Richard Mark Kirkner

The risk for gastroesophageal reflux disease and cancer of the larynx, tonsils, and other areas of the upper aerodigestive tract was strongly associated in a longitudinal-based population study of the U.S. elderly population.

A total of 13,805 cases involving gastroesophageal reflux disease (GERD) and malignancies of the upper aerodigestive tract (UADT) and 13,805 GERD cases with no UADT from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER)-Medicare linked database in patients aged 66 years and older from 2003 through 2011 were examined. Only those who had no malignancy before they were diagnosed with GERD were included in the study, which was published in JAMA Otolaryngology–Head & Neck Surgery (doi: 10.1001/jamaoto.2017.2561.

Lead author Charles A. Riley, MD, of Tulane University in New Orleans, and his coauthors noted that previous studies had drawn conflicting conclusions about the link between GERD and UADT malignancies. To their knowledge, this is the first study to investigate UADT malignancies specifically in the elderly in the United States.

“The increased relative risk for laryngeal and pharyngeal cancers in this population suggests an opportunity for earlier detection and intervention,” Dr. Riley and his colleagues said.

For the study, they calculated the adjusted odds ratios (aOR) of cancer in six areas of the UADT in patients with GERD vs. patients who never had GERD: larynx (2.86), hypopharynx (2.54), oropharynx (2.47), tonsil (2.14), nasopharynx (2.04), and paranasal sinuses (1.40).

The study also evaluated the relative risk of malignancy with GERD and without GERD. “These data suggest that elderly patients with GERD in the United States are 3.47, 3.23, 2.88, and 2.37 times as likely as those without GERD to be diagnosed with laryngeal, hypopharyngeal, oropharyngeal and tonsillar cancers, respectively,” Dr. Riley and his associates wrote.

These findings may point to a need for a paradigm shift like that which led to the use of screening esophagogastroduodenoscopy for patients at risk of Barrett esophagus and esophageal cancer. “A similar screening platform may benefit those patients at higher risk for the development of malignancy of the UADT, though further research is necessary,” they said.

Dr. Riley and his coauthors reported having no financial disclosures.

Source: Riley C et al. JAMA Otolaryngol Head Neck Surg. 2017 Dec 21. doi: 10.1001/jamaoto.2017.2561.

The risk for gastroesophageal reflux disease and cancer of the larynx, tonsils, and other areas of the upper aerodigestive tract was strongly associated in a longitudinal-based population study of the U.S. elderly population.

A total of 13,805 cases involving gastroesophageal reflux disease (GERD) and malignancies of the upper aerodigestive tract (UADT) and 13,805 GERD cases with no UADT from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER)-Medicare linked database in patients aged 66 years and older from 2003 through 2011 were examined. Only those who had no malignancy before they were diagnosed with GERD were included in the study, which was published in JAMA Otolaryngology–Head & Neck Surgery (doi: 10.1001/jamaoto.2017.2561.

Lead author Charles A. Riley, MD, of Tulane University in New Orleans, and his coauthors noted that previous studies had drawn conflicting conclusions about the link between GERD and UADT malignancies. To their knowledge, this is the first study to investigate UADT malignancies specifically in the elderly in the United States.

“The increased relative risk for laryngeal and pharyngeal cancers in this population suggests an opportunity for earlier detection and intervention,” Dr. Riley and his colleagues said.

For the study, they calculated the adjusted odds ratios (aOR) of cancer in six areas of the UADT in patients with GERD vs. patients who never had GERD: larynx (2.86), hypopharynx (2.54), oropharynx (2.47), tonsil (2.14), nasopharynx (2.04), and paranasal sinuses (1.40).

The study also evaluated the relative risk of malignancy with GERD and without GERD. “These data suggest that elderly patients with GERD in the United States are 3.47, 3.23, 2.88, and 2.37 times as likely as those without GERD to be diagnosed with laryngeal, hypopharyngeal, oropharyngeal and tonsillar cancers, respectively,” Dr. Riley and his associates wrote.

These findings may point to a need for a paradigm shift like that which led to the use of screening esophagogastroduodenoscopy for patients at risk of Barrett esophagus and esophageal cancer. “A similar screening platform may benefit those patients at higher risk for the development of malignancy of the UADT, though further research is necessary,” they said.

Dr. Riley and his coauthors reported having no financial disclosures.

Source: Riley C et al. JAMA Otolaryngol Head Neck Surg. 2017 Dec 21. doi: 10.1001/jamaoto.2017.2561.

The risk for gastroesophageal reflux disease and cancer of the larynx, tonsils, and other areas of the upper aerodigestive tract was strongly associated in a longitudinal-based population study of the U.S. elderly population.

A total of 13,805 cases involving gastroesophageal reflux disease (GERD) and malignancies of the upper aerodigestive tract (UADT) and 13,805 GERD cases with no UADT from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER)-Medicare linked database in patients aged 66 years and older from 2003 through 2011 were examined. Only those who had no malignancy before they were diagnosed with GERD were included in the study, which was published in JAMA Otolaryngology–Head & Neck Surgery (doi: 10.1001/jamaoto.2017.2561.

Lead author Charles A. Riley, MD, of Tulane University in New Orleans, and his coauthors noted that previous studies had drawn conflicting conclusions about the link between GERD and UADT malignancies. To their knowledge, this is the first study to investigate UADT malignancies specifically in the elderly in the United States.

“The increased relative risk for laryngeal and pharyngeal cancers in this population suggests an opportunity for earlier detection and intervention,” Dr. Riley and his colleagues said.

For the study, they calculated the adjusted odds ratios (aOR) of cancer in six areas of the UADT in patients with GERD vs. patients who never had GERD: larynx (2.86), hypopharynx (2.54), oropharynx (2.47), tonsil (2.14), nasopharynx (2.04), and paranasal sinuses (1.40).

The study also evaluated the relative risk of malignancy with GERD and without GERD. “These data suggest that elderly patients with GERD in the United States are 3.47, 3.23, 2.88, and 2.37 times as likely as those without GERD to be diagnosed with laryngeal, hypopharyngeal, oropharyngeal and tonsillar cancers, respectively,” Dr. Riley and his associates wrote.

These findings may point to a need for a paradigm shift like that which led to the use of screening esophagogastroduodenoscopy for patients at risk of Barrett esophagus and esophageal cancer. “A similar screening platform may benefit those patients at higher risk for the development of malignancy of the UADT, though further research is necessary,” they said.

Dr. Riley and his coauthors reported having no financial disclosures.

Source: Riley C et al. JAMA Otolaryngol Head Neck Surg. 2017 Dec 21. doi: 10.1001/jamaoto.2017.2561.

CONCORD, N.C. – Teenage sickle cell disease patients transitioning to adulthood can often find the move to adult providers challenging, causing some patients to lose interest in self-care at a critical point in life, but a transitional program can help them develop the skills they need to manage their disease and avoid risky behaviors, according to psychologist Anya Griffin, PhD.

Managing pain in teenagers and young adults with sickle cell disease (SCD) is fraught with challenges, said Dr. Griffin, who led the SCD transition program at Children’s Healthcare of Atlanta and is now the clinical director of the Stanford (Calif.) Children’s Health Pediatric Rehabilitation Program, an intensive pain management program for pediatric chronic pain.

“Think about who you are when you’re a teenager, when you’re a young adult, what’s going on: dating, sex, parties, college, all-night study sessions,” she said at a Sickle Cell Disease Symposium held by Carolinas Health Care System. “But in the world of sickle cell, these are critical choices that have dire consequences.” Those consequences include dehydration from drinking, fatigue from lack of sleep, and pain crises.

Compounding these challenges is the prevalence of depression and other psychological complications in this age group. And among SCD patients, there can be a sense of grief, Dr. Griffin said.

“Grief is something we tend not to talk too much about,” she said. That grief can manifest in excessive absences from school or work. “Sudden academic declines are something we really have to pay attention to,” Dr. Griffin said.

Silent strokes are also of concern in this age group. “I don’t know if we fully understand the impact on each individual unless we do neuropsychological testing,” she said. The intervals for neuropsychological testing should be in childhood to determine a baseline, then again in adolescence and adulthood. For college-bound students, testing may be a requirement for them to receive medical and physical accommodations, Dr. Griffin said.

While in their late teens and early twenties, SCD patients often rely on pediatric care and can get caught between pediatric and adult providers, she said. That prompted Children’s Healthcare of Atlanta to start a program that essentially hands off those patients from pediatric to adult providers and works with patients to reduce their risks.

As teens approach age 18, they come to the clinic to meet with adult providers and tour the facility. The program involves social workers, vocational and school counselors, and mentors and peer support. “It takes an entire village to address the concerns of transition,” Dr. Griffin said.

Support groups and home visits by providers can also play a key role in the transition protocol, as can telemedicine. “The technology is now there; now we have to figure out how we’re going to start using it,” she said.

This full transitional process can involve multiple appointments with a variety of providers. It’s also important that patients – not parents – interact with providers, Dr. Griffin said.

From January 2007 to September 2012, 74 patients participated in the SCD transition at Children’s Healthcare of Atlanta. Participants who attended more than one transition clinic visit in Atlanta (n = 9) had an average baseline score of 60% on an SCD knowledge questionnaire. But 6 months later, those scores improved to 80%, on average. “We found that teenagers who came to that type of clinic more than once improved pretty well,” Dr. Griffin said.

Dr. Griffin reported having no relevant financial disclosures.

