For men with prostate cancer who have a low prostate-specific antigen (PSA) level prior to salvage radiation therapy (SRT), adding an antiandrogen may increase the risk of other-cause mortality by twofold or more, according to investigators.

This finding was drawn from a secondary analysis of the NRG Oncology/RTOG 9601 phase 3 trial, a practice-changing study that showed that 2 years of antiandrogen therapy with bicalutamide improved overall survival when added to SRT, compared with that of SRT alone.

Results from the present analysis paint a more complex picture, revealing that patients with low PSA levels who received hormone therapy had a higher rate of other-cause mortality, primarily because of high-grade cardiac and neurologic events, reported lead author Daniel Spratt, MD, of the University of Michigan Rogel Cancer Center, Ann Arbor, who presented findings at the annual meeting of the American Society for Radiation Oncology.

Dr. Spratt described how treatment paradigms have changed since RTOG 9601 began in 1998, which prompted a revisitation of the trial. “Almost half of the men [in the trial] had a persistently elevated PSA after they underwent their initial surgery,” Dr. Spratt said. “This is uncommonly seen today. Additionally, about 60% of patients received what we call late salvage radiation therapy, where PSA was monitored and continued to rise beyond 0.5 [ng/mL]; again, this is not what is recommended to be used today.”

In the present analysis, the investigators stratified patients by PSA level. Of the 760 men involved, 85% had a PSA of 0.2-1.5 ng/mL. Patients were further subgrouped by those with a PSA of 0.2-0.6 ng/mL and those with a very low PSA, of 0.2-0.3 ng/mL. Multiple endpoints were assessed, including overall survival, other-cause mortality, distant metastasis, and rates of grade 3-5 cardiac or neurologic events.

The analysis showed that men with a PSA greater than 1.5 ng/mL had improved survival (hazard ratio, 0.45; 95% confidence interval, 0.25-0.81) when treated with bicalutamide, but those with PSA of 1.5 ng/mL or less did not (HR, 0.87; 95% CI, 0.66-1.16). Looking more closely at patients with a PSA of 1.5 ng/mL or less, those with a PSA of 0.2-0.6 ng/mL had a twofold increased rate of other-cause mortality (subdistribution HR, 1.94; P = .009). The picture became even more concerning for patients with a PSA of 0.2-0.3 ng/mL who were treated with bicalutamide: They had a fourfold increased risk of other cause mortality (sHR, 4.14). Among the cases with elevated other-cause mortality, grade 3-4 cardiac and neurologic events were likely to be blamed.

“What is likely driving this, and of concern, is that for [patients with a] PSA of less than 1.5 [ng/mL] … there was a three- to four-and-a-half-fold increased risk of high grade cardiac events,” Dr. Spratt said.

“The current guidelines recommend that all men be offered hormone therapy when receiving salvage radiation therapy, but our data demonstrate that men with lower PSA’s are probably more harmed than helped by long-term hormone therapy,” Dr. Spratt concluded. “We now have three randomized trials with over 2,400 men in total, [none of which showed that] short- or long-term hormone therapy improves overall survival in men [with a low PSA level who receive] early salvage radiotherapy. Thus, PSA prior to salvage radiation actually is not only prognostic, it predicts who will benefit most from hormone therapy, and guidelines should now be updated to reflect this finding.”

The session moderator, Anthony Zietman, MD, of Massachusetts General Hospital, Boston, helped put the findings in perspective: “This really suggests that we’ve got to hold back a little,” Dr. Zietman said. “There are some people who really benefit [from hormone therapy], some who don’t benefit, and some who just might be harmed, so I think we can be much more thoughtful and cautious in the future. … Thirty thousand men a year are in this situation who could be receiving this treatment. You could fill Fenway Park with that many people. So there are some big downstream implications. From here on out, I’m going to be a lot more cautious with my patients.”

The study was primarily funded by AstraZeneca with additional support from the Korea Institute of Radiological and Medical Sciences. The investigators disclosed relationships with Novartis, Roche, Amgen, and others.

SOURCE: Spratt et al. ASTRO 2019, Abstract LBA1.

For men with prostate cancer who have a low prostate-specific antigen (PSA) level prior to salvage radiation therapy (SRT), adding an antiandrogen may increase the risk of other-cause mortality by twofold or more, according to investigators.

This finding was drawn from a secondary analysis of the NRG Oncology/RTOG 9601 phase 3 trial, a practice-changing study that showed that 2 years of antiandrogen therapy with bicalutamide improved overall survival when added to SRT, compared with that of SRT alone.

Results from the present analysis paint a more complex picture, revealing that patients with low PSA levels who received hormone therapy had a higher rate of other-cause mortality, primarily because of high-grade cardiac and neurologic events, reported lead author Daniel Spratt, MD, of the University of Michigan Rogel Cancer Center, Ann Arbor, who presented findings at the annual meeting of the American Society for Radiation Oncology.

Dr. Spratt described how treatment paradigms have changed since RTOG 9601 began in 1998, which prompted a revisitation of the trial. “Almost half of the men [in the trial] had a persistently elevated PSA after they underwent their initial surgery,” Dr. Spratt said. “This is uncommonly seen today. Additionally, about 60% of patients received what we call late salvage radiation therapy, where PSA was monitored and continued to rise beyond 0.5 [ng/mL]; again, this is not what is recommended to be used today.”

In the present analysis, the investigators stratified patients by PSA level. Of the 760 men involved, 85% had a PSA of 0.2-1.5 ng/mL. Patients were further subgrouped by those with a PSA of 0.2-0.6 ng/mL and those with a very low PSA, of 0.2-0.3 ng/mL. Multiple endpoints were assessed, including overall survival, other-cause mortality, distant metastasis, and rates of grade 3-5 cardiac or neurologic events.

The analysis showed that men with a PSA greater than 1.5 ng/mL had improved survival (hazard ratio, 0.45; 95% confidence interval, 0.25-0.81) when treated with bicalutamide, but those with PSA of 1.5 ng/mL or less did not (HR, 0.87; 95% CI, 0.66-1.16). Looking more closely at patients with a PSA of 1.5 ng/mL or less, those with a PSA of 0.2-0.6 ng/mL had a twofold increased rate of other-cause mortality (subdistribution HR, 1.94; P = .009). The picture became even more concerning for patients with a PSA of 0.2-0.3 ng/mL who were treated with bicalutamide: They had a fourfold increased risk of other cause mortality (sHR, 4.14). Among the cases with elevated other-cause mortality, grade 3-4 cardiac and neurologic events were likely to be blamed.

“What is likely driving this, and of concern, is that for [patients with a] PSA of less than 1.5 [ng/mL] … there was a three- to four-and-a-half-fold increased risk of high grade cardiac events,” Dr. Spratt said.

“The current guidelines recommend that all men be offered hormone therapy when receiving salvage radiation therapy, but our data demonstrate that men with lower PSA’s are probably more harmed than helped by long-term hormone therapy,” Dr. Spratt concluded. “We now have three randomized trials with over 2,400 men in total, [none of which showed that] short- or long-term hormone therapy improves overall survival in men [with a low PSA level who receive] early salvage radiotherapy. Thus, PSA prior to salvage radiation actually is not only prognostic, it predicts who will benefit most from hormone therapy, and guidelines should now be updated to reflect this finding.”

The session moderator, Anthony Zietman, MD, of Massachusetts General Hospital, Boston, helped put the findings in perspective: “This really suggests that we’ve got to hold back a little,” Dr. Zietman said. “There are some people who really benefit [from hormone therapy], some who don’t benefit, and some who just might be harmed, so I think we can be much more thoughtful and cautious in the future. … Thirty thousand men a year are in this situation who could be receiving this treatment. You could fill Fenway Park with that many people. So there are some big downstream implications. From here on out, I’m going to be a lot more cautious with my patients.”

The study was primarily funded by AstraZeneca with additional support from the Korea Institute of Radiological and Medical Sciences. The investigators disclosed relationships with Novartis, Roche, Amgen, and others.

SOURCE: Spratt et al. ASTRO 2019, Abstract LBA1.

For men with prostate cancer who have a low prostate-specific antigen (PSA) level prior to salvage radiation therapy (SRT), adding an antiandrogen may increase the risk of other-cause mortality by twofold or more, according to investigators.

This finding was drawn from a secondary analysis of the NRG Oncology/RTOG 9601 phase 3 trial, a practice-changing study that showed that 2 years of antiandrogen therapy with bicalutamide improved overall survival when added to SRT, compared with that of SRT alone.

Results from the present analysis paint a more complex picture, revealing that patients with low PSA levels who received hormone therapy had a higher rate of other-cause mortality, primarily because of high-grade cardiac and neurologic events, reported lead author Daniel Spratt, MD, of the University of Michigan Rogel Cancer Center, Ann Arbor, who presented findings at the annual meeting of the American Society for Radiation Oncology.

Dr. Spratt described how treatment paradigms have changed since RTOG 9601 began in 1998, which prompted a revisitation of the trial. “Almost half of the men [in the trial] had a persistently elevated PSA after they underwent their initial surgery,” Dr. Spratt said. “This is uncommonly seen today. Additionally, about 60% of patients received what we call late salvage radiation therapy, where PSA was monitored and continued to rise beyond 0.5 [ng/mL]; again, this is not what is recommended to be used today.”

In the present analysis, the investigators stratified patients by PSA level. Of the 760 men involved, 85% had a PSA of 0.2-1.5 ng/mL. Patients were further subgrouped by those with a PSA of 0.2-0.6 ng/mL and those with a very low PSA, of 0.2-0.3 ng/mL. Multiple endpoints were assessed, including overall survival, other-cause mortality, distant metastasis, and rates of grade 3-5 cardiac or neurologic events.

The analysis showed that men with a PSA greater than 1.5 ng/mL had improved survival (hazard ratio, 0.45; 95% confidence interval, 0.25-0.81) when treated with bicalutamide, but those with PSA of 1.5 ng/mL or less did not (HR, 0.87; 95% CI, 0.66-1.16). Looking more closely at patients with a PSA of 1.5 ng/mL or less, those with a PSA of 0.2-0.6 ng/mL had a twofold increased rate of other-cause mortality (subdistribution HR, 1.94; P = .009). The picture became even more concerning for patients with a PSA of 0.2-0.3 ng/mL who were treated with bicalutamide: They had a fourfold increased risk of other cause mortality (sHR, 4.14). Among the cases with elevated other-cause mortality, grade 3-4 cardiac and neurologic events were likely to be blamed.

“What is likely driving this, and of concern, is that for [patients with a] PSA of less than 1.5 [ng/mL] … there was a three- to four-and-a-half-fold increased risk of high grade cardiac events,” Dr. Spratt said.

“The current guidelines recommend that all men be offered hormone therapy when receiving salvage radiation therapy, but our data demonstrate that men with lower PSA’s are probably more harmed than helped by long-term hormone therapy,” Dr. Spratt concluded. “We now have three randomized trials with over 2,400 men in total, [none of which showed that] short- or long-term hormone therapy improves overall survival in men [with a low PSA level who receive] early salvage radiotherapy. Thus, PSA prior to salvage radiation actually is not only prognostic, it predicts who will benefit most from hormone therapy, and guidelines should now be updated to reflect this finding.”

The session moderator, Anthony Zietman, MD, of Massachusetts General Hospital, Boston, helped put the findings in perspective: “This really suggests that we’ve got to hold back a little,” Dr. Zietman said. “There are some people who really benefit [from hormone therapy], some who don’t benefit, and some who just might be harmed, so I think we can be much more thoughtful and cautious in the future. … Thirty thousand men a year are in this situation who could be receiving this treatment. You could fill Fenway Park with that many people. So there are some big downstream implications. From here on out, I’m going to be a lot more cautious with my patients.”

The study was primarily funded by AstraZeneca with additional support from the Korea Institute of Radiological and Medical Sciences. The investigators disclosed relationships with Novartis, Roche, Amgen, and others.

SOURCE: Spratt et al. ASTRO 2019, Abstract LBA1.

The Diagnosis: Irritant Contact Dermatitis  

A slang term for volatile alkyl nitrites, poppers are inhaled for recreational purposes. They produce    rapid-onset euphoria and sexual arousal, as well as relax anal and vaginal sphincters, facilitating sexual intercourse. Alkyl nitrites initially were developed to treat coronary disease and angina but were replaced by more potent drugs.¹ Because of their psychoactive effects and smooth muscle relaxation properties, they are widely used by homosexual and bisexual men.^1-3 The term poppers was originated by the sound generated when the glass vials are crushed; currently, they also may be found in other formats.¹  

Nausea, hypotension, and headache are mild common adverse effects of volatile alkyl nitrites¹; cardiac arrhythmia, oxidative hemolysis,⁴ and poppers maculopathy^5,6 with permanent eye damage also have been reported.⁷ On the skin, volatile alkyl nitrites induce irritant contact dermatitis that heals without scarring, characteristically involving the face and upper thoracic region, as they are volatile vapors.² However, the reaction can occur elsewhere. There have been reports of contact dermatitis on other locations, such as the thigh or the ankle, due to vials broken while stored in pockets or on the cuff of the socks.¹ There also is a report of irritant contact dermatitis manifesting as a penile ulcer.³ Albeit rare, allergic contact dermatitis to volatile alkyl nitrites and other nitrites also can occur.⁸  

The abuse of alkyl nitrites may increase the risk for sexually transmitted infections (STIs), as they may decrease safer sexual practices and increase the propensity to engage in risky sexual behavior. It has been suggested to screen for STIs in patients with history of volatile alkyl nitrite use. In the past, volatile alkyl nitrites were believed to be a potential vector of human immunodeficiency virus.⁹ Other popular drugs used in social context or "club drugs," such as 3,4-methylenedioxymethamphetamine, gamma hydroxybutyrate, methamphetamine, and ketamine, do not produce irritant dermatitis as an adverse cutaneous reaction.¹⁰ The differential diagnosis in our patient included herpes simplex virus and contagious impetigo¹ as well as bullous lupus erythematosus and periorificial dermatitis; however, the clinical picture, acute onset of the reaction, and the patient's medical history were critical in making the correct diagnosis.  

