer, but age “does not perform as well” at patient level, the experts said. They emphasized the role of other risk factors, such as male sex, having a first-degree relative with colorectal cancer, high body mass index, metabolic syndrome, cigarette smoking, diet, adherence to screening, and use of aspirin, nonsteroidal anti-inflammatory drugs, and hormone therapy. “The goal for providers and health systems is to determine whether and how to change screening practice and policy, and how to incorporate this new recommendation into practice, a necessarily complex process that requires knowing patient risk, patient preferences, and the long-term balance of benefits and burdens,” they concluded (Clin Gastroenterol Hepatol. 2018 Aug 13. doi: 10.1016/j.cgh.2018.08.023).

Dr. Imperiale and coauthor Charles J. Kahi, MD, MS, had no disclosures. Coauthor Douglas K. Rex, MD, disclosed ties to Aries Pharmaceutical, Cosmo Pharmaceuticals, Boston Scientific, Sebela, Medtronic, EndoAid Ltd, Olympus, Paion, Braintree, and Medivators. He also chairs the U.S. Multi-Society Task Force on Colorectal Cancer.

* This story was updated on 10/16/2018.

Diets promoting colonic inflammation were associated with a greater risk of colorectal carcinomas containing Fusobacterium nucleatum bacteria, according to a report in the October issue of Clinical Gastroenterology and Hepatology.

Courtesy American Gastroenterological Association

Proinflammatory diets were not linked to heightened risk for colon cancers without these bacteria, reported Li Liu, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston. “These findings indicate that diet-induced intestinal inflammation alters the gut microbiome to contribute to colorectal carcinogenesis,” they wrote. “Nutritional interventions might be used in precision medicine and cancer prevention.”

Intestinal inflammation, a risk factor for colorectal cancer, is associated with high levels of circulating interleukin 6, C-reactive protein, and tumor necrosis factor–receptor superfamily member 1B. Colonic inflammation impairs the mucosal barrier and alters immune cell responses, which affects the composition of colonic microbiota. Among these, F. nucleatum is known to potentiate colorectal tumors and is associated with proximal tumor location, other tumor features, and cancer progression and chemoresistance.

For the study, the investigators examined self-reported data from more than 124,000 individuals followed for 28 years as part of the Nurses’ Health Study and the Health Professionals Follow-Up Study. They calculated average dietary patterns based on the empiric dietary inflammatory pattern (EDIP) score, which sums weighted intake scores for 18 foods (such as red and processed meat, coffee, tea, and leafy green or dark yellow vegetables) that are known to affect plasma levels of interleukin 6, C-reactive protein, tumor necrosis factor–receptor superfamily member 1B, and tumor necrosis factor alpha–receptor 2. A higher EDIP score denotes a more inflammatory diet.

During the 28-year follow-up period, 951 individuals developed colorectal carcinomas that were tested with a polymerase chain reaction assay for F. nucleatum DNA. A total of 115 tumors tested positive for F. nucleatum. After the researchers controlled for potential confounders, individuals whose EDIP scores were in the highest tertile were significantly more likely to develop F. nucleatum–positive colorectal cancer than were those who scored in the lowest tertile (adjusted hazard ratio, 1.63; 95% confidence interval, 1.03 to 2.58; P = .03). This differential association “appeared to be stronger in proximal colon cancer than in distal colon and rectal cancer,” the researchers said.

More than 90% of individuals in this study were non-Hispanic white, the researchers noted. Tumor tissue was not available from all cases of colorectal cancer and a fairly small number of cases tested positive for tumor F. nucleatum. Nonetheless, the findings suggest that an inflammatory diet could help amplify gut microbiota involved in tumorigenesis, they said. Pending confirmatory studies, they recommended an anti-inflammatory diet with high intake of green leafy vegetables, dark yellow vegetables, coffee, and tea, and with low intake of red meat, processed meat, refined grain, and sugary beverages. They also recommended studying whether F. nucleatum tumor or stool tests could help personalize dietary interventions.

Funders included the National Institutes of Health, Dana Farber Harvard Cancer, Project P. Fund for Colorectal Cancer Research, Friends of the Dana-Farber Cancer Institute, Bennett Family Fund, the Entertainment Industry Foundation, and American Association for Cancer Research, National Natural Science Foundation of China, Chinese Scholarship Council, Huazhong University of Science and Technology, and others. Dr. Liu had no disclosures. One coinvestigator disclosed ties to Genentech/Roche, Lilly, Sanofi, Bayer, and several other biomedical companies.