[email protected]

CONCORD, N.C. – Teenage sickle cell disease patients transitioning to adulthood can often find the move to adult providers challenging, causing some patients to lose interest in self-care at a critical point in life, but a transitional program can help them develop the skills they need to manage their disease and avoid risky behaviors, according to psychologist Anya Griffin, PhD.

Managing pain in teenagers and young adults with sickle cell disease (SCD) is fraught with challenges, said Dr. Griffin, who led the SCD transition program at Children’s Healthcare of Atlanta and is now the clinical director of the Stanford (Calif.) Children’s Health Pediatric Rehabilitation Program, an intensive pain management program for pediatric chronic pain.

“Think about who you are when you’re a teenager, when you’re a young adult, what’s going on: dating, sex, parties, college, all-night study sessions,” she said at a Sickle Cell Disease Symposium held by Carolinas Health Care System. “But in the world of sickle cell, these are critical choices that have dire consequences.” Those consequences include dehydration from drinking, fatigue from lack of sleep, and pain crises.

Compounding these challenges is the prevalence of depression and other psychological complications in this age group. And among SCD patients, there can be a sense of grief, Dr. Griffin said.

“Grief is something we tend not to talk too much about,” she said. That grief can manifest in excessive absences from school or work. “Sudden academic declines are something we really have to pay attention to,” Dr. Griffin said.

Silent strokes are also of concern in this age group. “I don’t know if we fully understand the impact on each individual unless we do neuropsychological testing,” she said. The intervals for neuropsychological testing should be in childhood to determine a baseline, then again in adolescence and adulthood. For college-bound students, testing may be a requirement for them to receive medical and physical accommodations, Dr. Griffin said.

While in their late teens and early twenties, SCD patients often rely on pediatric care and can get caught between pediatric and adult providers, she said. That prompted Children’s Healthcare of Atlanta to start a program that essentially hands off those patients from pediatric to adult providers and works with patients to reduce their risks.

As teens approach age 18, they come to the clinic to meet with adult providers and tour the facility. The program involves social workers, vocational and school counselors, and mentors and peer support. “It takes an entire village to address the concerns of transition,” Dr. Griffin said.

Support groups and home visits by providers can also play a key role in the transition protocol, as can telemedicine. “The technology is now there; now we have to figure out how we’re going to start using it,” she said.

This full transitional process can involve multiple appointments with a variety of providers. It’s also important that patients – not parents – interact with providers, Dr. Griffin said.

From January 2007 to September 2012, 74 patients participated in the SCD transition at Children’s Healthcare of Atlanta. Participants who attended more than one transition clinic visit in Atlanta (n = 9) had an average baseline score of 60% on an SCD knowledge questionnaire. But 6 months later, those scores improved to 80%, on average. “We found that teenagers who came to that type of clinic more than once improved pretty well,” Dr. Griffin said.

Dr. Griffin reported having no relevant financial disclosures.

[email protected]

CONCORD, N.C. – Teenage sickle cell disease patients transitioning to adulthood can often find the move to adult providers challenging, causing some patients to lose interest in self-care at a critical point in life, but a transitional program can help them develop the skills they need to manage their disease and avoid risky behaviors, according to psychologist Anya Griffin, PhD.

Managing pain in teenagers and young adults with sickle cell disease (SCD) is fraught with challenges, said Dr. Griffin, who led the SCD transition program at Children’s Healthcare of Atlanta and is now the clinical director of the Stanford (Calif.) Children’s Health Pediatric Rehabilitation Program, an intensive pain management program for pediatric chronic pain.

“Think about who you are when you’re a teenager, when you’re a young adult, what’s going on: dating, sex, parties, college, all-night study sessions,” she said at a Sickle Cell Disease Symposium held by Carolinas Health Care System. “But in the world of sickle cell, these are critical choices that have dire consequences.” Those consequences include dehydration from drinking, fatigue from lack of sleep, and pain crises.

Compounding these challenges is the prevalence of depression and other psychological complications in this age group. And among SCD patients, there can be a sense of grief, Dr. Griffin said.

“Grief is something we tend not to talk too much about,” she said. That grief can manifest in excessive absences from school or work. “Sudden academic declines are something we really have to pay attention to,” Dr. Griffin said.

Silent strokes are also of concern in this age group. “I don’t know if we fully understand the impact on each individual unless we do neuropsychological testing,” she said. The intervals for neuropsychological testing should be in childhood to determine a baseline, then again in adolescence and adulthood. For college-bound students, testing may be a requirement for them to receive medical and physical accommodations, Dr. Griffin said.

While in their late teens and early twenties, SCD patients often rely on pediatric care and can get caught between pediatric and adult providers, she said. That prompted Children’s Healthcare of Atlanta to start a program that essentially hands off those patients from pediatric to adult providers and works with patients to reduce their risks.

As teens approach age 18, they come to the clinic to meet with adult providers and tour the facility. The program involves social workers, vocational and school counselors, and mentors and peer support. “It takes an entire village to address the concerns of transition,” Dr. Griffin said.

Support groups and home visits by providers can also play a key role in the transition protocol, as can telemedicine. “The technology is now there; now we have to figure out how we’re going to start using it,” she said.

This full transitional process can involve multiple appointments with a variety of providers. It’s also important that patients – not parents – interact with providers, Dr. Griffin said.

From January 2007 to September 2012, 74 patients participated in the SCD transition at Children’s Healthcare of Atlanta. Participants who attended more than one transition clinic visit in Atlanta (n = 9) had an average baseline score of 60% on an SCD knowledge questionnaire. But 6 months later, those scores improved to 80%, on average. “We found that teenagers who came to that type of clinic more than once improved pretty well,” Dr. Griffin said.

Dr. Griffin reported having no relevant financial disclosures.

[email protected]

Implementing quality initiatives and creating reporting mechanisms for lung cancer patients can lead to better outcomes, including overall survival. While barriers exist – namely the conflicting perspectives of providers, payers, hospitals, and patients – thoracic oncologic surgeons should seize the opportunity to establish robust quality and value metrics for lung cancer programs, said Whitney S. Brandt, MD, and her coauthors in an expert opinion in the Journal of Thoracic and Cardiovascular Surgery (2017;154:1397-403).

Dr. Brandt, a surgeon at Memorial Sloan Kettering Cancer Center in New York, and her coauthors examined the key elements of quality and value initiatives, categorizing them into preoperative, intraoperative, and postoperative components and primarily focusing on early stage lung cancer. The National Institutes of Health/National Cancer Center provided a grant for the authors’ work.

The preoperative evaluation should at least include CT imaging of the tumor and, for smokers, smoking cessation, said Dr. Brandt and her coauthors. All candidates for pulmonary lung resection should have spirometry and diffusion capacity tests; furthermore, both predicted postoperative forced expiratory volume in 1 second and diffusing capacity of the lungs for CO should be calculated. “Patients with a predicted postoperative value less than 40% for either measurement should be considered high risk for lobectomy and should be offered either sublobar resection or nonsurgical therapy,” they recommended.

Dr. Brandt and her colleagues also clarified preoperative management of patients with cardiac disease. Only patients with significant cardiac disease risk factors need to undergo cardiac testing before lung surgery, and patients with stable cardiac disease do not require revascularization beforehand.

For preoperative staging, the most comprehensive clinical guidelines come from the National Comprehensive Cancer Network, they stated. The guidelines recommend that all patients with a small cell lung cancer or stage II to IV non–small cell lung cancer (NSCLC) receive a brain MRI or – if that’s not available – a head CT with contrast to assess for brain metastasis.

Intraoperative quality measures take into account the surgical approach, including cost, resection and margins, and lymph node evaluation. With regard to surgical approach, trials have shown traditional video-assisted surgery (VATS) lobectomy results in shorter hospital stays and thereby lower costs, as well as fewer complications and deaths, than thoracotomy, said Dr. Brandt and her coauthors. But that cost advantage has not yet carried over to robotic-assisted VATS. That said, “robotic-assisted VATS remains a relatively new technology, and with time and increased robotic platform competition, costs will likely decrease.”

Dr. Brandt and her coauthors also noted that clinical trials support resection margins of 2 cm in patients having surgery for NSCLC and that adequate lymph node evaluation is a critical component of a lung cancer quality initiative. “Regardless of whether lymph nodes are sampled or dissected, we believe that systematic acquisition of mediastinal nodal tissue based on nodal station(s) is a useful quality metric, and, therefore, we recommend each program adopt a preferred approach and track adherence,” they said.

As for postoperative quality metrics, the most obvious are morbidity and mortality. “A quality program should track 30-day or in-hospital mortality, as well as 90-day mortality, following lung cancer resection.” Such metrics can serve as “starting points” for quality improvement initiatives. Length of stay has also emerged as an important metric because it is a surrogate of other metrics, such as patient comorbidities, age, and socioeconomic status. “Length-of-stay metrics likely need to be risk-stratified on the basis of these and other variables to be meaningful to a practicing surgeon,” Dr. Brandt and her coauthors said, adding that: “Studying the effectiveness of enhanced recovery after surgery programs in thoracic surgical oncology poses an opportunity for a well-designed trial.”

Two other key quality metrics for lung cancer programs that need further development were pointed out in the paper: hospital readmissions and tracking of adjuvant therapies. “Programmatic oncologic quality metrics to track appropriate and inappropriate referrals for adjuvant therapy and the number of patients who complete such therapy are important,” they said.