The patient was treated with topical hydrocortisone and fusidic acid cream twice daily for 7 days with complete response. Sexually transmitted infection screening was unremarkable. We suggest performing an STI workup on patients with history of volatile alkyl nitrite use. 

The Diagnosis: Irritant Contact Dermatitis  

A slang term for volatile alkyl nitrites, poppers are inhaled for recreational purposes. They produce    rapid-onset euphoria and sexual arousal, as well as relax anal and vaginal sphincters, facilitating sexual intercourse. Alkyl nitrites initially were developed to treat coronary disease and angina but were replaced by more potent drugs.¹ Because of their psychoactive effects and smooth muscle relaxation properties, they are widely used by homosexual and bisexual men.^1-3 The term poppers was originated by the sound generated when the glass vials are crushed; currently, they also may be found in other formats.¹  

Nausea, hypotension, and headache are mild common adverse effects of volatile alkyl nitrites¹; cardiac arrhythmia, oxidative hemolysis,⁴ and poppers maculopathy^5,6 with permanent eye damage also have been reported.⁷ On the skin, volatile alkyl nitrites induce irritant contact dermatitis that heals without scarring, characteristically involving the face and upper thoracic region, as they are volatile vapors.² However, the reaction can occur elsewhere. There have been reports of contact dermatitis on other locations, such as the thigh or the ankle, due to vials broken while stored in pockets or on the cuff of the socks.¹ There also is a report of irritant contact dermatitis manifesting as a penile ulcer.³ Albeit rare, allergic contact dermatitis to volatile alkyl nitrites and other nitrites also can occur.⁸  

The abuse of alkyl nitrites may increase the risk for sexually transmitted infections (STIs), as they may decrease safer sexual practices and increase the propensity to engage in risky sexual behavior. It has been suggested to screen for STIs in patients with history of volatile alkyl nitrite use. In the past, volatile alkyl nitrites were believed to be a potential vector of human immunodeficiency virus.⁹ Other popular drugs used in social context or "club drugs," such as 3,4-methylenedioxymethamphetamine, gamma hydroxybutyrate, methamphetamine, and ketamine, do not produce irritant dermatitis as an adverse cutaneous reaction.¹⁰ The differential diagnosis in our patient included herpes simplex virus and contagious impetigo¹ as well as bullous lupus erythematosus and periorificial dermatitis; however, the clinical picture, acute onset of the reaction, and the patient's medical history were critical in making the correct diagnosis.  

The patient was treated with topical hydrocortisone and fusidic acid cream twice daily for 7 days with complete response. Sexually transmitted infection screening was unremarkable. We suggest performing an STI workup on patients with history of volatile alkyl nitrite use. 

The Diagnosis: Irritant Contact Dermatitis  

A slang term for volatile alkyl nitrites, poppers are inhaled for recreational purposes. They produce    rapid-onset euphoria and sexual arousal, as well as relax anal and vaginal sphincters, facilitating sexual intercourse. Alkyl nitrites initially were developed to treat coronary disease and angina but were replaced by more potent drugs.¹ Because of their psychoactive effects and smooth muscle relaxation properties, they are widely used by homosexual and bisexual men.^1-3 The term poppers was originated by the sound generated when the glass vials are crushed; currently, they also may be found in other formats.¹  

Nausea, hypotension, and headache are mild common adverse effects of volatile alkyl nitrites¹; cardiac arrhythmia, oxidative hemolysis,⁴ and poppers maculopathy^5,6 with permanent eye damage also have been reported.⁷ On the skin, volatile alkyl nitrites induce irritant contact dermatitis that heals without scarring, characteristically involving the face and upper thoracic region, as they are volatile vapors.² However, the reaction can occur elsewhere. There have been reports of contact dermatitis on other locations, such as the thigh or the ankle, due to vials broken while stored in pockets or on the cuff of the socks.¹ There also is a report of irritant contact dermatitis manifesting as a penile ulcer.³ Albeit rare, allergic contact dermatitis to volatile alkyl nitrites and other nitrites also can occur.⁸  

The abuse of alkyl nitrites may increase the risk for sexually transmitted infections (STIs), as they may decrease safer sexual practices and increase the propensity to engage in risky sexual behavior. It has been suggested to screen for STIs in patients with history of volatile alkyl nitrite use. In the past, volatile alkyl nitrites were believed to be a potential vector of human immunodeficiency virus.⁹ Other popular drugs used in social context or "club drugs," such as 3,4-methylenedioxymethamphetamine, gamma hydroxybutyrate, methamphetamine, and ketamine, do not produce irritant dermatitis as an adverse cutaneous reaction.¹⁰ The differential diagnosis in our patient included herpes simplex virus and contagious impetigo¹ as well as bullous lupus erythematosus and periorificial dermatitis; however, the clinical picture, acute onset of the reaction, and the patient's medical history were critical in making the correct diagnosis.  

The patient was treated with topical hydrocortisone and fusidic acid cream twice daily for 7 days with complete response. Sexually transmitted infection screening was unremarkable. We suggest performing an STI workup on patients with history of volatile alkyl nitrite use. 

American diets have improved in the last several decades, with declines in consumption of low-quality carbohydrates and increases in plant protein and healthy fats, based on data from a nationally representative sample of 43,996 adults.

Changes in the economy, food policies, and food processing can affect diet over time, but trends in consumption of macronutrients in the U.S. have not been well studied, wrote Zhilei Shan, MD, of Harvard T.H. Chan School of Public Health, Boston, and colleagues.

In a study published in JAMA, the researchers reviewed data from nine consecutive cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2016 to determine trends in macronutrient intake. The study population included adults aged 20 years and older who could provide at least 1 valid dietary recall questionnaire. The average age was 47 years, and 52% were women.

Overall, total carbohydrate consumption decreased from 52.5% to 50.5%, the estimated energy from high-quality carbohydrates increased from 7.42% to 8.65%, and the estimated energy from low-quality carbohydrates decreased from 45.1% to 41.8%. Total protein consumption increased from 15.5% to 16.4%, and plant protein consumption increased from 5.38% to 5.76%. Total fat consumption increased from 32.0% to 33.2%, including a 0.36% increase in saturated fatty acids from 11.5% to 11.9% and a 0.65% increase in polyunsaturated fatty acids from 7.58% to 8.23%.

Although the changes in total carbohydrates, total protein, and total fat were significant, 42% of energy intake came from low-quality carbohydrates and 10% came from saturated fat, the researchers noted. Also, the overall diet quality as measured by the Healthy Eating Index 2015 (HEI-2015) improved from 55.7 in 1999 to 57.7 in 2016. The HEI-2015 measures how diet data adheres to recommendations in the 2015-2020 Dietary Guidelines for Americans on a scale of 0-100.

“Improvements in intakes of whole grains and plant protein are encouraging, but how much do popular foods such as pizza, fast food sandwiches and burgers, and foods categorized as ‘snacks’ and ‘desserts’ contribute to the U.S. eating pattern?” wrote Linda Van Horn, PhD, RDN, and Marilyn C. Cornelis, PhD, of Northwestern University, Chicago, in an editorial accompanying the study. They cited a closer look at the NHANES data in the USDA’s “What We Eat in America” report and noted the differences in ethnicity with regard to macronutrient consumption.

“Non-Hispanic whites consume more alcohol, pizza, and fast food sandwiches (24% of total energy), while non-Hispanic blacks consume more salty snacks and sweet desserts (17% of total energy), and Hispanics consume more sugar-sweetened beverages (8% of total energy) and the least alcohol compared with the other racial/ethnic groups,” they said. “Public health efforts to educate, inform, and incent better adherence to the recommended nutrient-dense food groups are clearly needed,” they emphasized.

The study findings were limited by several factors, including the use of self-reports and changes in dietary assessments over time, the researchers noted. However, the results are strengthened by the large sample size and suggest improvements in the overall American diet, but also highlight the need for continuing public education and intervention, they said.

The study was supported by the National Institutes of Health and the Young Scientists Fund of the National Natural Science Foundation of China. Dr. Shan had no financial conflicts to disclose. Dr. Van Horn disclosed being a member of the 2020 US Dietary Guidelines Advisory Committee.

SOURCE: Shan Z et al. JAMA. 2019. doi: 10.1001/jama.2019.13771.

American diets have improved in the last several decades, with declines in consumption of low-quality carbohydrates and increases in plant protein and healthy fats, based on data from a nationally representative sample of 43,996 adults.

Changes in the economy, food policies, and food processing can affect diet over time, but trends in consumption of macronutrients in the U.S. have not been well studied, wrote Zhilei Shan, MD, of Harvard T.H. Chan School of Public Health, Boston, and colleagues.

In a study published in JAMA, the researchers reviewed data from nine consecutive cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2016 to determine trends in macronutrient intake. The study population included adults aged 20 years and older who could provide at least 1 valid dietary recall questionnaire. The average age was 47 years, and 52% were women.

Overall, total carbohydrate consumption decreased from 52.5% to 50.5%, the estimated energy from high-quality carbohydrates increased from 7.42% to 8.65%, and the estimated energy from low-quality carbohydrates decreased from 45.1% to 41.8%. Total protein consumption increased from 15.5% to 16.4%, and plant protein consumption increased from 5.38% to 5.76%. Total fat consumption increased from 32.0% to 33.2%, including a 0.36% increase in saturated fatty acids from 11.5% to 11.9% and a 0.65% increase in polyunsaturated fatty acids from 7.58% to 8.23%.

Although the changes in total carbohydrates, total protein, and total fat were significant, 42% of energy intake came from low-quality carbohydrates and 10% came from saturated fat, the researchers noted. Also, the overall diet quality as measured by the Healthy Eating Index 2015 (HEI-2015) improved from 55.7 in 1999 to 57.7 in 2016. The HEI-2015 measures how diet data adheres to recommendations in the 2015-2020 Dietary Guidelines for Americans on a scale of 0-100.

“Improvements in intakes of whole grains and plant protein are encouraging, but how much do popular foods such as pizza, fast food sandwiches and burgers, and foods categorized as ‘snacks’ and ‘desserts’ contribute to the U.S. eating pattern?” wrote Linda Van Horn, PhD, RDN, and Marilyn C. Cornelis, PhD, of Northwestern University, Chicago, in an editorial accompanying the study. They cited a closer look at the NHANES data in the USDA’s “What We Eat in America” report and noted the differences in ethnicity with regard to macronutrient consumption.

“Non-Hispanic whites consume more alcohol, pizza, and fast food sandwiches (24% of total energy), while non-Hispanic blacks consume more salty snacks and sweet desserts (17% of total energy), and Hispanics consume more sugar-sweetened beverages (8% of total energy) and the least alcohol compared with the other racial/ethnic groups,” they said. “Public health efforts to educate, inform, and incent better adherence to the recommended nutrient-dense food groups are clearly needed,” they emphasized.

The study findings were limited by several factors, including the use of self-reports and changes in dietary assessments over time, the researchers noted. However, the results are strengthened by the large sample size and suggest improvements in the overall American diet, but also highlight the need for continuing public education and intervention, they said.

The study was supported by the National Institutes of Health and the Young Scientists Fund of the National Natural Science Foundation of China. Dr. Shan had no financial conflicts to disclose. Dr. Van Horn disclosed being a member of the 2020 US Dietary Guidelines Advisory Committee.

SOURCE: Shan Z et al. JAMA. 2019. doi: 10.1001/jama.2019.13771.

American diets have improved in the last several decades, with declines in consumption of low-quality carbohydrates and increases in plant protein and healthy fats, based on data from a nationally representative sample of 43,996 adults.

Changes in the economy, food policies, and food processing can affect diet over time, but trends in consumption of macronutrients in the U.S. have not been well studied, wrote Zhilei Shan, MD, of Harvard T.H. Chan School of Public Health, Boston, and colleagues.

In a study published in JAMA, the researchers reviewed data from nine consecutive cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2016 to determine trends in macronutrient intake. The study population included adults aged 20 years and older who could provide at least 1 valid dietary recall questionnaire. The average age was 47 years, and 52% were women.

Overall, total carbohydrate consumption decreased from 52.5% to 50.5%, the estimated energy from high-quality carbohydrates increased from 7.42% to 8.65%, and the estimated energy from low-quality carbohydrates decreased from 45.1% to 41.8%. Total protein consumption increased from 15.5% to 16.4%, and plant protein consumption increased from 5.38% to 5.76%. Total fat consumption increased from 32.0% to 33.2%, including a 0.36% increase in saturated fatty acids from 11.5% to 11.9% and a 0.65% increase in polyunsaturated fatty acids from 7.58% to 8.23%.