SOURCE: Liu L et al. Clin Gastroenterol Hepatol. 2018 Apr 24. doi: 10.1016/j.cgh.2018.04.030.

Diets promoting colonic inflammation were associated with a greater risk of colorectal carcinomas containing Fusobacterium nucleatum bacteria, according to a report in the October issue of Clinical Gastroenterology and Hepatology.

Courtesy American Gastroenterological Association

Proinflammatory diets were not linked to heightened risk for colon cancers without these bacteria, reported Li Liu, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston. “These findings indicate that diet-induced intestinal inflammation alters the gut microbiome to contribute to colorectal carcinogenesis,” they wrote. “Nutritional interventions might be used in precision medicine and cancer prevention.”

Intestinal inflammation, a risk factor for colorectal cancer, is associated with high levels of circulating interleukin 6, C-reactive protein, and tumor necrosis factor–receptor superfamily member 1B. Colonic inflammation impairs the mucosal barrier and alters immune cell responses, which affects the composition of colonic microbiota. Among these, F. nucleatum is known to potentiate colorectal tumors and is associated with proximal tumor location, other tumor features, and cancer progression and chemoresistance.

For the study, the investigators examined self-reported data from more than 124,000 individuals followed for 28 years as part of the Nurses’ Health Study and the Health Professionals Follow-Up Study. They calculated average dietary patterns based on the empiric dietary inflammatory pattern (EDIP) score, which sums weighted intake scores for 18 foods (such as red and processed meat, coffee, tea, and leafy green or dark yellow vegetables) that are known to affect plasma levels of interleukin 6, C-reactive protein, tumor necrosis factor–receptor superfamily member 1B, and tumor necrosis factor alpha–receptor 2. A higher EDIP score denotes a more inflammatory diet.

During the 28-year follow-up period, 951 individuals developed colorectal carcinomas that were tested with a polymerase chain reaction assay for F. nucleatum DNA. A total of 115 tumors tested positive for F. nucleatum. After the researchers controlled for potential confounders, individuals whose EDIP scores were in the highest tertile were significantly more likely to develop F. nucleatum–positive colorectal cancer than were those who scored in the lowest tertile (adjusted hazard ratio, 1.63; 95% confidence interval, 1.03 to 2.58; P = .03). This differential association “appeared to be stronger in proximal colon cancer than in distal colon and rectal cancer,” the researchers said.

More than 90% of individuals in this study were non-Hispanic white, the researchers noted. Tumor tissue was not available from all cases of colorectal cancer and a fairly small number of cases tested positive for tumor F. nucleatum. Nonetheless, the findings suggest that an inflammatory diet could help amplify gut microbiota involved in tumorigenesis, they said. Pending confirmatory studies, they recommended an anti-inflammatory diet with high intake of green leafy vegetables, dark yellow vegetables, coffee, and tea, and with low intake of red meat, processed meat, refined grain, and sugary beverages. They also recommended studying whether F. nucleatum tumor or stool tests could help personalize dietary interventions.

Funders included the National Institutes of Health, Dana Farber Harvard Cancer, Project P. Fund for Colorectal Cancer Research, Friends of the Dana-Farber Cancer Institute, Bennett Family Fund, the Entertainment Industry Foundation, and American Association for Cancer Research, National Natural Science Foundation of China, Chinese Scholarship Council, Huazhong University of Science and Technology, and others. Dr. Liu had no disclosures. One coinvestigator disclosed ties to Genentech/Roche, Lilly, Sanofi, Bayer, and several other biomedical companies.

SOURCE: Liu L et al. Clin Gastroenterol Hepatol. 2018 Apr 24. doi: 10.1016/j.cgh.2018.04.030.

Diets promoting colonic inflammation were associated with a greater risk of colorectal carcinomas containing Fusobacterium nucleatum bacteria, according to a report in the October issue of Clinical Gastroenterology and Hepatology.

Courtesy American Gastroenterological Association

Proinflammatory diets were not linked to heightened risk for colon cancers without these bacteria, reported Li Liu, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston. “These findings indicate that diet-induced intestinal inflammation alters the gut microbiome to contribute to colorectal carcinogenesis,” they wrote. “Nutritional interventions might be used in precision medicine and cancer prevention.”