Another step programs should take: Participating in a national or regional database, as recommended by the Society of Thoracic Surgeons, and taking advantage of the “clear benefits to benchmarking your program to others.”

Dr. Brandt and her coauthors reported having no financial disclosures. The National Institutes of Health/National Cancer Center provided grant support.
 

Implementing quality initiatives and creating reporting mechanisms for lung cancer patients can lead to better outcomes, including overall survival. While barriers exist – namely the conflicting perspectives of providers, payers, hospitals, and patients – thoracic oncologic surgeons should seize the opportunity to establish robust quality and value metrics for lung cancer programs, said Whitney S. Brandt, MD, and her coauthors in an expert opinion in the Journal of Thoracic and Cardiovascular Surgery (2017;154:1397-403).

Dr. Brandt, a surgeon at Memorial Sloan Kettering Cancer Center in New York, and her coauthors examined the key elements of quality and value initiatives, categorizing them into preoperative, intraoperative, and postoperative components and primarily focusing on early stage lung cancer. The National Institutes of Health/National Cancer Center provided a grant for the authors’ work.

The preoperative evaluation should at least include CT imaging of the tumor and, for smokers, smoking cessation, said Dr. Brandt and her coauthors. All candidates for pulmonary lung resection should have spirometry and diffusion capacity tests; furthermore, both predicted postoperative forced expiratory volume in 1 second and diffusing capacity of the lungs for CO should be calculated. “Patients with a predicted postoperative value less than 40% for either measurement should be considered high risk for lobectomy and should be offered either sublobar resection or nonsurgical therapy,” they recommended.

Dr. Brandt and her colleagues also clarified preoperative management of patients with cardiac disease. Only patients with significant cardiac disease risk factors need to undergo cardiac testing before lung surgery, and patients with stable cardiac disease do not require revascularization beforehand.

For preoperative staging, the most comprehensive clinical guidelines come from the National Comprehensive Cancer Network, they stated. The guidelines recommend that all patients with a small cell lung cancer or stage II to IV non–small cell lung cancer (NSCLC) receive a brain MRI or – if that’s not available – a head CT with contrast to assess for brain metastasis.

Intraoperative quality measures take into account the surgical approach, including cost, resection and margins, and lymph node evaluation. With regard to surgical approach, trials have shown traditional video-assisted surgery (VATS) lobectomy results in shorter hospital stays and thereby lower costs, as well as fewer complications and deaths, than thoracotomy, said Dr. Brandt and her coauthors. But that cost advantage has not yet carried over to robotic-assisted VATS. That said, “robotic-assisted VATS remains a relatively new technology, and with time and increased robotic platform competition, costs will likely decrease.”

Dr. Brandt and her coauthors also noted that clinical trials support resection margins of 2 cm in patients having surgery for NSCLC and that adequate lymph node evaluation is a critical component of a lung cancer quality initiative. “Regardless of whether lymph nodes are sampled or dissected, we believe that systematic acquisition of mediastinal nodal tissue based on nodal station(s) is a useful quality metric, and, therefore, we recommend each program adopt a preferred approach and track adherence,” they said.

As for postoperative quality metrics, the most obvious are morbidity and mortality. “A quality program should track 30-day or in-hospital mortality, as well as 90-day mortality, following lung cancer resection.” Such metrics can serve as “starting points” for quality improvement initiatives. Length of stay has also emerged as an important metric because it is a surrogate of other metrics, such as patient comorbidities, age, and socioeconomic status. “Length-of-stay metrics likely need to be risk-stratified on the basis of these and other variables to be meaningful to a practicing surgeon,” Dr. Brandt and her coauthors said, adding that: “Studying the effectiveness of enhanced recovery after surgery programs in thoracic surgical oncology poses an opportunity for a well-designed trial.”

Two other key quality metrics for lung cancer programs that need further development were pointed out in the paper: hospital readmissions and tracking of adjuvant therapies. “Programmatic oncologic quality metrics to track appropriate and inappropriate referrals for adjuvant therapy and the number of patients who complete such therapy are important,” they said.

Another step programs should take: Participating in a national or regional database, as recommended by the Society of Thoracic Surgeons, and taking advantage of the “clear benefits to benchmarking your program to others.”

Dr. Brandt and her coauthors reported having no financial disclosures. The National Institutes of Health/National Cancer Center provided grant support.
 

Implementing quality initiatives and creating reporting mechanisms for lung cancer patients can lead to better outcomes, including overall survival. While barriers exist – namely the conflicting perspectives of providers, payers, hospitals, and patients – thoracic oncologic surgeons should seize the opportunity to establish robust quality and value metrics for lung cancer programs, said Whitney S. Brandt, MD, and her coauthors in an expert opinion in the Journal of Thoracic and Cardiovascular Surgery (2017;154:1397-403).

Dr. Brandt, a surgeon at Memorial Sloan Kettering Cancer Center in New York, and her coauthors examined the key elements of quality and value initiatives, categorizing them into preoperative, intraoperative, and postoperative components and primarily focusing on early stage lung cancer. The National Institutes of Health/National Cancer Center provided a grant for the authors’ work.

The preoperative evaluation should at least include CT imaging of the tumor and, for smokers, smoking cessation, said Dr. Brandt and her coauthors. All candidates for pulmonary lung resection should have spirometry and diffusion capacity tests; furthermore, both predicted postoperative forced expiratory volume in 1 second and diffusing capacity of the lungs for CO should be calculated. “Patients with a predicted postoperative value less than 40% for either measurement should be considered high risk for lobectomy and should be offered either sublobar resection or nonsurgical therapy,” they recommended.

Dr. Brandt and her colleagues also clarified preoperative management of patients with cardiac disease. Only patients with significant cardiac disease risk factors need to undergo cardiac testing before lung surgery, and patients with stable cardiac disease do not require revascularization beforehand.

For preoperative staging, the most comprehensive clinical guidelines come from the National Comprehensive Cancer Network, they stated. The guidelines recommend that all patients with a small cell lung cancer or stage II to IV non–small cell lung cancer (NSCLC) receive a brain MRI or – if that’s not available – a head CT with contrast to assess for brain metastasis.

Intraoperative quality measures take into account the surgical approach, including cost, resection and margins, and lymph node evaluation. With regard to surgical approach, trials have shown traditional video-assisted surgery (VATS) lobectomy results in shorter hospital stays and thereby lower costs, as well as fewer complications and deaths, than thoracotomy, said Dr. Brandt and her coauthors. But that cost advantage has not yet carried over to robotic-assisted VATS. That said, “robotic-assisted VATS remains a relatively new technology, and with time and increased robotic platform competition, costs will likely decrease.”

Dr. Brandt and her coauthors also noted that clinical trials support resection margins of 2 cm in patients having surgery for NSCLC and that adequate lymph node evaluation is a critical component of a lung cancer quality initiative. “Regardless of whether lymph nodes are sampled or dissected, we believe that systematic acquisition of mediastinal nodal tissue based on nodal station(s) is a useful quality metric, and, therefore, we recommend each program adopt a preferred approach and track adherence,” they said.

As for postoperative quality metrics, the most obvious are morbidity and mortality. “A quality program should track 30-day or in-hospital mortality, as well as 90-day mortality, following lung cancer resection.” Such metrics can serve as “starting points” for quality improvement initiatives. Length of stay has also emerged as an important metric because it is a surrogate of other metrics, such as patient comorbidities, age, and socioeconomic status. “Length-of-stay metrics likely need to be risk-stratified on the basis of these and other variables to be meaningful to a practicing surgeon,” Dr. Brandt and her coauthors said, adding that: “Studying the effectiveness of enhanced recovery after surgery programs in thoracic surgical oncology poses an opportunity for a well-designed trial.”

Two other key quality metrics for lung cancer programs that need further development were pointed out in the paper: hospital readmissions and tracking of adjuvant therapies. “Programmatic oncologic quality metrics to track appropriate and inappropriate referrals for adjuvant therapy and the number of patients who complete such therapy are important,” they said.

Another step programs should take: Participating in a national or regional database, as recommended by the Society of Thoracic Surgeons, and taking advantage of the “clear benefits to benchmarking your program to others.”

Dr. Brandt and her coauthors reported having no financial disclosures. The National Institutes of Health/National Cancer Center provided grant support.
 

What may be the largest study comparing unilateral and bilateral antegrade cerebral perfusion during total arch replacement for type A aortic dissection has reported that outcomes between the two approaches are comparable, although the bilateral approach showed some advantages during the operation itself, investigators from China reported in the Journal of Thoracic and Cardiovascular Surgery (2017;154:767-75).

The effectiveness of bilateral antegrade cerebral perfusion (b-ACP) vs. unilateral antegrade cerebral perfusion (u-ACP) has been the focus of extensive debate, lead study author Guang Tong, MD, of the Guangzhou (China) General Hospital, and coauthors said. They compared outcomes in six different metrics, ranging from cardiopulmonary bypass time to length of stay (LOS) in the ICU and hospital, in 203 patients with type A aortic dissection who had total aortic arch replacement with hypothermic circulatory arrest over an 8-year period ending in August 2014; 121 had b-ACP and 82 had u-ACP. “The issue of u-ACP vs. b-ACP has been examined in aortic arch surgery, but few reports have focused on type A aortic dissection,” Dr. Tong and coauthors wrote.