Although the changes in total carbohydrates, total protein, and total fat were significant, 42% of energy intake came from low-quality carbohydrates and 10% came from saturated fat, the researchers noted. Also, the overall diet quality as measured by the Healthy Eating Index 2015 (HEI-2015) improved from 55.7 in 1999 to 57.7 in 2016. The HEI-2015 measures how diet data adheres to recommendations in the 2015-2020 Dietary Guidelines for Americans on a scale of 0-100.

“Improvements in intakes of whole grains and plant protein are encouraging, but how much do popular foods such as pizza, fast food sandwiches and burgers, and foods categorized as ‘snacks’ and ‘desserts’ contribute to the U.S. eating pattern?” wrote Linda Van Horn, PhD, RDN, and Marilyn C. Cornelis, PhD, of Northwestern University, Chicago, in an editorial accompanying the study. They cited a closer look at the NHANES data in the USDA’s “What We Eat in America” report and noted the differences in ethnicity with regard to macronutrient consumption.

“Non-Hispanic whites consume more alcohol, pizza, and fast food sandwiches (24% of total energy), while non-Hispanic blacks consume more salty snacks and sweet desserts (17% of total energy), and Hispanics consume more sugar-sweetened beverages (8% of total energy) and the least alcohol compared with the other racial/ethnic groups,” they said. “Public health efforts to educate, inform, and incent better adherence to the recommended nutrient-dense food groups are clearly needed,” they emphasized.

The study findings were limited by several factors, including the use of self-reports and changes in dietary assessments over time, the researchers noted. However, the results are strengthened by the large sample size and suggest improvements in the overall American diet, but also highlight the need for continuing public education and intervention, they said.

The study was supported by the National Institutes of Health and the Young Scientists Fund of the National Natural Science Foundation of China. Dr. Shan had no financial conflicts to disclose. Dr. Van Horn disclosed being a member of the 2020 US Dietary Guidelines Advisory Committee.

SOURCE: Shan Z et al. JAMA. 2019. doi: 10.1001/jama.2019.13771.

Nearly a quarter of resources used by the intensive care unit (ICU) are for substance abuse-related admissions, according to results from a retrospective chart review.

Hemera Technologies/Thinkstock

The abuse of illicit drugs topped substance abuse–related ICU stays, accounting for 13% of total admissions, which represented 11% of total charges.

“We conducted a study to provide updated data on ICU utilization and costs related to licit and illicit abuse at a large county hospital,” wrote Donald Westerhausen, MD, of Indiana University, Indianapolis, and colleagues. The findings were reported in Chest .

The single-center study comprised 594 patients who were admitted for prescription, alcohol, or illicit drug use between May 2017 and October 2017. The team used laboratory data, in addition to medical history, to define substance abuse–related admissions.

A total of 611 admissions occurred during the 6-month study period. The researchers collected information on patient demographics, hospital charges, insurance coverage, and other clinical parameters.

After analysis, they found that patients admitted for substance abuse were generally younger than were those admitted for other reasons (44 years vs. 59 years; P less than .001). In addition, patients were more often male (64% vs. 48%), had greater mortality (14%), and experienced longer hospital stays (median, 6 days).

In total, 25.7% of ICU admissions were related to substance abuse, which comprised 23.1% of charges. In particular, 9.5% and 2.9% of admissions were related to alcohol use and prescription drugs, which represented 7.6% and 4.2% of total charges, respectively.

“Polysubstance abuse was the most frequent subcategory of illicit and prescription drug admissions,” the researchers wrote.

They acknowledged two limitations of the study: the short duration and single-center design. Future studies should account for seasonal differences in ICU admissions, they noted.

“Identifying and accurately describing the landscape of this current health crisis will help us take appropriate action in the future,” they concluded.

No funding sources were reported. The authors did not disclose any conflicts of interest.

SOURCE: Westerhausen D et al. Chest. 2019 Sep 5. doi: 10.1016/j.chest.2019.08.2180.

Nearly a quarter of resources used by the intensive care unit (ICU) are for substance abuse-related admissions, according to results from a retrospective chart review.

Hemera Technologies/Thinkstock

The abuse of illicit drugs topped substance abuse–related ICU stays, accounting for 13% of total admissions, which represented 11% of total charges.

“We conducted a study to provide updated data on ICU utilization and costs related to licit and illicit abuse at a large county hospital,” wrote Donald Westerhausen, MD, of Indiana University, Indianapolis, and colleagues. The findings were reported in Chest .

The single-center study comprised 594 patients who were admitted for prescription, alcohol, or illicit drug use between May 2017 and October 2017. The team used laboratory data, in addition to medical history, to define substance abuse–related admissions.

A total of 611 admissions occurred during the 6-month study period. The researchers collected information on patient demographics, hospital charges, insurance coverage, and other clinical parameters.

After analysis, they found that patients admitted for substance abuse were generally younger than were those admitted for other reasons (44 years vs. 59 years; P less than .001). In addition, patients were more often male (64% vs. 48%), had greater mortality (14%), and experienced longer hospital stays (median, 6 days).

In total, 25.7% of ICU admissions were related to substance abuse, which comprised 23.1% of charges. In particular, 9.5% and 2.9% of admissions were related to alcohol use and prescription drugs, which represented 7.6% and 4.2% of total charges, respectively.

“Polysubstance abuse was the most frequent subcategory of illicit and prescription drug admissions,” the researchers wrote.

They acknowledged two limitations of the study: the short duration and single-center design. Future studies should account for seasonal differences in ICU admissions, they noted.

“Identifying and accurately describing the landscape of this current health crisis will help us take appropriate action in the future,” they concluded.

No funding sources were reported. The authors did not disclose any conflicts of interest.

SOURCE: Westerhausen D et al. Chest. 2019 Sep 5. doi: 10.1016/j.chest.2019.08.2180.

Nearly a quarter of resources used by the intensive care unit (ICU) are for substance abuse-related admissions, according to results from a retrospective chart review.

Hemera Technologies/Thinkstock

The abuse of illicit drugs topped substance abuse–related ICU stays, accounting for 13% of total admissions, which represented 11% of total charges.

“We conducted a study to provide updated data on ICU utilization and costs related to licit and illicit abuse at a large county hospital,” wrote Donald Westerhausen, MD, of Indiana University, Indianapolis, and colleagues. The findings were reported in Chest .

The single-center study comprised 594 patients who were admitted for prescription, alcohol, or illicit drug use between May 2017 and October 2017. The team used laboratory data, in addition to medical history, to define substance abuse–related admissions.

A total of 611 admissions occurred during the 6-month study period. The researchers collected information on patient demographics, hospital charges, insurance coverage, and other clinical parameters.

After analysis, they found that patients admitted for substance abuse were generally younger than were those admitted for other reasons (44 years vs. 59 years; P less than .001). In addition, patients were more often male (64% vs. 48%), had greater mortality (14%), and experienced longer hospital stays (median, 6 days).

In total, 25.7% of ICU admissions were related to substance abuse, which comprised 23.1% of charges. In particular, 9.5% and 2.9% of admissions were related to alcohol use and prescription drugs, which represented 7.6% and 4.2% of total charges, respectively.

“Polysubstance abuse was the most frequent subcategory of illicit and prescription drug admissions,” the researchers wrote.

They acknowledged two limitations of the study: the short duration and single-center design. Future studies should account for seasonal differences in ICU admissions, they noted.

“Identifying and accurately describing the landscape of this current health crisis will help us take appropriate action in the future,” they concluded.

No funding sources were reported. The authors did not disclose any conflicts of interest.

SOURCE: Westerhausen D et al. Chest. 2019 Sep 5. doi: 10.1016/j.chest.2019.08.2180.

Combined hormone therapy and targeted therapy should be the first choice for most postmenopausal women with recently diagnosed hormone receptor–positive, HER2-negative metastatic breast cancer, new data suggest.

Although guidelines support use of hormone therapies with or without targeted therapies in this population, up-front chemotherapy is still commonly used even in the absence of a visceral crisis, noted lead investigator Mario Giuliano, MD, PhD, of the department of clinical medicine and surgery at the University of Naples (Italy) Federico II, and colleagues.

The investigators undertook a systematic review and network meta-analysis of 140 randomized, controlled trials among 50,029 postmenopausal patients with hormone receptor–positive, HER2-negative metastatic breast cancer treated in the first- and/or second-line setting.

Study results, reported in Lancet Oncology, showed that relative to standard hormone therapy alone, the combination of hormone therapy with a targeted therapy – a CDK4/6 inhibitor, an mammalian target of rapamycin inhibitor, or an indicated phosphoinositide 3-kinase inhibitor – had significantly better efficacy, reducing the risk of progression-free survival events by more than half. In addition, no chemotherapy regimen, with or without targeted therapy, significantly outperformed the combination of hormone therapy with a CDK4/6 inhibitor.

Meanwhile, the hormone therapy–targeted therapy combinations had manageable toxicity, with the severity of adverse effects intermediate between that of hormone therapy alone and that of chemotherapy with or without targeted therapies.

“This study is, to our knowledge, the first to compare the efficacy and activity of all currently available chemotherapy and hormone therapy regimens, in combination with or without targeted therapies,” Dr. Giuliano and coinvestigators wrote. “[O]ur results corroborate the treatment algorithms recommended by the official oncology guidelines, supporting the use of new combinations of hormone therapies plus targeted therapies in the first-line or second-line setting in patients with hormone receptor-positive, HER2-negative metastatic breast cancer without visceral crisis.”

For the study, the investigators identified relevant phase 2 and phase 3 randomized, controlled trials published between 2000 and 2017, with the addition of several recently reported trials such as BOLERO-6 (JAMA Oncol. 2018;4:1367-74). Of the 140 trials ultimately included, 114 were used in the analysis of progression-free survival and time to progression, and 135 were used in the analysis of overall response.

Study results showed that when anastrozole (Arimidex) alone was the comparator, progression-free survival was significantly better with palbociclib (Ibrance) plus letrozole (Femara) (hazard ratio for events, 0.42); ribociclib (Kisqali) plus letrozole (HR, 0.43); abemaciclib (Verzenio) plus anastrozole or letrozole (HR, 0.42); palbociclib plus fulvestrant (Faslodex) (HR, 0.37); ribociclib plus fulvestrant (HR, 0.48); abemaciclib plus fulvestrant (HR, 0.44); everolimus (Afinitor) plus exemestane (Aromasin) (HR, 0.42); and, in patients with a PIK3CA mutation, the PI3K inhibitor alpelisib (Piqray) plus fulvestrant (HR, 0.39).

Several chemotherapy-based regimens, including anthracycline- and taxane-containing regimens, were also superior to anastrozole alone (hazard ratios, 0.41-0.47).

When palbociclib plus letrozole was the comparator, no chemotherapy or hormone therapy regimen yielded significantly better progression-free survival.

For the outcome of overall response, paclitaxel (Taxol) plus bevacizumab (Avastin) was the only clinically relevant regimen that significantly improved the likelihood of response relative to palbociclib plus letrozole (odds ratio, 8.95).

Dr. Giuliano reported that he receives honoraria from Amgen, AstraZeneca, Celgene, Eisai, Eli Lilly, Novartis, Pfizer,and Roche. The study did not receive any funding.

SOURCE: Giuliano M et al. Lancet Oncol. 2019 Sep 4. doi: 10.1016/S1470-2045(19)30420-6.

Combined hormone therapy and targeted therapy should be the first choice for most postmenopausal women with recently diagnosed hormone receptor–positive, HER2-negative metastatic breast cancer, new data suggest.

Although guidelines support use of hormone therapies with or without targeted therapies in this population, up-front chemotherapy is still commonly used even in the absence of a visceral crisis, noted lead investigator Mario Giuliano, MD, PhD, of the department of clinical medicine and surgery at the University of Naples (Italy) Federico II, and colleagues.

The investigators undertook a systematic review and network meta-analysis of 140 randomized, controlled trials among 50,029 postmenopausal patients with hormone receptor–positive, HER2-negative metastatic breast cancer treated in the first- and/or second-line setting.

Study results, reported in Lancet Oncology, showed that relative to standard hormone therapy alone, the combination of hormone therapy with a targeted therapy – a CDK4/6 inhibitor, an mammalian target of rapamycin inhibitor, or an indicated phosphoinositide 3-kinase inhibitor – had significantly better efficacy, reducing the risk of progression-free survival events by more than half. In addition, no chemotherapy regimen, with or without targeted therapy, significantly outperformed the combination of hormone therapy with a CDK4/6 inhibitor.

Meanwhile, the hormone therapy–targeted therapy combinations had manageable toxicity, with the severity of adverse effects intermediate between that of hormone therapy alone and that of chemotherapy with or without targeted therapies.

“This study is, to our knowledge, the first to compare the efficacy and activity of all currently available chemotherapy and hormone therapy regimens, in combination with or without targeted therapies,” Dr. Giuliano and coinvestigators wrote. “[O]ur results corroborate the treatment algorithms recommended by the official oncology guidelines, supporting the use of new combinations of hormone therapies plus targeted therapies in the first-line or second-line setting in patients with hormone receptor-positive, HER2-negative metastatic breast cancer without visceral crisis.”

For the study, the investigators identified relevant phase 2 and phase 3 randomized, controlled trials published between 2000 and 2017, with the addition of several recently reported trials such as BOLERO-6 (JAMA Oncol. 2018;4:1367-74). Of the 140 trials ultimately included, 114 were used in the analysis of progression-free survival and time to progression, and 135 were used in the analysis of overall response.