Intestinal inflammation, a risk factor for colorectal cancer, is associated with high levels of circulating interleukin 6, C-reactive protein, and tumor necrosis factor–receptor superfamily member 1B. Colonic inflammation impairs the mucosal barrier and alters immune cell responses, which affects the composition of colonic microbiota. Among these, F. nucleatum is known to potentiate colorectal tumors and is associated with proximal tumor location, other tumor features, and cancer progression and chemoresistance.

For the study, the investigators examined self-reported data from more than 124,000 individuals followed for 28 years as part of the Nurses’ Health Study and the Health Professionals Follow-Up Study. They calculated average dietary patterns based on the empiric dietary inflammatory pattern (EDIP) score, which sums weighted intake scores for 18 foods (such as red and processed meat, coffee, tea, and leafy green or dark yellow vegetables) that are known to affect plasma levels of interleukin 6, C-reactive protein, tumor necrosis factor–receptor superfamily member 1B, and tumor necrosis factor alpha–receptor 2. A higher EDIP score denotes a more inflammatory diet.

During the 28-year follow-up period, 951 individuals developed colorectal carcinomas that were tested with a polymerase chain reaction assay for F. nucleatum DNA. A total of 115 tumors tested positive for F. nucleatum. After the researchers controlled for potential confounders, individuals whose EDIP scores were in the highest tertile were significantly more likely to develop F. nucleatum–positive colorectal cancer than were those who scored in the lowest tertile (adjusted hazard ratio, 1.63; 95% confidence interval, 1.03 to 2.58; P = .03). This differential association “appeared to be stronger in proximal colon cancer than in distal colon and rectal cancer,” the researchers said.

More than 90% of individuals in this study were non-Hispanic white, the researchers noted. Tumor tissue was not available from all cases of colorectal cancer and a fairly small number of cases tested positive for tumor F. nucleatum. Nonetheless, the findings suggest that an inflammatory diet could help amplify gut microbiota involved in tumorigenesis, they said. Pending confirmatory studies, they recommended an anti-inflammatory diet with high intake of green leafy vegetables, dark yellow vegetables, coffee, and tea, and with low intake of red meat, processed meat, refined grain, and sugary beverages. They also recommended studying whether F. nucleatum tumor or stool tests could help personalize dietary interventions.

Funders included the National Institutes of Health, Dana Farber Harvard Cancer, Project P. Fund for Colorectal Cancer Research, Friends of the Dana-Farber Cancer Institute, Bennett Family Fund, the Entertainment Industry Foundation, and American Association for Cancer Research, National Natural Science Foundation of China, Chinese Scholarship Council, Huazhong University of Science and Technology, and others. Dr. Liu had no disclosures. One coinvestigator disclosed ties to Genentech/Roche, Lilly, Sanofi, Bayer, and several other biomedical companies.

SOURCE: Liu L et al. Clin Gastroenterol Hepatol. 2018 Apr 24. doi: 10.1016/j.cgh.2018.04.030.

In a case-control study of patients with cirrhosis, screening for hepatocellular carcinoma up to 4 years prior to diagnosis was not associated with lower mortality.

Copyright Sebastian Kaulitzki/Thinkstock

Similar proportions of cases and controls underwent screening with abdominal ultrasonography, serum alpha-fetoprotein (AFP) testing, or both, reported Andrew M. Moon, MD, MPH, of the University of North Carolina at Chapel Hill, and his associates. “There was also no difference in receipt of these screening tests within 1, 2, or 3 years prior to the index date,” they wrote. The report was published in Gastroenterology. The findings “[suggest] that either these screening tests or the currently available treatments [for liver cancer], or both, are suboptimal and need to be improved.”

Because cirrhosis significantly increases the risk of hepatocellular carcinoma, the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Asian Pacific Association for the Study of the Liver recommend screening cirrhotic patients every 6 months with abdominal ultrasonography with or without concomitant serum AFP. But nonliver societies have not endorsed this approach, citing a lack of high-quality data. One problem is that studies have compared patients whose liver cancer was diagnosed by screening with those diagnosed after they became symptomatic, which creates a lead-time bias that inherently favors screening, Dr. Moon and his associates noted.