They acknowledged that some surgeons are reluctant to use b-ACP because of its complexity, but their study found no increase in cross-clamp time, cardiopulmonary bypass time, or surgery time in the b-ACP group. They cited another reason surgeons give for avoiding b-ACP: the risk of embolic injury caused by canulating the left common carotid artery in an atheromatous aorta. “In the present study, this risk was avoided by attaching the left common carotid artery to the four-branched prosthetic graft for left hemisphere perfusion,” Dr. Tong and coauthors wrote.

Key outcomes that the researchers found not statistically significant were:

• Overall 30-day mortality (11.6% for b-ACP vs. 20.7% for u-ACP; P = .075).
• Prevalence of postoperative permanent neurologic dysfunction (8.4% vs. 16.9%; P = .091).
• Average ICU LOS (16 ± 17.75 days vs. 17 ± 11.5 days, P =.454).
• Average hospital LOS (26.5 ± 20.6 days vs. 24.8 ± 10.3 days, P = .434).

However, average ventilation time was lower in the b-ACP group (95.5 hours vs. 147 hours; P less than or equal to.001).

Dr. Tong and coauthors used an aggressive approach, as advocated by Dhaval Trivedi, MD, and colleagues (Ann Thorac Surg. 2016;101:896-903), and had a total arch replacement rate of 57.8%. This rate is higher than most published series in the west but comparable to other studies from China, perhaps because of the relatively young age of this study cohort – an average age of 51 years – compared to data sets other studies have used. Dr. Tong and coauthors used a b-ACP strategy that established both cerebral perfusion routes before circulatory arrest.

Rates of the following complications were also not significantly different across the study population: paraplegia (2.8% for b-ACP vs. 3.1% for u-ACP), temporary neurologic dysfunction (4.7% vs. 9.2%), permanent neurologic dysfunction (8.4% vs. 16.9%), renal failure (18% vs. 23.1%), reoperation for bleeding (2.8% vs. 4.6%), and mediastinal infection (3.7% vs. 6.2%).

While b-ACP patients did not have a statistically significant lower incidence of TND, Dr. Tong and coauthors noted the shorter time on ventilation and significantly lower tracheostomy rates for the b-ACP patients, 3.7% vs. 16.9% for the u-ACP group (P = .003). “In our institute, protocols to wean patients from ventilation were normally initiated as soon as consciousness was regained,” Dr. Tong and coauthors wrote.

Among the study limits Dr. Tong and coauthors acknowledged were its retrospective, nonrandomized, single-center nature, and the fact that the surgeries were performed over an 8-year period representing different eras.

The investigators reported having no relevant financial disclosures.

What may be the largest study comparing unilateral and bilateral antegrade cerebral perfusion during total arch replacement for type A aortic dissection has reported that outcomes between the two approaches are comparable, although the bilateral approach showed some advantages during the operation itself, investigators from China reported in the Journal of Thoracic and Cardiovascular Surgery (2017;154:767-75).

The effectiveness of bilateral antegrade cerebral perfusion (b-ACP) vs. unilateral antegrade cerebral perfusion (u-ACP) has been the focus of extensive debate, lead study author Guang Tong, MD, of the Guangzhou (China) General Hospital, and coauthors said. They compared outcomes in six different metrics, ranging from cardiopulmonary bypass time to length of stay (LOS) in the ICU and hospital, in 203 patients with type A aortic dissection who had total aortic arch replacement with hypothermic circulatory arrest over an 8-year period ending in August 2014; 121 had b-ACP and 82 had u-ACP. “The issue of u-ACP vs. b-ACP has been examined in aortic arch surgery, but few reports have focused on type A aortic dissection,” Dr. Tong and coauthors wrote.

They acknowledged that some surgeons are reluctant to use b-ACP because of its complexity, but their study found no increase in cross-clamp time, cardiopulmonary bypass time, or surgery time in the b-ACP group. They cited another reason surgeons give for avoiding b-ACP: the risk of embolic injury caused by canulating the left common carotid artery in an atheromatous aorta. “In the present study, this risk was avoided by attaching the left common carotid artery to the four-branched prosthetic graft for left hemisphere perfusion,” Dr. Tong and coauthors wrote.

Key outcomes that the researchers found not statistically significant were:

• Overall 30-day mortality (11.6% for b-ACP vs. 20.7% for u-ACP; P = .075).
• Prevalence of postoperative permanent neurologic dysfunction (8.4% vs. 16.9%; P = .091).
• Average ICU LOS (16 ± 17.75 days vs. 17 ± 11.5 days, P =.454).
• Average hospital LOS (26.5 ± 20.6 days vs. 24.8 ± 10.3 days, P = .434).

However, average ventilation time was lower in the b-ACP group (95.5 hours vs. 147 hours; P less than or equal to.001).

Dr. Tong and coauthors used an aggressive approach, as advocated by Dhaval Trivedi, MD, and colleagues (Ann Thorac Surg. 2016;101:896-903), and had a total arch replacement rate of 57.8%. This rate is higher than most published series in the west but comparable to other studies from China, perhaps because of the relatively young age of this study cohort – an average age of 51 years – compared to data sets other studies have used. Dr. Tong and coauthors used a b-ACP strategy that established both cerebral perfusion routes before circulatory arrest.

Rates of the following complications were also not significantly different across the study population: paraplegia (2.8% for b-ACP vs. 3.1% for u-ACP), temporary neurologic dysfunction (4.7% vs. 9.2%), permanent neurologic dysfunction (8.4% vs. 16.9%), renal failure (18% vs. 23.1%), reoperation for bleeding (2.8% vs. 4.6%), and mediastinal infection (3.7% vs. 6.2%).

While b-ACP patients did not have a statistically significant lower incidence of TND, Dr. Tong and coauthors noted the shorter time on ventilation and significantly lower tracheostomy rates for the b-ACP patients, 3.7% vs. 16.9% for the u-ACP group (P = .003). “In our institute, protocols to wean patients from ventilation were normally initiated as soon as consciousness was regained,” Dr. Tong and coauthors wrote.

Among the study limits Dr. Tong and coauthors acknowledged were its retrospective, nonrandomized, single-center nature, and the fact that the surgeries were performed over an 8-year period representing different eras.

The investigators reported having no relevant financial disclosures.

What may be the largest study comparing unilateral and bilateral antegrade cerebral perfusion during total arch replacement for type A aortic dissection has reported that outcomes between the two approaches are comparable, although the bilateral approach showed some advantages during the operation itself, investigators from China reported in the Journal of Thoracic and Cardiovascular Surgery (2017;154:767-75).

The effectiveness of bilateral antegrade cerebral perfusion (b-ACP) vs. unilateral antegrade cerebral perfusion (u-ACP) has been the focus of extensive debate, lead study author Guang Tong, MD, of the Guangzhou (China) General Hospital, and coauthors said. They compared outcomes in six different metrics, ranging from cardiopulmonary bypass time to length of stay (LOS) in the ICU and hospital, in 203 patients with type A aortic dissection who had total aortic arch replacement with hypothermic circulatory arrest over an 8-year period ending in August 2014; 121 had b-ACP and 82 had u-ACP. “The issue of u-ACP vs. b-ACP has been examined in aortic arch surgery, but few reports have focused on type A aortic dissection,” Dr. Tong and coauthors wrote.

They acknowledged that some surgeons are reluctant to use b-ACP because of its complexity, but their study found no increase in cross-clamp time, cardiopulmonary bypass time, or surgery time in the b-ACP group. They cited another reason surgeons give for avoiding b-ACP: the risk of embolic injury caused by canulating the left common carotid artery in an atheromatous aorta. “In the present study, this risk was avoided by attaching the left common carotid artery to the four-branched prosthetic graft for left hemisphere perfusion,” Dr. Tong and coauthors wrote.

Key outcomes that the researchers found not statistically significant were:

• Overall 30-day mortality (11.6% for b-ACP vs. 20.7% for u-ACP; P = .075).
• Prevalence of postoperative permanent neurologic dysfunction (8.4% vs. 16.9%; P = .091).
• Average ICU LOS (16 ± 17.75 days vs. 17 ± 11.5 days, P =.454).
• Average hospital LOS (26.5 ± 20.6 days vs. 24.8 ± 10.3 days, P = .434).

However, average ventilation time was lower in the b-ACP group (95.5 hours vs. 147 hours; P less than or equal to.001).

Dr. Tong and coauthors used an aggressive approach, as advocated by Dhaval Trivedi, MD, and colleagues (Ann Thorac Surg. 2016;101:896-903), and had a total arch replacement rate of 57.8%. This rate is higher than most published series in the west but comparable to other studies from China, perhaps because of the relatively young age of this study cohort – an average age of 51 years – compared to data sets other studies have used. Dr. Tong and coauthors used a b-ACP strategy that established both cerebral perfusion routes before circulatory arrest.

Rates of the following complications were also not significantly different across the study population: paraplegia (2.8% for b-ACP vs. 3.1% for u-ACP), temporary neurologic dysfunction (4.7% vs. 9.2%), permanent neurologic dysfunction (8.4% vs. 16.9%), renal failure (18% vs. 23.1%), reoperation for bleeding (2.8% vs. 4.6%), and mediastinal infection (3.7% vs. 6.2%).

While b-ACP patients did not have a statistically significant lower incidence of TND, Dr. Tong and coauthors noted the shorter time on ventilation and significantly lower tracheostomy rates for the b-ACP patients, 3.7% vs. 16.9% for the u-ACP group (P = .003). “In our institute, protocols to wean patients from ventilation were normally initiated as soon as consciousness was regained,” Dr. Tong and coauthors wrote.