Study results showed that when anastrozole (Arimidex) alone was the comparator, progression-free survival was significantly better with palbociclib (Ibrance) plus letrozole (Femara) (hazard ratio for events, 0.42); ribociclib (Kisqali) plus letrozole (HR, 0.43); abemaciclib (Verzenio) plus anastrozole or letrozole (HR, 0.42); palbociclib plus fulvestrant (Faslodex) (HR, 0.37); ribociclib plus fulvestrant (HR, 0.48); abemaciclib plus fulvestrant (HR, 0.44); everolimus (Afinitor) plus exemestane (Aromasin) (HR, 0.42); and, in patients with a PIK3CA mutation, the PI3K inhibitor alpelisib (Piqray) plus fulvestrant (HR, 0.39).

Several chemotherapy-based regimens, including anthracycline- and taxane-containing regimens, were also superior to anastrozole alone (hazard ratios, 0.41-0.47).

When palbociclib plus letrozole was the comparator, no chemotherapy or hormone therapy regimen yielded significantly better progression-free survival.

For the outcome of overall response, paclitaxel (Taxol) plus bevacizumab (Avastin) was the only clinically relevant regimen that significantly improved the likelihood of response relative to palbociclib plus letrozole (odds ratio, 8.95).

Dr. Giuliano reported that he receives honoraria from Amgen, AstraZeneca, Celgene, Eisai, Eli Lilly, Novartis, Pfizer,and Roche. The study did not receive any funding.

SOURCE: Giuliano M et al. Lancet Oncol. 2019 Sep 4. doi: 10.1016/S1470-2045(19)30420-6.

Combined hormone therapy and targeted therapy should be the first choice for most postmenopausal women with recently diagnosed hormone receptor–positive, HER2-negative metastatic breast cancer, new data suggest.

Although guidelines support use of hormone therapies with or without targeted therapies in this population, up-front chemotherapy is still commonly used even in the absence of a visceral crisis, noted lead investigator Mario Giuliano, MD, PhD, of the department of clinical medicine and surgery at the University of Naples (Italy) Federico II, and colleagues.

The investigators undertook a systematic review and network meta-analysis of 140 randomized, controlled trials among 50,029 postmenopausal patients with hormone receptor–positive, HER2-negative metastatic breast cancer treated in the first- and/or second-line setting.

Study results, reported in Lancet Oncology, showed that relative to standard hormone therapy alone, the combination of hormone therapy with a targeted therapy – a CDK4/6 inhibitor, an mammalian target of rapamycin inhibitor, or an indicated phosphoinositide 3-kinase inhibitor – had significantly better efficacy, reducing the risk of progression-free survival events by more than half. In addition, no chemotherapy regimen, with or without targeted therapy, significantly outperformed the combination of hormone therapy with a CDK4/6 inhibitor.

Meanwhile, the hormone therapy–targeted therapy combinations had manageable toxicity, with the severity of adverse effects intermediate between that of hormone therapy alone and that of chemotherapy with or without targeted therapies.

“This study is, to our knowledge, the first to compare the efficacy and activity of all currently available chemotherapy and hormone therapy regimens, in combination with or without targeted therapies,” Dr. Giuliano and coinvestigators wrote. “[O]ur results corroborate the treatment algorithms recommended by the official oncology guidelines, supporting the use of new combinations of hormone therapies plus targeted therapies in the first-line or second-line setting in patients with hormone receptor-positive, HER2-negative metastatic breast cancer without visceral crisis.”

For the study, the investigators identified relevant phase 2 and phase 3 randomized, controlled trials published between 2000 and 2017, with the addition of several recently reported trials such as BOLERO-6 (JAMA Oncol. 2018;4:1367-74). Of the 140 trials ultimately included, 114 were used in the analysis of progression-free survival and time to progression, and 135 were used in the analysis of overall response.

Study results showed that when anastrozole (Arimidex) alone was the comparator, progression-free survival was significantly better with palbociclib (Ibrance) plus letrozole (Femara) (hazard ratio for events, 0.42); ribociclib (Kisqali) plus letrozole (HR, 0.43); abemaciclib (Verzenio) plus anastrozole or letrozole (HR, 0.42); palbociclib plus fulvestrant (Faslodex) (HR, 0.37); ribociclib plus fulvestrant (HR, 0.48); abemaciclib plus fulvestrant (HR, 0.44); everolimus (Afinitor) plus exemestane (Aromasin) (HR, 0.42); and, in patients with a PIK3CA mutation, the PI3K inhibitor alpelisib (Piqray) plus fulvestrant (HR, 0.39).

Several chemotherapy-based regimens, including anthracycline- and taxane-containing regimens, were also superior to anastrozole alone (hazard ratios, 0.41-0.47).

When palbociclib plus letrozole was the comparator, no chemotherapy or hormone therapy regimen yielded significantly better progression-free survival.

For the outcome of overall response, paclitaxel (Taxol) plus bevacizumab (Avastin) was the only clinically relevant regimen that significantly improved the likelihood of response relative to palbociclib plus letrozole (odds ratio, 8.95).

Dr. Giuliano reported that he receives honoraria from Amgen, AstraZeneca, Celgene, Eisai, Eli Lilly, Novartis, Pfizer,and Roche. The study did not receive any funding.

SOURCE: Giuliano M et al. Lancet Oncol. 2019 Sep 4. doi: 10.1016/S1470-2045(19)30420-6.

Parental sensitive responsiveness, more than warmth, was associated with better child language skills, according to a meta-analysis in Pediatrics.

Mapodile/E+/Getty Images

Sheri Madigan, PhD, of the department of psychology at the University of Calgary (Alta.) and the Alberta Children’s Hospital Research Institute, also in Calgary, and colleagues brought together 37 studies of the association of either parental sensitive responsiveness, warmth, or both with children’s language skills. The studies ranged in sample sizes from 9 mother-child dyads to 1,026. For the purposes of the study, sensitive responsiveness was defined as “a parent’s ability to perceive and interpret the child’s signals and cues and to respond to those signals and cues promptly and appropriately,” and warmth was defined as “caregiver physical affection or their positive affective quality during contact and involvement with the child.”

Across 36 samples with a total of 7,315 dyads, an association was seen between sensitive responsiveness and child language, with a correlation coefficient of 0.26 (95% confidence interval, 0.21-0.33), whereas the analysis exploring parental warmth with 13 samples (1,961 dyads) found a somewhat weaker association, with a correlation coefficient of 0.16 (95% CI, 0.09-0.21), according to the investigators.

“A sensitive-responsive parent can build on the moment-to-moment shifts in children’s attention, providing a finely tuned enhancement to the child’s experience,” the researchers suggested in regard to the greater effect seen with sensitive responsiveness. “Neural development is thought to occur through internalization of these finely tuned, reciprocal interactions. Warmth, on the other hand, does not involve contingency or reciprocity.”

Interestingly, moderator analyses revealed variations in effect sizes according to socioeconomic status – with greater effect sizes associated with lower socioeconomic status.

“A possible interpretation of this finding is that maternal sensitive responsiveness is particularly advantageous to children’s language when they are raise in socially disadvantaged families,” they wrote, noting that such an interpretation would be in line with previous research that showed “the protective effect of high-quality parent-child interactions in the context of adversity.”

Limitations of the analysis include that meta-analyses of observational studies are correlational in nature and are generally unable to demonstrate inferences about causality. Another is that the studies in this analysis were limited to children who developed in typical fashion, which limits generalizability to children with language delay, intellectual disability, autism, or hearing/vision difficulties. The analysis was also limited to only mother-child dyads, so the effects of paternal parenting are absent.

“The findings indicate a moderate association between sensitive-responsive parenting and children’s language skills,” the researchers concluded. “Sensitive responsiveness is a modifiable risk that has been successfully trained in parents in randomized trials and shown to improve language development of children.”

A grant from the Social Sciences and Humanities Research Council was awarded to the two of the study’s authors. Two authors’ individual contributions were supported by funding from the Alberta Children’s Hospital Foundation. The authors indicated they have no financial relationships relevant to this article or conflicts of interest to disclose.

[email protected]

SOURCE: Madigan S et al. Pediatrics. 2019 Sep 24. doi: 10.1542/peds.2018-3556.

Parental sensitive responsiveness, more than warmth, was associated with better child language skills, according to a meta-analysis in Pediatrics.

Mapodile/E+/Getty Images

Sheri Madigan, PhD, of the department of psychology at the University of Calgary (Alta.) and the Alberta Children’s Hospital Research Institute, also in Calgary, and colleagues brought together 37 studies of the association of either parental sensitive responsiveness, warmth, or both with children’s language skills. The studies ranged in sample sizes from 9 mother-child dyads to 1,026. For the purposes of the study, sensitive responsiveness was defined as “a parent’s ability to perceive and interpret the child’s signals and cues and to respond to those signals and cues promptly and appropriately,” and warmth was defined as “caregiver physical affection or their positive affective quality during contact and involvement with the child.”

Across 36 samples with a total of 7,315 dyads, an association was seen between sensitive responsiveness and child language, with a correlation coefficient of 0.26 (95% confidence interval, 0.21-0.33), whereas the analysis exploring parental warmth with 13 samples (1,961 dyads) found a somewhat weaker association, with a correlation coefficient of 0.16 (95% CI, 0.09-0.21), according to the investigators.

“A sensitive-responsive parent can build on the moment-to-moment shifts in children’s attention, providing a finely tuned enhancement to the child’s experience,” the researchers suggested in regard to the greater effect seen with sensitive responsiveness. “Neural development is thought to occur through internalization of these finely tuned, reciprocal interactions. Warmth, on the other hand, does not involve contingency or reciprocity.”

Interestingly, moderator analyses revealed variations in effect sizes according to socioeconomic status – with greater effect sizes associated with lower socioeconomic status.

“A possible interpretation of this finding is that maternal sensitive responsiveness is particularly advantageous to children’s language when they are raise in socially disadvantaged families,” they wrote, noting that such an interpretation would be in line with previous research that showed “the protective effect of high-quality parent-child interactions in the context of adversity.”

Limitations of the analysis include that meta-analyses of observational studies are correlational in nature and are generally unable to demonstrate inferences about causality. Another is that the studies in this analysis were limited to children who developed in typical fashion, which limits generalizability to children with language delay, intellectual disability, autism, or hearing/vision difficulties. The analysis was also limited to only mother-child dyads, so the effects of paternal parenting are absent.

“The findings indicate a moderate association between sensitive-responsive parenting and children’s language skills,” the researchers concluded. “Sensitive responsiveness is a modifiable risk that has been successfully trained in parents in randomized trials and shown to improve language development of children.”

A grant from the Social Sciences and Humanities Research Council was awarded to the two of the study’s authors. Two authors’ individual contributions were supported by funding from the Alberta Children’s Hospital Foundation. The authors indicated they have no financial relationships relevant to this article or conflicts of interest to disclose.

[email protected]

SOURCE: Madigan S et al. Pediatrics. 2019 Sep 24. doi: 10.1542/peds.2018-3556.

Parental sensitive responsiveness, more than warmth, was associated with better child language skills, according to a meta-analysis in Pediatrics.

Mapodile/E+/Getty Images

Sheri Madigan, PhD, of the department of psychology at the University of Calgary (Alta.) and the Alberta Children’s Hospital Research Institute, also in Calgary, and colleagues brought together 37 studies of the association of either parental sensitive responsiveness, warmth, or both with children’s language skills. The studies ranged in sample sizes from 9 mother-child dyads to 1,026. For the purposes of the study, sensitive responsiveness was defined as “a parent’s ability to perceive and interpret the child’s signals and cues and to respond to those signals and cues promptly and appropriately,” and warmth was defined as “caregiver physical affection or their positive affective quality during contact and involvement with the child.”

Across 36 samples with a total of 7,315 dyads, an association was seen between sensitive responsiveness and child language, with a correlation coefficient of 0.26 (95% confidence interval, 0.21-0.33), whereas the analysis exploring parental warmth with 13 samples (1,961 dyads) found a somewhat weaker association, with a correlation coefficient of 0.16 (95% CI, 0.09-0.21), according to the investigators.

“A sensitive-responsive parent can build on the moment-to-moment shifts in children’s attention, providing a finely tuned enhancement to the child’s experience,” the researchers suggested in regard to the greater effect seen with sensitive responsiveness. “Neural development is thought to occur through internalization of these finely tuned, reciprocal interactions. Warmth, on the other hand, does not involve contingency or reciprocity.”

Interestingly, moderator analyses revealed variations in effect sizes according to socioeconomic status – with greater effect sizes associated with lower socioeconomic status.

“A possible interpretation of this finding is that maternal sensitive responsiveness is particularly advantageous to children’s language when they are raise in socially disadvantaged families,” they wrote, noting that such an interpretation would be in line with previous research that showed “the protective effect of high-quality parent-child interactions in the context of adversity.”

Limitations of the analysis include that meta-analyses of observational studies are correlational in nature and are generally unable to demonstrate inferences about causality. Another is that the studies in this analysis were limited to children who developed in typical fashion, which limits generalizability to children with language delay, intellectual disability, autism, or hearing/vision difficulties. The analysis was also limited to only mother-child dyads, so the effects of paternal parenting are absent.