To help fill the evidence gap, they identified 238 patients from the Veterans Affairs health care system who had died of hepatocellular carcinoma between 2013 and 2015 and who had been diagnosed with cirrhosis at least 4 years beforehand. They compared these cases with an equal number of patients with cirrhosis who had been in VA care for a similar amount of time and had not died of hepatocellular carcinoma. Cases and controls were matched by etiology of cirrhosis, year that cirrhosis was diagnosed, race, age, sex, Model for End-Stage Liver Disease score, and VA medical center. The researchers identified screening tests by reviewing blinded medical charts.

There were no significant differences in the proportions of cases and controls who underwent screening ultrasonography (52.9% versus 54.2%, respectively), screening serum AFP (74.8% versus 73.5%), either test (81.1% versus 79.4%), or both tests (46.6% versus 48.3%) within 4 years of the index date or the matched control. The result was similar after potential confounders were controlled for and when examining shorter time frames of 1, 2, and 3 years.

It was unlikely that these results reflect delayed diagnosis of liver cancer or a lack of treatment within the VA system, the experts wrote. A total of 51.3% of cases were diagnosed with Milan criteria, which exceeds the proportion in the national Surveillance, Epidemiology, and End Results registry, they noted. None of the fatal cases underwent liver transplantation, but 66.8% received other treatments for liver cancer.

Funders included the National Institutes of Health and the Veterans Affairs Clinical Science Research & Development. The investigators reported having no conflicts of interest.

SOURCE: Moon AM et al. Gastroenterology. 2018 Jul 5. doi: 10.1053/j.gastro.2018.06.079.

In a case-control study of patients with cirrhosis, screening for hepatocellular carcinoma up to 4 years prior to diagnosis was not associated with lower mortality.

Copyright Sebastian Kaulitzki/Thinkstock

Similar proportions of cases and controls underwent screening with abdominal ultrasonography, serum alpha-fetoprotein (AFP) testing, or both, reported Andrew M. Moon, MD, MPH, of the University of North Carolina at Chapel Hill, and his associates. “There was also no difference in receipt of these screening tests within 1, 2, or 3 years prior to the index date,” they wrote. The report was published in Gastroenterology. The findings “[suggest] that either these screening tests or the currently available treatments [for liver cancer], or both, are suboptimal and need to be improved.”

Because cirrhosis significantly increases the risk of hepatocellular carcinoma, the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Asian Pacific Association for the Study of the Liver recommend screening cirrhotic patients every 6 months with abdominal ultrasonography with or without concomitant serum AFP. But nonliver societies have not endorsed this approach, citing a lack of high-quality data. One problem is that studies have compared patients whose liver cancer was diagnosed by screening with those diagnosed after they became symptomatic, which creates a lead-time bias that inherently favors screening, Dr. Moon and his associates noted.

To help fill the evidence gap, they identified 238 patients from the Veterans Affairs health care system who had died of hepatocellular carcinoma between 2013 and 2015 and who had been diagnosed with cirrhosis at least 4 years beforehand. They compared these cases with an equal number of patients with cirrhosis who had been in VA care for a similar amount of time and had not died of hepatocellular carcinoma. Cases and controls were matched by etiology of cirrhosis, year that cirrhosis was diagnosed, race, age, sex, Model for End-Stage Liver Disease score, and VA medical center. The researchers identified screening tests by reviewing blinded medical charts.

There were no significant differences in the proportions of cases and controls who underwent screening ultrasonography (52.9% versus 54.2%, respectively), screening serum AFP (74.8% versus 73.5%), either test (81.1% versus 79.4%), or both tests (46.6% versus 48.3%) within 4 years of the index date or the matched control. The result was similar after potential confounders were controlled for and when examining shorter time frames of 1, 2, and 3 years.

It was unlikely that these results reflect delayed diagnosis of liver cancer or a lack of treatment within the VA system, the experts wrote. A total of 51.3% of cases were diagnosed with Milan criteria, which exceeds the proportion in the national Surveillance, Epidemiology, and End Results registry, they noted. None of the fatal cases underwent liver transplantation, but 66.8% received other treatments for liver cancer.

Funders included the National Institutes of Health and the Veterans Affairs Clinical Science Research & Development. The investigators reported having no conflicts of interest.

SOURCE: Moon AM et al. Gastroenterology. 2018 Jul 5. doi: 10.1053/j.gastro.2018.06.079.

In a case-control study of patients with cirrhosis, screening for hepatocellular carcinoma up to 4 years prior to diagnosis was not associated with lower mortality.