Among the study limits Dr. Tong and coauthors acknowledged were its retrospective, nonrandomized, single-center nature, and the fact that the surgeries were performed over an 8-year period representing different eras.

The investigators reported having no relevant financial disclosures.

WASHINGTON – Nonalcoholic fatty liver disease (NAFLD) is a complex disease that involves multiple systems, and several standout abstracts at the annual meeting of the American Association for the Study of Liver Diseases emphasized the importance of multisystem management and the potential of combination therapies, Kymberly D. Watt, MD, said during the final debrief.

“The actual underlying mechanisms and the underlying processes that are going on are way more complicated than just inflammation and scarring,” said Dr. Watt, associate professor of medicine and medical director of liver transplantation at the Mayo Clinic, Rochester, Minn. “We have numerous areas to target, including insulin resistance, lipid metabolism, oxidative stress, inflammation, immune modulation, cell death, etc.”

She noted several studies that evaluated the prevalence of NAFLD, including a study that found that “about one-third of patients walking through the door of the clinic had nonalcoholic steatohepatitis [NASH],” suggesting physicians should consider screening at-risk patients (abstract 58). A Korean study found about 18% of asymptomatic lean individuals (body mass index less than 23 kg/m²) had NAFLD and identified sarcopenia as a significant risk factor for NAFLD in these lean patients (abstract 59). “Sarcopenia is something that we really need to pay a lot more attention to,” Dr. Watt said.

Other studies better outlined the increasing association between NAFLD and hepatocellular carcinoma, Dr. Watt noted (abstracts 2119 and 2102). Another study confirmed that men with NAFLD/NASH have almost twice the incidence of hepatocellular carcinoma (HCC) as women — 0.43%-0.5% vs. 0.22%-0.28%, with both groups significantly higher than the general population (abstract 2116). “And looking further, we can actually quote an HCC incidence in NASH of 0.009%,” she added.

Again emphasizing the multisystem impact of NAFLD, Dr. Watt cited a study that calculated the cardiovascular risks incumbent with liver disease. Researchers reported that men and women at the time of NAFLD diagnosis had significantly higher rates of either angina/ischemic heart disease or heart failure (abstract 55). Women, specifically, had a higher risk for cardiovascular events earlier than men and overall are at equal risk to men, unlike in the general population where women are at lower risk. “We need to start looking at screening and prevention of other diseases in our patients with NASH,” Dr. Watt said. “In addition, we need to be more aware of the elevated risk in these patients and not just approach them in the same way as the general population.”

Physicians may be tempted to discontinue statin therapy in patients with chronic liver disease, but Dr. Watt cited a poster that showed that this results in worse outcomes (abstract 2106). The researchers found that continued statin use was associated with a lower risk of death with compensated and decompensated liver function. “These data help to educate certain patients of their risk of decompensation over time,” Dr. Watt said.

An international study determined that the severity of advanced compensated liver disease is a key determinant in outcomes, finding that those with bridging fibrosis are at greater risk of vascular events, but those with cirrhosis and Child-Turcotte-Pugh A5 and A6 disease have much higher risks of hepatic decompensation and HCC out to 14 years (abstract 60). “The reason to look at these is to be able to tell your patients that they probably have a 30% increased risk of decompensation by 4 years,” Dr. Watt said.

Dr. Watt pointed out three studies that shed more light on important biomarkers of NAFLD. One study reported that three biomarkers – alpha-2-macroglobulin, hyaluronic acid, and tissue inhibitor of metalloproteinase-1 – have a high sensitivity for differentiating low-stage and stage F3-F4 disease (abstract 95). Another study found that a measure using Pro-C3 and other clinical markers were predictive of F3 or F4 fibrosis in NAFLD (abstract 93). And, other researchers found that a HepQuant-STAT measure of greater than 0.50 microM in patients who ingested deuterated cholic acid (d4-CA) solution may be a minimally invasive alternative to biopsy for diagnosing NASH (abstract 96).

Management studies focusing on varying targets were also presented. A trial of fibroblast growth factor–21 for treatment of NAFLD found that patients in the 10- and 20-mg dose arms showed improvement in MRI hepatic fat fraction, ALT, AST, and liver stiffness at 16 weeks vs. placebo. A few patients had some mild elevation to their liver enzymes on treatment (abstract 182). “So I think we need to remain cautious and watch these patients closely, but overall it seems to be reasonably safe data,” she said. Another drug trial of the acetyl-CoA carboxylase inhibitor GS-0976 also showed promise for overall improvement in MRI steatosis measures (abstract LB-9).

Three preclinical studies of dual-agent therapies in animals have demonstrated improvement in inflammatory and fibrosis scores, Dr. Watt noted (abstracts 2,000, 2,002 and 2,052). “There’s no one drug that’s going to be likely the magic cure,” Dr. Watt said. “There will likely be a lot more focus and data coming out on dual-action agents.” Another animal study addressed the burning question if decaffeinated coffee has the same protective effect against NASH as caffeinated coffee (abstract 2093). Said Dr. Watt: “If you are interested in the potential benefits of coffee but really can’t handle the caffeine, this study suggests, you may still be OK.”

Finally, Dr. Watt noted an early study of three-dimensional printing has shown potential for replicating NASH tissue for bench studies (abstract 1963). “3-D printing is certainly a wave of the future,” she said, pointing out that researchers have created a 3-D model that has some metabolic equivalency to NASH, with the inflammatory cytokine release, hepatic stellate cell activation, “and all of the features that we see in NASH. This may be of potential use down the road to avoid relying on animal models in preclinical studies.”

The Liver Meeting next convenes Nov. 9-13, 2018, in San Francisco.

Dr. Watt disclosed ties to Bristol-Myers Squibb, Exelixis, and Seattle Genetics.

WASHINGTON – Nonalcoholic fatty liver disease (NAFLD) is a complex disease that involves multiple systems, and several standout abstracts at the annual meeting of the American Association for the Study of Liver Diseases emphasized the importance of multisystem management and the potential of combination therapies, Kymberly D. Watt, MD, said during the final debrief.

“The actual underlying mechanisms and the underlying processes that are going on are way more complicated than just inflammation and scarring,” said Dr. Watt, associate professor of medicine and medical director of liver transplantation at the Mayo Clinic, Rochester, Minn. “We have numerous areas to target, including insulin resistance, lipid metabolism, oxidative stress, inflammation, immune modulation, cell death, etc.”

She noted several studies that evaluated the prevalence of NAFLD, including a study that found that “about one-third of patients walking through the door of the clinic had nonalcoholic steatohepatitis [NASH],” suggesting physicians should consider screening at-risk patients (abstract 58). A Korean study found about 18% of asymptomatic lean individuals (body mass index less than 23 kg/m²) had NAFLD and identified sarcopenia as a significant risk factor for NAFLD in these lean patients (abstract 59). “Sarcopenia is something that we really need to pay a lot more attention to,” Dr. Watt said.

Other studies better outlined the increasing association between NAFLD and hepatocellular carcinoma, Dr. Watt noted (abstracts 2119 and 2102). Another study confirmed that men with NAFLD/NASH have almost twice the incidence of hepatocellular carcinoma (HCC) as women — 0.43%-0.5% vs. 0.22%-0.28%, with both groups significantly higher than the general population (abstract 2116). “And looking further, we can actually quote an HCC incidence in NASH of 0.009%,” she added.

Again emphasizing the multisystem impact of NAFLD, Dr. Watt cited a study that calculated the cardiovascular risks incumbent with liver disease. Researchers reported that men and women at the time of NAFLD diagnosis had significantly higher rates of either angina/ischemic heart disease or heart failure (abstract 55). Women, specifically, had a higher risk for cardiovascular events earlier than men and overall are at equal risk to men, unlike in the general population where women are at lower risk. “We need to start looking at screening and prevention of other diseases in our patients with NASH,” Dr. Watt said. “In addition, we need to be more aware of the elevated risk in these patients and not just approach them in the same way as the general population.”

Physicians may be tempted to discontinue statin therapy in patients with chronic liver disease, but Dr. Watt cited a poster that showed that this results in worse outcomes (abstract 2106). The researchers found that continued statin use was associated with a lower risk of death with compensated and decompensated liver function. “These data help to educate certain patients of their risk of decompensation over time,” Dr. Watt said.

An international study determined that the severity of advanced compensated liver disease is a key determinant in outcomes, finding that those with bridging fibrosis are at greater risk of vascular events, but those with cirrhosis and Child-Turcotte-Pugh A5 and A6 disease have much higher risks of hepatic decompensation and HCC out to 14 years (abstract 60). “The reason to look at these is to be able to tell your patients that they probably have a 30% increased risk of decompensation by 4 years,” Dr. Watt said.

Dr. Watt pointed out three studies that shed more light on important biomarkers of NAFLD. One study reported that three biomarkers – alpha-2-macroglobulin, hyaluronic acid, and tissue inhibitor of metalloproteinase-1 – have a high sensitivity for differentiating low-stage and stage F3-F4 disease (abstract 95). Another study found that a measure using Pro-C3 and other clinical markers were predictive of F3 or F4 fibrosis in NAFLD (abstract 93). And, other researchers found that a HepQuant-STAT measure of greater than 0.50 microM in patients who ingested deuterated cholic acid (d4-CA) solution may be a minimally invasive alternative to biopsy for diagnosing NASH (abstract 96).