“The findings indicate a moderate association between sensitive-responsive parenting and children’s language skills,” the researchers concluded. “Sensitive responsiveness is a modifiable risk that has been successfully trained in parents in randomized trials and shown to improve language development of children.”

A grant from the Social Sciences and Humanities Research Council was awarded to the two of the study’s authors. Two authors’ individual contributions were supported by funding from the Alberta Children’s Hospital Foundation. The authors indicated they have no financial relationships relevant to this article or conflicts of interest to disclose.

[email protected]

SOURCE: Madigan S et al. Pediatrics. 2019 Sep 24. doi: 10.1542/peds.2018-3556.

If you are still struggling to understand the ADHD phenomenon and its meteoric rise to prominence over the last 3 or 4 decades, a study published in the September 2019 Pediatrics may help you make sense of why you are spending a large part of your professional day counseling parents and treating children whose lives are disrupted by their impulsivity, distractibility, and inattentiveness (“24-hour movement behaviors and impulsivity.” doi: 10.1542/peds.2019-0187). Researchers at the Children’s Hospital of Eastern Ontario (Canada) Research Institute used data collected over 10 years in 21 sites across the United States on more than 4,500 children aged 8-11 years, looking for possible associations between impulsivity and three factors – sleep duration, screen time, and physical activity.

Goads Agency/Getty Images

They found that children who were exposed to fewer than 2 hours of recreational screen time each day and slept 9-11 hours nightly had significantly reduced scores on a range of impulsivity scores. While participating in at least 60 minutes of vigorous physical activity per day also was associated with less impulsivity, the effect added little to the benefit of the sleep/screen time combination. Although these nonpharmacologic strategies aimed at decreasing impulsivity may not be a cure-all for every child with symptoms that suggest ADHD, the data are compelling.

I hope that the associations these Canadian researchers have unearthed is not news to you. But their observation that 30% of the sample population met none of the recommendations for sleep, screen time, and activity and that only 5% of the sample did suggests that too few of us are delivering the message with sufficient enthusiasm and/or too many parents aren’t taking it seriously.

Over the last several years I have been encouraged to find sleep and screen time limits mentioned in articles on ADHD for both professionals and parents, but these potent contributors to impulsivity and distractibility always seem to be relegated to the oh-by-the-way category at the end of the article after a lengthy discussion of the relative values of medication and cognitive-behavioral therapy. And unfortunately, meeting these behavioral guidelines can be difficult to achieve and cannot be subcontracted out to a therapist or a pharmacist. They require parents to set and enforce limits. Saying no is difficult for all of us, particularly those without much prior experience.

Have you observed the association between inadequate sleep, excessive screen time, and impulsivity? How robustly have you bought into the idea that more sleep and less screen time are, if not THE answers, at least are the two we should start with? Where do your recommendations about screen time, sleep, and physical activity fit into the script when you are talking with parents about their child’s ADHD-ish behaviors? Have you put them in the oh-by-the-way category?

Do you ever say, “I know you may be expecting me to talk about medication at this visit, but I suggest you try setting and enforcing these limits on sleep and screen time for a few months and we will see how things are going”? “And I am going to give you some suggestions on how you can do this, and we will meet again as often as you feel is necessary to ease the process.”

Do you think you have the time to try this approach? Do you feel you have the skills to counsel on sleep and behavior? Do you think you can find someone with the time and experience who shares your priorities about screen time and sleep to do the parental coaching for you? It’s an approach worth considering when you step back and take the longer look at why we are living through this decades-long ADHD phenomenon.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

If you are still struggling to understand the ADHD phenomenon and its meteoric rise to prominence over the last 3 or 4 decades, a study published in the September 2019 Pediatrics may help you make sense of why you are spending a large part of your professional day counseling parents and treating children whose lives are disrupted by their impulsivity, distractibility, and inattentiveness (“24-hour movement behaviors and impulsivity.” doi: 10.1542/peds.2019-0187). Researchers at the Children’s Hospital of Eastern Ontario (Canada) Research Institute used data collected over 10 years in 21 sites across the United States on more than 4,500 children aged 8-11 years, looking for possible associations between impulsivity and three factors – sleep duration, screen time, and physical activity.

Goads Agency/Getty Images

They found that children who were exposed to fewer than 2 hours of recreational screen time each day and slept 9-11 hours nightly had significantly reduced scores on a range of impulsivity scores. While participating in at least 60 minutes of vigorous physical activity per day also was associated with less impulsivity, the effect added little to the benefit of the sleep/screen time combination. Although these nonpharmacologic strategies aimed at decreasing impulsivity may not be a cure-all for every child with symptoms that suggest ADHD, the data are compelling.

I hope that the associations these Canadian researchers have unearthed is not news to you. But their observation that 30% of the sample population met none of the recommendations for sleep, screen time, and activity and that only 5% of the sample did suggests that too few of us are delivering the message with sufficient enthusiasm and/or too many parents aren’t taking it seriously.

Over the last several years I have been encouraged to find sleep and screen time limits mentioned in articles on ADHD for both professionals and parents, but these potent contributors to impulsivity and distractibility always seem to be relegated to the oh-by-the-way category at the end of the article after a lengthy discussion of the relative values of medication and cognitive-behavioral therapy. And unfortunately, meeting these behavioral guidelines can be difficult to achieve and cannot be subcontracted out to a therapist or a pharmacist. They require parents to set and enforce limits. Saying no is difficult for all of us, particularly those without much prior experience.

Have you observed the association between inadequate sleep, excessive screen time, and impulsivity? How robustly have you bought into the idea that more sleep and less screen time are, if not THE answers, at least are the two we should start with? Where do your recommendations about screen time, sleep, and physical activity fit into the script when you are talking with parents about their child’s ADHD-ish behaviors? Have you put them in the oh-by-the-way category?

Do you ever say, “I know you may be expecting me to talk about medication at this visit, but I suggest you try setting and enforcing these limits on sleep and screen time for a few months and we will see how things are going”? “And I am going to give you some suggestions on how you can do this, and we will meet again as often as you feel is necessary to ease the process.”

Do you think you have the time to try this approach? Do you feel you have the skills to counsel on sleep and behavior? Do you think you can find someone with the time and experience who shares your priorities about screen time and sleep to do the parental coaching for you? It’s an approach worth considering when you step back and take the longer look at why we are living through this decades-long ADHD phenomenon.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

If you are still struggling to understand the ADHD phenomenon and its meteoric rise to prominence over the last 3 or 4 decades, a study published in the September 2019 Pediatrics may help you make sense of why you are spending a large part of your professional day counseling parents and treating children whose lives are disrupted by their impulsivity, distractibility, and inattentiveness (“24-hour movement behaviors and impulsivity.” doi: 10.1542/peds.2019-0187). Researchers at the Children’s Hospital of Eastern Ontario (Canada) Research Institute used data collected over 10 years in 21 sites across the United States on more than 4,500 children aged 8-11 years, looking for possible associations between impulsivity and three factors – sleep duration, screen time, and physical activity.

Goads Agency/Getty Images

They found that children who were exposed to fewer than 2 hours of recreational screen time each day and slept 9-11 hours nightly had significantly reduced scores on a range of impulsivity scores. While participating in at least 60 minutes of vigorous physical activity per day also was associated with less impulsivity, the effect added little to the benefit of the sleep/screen time combination. Although these nonpharmacologic strategies aimed at decreasing impulsivity may not be a cure-all for every child with symptoms that suggest ADHD, the data are compelling.

I hope that the associations these Canadian researchers have unearthed is not news to you. But their observation that 30% of the sample population met none of the recommendations for sleep, screen time, and activity and that only 5% of the sample did suggests that too few of us are delivering the message with sufficient enthusiasm and/or too many parents aren’t taking it seriously.

Over the last several years I have been encouraged to find sleep and screen time limits mentioned in articles on ADHD for both professionals and parents, but these potent contributors to impulsivity and distractibility always seem to be relegated to the oh-by-the-way category at the end of the article after a lengthy discussion of the relative values of medication and cognitive-behavioral therapy. And unfortunately, meeting these behavioral guidelines can be difficult to achieve and cannot be subcontracted out to a therapist or a pharmacist. They require parents to set and enforce limits. Saying no is difficult for all of us, particularly those without much prior experience.

Have you observed the association between inadequate sleep, excessive screen time, and impulsivity? How robustly have you bought into the idea that more sleep and less screen time are, if not THE answers, at least are the two we should start with? Where do your recommendations about screen time, sleep, and physical activity fit into the script when you are talking with parents about their child’s ADHD-ish behaviors? Have you put them in the oh-by-the-way category?

Do you ever say, “I know you may be expecting me to talk about medication at this visit, but I suggest you try setting and enforcing these limits on sleep and screen time for a few months and we will see how things are going”? “And I am going to give you some suggestions on how you can do this, and we will meet again as often as you feel is necessary to ease the process.”

Do you think you have the time to try this approach? Do you feel you have the skills to counsel on sleep and behavior? Do you think you can find someone with the time and experience who shares your priorities about screen time and sleep to do the parental coaching for you? It’s an approach worth considering when you step back and take the longer look at why we are living through this decades-long ADHD phenomenon.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

Most patients with stage III non–small cell lung cancer (NSCLC) who have distant progression on standard therapy typically have one or two new lesions, often in the same organ, which suggests a role for local ablative therapy, according to investigators.

This conclusion was drawn from an exploratory analysis of the phase 3 PACIFIC trial, which previously showed that durvalumab prolonged survival among patients with NSCLC who did not progress after chemoradiotherapy, which turned the trial protocol into a new standard of care.

At the annual meeting of the American Society for Radiation Oncology, coauthor Andreas Rimner, MD, of the Memorial Sloan Kettering Cancer Center in New York presented findings.

“There were always questions regarding detailed patterns of failure and disease progression in [the PACIFIC] trial,” Dr. Rimner said. “This study ... focuses on these patterns of failure, including the type of first progression in the patients on the PACIFIC trial.”

During the trial, 713 patients with NSCLC were randomized in a 2:1 ratio to receive either durvalumab or placebo. After a median follow-up of 25.2 months, the superiority of durvalumab was clear, with a lower rate of progression (45.4% vs. 64.6%).

But the present analysis dug deeper into this finding by dividing patients into three groups based on site or sites of first progression: local (intrathoracic) progression only, distant (extrathoracic) progression only, or simultaneously local and distant progression. Scans were reviewed by an independent radiologist who was not involved in the original PACIFIC trial. In addition to spatial data, the investigators reported times until progression.

Regardless of site, durvalumab was associated with a longer time until progression or death. Although comparative values were not reached for distant or simultaneous spread, median time until local progression or death was reportable, at 25.2 months in the durvalumab group versus with 9.2 months in the placebo group.

These values were available, in part, because local spread was the most common type of progression: It occurred in 80.6% of patients who progressed on durvalumab and 74.5% of progressors in the placebo group.

Durvalumab reduced the rate of progression across the three spatial categories, compared with placebo, including local only (36.6% vs. 48.1%, respectively), distant only (6.9% vs. 13.1%), and simultaneously local and distant (1.9% vs. 3.4%). This means that, at first progression, new distant lesions were found in 8.8% of patients treated with durvalumab, compared with 16.5% of those treated with placebo. Of note, approximately two-thirds of patients with distant progression had only one or two distant lesions, often confined to one organ, most commonly the brain. This pattern of progression was observed in both treatment arms.

According to Dr. Rimner, this finding is clinically relevant because it suggests a potential role for local ablative therapy.

Expert perspective on the analysis was provided by Benjamin Movsas, MD, chair of radiation oncology at the Henry Ford Cancer Institute in Detroit.

“The PACIFIC trial has really transformed the standard of care for patients with locally advanced, inoperable non–small cell lung cancer by adding immunotherapy to the prior standard of care combining chemotherapy and radiation, and this has shown a dramatic improvement in survival,” Dr. Movsas said.

“By adding the immunotherapy durvalumab, you can reduce risk of local failure, you can reduce the risk of distant failure, and interestingly enough, when patients do fail distantly, and this is true in both arms, they tended to fail in only one or two spots, which is encouraging because that suggests maybe a window of opportunity to treat those one or two spots, and we have newer technologies that allow us to consider that. So we really have a new paradigm.”

The study was funded by AstraZeneca. The investigators disclosed additional relationships with Merck, Nanobiotix, Boehringer Ingelheim, and others.

SOURCE: Rimner A et al. ASTRO 2019, Abstract LBA6.

Most patients with stage III non–small cell lung cancer (NSCLC) who have distant progression on standard therapy typically have one or two new lesions, often in the same organ, which suggests a role for local ablative therapy, according to investigators.

This conclusion was drawn from an exploratory analysis of the phase 3 PACIFIC trial, which previously showed that durvalumab prolonged survival among patients with NSCLC who did not progress after chemoradiotherapy, which turned the trial protocol into a new standard of care.

At the annual meeting of the American Society for Radiation Oncology, coauthor Andreas Rimner, MD, of the Memorial Sloan Kettering Cancer Center in New York presented findings.

“There were always questions regarding detailed patterns of failure and disease progression in [the PACIFIC] trial,” Dr. Rimner said. “This study ... focuses on these patterns of failure, including the type of first progression in the patients on the PACIFIC trial.”

During the trial, 713 patients with NSCLC were randomized in a 2:1 ratio to receive either durvalumab or placebo. After a median follow-up of 25.2 months, the superiority of durvalumab was clear, with a lower rate of progression (45.4% vs. 64.6%).