Copyright Sebastian Kaulitzki/Thinkstock

Similar proportions of cases and controls underwent screening with abdominal ultrasonography, serum alpha-fetoprotein (AFP) testing, or both, reported Andrew M. Moon, MD, MPH, of the University of North Carolina at Chapel Hill, and his associates. “There was also no difference in receipt of these screening tests within 1, 2, or 3 years prior to the index date,” they wrote. The report was published in Gastroenterology. The findings “[suggest] that either these screening tests or the currently available treatments [for liver cancer], or both, are suboptimal and need to be improved.”

Because cirrhosis significantly increases the risk of hepatocellular carcinoma, the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Asian Pacific Association for the Study of the Liver recommend screening cirrhotic patients every 6 months with abdominal ultrasonography with or without concomitant serum AFP. But nonliver societies have not endorsed this approach, citing a lack of high-quality data. One problem is that studies have compared patients whose liver cancer was diagnosed by screening with those diagnosed after they became symptomatic, which creates a lead-time bias that inherently favors screening, Dr. Moon and his associates noted.

To help fill the evidence gap, they identified 238 patients from the Veterans Affairs health care system who had died of hepatocellular carcinoma between 2013 and 2015 and who had been diagnosed with cirrhosis at least 4 years beforehand. They compared these cases with an equal number of patients with cirrhosis who had been in VA care for a similar amount of time and had not died of hepatocellular carcinoma. Cases and controls were matched by etiology of cirrhosis, year that cirrhosis was diagnosed, race, age, sex, Model for End-Stage Liver Disease score, and VA medical center. The researchers identified screening tests by reviewing blinded medical charts.

There were no significant differences in the proportions of cases and controls who underwent screening ultrasonography (52.9% versus 54.2%, respectively), screening serum AFP (74.8% versus 73.5%), either test (81.1% versus 79.4%), or both tests (46.6% versus 48.3%) within 4 years of the index date or the matched control. The result was similar after potential confounders were controlled for and when examining shorter time frames of 1, 2, and 3 years.

It was unlikely that these results reflect delayed diagnosis of liver cancer or a lack of treatment within the VA system, the experts wrote. A total of 51.3% of cases were diagnosed with Milan criteria, which exceeds the proportion in the national Surveillance, Epidemiology, and End Results registry, they noted. None of the fatal cases underwent liver transplantation, but 66.8% received other treatments for liver cancer.

Funders included the National Institutes of Health and the Veterans Affairs Clinical Science Research & Development. The investigators reported having no conflicts of interest.

SOURCE: Moon AM et al. Gastroenterology. 2018 Jul 5. doi: 10.1053/j.gastro.2018.06.079.

The diagnosis of eosinophilic esophagitis no longer needs to include a trial of proton pump inhibitor (PPI) therapy, according to an updated international consensus statement published in the October issue of Gastroenterology.

Dr. Graham Beards/Wikimedia Commons/CC ASA 3.0

“An initial rationale for the PPI trial was to distinguish eosinophilic esophagitis from gastroesophageal reflux disease, but it is now known that these conditions have a complex relationship and are not necessarily mutually exclusive,” wrote Evan S. Dellon, MD, of the University of North Carolina at Chapel Hill, and his associates. According to current evidence, “PPIs are better classified as a treatment for esophageal eosinophilia that may be due to eosinophilic esophagitis than as a diagnostic criterion,” they said.

Diagnostic guidelines for eosinophilic esophagitis were published first in 2007 and were updated in 2011. The guideline authors recommended either pH monitoring or an 8-week trial of high-dose PPI therapy to rule out inflammation from gastroesophageal reflux disease (GERD).

But subsequent publications described patients with symptomatic esophageal eosinophilia who responded to PPIs and lacked classic GERD symptoms. Guidelines called this condition “PPI-responsive esophageal eosinophilia” and considered it a separate entity from GERD.

However, an “evolving body of research” shows that eosinophilic esophagitis can overlap with GERD, Dr. Dellon and his associates wrote. Furthermore, each of these conditions can trigger the other. Eosinophilic esophagitis can decrease esophageal compliance, leading to secondary reflux, while gastroesophageal reflux can erode the esophageal epithelium, triggering antigen exposure and eosinophilia.