Management studies focusing on varying targets were also presented. A trial of fibroblast growth factor–21 for treatment of NAFLD found that patients in the 10- and 20-mg dose arms showed improvement in MRI hepatic fat fraction, ALT, AST, and liver stiffness at 16 weeks vs. placebo. A few patients had some mild elevation to their liver enzymes on treatment (abstract 182). “So I think we need to remain cautious and watch these patients closely, but overall it seems to be reasonably safe data,” she said. Another drug trial of the acetyl-CoA carboxylase inhibitor GS-0976 also showed promise for overall improvement in MRI steatosis measures (abstract LB-9).

Three preclinical studies of dual-agent therapies in animals have demonstrated improvement in inflammatory and fibrosis scores, Dr. Watt noted (abstracts 2,000, 2,002 and 2,052). “There’s no one drug that’s going to be likely the magic cure,” Dr. Watt said. “There will likely be a lot more focus and data coming out on dual-action agents.” Another animal study addressed the burning question if decaffeinated coffee has the same protective effect against NASH as caffeinated coffee (abstract 2093). Said Dr. Watt: “If you are interested in the potential benefits of coffee but really can’t handle the caffeine, this study suggests, you may still be OK.”

Finally, Dr. Watt noted an early study of three-dimensional printing has shown potential for replicating NASH tissue for bench studies (abstract 1963). “3-D printing is certainly a wave of the future,” she said, pointing out that researchers have created a 3-D model that has some metabolic equivalency to NASH, with the inflammatory cytokine release, hepatic stellate cell activation, “and all of the features that we see in NASH. This may be of potential use down the road to avoid relying on animal models in preclinical studies.”

The Liver Meeting next convenes Nov. 9-13, 2018, in San Francisco.

Dr. Watt disclosed ties to Bristol-Myers Squibb, Exelixis, and Seattle Genetics.

WASHINGTON – Nonalcoholic fatty liver disease (NAFLD) is a complex disease that involves multiple systems, and several standout abstracts at the annual meeting of the American Association for the Study of Liver Diseases emphasized the importance of multisystem management and the potential of combination therapies, Kymberly D. Watt, MD, said during the final debrief.

“The actual underlying mechanisms and the underlying processes that are going on are way more complicated than just inflammation and scarring,” said Dr. Watt, associate professor of medicine and medical director of liver transplantation at the Mayo Clinic, Rochester, Minn. “We have numerous areas to target, including insulin resistance, lipid metabolism, oxidative stress, inflammation, immune modulation, cell death, etc.”

She noted several studies that evaluated the prevalence of NAFLD, including a study that found that “about one-third of patients walking through the door of the clinic had nonalcoholic steatohepatitis [NASH],” suggesting physicians should consider screening at-risk patients (abstract 58). A Korean study found about 18% of asymptomatic lean individuals (body mass index less than 23 kg/m²) had NAFLD and identified sarcopenia as a significant risk factor for NAFLD in these lean patients (abstract 59). “Sarcopenia is something that we really need to pay a lot more attention to,” Dr. Watt said.

Other studies better outlined the increasing association between NAFLD and hepatocellular carcinoma, Dr. Watt noted (abstracts 2119 and 2102). Another study confirmed that men with NAFLD/NASH have almost twice the incidence of hepatocellular carcinoma (HCC) as women — 0.43%-0.5% vs. 0.22%-0.28%, with both groups significantly higher than the general population (abstract 2116). “And looking further, we can actually quote an HCC incidence in NASH of 0.009%,” she added.

Again emphasizing the multisystem impact of NAFLD, Dr. Watt cited a study that calculated the cardiovascular risks incumbent with liver disease. Researchers reported that men and women at the time of NAFLD diagnosis had significantly higher rates of either angina/ischemic heart disease or heart failure (abstract 55). Women, specifically, had a higher risk for cardiovascular events earlier than men and overall are at equal risk to men, unlike in the general population where women are at lower risk. “We need to start looking at screening and prevention of other diseases in our patients with NASH,” Dr. Watt said. “In addition, we need to be more aware of the elevated risk in these patients and not just approach them in the same way as the general population.”

Physicians may be tempted to discontinue statin therapy in patients with chronic liver disease, but Dr. Watt cited a poster that showed that this results in worse outcomes (abstract 2106). The researchers found that continued statin use was associated with a lower risk of death with compensated and decompensated liver function. “These data help to educate certain patients of their risk of decompensation over time,” Dr. Watt said.

An international study determined that the severity of advanced compensated liver disease is a key determinant in outcomes, finding that those with bridging fibrosis are at greater risk of vascular events, but those with cirrhosis and Child-Turcotte-Pugh A5 and A6 disease have much higher risks of hepatic decompensation and HCC out to 14 years (abstract 60). “The reason to look at these is to be able to tell your patients that they probably have a 30% increased risk of decompensation by 4 years,” Dr. Watt said.

Dr. Watt pointed out three studies that shed more light on important biomarkers of NAFLD. One study reported that three biomarkers – alpha-2-macroglobulin, hyaluronic acid, and tissue inhibitor of metalloproteinase-1 – have a high sensitivity for differentiating low-stage and stage F3-F4 disease (abstract 95). Another study found that a measure using Pro-C3 and other clinical markers were predictive of F3 or F4 fibrosis in NAFLD (abstract 93). And, other researchers found that a HepQuant-STAT measure of greater than 0.50 microM in patients who ingested deuterated cholic acid (d4-CA) solution may be a minimally invasive alternative to biopsy for diagnosing NASH (abstract 96).

Management studies focusing on varying targets were also presented. A trial of fibroblast growth factor–21 for treatment of NAFLD found that patients in the 10- and 20-mg dose arms showed improvement in MRI hepatic fat fraction, ALT, AST, and liver stiffness at 16 weeks vs. placebo. A few patients had some mild elevation to their liver enzymes on treatment (abstract 182). “So I think we need to remain cautious and watch these patients closely, but overall it seems to be reasonably safe data,” she said. Another drug trial of the acetyl-CoA carboxylase inhibitor GS-0976 also showed promise for overall improvement in MRI steatosis measures (abstract LB-9).

Three preclinical studies of dual-agent therapies in animals have demonstrated improvement in inflammatory and fibrosis scores, Dr. Watt noted (abstracts 2,000, 2,002 and 2,052). “There’s no one drug that’s going to be likely the magic cure,” Dr. Watt said. “There will likely be a lot more focus and data coming out on dual-action agents.” Another animal study addressed the burning question if decaffeinated coffee has the same protective effect against NASH as caffeinated coffee (abstract 2093). Said Dr. Watt: “If you are interested in the potential benefits of coffee but really can’t handle the caffeine, this study suggests, you may still be OK.”

Finally, Dr. Watt noted an early study of three-dimensional printing has shown potential for replicating NASH tissue for bench studies (abstract 1963). “3-D printing is certainly a wave of the future,” she said, pointing out that researchers have created a 3-D model that has some metabolic equivalency to NASH, with the inflammatory cytokine release, hepatic stellate cell activation, “and all of the features that we see in NASH. This may be of potential use down the road to avoid relying on animal models in preclinical studies.”

The Liver Meeting next convenes Nov. 9-13, 2018, in San Francisco.

Dr. Watt disclosed ties to Bristol-Myers Squibb, Exelixis, and Seattle Genetics.

CONCORD, N.C. – Approved treatments for sickle cell disease have been extremely limited, but there are several therapies in the research pipeline that use new pathways to target the disease.

“We do have much better understanding of the pathophysiology, which is getting us a few more targets to aim at,” Julie Kanter, MD, director of sickle cell research at the Medical University of South Carolina, Charleston, said at Sickle Cell Disease Symposium held by Carolinas Health Care System. These targets include influencing how cells interact with the vascular endothelium, inhibiting platelets, and preventing cell sickling and inflammation.

SCD pipeline

Deeper in the sickle cell pipeline is a class of antisickling agents known as hemoglobin modifiers. “We’re tying to change the way hemoglobin binds to oxygen, and if we can keep hemoglobin binding to oxygen longer, it actually decreases the risk of hemoglobin sickling and polymerizing in the cell,” Dr. Kanter explained.

One hemoglobin modifier is voxelotor (previously called GBT440), a once-daily oral agent that Global Blood Therapeutics has in development.

Another category of antisickling agents that researchers are looking at is anti-inflammatory moderators, Dr. Kanter said. These include nitric oxide donors like sildenafil, which did not “quite work” in SCD, and arginine and glutamine, which increase the amount of nitric oxide once in the body “and hopefully reduce the risk of sickling,” she said. “If we can improve inflammation, we might be able to improve the risk of crisis.”

Cell adhesion modifiers are a drug class that aims to prevent cells from binding to each other. These include platelet inhibitors and endothelial blockers. “There are several antiplatelet agents that are approved really for stroke prevention or heart attack prevention, and we’re trying to see if we can repurpose these in sickle cell disease in a specific pathway that allows the platelet to stick to the endothelium, but if we only inhibit one pathway it should not increase the risk of bleeding,” Dr. Kanter said.

One platelet inhibition pathway that researchers are focused on is the P2Y₁₂ adenosine diphosphate blockade, which the platelet inhibitor prasugrel (Effient) acts on. A 2016 study of this pathway in SCD “wasn’t successful,” Dr. Kanter said, “but it had some interesting results” – namely that the drug may be most effective in adolescents (N Engl J Med. 2016 Feb 18;374[7]:625-35).