But the present analysis dug deeper into this finding by dividing patients into three groups based on site or sites of first progression: local (intrathoracic) progression only, distant (extrathoracic) progression only, or simultaneously local and distant progression. Scans were reviewed by an independent radiologist who was not involved in the original PACIFIC trial. In addition to spatial data, the investigators reported times until progression.

Regardless of site, durvalumab was associated with a longer time until progression or death. Although comparative values were not reached for distant or simultaneous spread, median time until local progression or death was reportable, at 25.2 months in the durvalumab group versus with 9.2 months in the placebo group.

These values were available, in part, because local spread was the most common type of progression: It occurred in 80.6% of patients who progressed on durvalumab and 74.5% of progressors in the placebo group.

Durvalumab reduced the rate of progression across the three spatial categories, compared with placebo, including local only (36.6% vs. 48.1%, respectively), distant only (6.9% vs. 13.1%), and simultaneously local and distant (1.9% vs. 3.4%). This means that, at first progression, new distant lesions were found in 8.8% of patients treated with durvalumab, compared with 16.5% of those treated with placebo. Of note, approximately two-thirds of patients with distant progression had only one or two distant lesions, often confined to one organ, most commonly the brain. This pattern of progression was observed in both treatment arms.

According to Dr. Rimner, this finding is clinically relevant because it suggests a potential role for local ablative therapy.

Expert perspective on the analysis was provided by Benjamin Movsas, MD, chair of radiation oncology at the Henry Ford Cancer Institute in Detroit.

“The PACIFIC trial has really transformed the standard of care for patients with locally advanced, inoperable non–small cell lung cancer by adding immunotherapy to the prior standard of care combining chemotherapy and radiation, and this has shown a dramatic improvement in survival,” Dr. Movsas said.

“By adding the immunotherapy durvalumab, you can reduce risk of local failure, you can reduce the risk of distant failure, and interestingly enough, when patients do fail distantly, and this is true in both arms, they tended to fail in only one or two spots, which is encouraging because that suggests maybe a window of opportunity to treat those one or two spots, and we have newer technologies that allow us to consider that. So we really have a new paradigm.”

The study was funded by AstraZeneca. The investigators disclosed additional relationships with Merck, Nanobiotix, Boehringer Ingelheim, and others.

SOURCE: Rimner A et al. ASTRO 2019, Abstract LBA6.

Most patients with stage III non–small cell lung cancer (NSCLC) who have distant progression on standard therapy typically have one or two new lesions, often in the same organ, which suggests a role for local ablative therapy, according to investigators.

This conclusion was drawn from an exploratory analysis of the phase 3 PACIFIC trial, which previously showed that durvalumab prolonged survival among patients with NSCLC who did not progress after chemoradiotherapy, which turned the trial protocol into a new standard of care.

At the annual meeting of the American Society for Radiation Oncology, coauthor Andreas Rimner, MD, of the Memorial Sloan Kettering Cancer Center in New York presented findings.

“There were always questions regarding detailed patterns of failure and disease progression in [the PACIFIC] trial,” Dr. Rimner said. “This study ... focuses on these patterns of failure, including the type of first progression in the patients on the PACIFIC trial.”

During the trial, 713 patients with NSCLC were randomized in a 2:1 ratio to receive either durvalumab or placebo. After a median follow-up of 25.2 months, the superiority of durvalumab was clear, with a lower rate of progression (45.4% vs. 64.6%).

But the present analysis dug deeper into this finding by dividing patients into three groups based on site or sites of first progression: local (intrathoracic) progression only, distant (extrathoracic) progression only, or simultaneously local and distant progression. Scans were reviewed by an independent radiologist who was not involved in the original PACIFIC trial. In addition to spatial data, the investigators reported times until progression.

Regardless of site, durvalumab was associated with a longer time until progression or death. Although comparative values were not reached for distant or simultaneous spread, median time until local progression or death was reportable, at 25.2 months in the durvalumab group versus with 9.2 months in the placebo group.

These values were available, in part, because local spread was the most common type of progression: It occurred in 80.6% of patients who progressed on durvalumab and 74.5% of progressors in the placebo group.

Durvalumab reduced the rate of progression across the three spatial categories, compared with placebo, including local only (36.6% vs. 48.1%, respectively), distant only (6.9% vs. 13.1%), and simultaneously local and distant (1.9% vs. 3.4%). This means that, at first progression, new distant lesions were found in 8.8% of patients treated with durvalumab, compared with 16.5% of those treated with placebo. Of note, approximately two-thirds of patients with distant progression had only one or two distant lesions, often confined to one organ, most commonly the brain. This pattern of progression was observed in both treatment arms.

According to Dr. Rimner, this finding is clinically relevant because it suggests a potential role for local ablative therapy.

Expert perspective on the analysis was provided by Benjamin Movsas, MD, chair of radiation oncology at the Henry Ford Cancer Institute in Detroit.

“The PACIFIC trial has really transformed the standard of care for patients with locally advanced, inoperable non–small cell lung cancer by adding immunotherapy to the prior standard of care combining chemotherapy and radiation, and this has shown a dramatic improvement in survival,” Dr. Movsas said.

“By adding the immunotherapy durvalumab, you can reduce risk of local failure, you can reduce the risk of distant failure, and interestingly enough, when patients do fail distantly, and this is true in both arms, they tended to fail in only one or two spots, which is encouraging because that suggests maybe a window of opportunity to treat those one or two spots, and we have newer technologies that allow us to consider that. So we really have a new paradigm.”

The study was funded by AstraZeneca. The investigators disclosed additional relationships with Merck, Nanobiotix, Boehringer Ingelheim, and others.

SOURCE: Rimner A et al. ASTRO 2019, Abstract LBA6.

Stereotactic ablative radiation therapy (SABR) may be able to extend progression-free survival (PFS) among patients with oligometastatic prostate cancer, based on results from the phase 2 ORIOLE trial.

Will Pass/MDedge News

SABR appeared to control disease, in part, by triggering a systemic immune response, reported lead author Ryan Phillips, MD, PhD, chief resident of radiation oncology at Johns Hopkins Sidney Kimmel Cancer Center in Baltimore, at the annual meeting of the American Society for Radiation Oncology. This is a particularly noteworthy finding, since prostate cancer is generally considered to be immunologically cold, Dr. Phillips explained.

The ORIOLE trial also demonstrated how prostate-specific membrane antigen (PSMA)–based PET/CT scans can be used to more accurately predict metastasis by detecting lesions that would otherwise be missed by standard imaging.

“There’s a hypothesis that these first few sites of spread pave the way for additional widespread metastasis down the road,” Dr. Phillips said, “and that if we can treat all detectable disease early enough, we may be able to provide long-term control or in the best-case scenario, be able to cure these patients of early metastatic disease.”

The trial involved 54 men with recurrent, hormone-sensitive prostate cancer who had been previously treated with radiation therapy or surgery. Additional eligibility requirements included one to three lesions that were 5 cm or smaller, detectable by MRI, CT, or bone scan; a prostate-specific antigen (PSA) doubling time of less than 15 months; and an Eastern Cooperative Oncology Group performance status of 2 or less.

Patients were randomized in a 2:1 ratio to receive either SABR or observation, with follow-up every 3 months including physical exam and PSA measurement, and at 6 months, CT and bone scan. The primary endpoint was disease progression at 6 months.

In addition to this protocol, biomarker correlative analyses were performed, including PSMA-based PET/CT, T-cell clonality testing, and circulating tumor DNA (ctDNA) assessment.

Results showed that significantly fewer men treated with SABR had disease progression at 6 months (19% vs. 61%; P = .005). This benefit extended beyond the primary endpoint, as median PFS among patients treated with SABR was not yet reached after more than a year of follow-up, while those in the observation group had a median PFS of 5.8 months (P = .0023).

“Clinically, this is promising,” Dr. Phillips said, “but we also were really interested in learning more about oligometastatic prostate cancer, and something that sets ORIOLE apart are the correlative studies.”

The first of these studies involved PSMA-based PET/CT, which can identify lesions that may be missed or underappreciated with conventional imaging. Within the SABR group, 35 of 36 men had PSMA-based PET/CT performed at baseline and 6 months later. Of these, 19 had all PSMA-based PET/CT–detectable lesions treated with SABR (total consolidation), while 16 had subtotal consolidation. This difference was predictive of outcome, as only 16% of patients with total consolidation developed new lesions 6 months later, compared with 63% of those who had subtotal consolidation (P = .006).

“Not only are we treating the disease we’re detecting, but it seems to be preventing the development of new metastases outside the areas that we treated,” Dr. Phillips said. “This also held when we looked at points beyond 6 months,” he added.

Further testing showed that SABR triggered a systemic adaptive immune response involving expansion of T-cell clones. “There’s a lot more activity and changes within the immune system that were only seen within the SABR arm,” Dr. Phillips said, noting that these changes were “similar in scope to what we see after a vaccination.”

Finally, the investigators assessed ctDNA, which showed that men with at least one high-risk mutation had similar outcomes regardless of treatment group; in contrast, those without any high-risk mutations had significantly better PFS when treated with SABR.

“These are low sample size, hypothesis-generating experiments,” Dr. Phillips said, “but it is promising that there may be measurable baseline factors that will help us decide which patients are likely to benefit from this approach, and which would really be better served with an alternate treatment strategy.”

Will Pass/MDedge News

Session moderator Anthony Zietman, MD, of Massachusetts General Hospital, Boston, suggested that the ORIOLE trial could have a big future. “This is a small study, but it’s a prospective study, and the findings are really provocative,” Dr. Zietman said. “Just imagine, if there was a patient with just two or three metastatic lesions, and by irradiating those, you could liberate proteins from the destroyed metastases, generate an immune response, and suppress the development of new metastases, that will be something extraordinary. So this trial will be followed very closely as it seems to be hinting at something that’s a bit of a Holy Grail in oncology.”

The investigators disclosed relationships with RefleXion Medical, Pfizer, Genentech, and others.

SOURCE: Phillips R et al. ASTRO 2019. Abstract LBA3.

Stereotactic ablative radiation therapy (SABR) may be able to extend progression-free survival (PFS) among patients with oligometastatic prostate cancer, based on results from the phase 2 ORIOLE trial.

Will Pass/MDedge News

SABR appeared to control disease, in part, by triggering a systemic immune response, reported lead author Ryan Phillips, MD, PhD, chief resident of radiation oncology at Johns Hopkins Sidney Kimmel Cancer Center in Baltimore, at the annual meeting of the American Society for Radiation Oncology. This is a particularly noteworthy finding, since prostate cancer is generally considered to be immunologically cold, Dr. Phillips explained.

The ORIOLE trial also demonstrated how prostate-specific membrane antigen (PSMA)–based PET/CT scans can be used to more accurately predict metastasis by detecting lesions that would otherwise be missed by standard imaging.

“There’s a hypothesis that these first few sites of spread pave the way for additional widespread metastasis down the road,” Dr. Phillips said, “and that if we can treat all detectable disease early enough, we may be able to provide long-term control or in the best-case scenario, be able to cure these patients of early metastatic disease.”

The trial involved 54 men with recurrent, hormone-sensitive prostate cancer who had been previously treated with radiation therapy or surgery. Additional eligibility requirements included one to three lesions that were 5 cm or smaller, detectable by MRI, CT, or bone scan; a prostate-specific antigen (PSA) doubling time of less than 15 months; and an Eastern Cooperative Oncology Group performance status of 2 or less.

Patients were randomized in a 2:1 ratio to receive either SABR or observation, with follow-up every 3 months including physical exam and PSA measurement, and at 6 months, CT and bone scan. The primary endpoint was disease progression at 6 months.

In addition to this protocol, biomarker correlative analyses were performed, including PSMA-based PET/CT, T-cell clonality testing, and circulating tumor DNA (ctDNA) assessment.

Results showed that significantly fewer men treated with SABR had disease progression at 6 months (19% vs. 61%; P = .005). This benefit extended beyond the primary endpoint, as median PFS among patients treated with SABR was not yet reached after more than a year of follow-up, while those in the observation group had a median PFS of 5.8 months (P = .0023).

“Clinically, this is promising,” Dr. Phillips said, “but we also were really interested in learning more about oligometastatic prostate cancer, and something that sets ORIOLE apart are the correlative studies.”

The first of these studies involved PSMA-based PET/CT, which can identify lesions that may be missed or underappreciated with conventional imaging. Within the SABR group, 35 of 36 men had PSMA-based PET/CT performed at baseline and 6 months later. Of these, 19 had all PSMA-based PET/CT–detectable lesions treated with SABR (total consolidation), while 16 had subtotal consolidation. This difference was predictive of outcome, as only 16% of patients with total consolidation developed new lesions 6 months later, compared with 63% of those who had subtotal consolidation (P = .006).

“Not only are we treating the disease we’re detecting, but it seems to be preventing the development of new metastases outside the areas that we treated,” Dr. Phillips said. “This also held when we looked at points beyond 6 months,” he added.

Further testing showed that SABR triggered a systemic adaptive immune response involving expansion of T-cell clones. “There’s a lot more activity and changes within the immune system that were only seen within the SABR arm,” Dr. Phillips said, noting that these changes were “similar in scope to what we see after a vaccination.”

Finally, the investigators assessed ctDNA, which showed that men with at least one high-risk mutation had similar outcomes regardless of treatment group; in contrast, those without any high-risk mutations had significantly better PFS when treated with SABR.