Therefore, Dr. Dellon and his associates recommended defining eosinophilic esophagitis as signs and symptoms of esophageal dysfunction and an esophageal biopsy showing at least 15 eosinophils per high-power field, or approximately 60 eosinophils per millimeter, with infiltration limited to the esophagus. They stressed the importance of esophageal biopsy even if endoscopy shows normal mucosa. “As per prior guidelines, multiple biopsies from two or more esophageal levels, targeting areas of apparent inflammation, are recommended to increase the diagnostic yield,” they added. “Gastric and duodenal biopsies should be obtained as clinically indicated by symptoms, endoscopic findings in the stomach or duodenum, or high index of suspicion for a mucosal process.”

Physicians should increase their suspicion of eosinophilic esophagitis if patients have other types of atopy or endoscopic findings of “rings, furrows, exudates, edema, stricture, narrowing, and crepe-paper mucosa,” they added. In addition to GERD, they recommended looking carefully for other conditions that can trigger esophageal eosinophilia, such as pemphigus, drug hypersensitivity reactions, achalasia, and Crohn’s disease with esophageal involvement.

To create the guideline, Dr. Dellon and his associates searched PubMed for studies of all designs and sizes published from 1966 through December 2016. Teams of experts on specific topics then reviewed and discussed relevant literature. In May 2017, 43 reviewers met for 8 hours to present and discuss conclusions. There was 100% agreement to remove the PPI trial from the diagnostic criteria, the experts noted.

The authors disclosed financial support from the International Gastrointestinal Eosinophilic Diseases Researchers (TIGERS), The David and Denise Bunning Family, and the Rare Disease Clinical Research Network. Dr. Dellon disclosed consulting relationships and receiving research funding from Adare, Celgene/Receptos, Regeneron, and Shire among others. The majority of his coauthors also disclosed relationships with numerous medical companies.

SOURCE: Dellon ES et al. Gastroenterology. 2018 Jul 12. doi: 10.1053/j.gastro.2018.07.009.

The diagnosis of eosinophilic esophagitis no longer needs to include a trial of proton pump inhibitor (PPI) therapy, according to an updated international consensus statement published in the October issue of Gastroenterology.

Dr. Graham Beards/Wikimedia Commons/CC ASA 3.0

“An initial rationale for the PPI trial was to distinguish eosinophilic esophagitis from gastroesophageal reflux disease, but it is now known that these conditions have a complex relationship and are not necessarily mutually exclusive,” wrote Evan S. Dellon, MD, of the University of North Carolina at Chapel Hill, and his associates. According to current evidence, “PPIs are better classified as a treatment for esophageal eosinophilia that may be due to eosinophilic esophagitis than as a diagnostic criterion,” they said.

Diagnostic guidelines for eosinophilic esophagitis were published first in 2007 and were updated in 2011. The guideline authors recommended either pH monitoring or an 8-week trial of high-dose PPI therapy to rule out inflammation from gastroesophageal reflux disease (GERD).

But subsequent publications described patients with symptomatic esophageal eosinophilia who responded to PPIs and lacked classic GERD symptoms. Guidelines called this condition “PPI-responsive esophageal eosinophilia” and considered it a separate entity from GERD.

However, an “evolving body of research” shows that eosinophilic esophagitis can overlap with GERD, Dr. Dellon and his associates wrote. Furthermore, each of these conditions can trigger the other. Eosinophilic esophagitis can decrease esophageal compliance, leading to secondary reflux, while gastroesophageal reflux can erode the esophageal epithelium, triggering antigen exposure and eosinophilia.

Therefore, Dr. Dellon and his associates recommended defining eosinophilic esophagitis as signs and symptoms of esophageal dysfunction and an esophageal biopsy showing at least 15 eosinophils per high-power field, or approximately 60 eosinophils per millimeter, with infiltration limited to the esophagus. They stressed the importance of esophageal biopsy even if endoscopy shows normal mucosa. “As per prior guidelines, multiple biopsies from two or more esophageal levels, targeting areas of apparent inflammation, are recommended to increase the diagnostic yield,” they added. “Gastric and duodenal biopsies should be obtained as clinically indicated by symptoms, endoscopic findings in the stomach or duodenum, or high index of suspicion for a mucosal process.”

Physicians should increase their suspicion of eosinophilic esophagitis if patients have other types of atopy or endoscopic findings of “rings, furrows, exudates, edema, stricture, narrowing, and crepe-paper mucosa,” they added. In addition to GERD, they recommended looking carefully for other conditions that can trigger esophageal eosinophilia, such as pemphigus, drug hypersensitivity reactions, achalasia, and Crohn’s disease with esophageal involvement.