Selectin-blocking medications are a drug class that act on white blood cell adhesion to, and movement through, the endothelium, Dr. Kanter said. “Neutrophils can instigate a sickle cell crisis, so if we can interrupt some of this rolling or sticking, could we decrease the risk of a sickle cell crisis?” The drug GMI-1070 is currently being studied in a phase III trial and so far has shown “a significant decrease in the amount of opioids used by those individuals who received the study drug,” she said.

Crizanlizumab (also known as SelG1) is a humanized monoclonal antibody with an affinity to P-selectin and is the subject of the phase II SUSTAIN trial, which included a cohort that also was taking hydroxyurea. Treatment with high-dose crizanlizumab resulted in an annual rate of sickle cell–related pain crises that was more than 45% lower than with placebo (N Engl J Med. 2017 Feb 2;376[5]:429-39).
 

Stem cell transplants

Besides drugs, stem cell transplants to treat SCD have advanced in recent years to the point where cure rates are exceeding 90%, Dr. Kanter noted. “However, the real issue with stem cells is that patients still don’t have enough donors,” she said.

SCD is also potentially amenable to gene therapy, Dr. Kanter said, noting that SCD gene therapy trials in progress are looking at harvesting patients’ own bone marrow, using the lentivirus viral vector, inserting a gene to increase production of nonsickle hemoglobin, and using myeloablative chemotherapy to remove old marrow and replace it with new, manipulated bone marrow.

Several programs are investigating using a gene editing technique, known as CRISPR/Cas9, to alter the BCL11A gene to maintain fetal hemoglobin production.

“We all make fetal hemoglobin at birth, and then over 6 months to 1 year of life, our bodies convert fetal hemoglobin to adult hemoglobin,” she said. “In sickle cell disease, it converts to sickle hemoglobin. What if we could prevent that conversion and keep the fetal hemoglobin turned on?” That could potentially eradicate the complications of SCD starting at an early age, Dr. Kanter said.

Dr. Kanter, who has been involved in several of the SCD trials, reported relationships with Pfizer, AstraZeneca, Bluebird Bio, Global Blood Therapeutics, Novartis, Guidepoint, GLG, ApoPharma, and Purdue Pharma.

CONCORD, N.C. – Approved treatments for sickle cell disease have been extremely limited, but there are several therapies in the research pipeline that use new pathways to target the disease.

“We do have much better understanding of the pathophysiology, which is getting us a few more targets to aim at,” Julie Kanter, MD, director of sickle cell research at the Medical University of South Carolina, Charleston, said at Sickle Cell Disease Symposium held by Carolinas Health Care System. These targets include influencing how cells interact with the vascular endothelium, inhibiting platelets, and preventing cell sickling and inflammation.

SCD pipeline

Deeper in the sickle cell pipeline is a class of antisickling agents known as hemoglobin modifiers. “We’re tying to change the way hemoglobin binds to oxygen, and if we can keep hemoglobin binding to oxygen longer, it actually decreases the risk of hemoglobin sickling and polymerizing in the cell,” Dr. Kanter explained.

One hemoglobin modifier is voxelotor (previously called GBT440), a once-daily oral agent that Global Blood Therapeutics has in development.

Another category of antisickling agents that researchers are looking at is anti-inflammatory moderators, Dr. Kanter said. These include nitric oxide donors like sildenafil, which did not “quite work” in SCD, and arginine and glutamine, which increase the amount of nitric oxide once in the body “and hopefully reduce the risk of sickling,” she said. “If we can improve inflammation, we might be able to improve the risk of crisis.”

Cell adhesion modifiers are a drug class that aims to prevent cells from binding to each other. These include platelet inhibitors and endothelial blockers. “There are several antiplatelet agents that are approved really for stroke prevention or heart attack prevention, and we’re trying to see if we can repurpose these in sickle cell disease in a specific pathway that allows the platelet to stick to the endothelium, but if we only inhibit one pathway it should not increase the risk of bleeding,” Dr. Kanter said.

One platelet inhibition pathway that researchers are focused on is the P2Y₁₂ adenosine diphosphate blockade, which the platelet inhibitor prasugrel (Effient) acts on. A 2016 study of this pathway in SCD “wasn’t successful,” Dr. Kanter said, “but it had some interesting results” – namely that the drug may be most effective in adolescents (N Engl J Med. 2016 Feb 18;374[7]:625-35).

Selectin-blocking medications are a drug class that act on white blood cell adhesion to, and movement through, the endothelium, Dr. Kanter said. “Neutrophils can instigate a sickle cell crisis, so if we can interrupt some of this rolling or sticking, could we decrease the risk of a sickle cell crisis?” The drug GMI-1070 is currently being studied in a phase III trial and so far has shown “a significant decrease in the amount of opioids used by those individuals who received the study drug,” she said.

Crizanlizumab (also known as SelG1) is a humanized monoclonal antibody with an affinity to P-selectin and is the subject of the phase II SUSTAIN trial, which included a cohort that also was taking hydroxyurea. Treatment with high-dose crizanlizumab resulted in an annual rate of sickle cell–related pain crises that was more than 45% lower than with placebo (N Engl J Med. 2017 Feb 2;376[5]:429-39).
 

Stem cell transplants

Besides drugs, stem cell transplants to treat SCD have advanced in recent years to the point where cure rates are exceeding 90%, Dr. Kanter noted. “However, the real issue with stem cells is that patients still don’t have enough donors,” she said.

SCD is also potentially amenable to gene therapy, Dr. Kanter said, noting that SCD gene therapy trials in progress are looking at harvesting patients’ own bone marrow, using the lentivirus viral vector, inserting a gene to increase production of nonsickle hemoglobin, and using myeloablative chemotherapy to remove old marrow and replace it with new, manipulated bone marrow.

Several programs are investigating using a gene editing technique, known as CRISPR/Cas9, to alter the BCL11A gene to maintain fetal hemoglobin production.

“We all make fetal hemoglobin at birth, and then over 6 months to 1 year of life, our bodies convert fetal hemoglobin to adult hemoglobin,” she said. “In sickle cell disease, it converts to sickle hemoglobin. What if we could prevent that conversion and keep the fetal hemoglobin turned on?” That could potentially eradicate the complications of SCD starting at an early age, Dr. Kanter said.

Dr. Kanter, who has been involved in several of the SCD trials, reported relationships with Pfizer, AstraZeneca, Bluebird Bio, Global Blood Therapeutics, Novartis, Guidepoint, GLG, ApoPharma, and Purdue Pharma.

CONCORD, N.C. – Approved treatments for sickle cell disease have been extremely limited, but there are several therapies in the research pipeline that use new pathways to target the disease.

“We do have much better understanding of the pathophysiology, which is getting us a few more targets to aim at,” Julie Kanter, MD, director of sickle cell research at the Medical University of South Carolina, Charleston, said at Sickle Cell Disease Symposium held by Carolinas Health Care System. These targets include influencing how cells interact with the vascular endothelium, inhibiting platelets, and preventing cell sickling and inflammation.

SCD pipeline

Deeper in the sickle cell pipeline is a class of antisickling agents known as hemoglobin modifiers. “We’re tying to change the way hemoglobin binds to oxygen, and if we can keep hemoglobin binding to oxygen longer, it actually decreases the risk of hemoglobin sickling and polymerizing in the cell,” Dr. Kanter explained.

One hemoglobin modifier is voxelotor (previously called GBT440), a once-daily oral agent that Global Blood Therapeutics has in development.

Another category of antisickling agents that researchers are looking at is anti-inflammatory moderators, Dr. Kanter said. These include nitric oxide donors like sildenafil, which did not “quite work” in SCD, and arginine and glutamine, which increase the amount of nitric oxide once in the body “and hopefully reduce the risk of sickling,” she said. “If we can improve inflammation, we might be able to improve the risk of crisis.”

Cell adhesion modifiers are a drug class that aims to prevent cells from binding to each other. These include platelet inhibitors and endothelial blockers. “There are several antiplatelet agents that are approved really for stroke prevention or heart attack prevention, and we’re trying to see if we can repurpose these in sickle cell disease in a specific pathway that allows the platelet to stick to the endothelium, but if we only inhibit one pathway it should not increase the risk of bleeding,” Dr. Kanter said.

One platelet inhibition pathway that researchers are focused on is the P2Y₁₂ adenosine diphosphate blockade, which the platelet inhibitor prasugrel (Effient) acts on. A 2016 study of this pathway in SCD “wasn’t successful,” Dr. Kanter said, “but it had some interesting results” – namely that the drug may be most effective in adolescents (N Engl J Med. 2016 Feb 18;374[7]:625-35).

Selectin-blocking medications are a drug class that act on white blood cell adhesion to, and movement through, the endothelium, Dr. Kanter said. “Neutrophils can instigate a sickle cell crisis, so if we can interrupt some of this rolling or sticking, could we decrease the risk of a sickle cell crisis?” The drug GMI-1070 is currently being studied in a phase III trial and so far has shown “a significant decrease in the amount of opioids used by those individuals who received the study drug,” she said.

Crizanlizumab (also known as SelG1) is a humanized monoclonal antibody with an affinity to P-selectin and is the subject of the phase II SUSTAIN trial, which included a cohort that also was taking hydroxyurea. Treatment with high-dose crizanlizumab resulted in an annual rate of sickle cell–related pain crises that was more than 45% lower than with placebo (N Engl J Med. 2017 Feb 2;376[5]:429-39).
 