“These are low sample size, hypothesis-generating experiments,” Dr. Phillips said, “but it is promising that there may be measurable baseline factors that will help us decide which patients are likely to benefit from this approach, and which would really be better served with an alternate treatment strategy.”

Will Pass/MDedge News

Session moderator Anthony Zietman, MD, of Massachusetts General Hospital, Boston, suggested that the ORIOLE trial could have a big future. “This is a small study, but it’s a prospective study, and the findings are really provocative,” Dr. Zietman said. “Just imagine, if there was a patient with just two or three metastatic lesions, and by irradiating those, you could liberate proteins from the destroyed metastases, generate an immune response, and suppress the development of new metastases, that will be something extraordinary. So this trial will be followed very closely as it seems to be hinting at something that’s a bit of a Holy Grail in oncology.”

The investigators disclosed relationships with RefleXion Medical, Pfizer, Genentech, and others.

SOURCE: Phillips R et al. ASTRO 2019. Abstract LBA3.

Stereotactic ablative radiation therapy (SABR) may be able to extend progression-free survival (PFS) among patients with oligometastatic prostate cancer, based on results from the phase 2 ORIOLE trial.

Will Pass/MDedge News

SABR appeared to control disease, in part, by triggering a systemic immune response, reported lead author Ryan Phillips, MD, PhD, chief resident of radiation oncology at Johns Hopkins Sidney Kimmel Cancer Center in Baltimore, at the annual meeting of the American Society for Radiation Oncology. This is a particularly noteworthy finding, since prostate cancer is generally considered to be immunologically cold, Dr. Phillips explained.

The ORIOLE trial also demonstrated how prostate-specific membrane antigen (PSMA)–based PET/CT scans can be used to more accurately predict metastasis by detecting lesions that would otherwise be missed by standard imaging.

“There’s a hypothesis that these first few sites of spread pave the way for additional widespread metastasis down the road,” Dr. Phillips said, “and that if we can treat all detectable disease early enough, we may be able to provide long-term control or in the best-case scenario, be able to cure these patients of early metastatic disease.”

The trial involved 54 men with recurrent, hormone-sensitive prostate cancer who had been previously treated with radiation therapy or surgery. Additional eligibility requirements included one to three lesions that were 5 cm or smaller, detectable by MRI, CT, or bone scan; a prostate-specific antigen (PSA) doubling time of less than 15 months; and an Eastern Cooperative Oncology Group performance status of 2 or less.

Patients were randomized in a 2:1 ratio to receive either SABR or observation, with follow-up every 3 months including physical exam and PSA measurement, and at 6 months, CT and bone scan. The primary endpoint was disease progression at 6 months.

In addition to this protocol, biomarker correlative analyses were performed, including PSMA-based PET/CT, T-cell clonality testing, and circulating tumor DNA (ctDNA) assessment.

Results showed that significantly fewer men treated with SABR had disease progression at 6 months (19% vs. 61%; P = .005). This benefit extended beyond the primary endpoint, as median PFS among patients treated with SABR was not yet reached after more than a year of follow-up, while those in the observation group had a median PFS of 5.8 months (P = .0023).

“Clinically, this is promising,” Dr. Phillips said, “but we also were really interested in learning more about oligometastatic prostate cancer, and something that sets ORIOLE apart are the correlative studies.”

The first of these studies involved PSMA-based PET/CT, which can identify lesions that may be missed or underappreciated with conventional imaging. Within the SABR group, 35 of 36 men had PSMA-based PET/CT performed at baseline and 6 months later. Of these, 19 had all PSMA-based PET/CT–detectable lesions treated with SABR (total consolidation), while 16 had subtotal consolidation. This difference was predictive of outcome, as only 16% of patients with total consolidation developed new lesions 6 months later, compared with 63% of those who had subtotal consolidation (P = .006).

“Not only are we treating the disease we’re detecting, but it seems to be preventing the development of new metastases outside the areas that we treated,” Dr. Phillips said. “This also held when we looked at points beyond 6 months,” he added.

Further testing showed that SABR triggered a systemic adaptive immune response involving expansion of T-cell clones. “There’s a lot more activity and changes within the immune system that were only seen within the SABR arm,” Dr. Phillips said, noting that these changes were “similar in scope to what we see after a vaccination.”

Finally, the investigators assessed ctDNA, which showed that men with at least one high-risk mutation had similar outcomes regardless of treatment group; in contrast, those without any high-risk mutations had significantly better PFS when treated with SABR.

“These are low sample size, hypothesis-generating experiments,” Dr. Phillips said, “but it is promising that there may be measurable baseline factors that will help us decide which patients are likely to benefit from this approach, and which would really be better served with an alternate treatment strategy.”

Will Pass/MDedge News

Session moderator Anthony Zietman, MD, of Massachusetts General Hospital, Boston, suggested that the ORIOLE trial could have a big future. “This is a small study, but it’s a prospective study, and the findings are really provocative,” Dr. Zietman said. “Just imagine, if there was a patient with just two or three metastatic lesions, and by irradiating those, you could liberate proteins from the destroyed metastases, generate an immune response, and suppress the development of new metastases, that will be something extraordinary. So this trial will be followed very closely as it seems to be hinting at something that’s a bit of a Holy Grail in oncology.”

The investigators disclosed relationships with RefleXion Medical, Pfizer, Genentech, and others.

SOURCE: Phillips R et al. ASTRO 2019. Abstract LBA3.

NEW YORK –The work of the dermatologist doesn’t need to stop at the lips, according to Nasim Fazel, MD, DDS, a board-certified dermatologist and dentist. With a light touch driven by understanding of the oral mucosa, dermatologists can confidently obtain high-quality specimens and manage many intra-oral cutaneous conditions, she said, speaking at a session focused on oral health and procedures at the American Academy of Dermatology summer meeting.

Whether to perform an incisional or excisional biopsy on the lips or within the oral cavity is a decision driven by the clinical scenario, said Dr. Fazel, professor of clinical dermatology and director of the oral mucosal disease clinic at the University of California, Davis. Variables to consider, she said, include the size of the lesion, as well as whether the lesion is symptomatic or there’s any functional impairment. Other factors to bear in mind are whether the patient has any comorbid inflammatory conditions and whether the lesion could be malignant.

An excisional biopsy is a good procedure for small lesions that are thought to be benign, especially if they are exophytic, she noted. An example would be a traumatic fibroma, she said. This technique is also appropriate if there’s concern for dysplasia or malignancy if an office excisional biopsy is feasible given lesion size and location.

On the labial mucosa, an elliptical incision is often a good choice.
 

Cutaneous lip procedures

On the cutaneous lip, a punch incision can be feasible. The vermilion border should be marked to maintain orientation. “Avoid transecting the vermilion border to the extent that it’s possible,” said Dr. Fazel. Keep the vascular anatomy in mind as well, she added, since there’s a risk of severing the superior or inferior labial artery with procedures in this area. If this should happen, the branch can be identified and ligated with 4-0 fast gut or chromic gut suture material, she advised.

Another option on the cutaneous lip is shave removal. Here, a chalazion clamp can be used for both exposure and hemostasis. “Always suture parallel to the lip lines, and caution the patient that there may be significant, noticeable blanching when lip anesthesia’s used,” she said.
 

Gingival and tongue procedures

Moving to territory that may be less familiar for some dermatologists, Dr. Fazel walked through the process of a gingival punch biopsy. “Use local anesthetic, but a small quantity is sufficient,” she said. Using gentle pressure, the operator can work the punch instrument down to periosteal bone. At that point, just scissors can be used for undermining the specimen, with minimal disturbance of the mucosal surface.

Hemostasis after a gingival punch can be accomplished with silver nitrate or aluminum chloride or by electrocautery. A permanent defect in the gingiva can occur even with good technique, she said – a fact that should be included in the informed consent document for the procedure.

For lesions on the tongue, a shave removal can be considered, as can an incisional punch biopsy. An assistant’s hands are invaluable for stabilizing the tongue, said Dr. Fazel, illustrating that small dry gauze squares help achieve a good grip.
 

Considerations in biopsy technique

Dr. Fazel offered some tips and considerations when a punch biopsy is being done in the context of a chronic oral inflammatory condition, and the plan is to submit for hematoxylin and eosin (H&E) staining and direct immunofluorescence (DIF). Conditions where an intraoral punch biopsy would be considered include bullous or mucous membrane pemphigoid, pemphigus, lichen planus, and systemic lupus erythematosus, she said.

“Select a site with the most significant inflammatory changes” and aim for the most anterior site that exhibits these characteristics to maximize exposure and ensure a good specimen. The labial mucosa is a better choice in general than buccal mucosa, she said. “Maxillary and mandibular sulci are tricky sites,” especially when perilesional and lesional tissue should be included in the biopsies.

Next, Dr. Fazel walked attendees through general principles of preparing for and performing punch biopsies for H&E and DIF. In planning the biopsies, the DIF specimen should ideally be collected before the H&E specimen because the former technique will have higher yield when the specimen is taken from a less bloody field. “The yield of DIF is higher from the gingiva than from nonkeratinized surfaces.”

When infiltrating the biopsy site with local anesthesia, the needle should be centered within the lesion or general area to be biopsied, and care should be taken to maintain the orientation of the lesion to the surrounding tissue. Anesthesia can be infiltrated within the submucosal plane; the resultant ballooning will elevate the tissue to be biopsied and ease the procedure, she said.

Choose a 3-mm punch tool for gingival biopsies; 4 mm is a good size for other nonkeratinized surfaces. Unlike the procedure used for cutaneous biopsies, on delicate oral tissues, “you don’t need to hub your punch tool,” Dr. Fazel said. Similarly, the tool can be driven with firm rotation in one direction, rather than ratcheting back and forth, which may fray and deform the biopsy margins, she added. The specimen can be freed from surrounding mucosa with scissors alone and a gentle snipping motion; everting the tissue will help achieve the desired clean and gentle technique.

Because of the delicacy of the tissue, “it’s important to minimize the use of forceps, as well as any unnecessary manipulation of tissue in the process of specimen collection,” she said.
 

Salivary gland biopsies and intraoral suturing

Even minor salivary glands can be biopsied in a fairly straightforward way, though there’s a risk of short- and long-term loss of sensation, as well as more scarring than in other routine intraoral biopsies. Though these salivary glands lie just beneath the oral mucosa, care must be taken to avoid laceration of the orbicularis oris muscle during excision, noted Dr. Fazel. With a minor salivary gland biopsy, as with some other intraoral procedures, sutures will be needed. Consideration for the friability of the oral mucosa should drive suture material choice and closure technique.

First, “take bigger bites on each side of the incision, to minimize the risk of the suture tearing through the mucosa,” she said. Avoid forceps while suturing if possible, but be gentle if they are employed, “and be gentle tying knots: retract the mucosa as little as possible and cinch the knots down tightly with your fingers.”

Electrocautery, silver nitrate, and aluminum chloride are all reasonable options for hemostasis, although patients should be alerted that the tissue will have a charred appearance if electrocautery is used. Primary closure may be all that’s needed for hemostasis, said Dr. Fazel.

If nonabsorbable suture materials are used, nylon and prolene should be avoided since they tend to tear through the oral mucosa. Soft or braided silk are good choices, she said, and sutures can come out in 5-7 days.

Absorbable sutures have the advantage of not requiring removal, but they can be more irritating to the surrounding mucosa. Chromic or fast gut are the choices here, said Dr. Fazel. Whether absorbable or nonabsorbable sutures are placed, the size should be 4-0 or 5-0, she said.
 

Postoperative care, complications, and the limits of the dermatologist

Postoperatively, patients should know that swelling is to be expected, especially with procedures like minor salivary gland biopsies that involve the lip. Icing 15 minutes per hour for the first few hours will help with swelling; wound care is optimized with gentle salt water rinses. A bland diet that avoids acidic, spicy, and excessively hot foods and beverages will minimize wound irritation. Foods with sharp edges like chips, crackers, and nuts can actually catch sutures and cause pain and bleeding, so these too should be avoided.

As with dental work, care should be taken with eating or drinking until anesthesia has worn off, which may take up to 3 hours. Patients should also be cautioned that sutures are likely to come out prematurely just because of the mobility of the structures of the mouth with normal activities such as eating and talking.

Should a wound infection occur, said Dr. Fazel, it’s likely that mixed aerobic and anaerobic bacteria are to blame; accordingly, broad-spectrum beta-lactam antibiotics can be a good first-line course. More severe infections are more likely to have an anaerobic or gram-negative etiology; metronidazole is a reasonable choice for anaerobic coverage, she noted. The life-threatening complication not to miss is cellulitis of the floor of the mouth, or Ludwig angina. The swelling results in superior and posterior displacement of the tongue, obstructing the upper airway, so any patient suspected of having Ludwig angina needs emergent evaluation and treatment.

When should a dermatologist consider referral to an otolaryngologist rather than diving into a biopsy in the dermatology clinic? If the area of concern is on the posterior third of the tongue, access without special tools or higher levels of anesthesia becomes tricky, Dr. Fazel pointed out. The posterior hard palate, the soft palate, and the floor of the mouth are also regions best left to otolaryngologists, she said.