To create the guideline, Dr. Dellon and his associates searched PubMed for studies of all designs and sizes published from 1966 through December 2016. Teams of experts on specific topics then reviewed and discussed relevant literature. In May 2017, 43 reviewers met for 8 hours to present and discuss conclusions. There was 100% agreement to remove the PPI trial from the diagnostic criteria, the experts noted.

The authors disclosed financial support from the International Gastrointestinal Eosinophilic Diseases Researchers (TIGERS), The David and Denise Bunning Family, and the Rare Disease Clinical Research Network. Dr. Dellon disclosed consulting relationships and receiving research funding from Adare, Celgene/Receptos, Regeneron, and Shire among others. The majority of his coauthors also disclosed relationships with numerous medical companies.

SOURCE: Dellon ES et al. Gastroenterology. 2018 Jul 12. doi: 10.1053/j.gastro.2018.07.009.

The diagnosis of eosinophilic esophagitis no longer needs to include a trial of proton pump inhibitor (PPI) therapy, according to an updated international consensus statement published in the October issue of Gastroenterology.

Dr. Graham Beards/Wikimedia Commons/CC ASA 3.0

“An initial rationale for the PPI trial was to distinguish eosinophilic esophagitis from gastroesophageal reflux disease, but it is now known that these conditions have a complex relationship and are not necessarily mutually exclusive,” wrote Evan S. Dellon, MD, of the University of North Carolina at Chapel Hill, and his associates. According to current evidence, “PPIs are better classified as a treatment for esophageal eosinophilia that may be due to eosinophilic esophagitis than as a diagnostic criterion,” they said.

Diagnostic guidelines for eosinophilic esophagitis were published first in 2007 and were updated in 2011. The guideline authors recommended either pH monitoring or an 8-week trial of high-dose PPI therapy to rule out inflammation from gastroesophageal reflux disease (GERD).

But subsequent publications described patients with symptomatic esophageal eosinophilia who responded to PPIs and lacked classic GERD symptoms. Guidelines called this condition “PPI-responsive esophageal eosinophilia” and considered it a separate entity from GERD.

However, an “evolving body of research” shows that eosinophilic esophagitis can overlap with GERD, Dr. Dellon and his associates wrote. Furthermore, each of these conditions can trigger the other. Eosinophilic esophagitis can decrease esophageal compliance, leading to secondary reflux, while gastroesophageal reflux can erode the esophageal epithelium, triggering antigen exposure and eosinophilia.

Therefore, Dr. Dellon and his associates recommended defining eosinophilic esophagitis as signs and symptoms of esophageal dysfunction and an esophageal biopsy showing at least 15 eosinophils per high-power field, or approximately 60 eosinophils per millimeter, with infiltration limited to the esophagus. They stressed the importance of esophageal biopsy even if endoscopy shows normal mucosa. “As per prior guidelines, multiple biopsies from two or more esophageal levels, targeting areas of apparent inflammation, are recommended to increase the diagnostic yield,” they added. “Gastric and duodenal biopsies should be obtained as clinically indicated by symptoms, endoscopic findings in the stomach or duodenum, or high index of suspicion for a mucosal process.”

Physicians should increase their suspicion of eosinophilic esophagitis if patients have other types of atopy or endoscopic findings of “rings, furrows, exudates, edema, stricture, narrowing, and crepe-paper mucosa,” they added. In addition to GERD, they recommended looking carefully for other conditions that can trigger esophageal eosinophilia, such as pemphigus, drug hypersensitivity reactions, achalasia, and Crohn’s disease with esophageal involvement.

To create the guideline, Dr. Dellon and his associates searched PubMed for studies of all designs and sizes published from 1966 through December 2016. Teams of experts on specific topics then reviewed and discussed relevant literature. In May 2017, 43 reviewers met for 8 hours to present and discuss conclusions. There was 100% agreement to remove the PPI trial from the diagnostic criteria, the experts noted.

The authors disclosed financial support from the International Gastrointestinal Eosinophilic Diseases Researchers (TIGERS), The David and Denise Bunning Family, and the Rare Disease Clinical Research Network. Dr. Dellon disclosed consulting relationships and receiving research funding from Adare, Celgene/Receptos, Regeneron, and Shire among others. The majority of his coauthors also disclosed relationships with numerous medical companies.

SOURCE: Dellon ES et al. Gastroenterology. 2018 Jul 12. doi: 10.1053/j.gastro.2018.07.009.