Stem cell transplants

Besides drugs, stem cell transplants to treat SCD have advanced in recent years to the point where cure rates are exceeding 90%, Dr. Kanter noted. “However, the real issue with stem cells is that patients still don’t have enough donors,” she said.

SCD is also potentially amenable to gene therapy, Dr. Kanter said, noting that SCD gene therapy trials in progress are looking at harvesting patients’ own bone marrow, using the lentivirus viral vector, inserting a gene to increase production of nonsickle hemoglobin, and using myeloablative chemotherapy to remove old marrow and replace it with new, manipulated bone marrow.

Several programs are investigating using a gene editing technique, known as CRISPR/Cas9, to alter the BCL11A gene to maintain fetal hemoglobin production.

“We all make fetal hemoglobin at birth, and then over 6 months to 1 year of life, our bodies convert fetal hemoglobin to adult hemoglobin,” she said. “In sickle cell disease, it converts to sickle hemoglobin. What if we could prevent that conversion and keep the fetal hemoglobin turned on?” That could potentially eradicate the complications of SCD starting at an early age, Dr. Kanter said.

Dr. Kanter, who has been involved in several of the SCD trials, reported relationships with Pfizer, AstraZeneca, Bluebird Bio, Global Blood Therapeutics, Novartis, Guidepoint, GLG, ApoPharma, and Purdue Pharma.

CONCORD, N.C. – A care center for acute sickle cell pain management, which includes a dedicated emergency room and a daytime management unit in the hospital, decreased health system costs and the frequency of acute care visits by sickle cell patients, James Eckman, MD, reported at Sickle Cell Disease Symposium held by Carolinas Health Care System.

“In the first 5 years of the center, acute care visits dropped from 16 per patient per year to 10, and admissions per active patient per year dropped from 2.1 to less than one,” said Dr. Eckman, former medical director of the Georgia Comprehensive Sickle Cell Center at Grady Health System in Atlanta.

CONCORD, N.C. – A care center for acute sickle cell pain management, which includes a dedicated emergency room and a daytime management unit in the hospital, decreased health system costs and the frequency of acute care visits by sickle cell patients, James Eckman, MD, reported at Sickle Cell Disease Symposium held by Carolinas Health Care System.

“In the first 5 years of the center, acute care visits dropped from 16 per patient per year to 10, and admissions per active patient per year dropped from 2.1 to less than one,” said Dr. Eckman, former medical director of the Georgia Comprehensive Sickle Cell Center at Grady Health System in Atlanta.

CONCORD, N.C. – A care center for acute sickle cell pain management, which includes a dedicated emergency room and a daytime management unit in the hospital, decreased health system costs and the frequency of acute care visits by sickle cell patients, James Eckman, MD, reported at Sickle Cell Disease Symposium held by Carolinas Health Care System.

“In the first 5 years of the center, acute care visits dropped from 16 per patient per year to 10, and admissions per active patient per year dropped from 2.1 to less than one,” said Dr. Eckman, former medical director of the Georgia Comprehensive Sickle Cell Center at Grady Health System in Atlanta.

WASHINGTON – During and after liver transplant, the reaction of the intestinal microbiota may be a critical determinant of outcomes; preliminary data from a cohort study may provide some clarification of what modulates gut microbiota post transplantation and shed light on predictive factors.

Anna-Catrin Uhlemann, MD, PhD, of Columbia University Medical Center, New York, noted that several studies in recent years sought to clarify influences on gut microbiota in people receiving liver transplants, but “there are still a number of important gaps in knowledge, including what exactly is the longitudinal evolution of the host transplant microbiome and what is the predictive value of pre- and early posttransplant dysbiosis on outcomes and complications.”

WASHINGTON – During and after liver transplant, the reaction of the intestinal microbiota may be a critical determinant of outcomes; preliminary data from a cohort study may provide some clarification of what modulates gut microbiota post transplantation and shed light on predictive factors.

Anna-Catrin Uhlemann, MD, PhD, of Columbia University Medical Center, New York, noted that several studies in recent years sought to clarify influences on gut microbiota in people receiving liver transplants, but “there are still a number of important gaps in knowledge, including what exactly is the longitudinal evolution of the host transplant microbiome and what is the predictive value of pre- and early posttransplant dysbiosis on outcomes and complications.”

WASHINGTON – During and after liver transplant, the reaction of the intestinal microbiota may be a critical determinant of outcomes; preliminary data from a cohort study may provide some clarification of what modulates gut microbiota post transplantation and shed light on predictive factors.

Anna-Catrin Uhlemann, MD, PhD, of Columbia University Medical Center, New York, noted that several studies in recent years sought to clarify influences on gut microbiota in people receiving liver transplants, but “there are still a number of important gaps in knowledge, including what exactly is the longitudinal evolution of the host transplant microbiome and what is the predictive value of pre- and early posttransplant dysbiosis on outcomes and complications.”

WASHINGTON – A multinational clinical trial has found that the metastatic cancer agent nivolumab can improve long-term survival and durable tumor responses in patients with advanced hepatocellular carcinoma (HCC) whether or not they’ve had previous treatment with a chemotherapy agent already approved for advanced primary liver cancer, a principal investigator reported at the annual meeting of the American Association for the Study of Liver Diseases.

“Nivolumab has demonstrated clinically meaningful efficacy across etiologies in sorafenib-naive and -experienced patients with extended follow-up,” Bruno Sangro, MD, of the University of Navarra in Pamplona, Spain, said in reporting results of the CheckMate-040 trial. “The median overall survival is 15 and 15.6 months in patients who were sorafenib-experienced in both the dose-escalation and expansion cohorts.”

WASHINGTON – A multinational clinical trial has found that the metastatic cancer agent nivolumab can improve long-term survival and durable tumor responses in patients with advanced hepatocellular carcinoma (HCC) whether or not they’ve had previous treatment with a chemotherapy agent already approved for advanced primary liver cancer, a principal investigator reported at the annual meeting of the American Association for the Study of Liver Diseases.

“Nivolumab has demonstrated clinically meaningful efficacy across etiologies in sorafenib-naive and -experienced patients with extended follow-up,” Bruno Sangro, MD, of the University of Navarra in Pamplona, Spain, said in reporting results of the CheckMate-040 trial. “The median overall survival is 15 and 15.6 months in patients who were sorafenib-experienced in both the dose-escalation and expansion cohorts.”

WASHINGTON – A multinational clinical trial has found that the metastatic cancer agent nivolumab can improve long-term survival and durable tumor responses in patients with advanced hepatocellular carcinoma (HCC) whether or not they’ve had previous treatment with a chemotherapy agent already approved for advanced primary liver cancer, a principal investigator reported at the annual meeting of the American Association for the Study of Liver Diseases.

“Nivolumab has demonstrated clinically meaningful efficacy across etiologies in sorafenib-naive and -experienced patients with extended follow-up,” Bruno Sangro, MD, of the University of Navarra in Pamplona, Spain, said in reporting results of the CheckMate-040 trial. “The median overall survival is 15 and 15.6 months in patients who were sorafenib-experienced in both the dose-escalation and expansion cohorts.”

WASHINGTON – Limited treatment options for nonalcoholic steatohepatitis (NASH) in nonalcoholic fatty liver disease mean that NASH is the fastest-growing reason for liver transplants in the United States, but preclinical and, now, phase 2 clinical results have shown that treatment with 24-nor-ursodeoxycholic acid, otherwise known as norUDCA, can improve steatosis and liver stiffness in selected patients, a principal investigator in a European study of the treatment reported at the 2017 annual meeting of the American Association for the Study of Liver Diseases.

“The norUDCA dose of 1,500 mg resulted in significant reduction of ALT [alanine aminotransferase] within 12 weeks,” said Michael Trauner, MD, head of the division of gastroenterology and hepatology at the Medical University of Vienna, a coinventor of the drug. “The results are supported by improvement in liver stiffness and steatosis in the subsets analyzed.”

WASHINGTON – Limited treatment options for nonalcoholic steatohepatitis (NASH) in nonalcoholic fatty liver disease mean that NASH is the fastest-growing reason for liver transplants in the United States, but preclinical and, now, phase 2 clinical results have shown that treatment with 24-nor-ursodeoxycholic acid, otherwise known as norUDCA, can improve steatosis and liver stiffness in selected patients, a principal investigator in a European study of the treatment reported at the 2017 annual meeting of the American Association for the Study of Liver Diseases.

“The norUDCA dose of 1,500 mg resulted in significant reduction of ALT [alanine aminotransferase] within 12 weeks,” said Michael Trauner, MD, head of the division of gastroenterology and hepatology at the Medical University of Vienna, a coinventor of the drug. “The results are supported by improvement in liver stiffness and steatosis in the subsets analyzed.”

WASHINGTON – Limited treatment options for nonalcoholic steatohepatitis (NASH) in nonalcoholic fatty liver disease mean that NASH is the fastest-growing reason for liver transplants in the United States, but preclinical and, now, phase 2 clinical results have shown that treatment with 24-nor-ursodeoxycholic acid, otherwise known as norUDCA, can improve steatosis and liver stiffness in selected patients, a principal investigator in a European study of the treatment reported at the 2017 annual meeting of the American Association for the Study of Liver Diseases.

“The norUDCA dose of 1,500 mg resulted in significant reduction of ALT [alanine aminotransferase] within 12 weeks,” said Michael Trauner, MD, head of the division of gastroenterology and hepatology at the Medical University of Vienna, a coinventor of the drug. “The results are supported by improvement in liver stiffness and steatosis in the subsets analyzed.”