[email protected]

NEW YORK –The work of the dermatologist doesn’t need to stop at the lips, according to Nasim Fazel, MD, DDS, a board-certified dermatologist and dentist. With a light touch driven by understanding of the oral mucosa, dermatologists can confidently obtain high-quality specimens and manage many intra-oral cutaneous conditions, she said, speaking at a session focused on oral health and procedures at the American Academy of Dermatology summer meeting.

Whether to perform an incisional or excisional biopsy on the lips or within the oral cavity is a decision driven by the clinical scenario, said Dr. Fazel, professor of clinical dermatology and director of the oral mucosal disease clinic at the University of California, Davis. Variables to consider, she said, include the size of the lesion, as well as whether the lesion is symptomatic or there’s any functional impairment. Other factors to bear in mind are whether the patient has any comorbid inflammatory conditions and whether the lesion could be malignant.

An excisional biopsy is a good procedure for small lesions that are thought to be benign, especially if they are exophytic, she noted. An example would be a traumatic fibroma, she said. This technique is also appropriate if there’s concern for dysplasia or malignancy if an office excisional biopsy is feasible given lesion size and location.

On the labial mucosa, an elliptical incision is often a good choice.
 

Cutaneous lip procedures

On the cutaneous lip, a punch incision can be feasible. The vermilion border should be marked to maintain orientation. “Avoid transecting the vermilion border to the extent that it’s possible,” said Dr. Fazel. Keep the vascular anatomy in mind as well, she added, since there’s a risk of severing the superior or inferior labial artery with procedures in this area. If this should happen, the branch can be identified and ligated with 4-0 fast gut or chromic gut suture material, she advised.

Another option on the cutaneous lip is shave removal. Here, a chalazion clamp can be used for both exposure and hemostasis. “Always suture parallel to the lip lines, and caution the patient that there may be significant, noticeable blanching when lip anesthesia’s used,” she said.
 

Gingival and tongue procedures

Moving to territory that may be less familiar for some dermatologists, Dr. Fazel walked through the process of a gingival punch biopsy. “Use local anesthetic, but a small quantity is sufficient,” she said. Using gentle pressure, the operator can work the punch instrument down to periosteal bone. At that point, just scissors can be used for undermining the specimen, with minimal disturbance of the mucosal surface.

Hemostasis after a gingival punch can be accomplished with silver nitrate or aluminum chloride or by electrocautery. A permanent defect in the gingiva can occur even with good technique, she said – a fact that should be included in the informed consent document for the procedure.

For lesions on the tongue, a shave removal can be considered, as can an incisional punch biopsy. An assistant’s hands are invaluable for stabilizing the tongue, said Dr. Fazel, illustrating that small dry gauze squares help achieve a good grip.
 

Considerations in biopsy technique

Dr. Fazel offered some tips and considerations when a punch biopsy is being done in the context of a chronic oral inflammatory condition, and the plan is to submit for hematoxylin and eosin (H&E) staining and direct immunofluorescence (DIF). Conditions where an intraoral punch biopsy would be considered include bullous or mucous membrane pemphigoid, pemphigus, lichen planus, and systemic lupus erythematosus, she said.

“Select a site with the most significant inflammatory changes” and aim for the most anterior site that exhibits these characteristics to maximize exposure and ensure a good specimen. The labial mucosa is a better choice in general than buccal mucosa, she said. “Maxillary and mandibular sulci are tricky sites,” especially when perilesional and lesional tissue should be included in the biopsies.

Next, Dr. Fazel walked attendees through general principles of preparing for and performing punch biopsies for H&E and DIF. In planning the biopsies, the DIF specimen should ideally be collected before the H&E specimen because the former technique will have higher yield when the specimen is taken from a less bloody field. “The yield of DIF is higher from the gingiva than from nonkeratinized surfaces.”

When infiltrating the biopsy site with local anesthesia, the needle should be centered within the lesion or general area to be biopsied, and care should be taken to maintain the orientation of the lesion to the surrounding tissue. Anesthesia can be infiltrated within the submucosal plane; the resultant ballooning will elevate the tissue to be biopsied and ease the procedure, she said.

Choose a 3-mm punch tool for gingival biopsies; 4 mm is a good size for other nonkeratinized surfaces. Unlike the procedure used for cutaneous biopsies, on delicate oral tissues, “you don’t need to hub your punch tool,” Dr. Fazel said. Similarly, the tool can be driven with firm rotation in one direction, rather than ratcheting back and forth, which may fray and deform the biopsy margins, she added. The specimen can be freed from surrounding mucosa with scissors alone and a gentle snipping motion; everting the tissue will help achieve the desired clean and gentle technique.

Because of the delicacy of the tissue, “it’s important to minimize the use of forceps, as well as any unnecessary manipulation of tissue in the process of specimen collection,” she said.
 

Salivary gland biopsies and intraoral suturing

Even minor salivary glands can be biopsied in a fairly straightforward way, though there’s a risk of short- and long-term loss of sensation, as well as more scarring than in other routine intraoral biopsies. Though these salivary glands lie just beneath the oral mucosa, care must be taken to avoid laceration of the orbicularis oris muscle during excision, noted Dr. Fazel. With a minor salivary gland biopsy, as with some other intraoral procedures, sutures will be needed. Consideration for the friability of the oral mucosa should drive suture material choice and closure technique.

First, “take bigger bites on each side of the incision, to minimize the risk of the suture tearing through the mucosa,” she said. Avoid forceps while suturing if possible, but be gentle if they are employed, “and be gentle tying knots: retract the mucosa as little as possible and cinch the knots down tightly with your fingers.”

Electrocautery, silver nitrate, and aluminum chloride are all reasonable options for hemostasis, although patients should be alerted that the tissue will have a charred appearance if electrocautery is used. Primary closure may be all that’s needed for hemostasis, said Dr. Fazel.

If nonabsorbable suture materials are used, nylon and prolene should be avoided since they tend to tear through the oral mucosa. Soft or braided silk are good choices, she said, and sutures can come out in 5-7 days.

Absorbable sutures have the advantage of not requiring removal, but they can be more irritating to the surrounding mucosa. Chromic or fast gut are the choices here, said Dr. Fazel. Whether absorbable or nonabsorbable sutures are placed, the size should be 4-0 or 5-0, she said.
 

Postoperative care, complications, and the limits of the dermatologist

Postoperatively, patients should know that swelling is to be expected, especially with procedures like minor salivary gland biopsies that involve the lip. Icing 15 minutes per hour for the first few hours will help with swelling; wound care is optimized with gentle salt water rinses. A bland diet that avoids acidic, spicy, and excessively hot foods and beverages will minimize wound irritation. Foods with sharp edges like chips, crackers, and nuts can actually catch sutures and cause pain and bleeding, so these too should be avoided.

As with dental work, care should be taken with eating or drinking until anesthesia has worn off, which may take up to 3 hours. Patients should also be cautioned that sutures are likely to come out prematurely just because of the mobility of the structures of the mouth with normal activities such as eating and talking.

Should a wound infection occur, said Dr. Fazel, it’s likely that mixed aerobic and anaerobic bacteria are to blame; accordingly, broad-spectrum beta-lactam antibiotics can be a good first-line course. More severe infections are more likely to have an anaerobic or gram-negative etiology; metronidazole is a reasonable choice for anaerobic coverage, she noted. The life-threatening complication not to miss is cellulitis of the floor of the mouth, or Ludwig angina. The swelling results in superior and posterior displacement of the tongue, obstructing the upper airway, so any patient suspected of having Ludwig angina needs emergent evaluation and treatment.

When should a dermatologist consider referral to an otolaryngologist rather than diving into a biopsy in the dermatology clinic? If the area of concern is on the posterior third of the tongue, access without special tools or higher levels of anesthesia becomes tricky, Dr. Fazel pointed out. The posterior hard palate, the soft palate, and the floor of the mouth are also regions best left to otolaryngologists, she said.

[email protected]

NEW YORK –The work of the dermatologist doesn’t need to stop at the lips, according to Nasim Fazel, MD, DDS, a board-certified dermatologist and dentist. With a light touch driven by understanding of the oral mucosa, dermatologists can confidently obtain high-quality specimens and manage many intra-oral cutaneous conditions, she said, speaking at a session focused on oral health and procedures at the American Academy of Dermatology summer meeting.

Whether to perform an incisional or excisional biopsy on the lips or within the oral cavity is a decision driven by the clinical scenario, said Dr. Fazel, professor of clinical dermatology and director of the oral mucosal disease clinic at the University of California, Davis. Variables to consider, she said, include the size of the lesion, as well as whether the lesion is symptomatic or there’s any functional impairment. Other factors to bear in mind are whether the patient has any comorbid inflammatory conditions and whether the lesion could be malignant.

An excisional biopsy is a good procedure for small lesions that are thought to be benign, especially if they are exophytic, she noted. An example would be a traumatic fibroma, she said. This technique is also appropriate if there’s concern for dysplasia or malignancy if an office excisional biopsy is feasible given lesion size and location.

On the labial mucosa, an elliptical incision is often a good choice.
 

Cutaneous lip procedures

On the cutaneous lip, a punch incision can be feasible. The vermilion border should be marked to maintain orientation. “Avoid transecting the vermilion border to the extent that it’s possible,” said Dr. Fazel. Keep the vascular anatomy in mind as well, she added, since there’s a risk of severing the superior or inferior labial artery with procedures in this area. If this should happen, the branch can be identified and ligated with 4-0 fast gut or chromic gut suture material, she advised.

Another option on the cutaneous lip is shave removal. Here, a chalazion clamp can be used for both exposure and hemostasis. “Always suture parallel to the lip lines, and caution the patient that there may be significant, noticeable blanching when lip anesthesia’s used,” she said.
 

Gingival and tongue procedures

Moving to territory that may be less familiar for some dermatologists, Dr. Fazel walked through the process of a gingival punch biopsy. “Use local anesthetic, but a small quantity is sufficient,” she said. Using gentle pressure, the operator can work the punch instrument down to periosteal bone. At that point, just scissors can be used for undermining the specimen, with minimal disturbance of the mucosal surface.

Hemostasis after a gingival punch can be accomplished with silver nitrate or aluminum chloride or by electrocautery. A permanent defect in the gingiva can occur even with good technique, she said – a fact that should be included in the informed consent document for the procedure.

For lesions on the tongue, a shave removal can be considered, as can an incisional punch biopsy. An assistant’s hands are invaluable for stabilizing the tongue, said Dr. Fazel, illustrating that small dry gauze squares help achieve a good grip.
 

Considerations in biopsy technique

Dr. Fazel offered some tips and considerations when a punch biopsy is being done in the context of a chronic oral inflammatory condition, and the plan is to submit for hematoxylin and eosin (H&E) staining and direct immunofluorescence (DIF). Conditions where an intraoral punch biopsy would be considered include bullous or mucous membrane pemphigoid, pemphigus, lichen planus, and systemic lupus erythematosus, she said.

“Select a site with the most significant inflammatory changes” and aim for the most anterior site that exhibits these characteristics to maximize exposure and ensure a good specimen. The labial mucosa is a better choice in general than buccal mucosa, she said. “Maxillary and mandibular sulci are tricky sites,” especially when perilesional and lesional tissue should be included in the biopsies.

Next, Dr. Fazel walked attendees through general principles of preparing for and performing punch biopsies for H&E and DIF. In planning the biopsies, the DIF specimen should ideally be collected before the H&E specimen because the former technique will have higher yield when the specimen is taken from a less bloody field. “The yield of DIF is higher from the gingiva than from nonkeratinized surfaces.”

When infiltrating the biopsy site with local anesthesia, the needle should be centered within the lesion or general area to be biopsied, and care should be taken to maintain the orientation of the lesion to the surrounding tissue. Anesthesia can be infiltrated within the submucosal plane; the resultant ballooning will elevate the tissue to be biopsied and ease the procedure, she said.

Choose a 3-mm punch tool for gingival biopsies; 4 mm is a good size for other nonkeratinized surfaces. Unlike the procedure used for cutaneous biopsies, on delicate oral tissues, “you don’t need to hub your punch tool,” Dr. Fazel said. Similarly, the tool can be driven with firm rotation in one direction, rather than ratcheting back and forth, which may fray and deform the biopsy margins, she added. The specimen can be freed from surrounding mucosa with scissors alone and a gentle snipping motion; everting the tissue will help achieve the desired clean and gentle technique.

Because of the delicacy of the tissue, “it’s important to minimize the use of forceps, as well as any unnecessary manipulation of tissue in the process of specimen collection,” she said.
 

Salivary gland biopsies and intraoral suturing

Even minor salivary glands can be biopsied in a fairly straightforward way, though there’s a risk of short- and long-term loss of sensation, as well as more scarring than in other routine intraoral biopsies. Though these salivary glands lie just beneath the oral mucosa, care must be taken to avoid laceration of the orbicularis oris muscle during excision, noted Dr. Fazel. With a minor salivary gland biopsy, as with some other intraoral procedures, sutures will be needed. Consideration for the friability of the oral mucosa should drive suture material choice and closure technique.

First, “take bigger bites on each side of the incision, to minimize the risk of the suture tearing through the mucosa,” she said. Avoid forceps while suturing if possible, but be gentle if they are employed, “and be gentle tying knots: retract the mucosa as little as possible and cinch the knots down tightly with your fingers.”

Electrocautery, silver nitrate, and aluminum chloride are all reasonable options for hemostasis, although patients should be alerted that the tissue will have a charred appearance if electrocautery is used. Primary closure may be all that’s needed for hemostasis, said Dr. Fazel.

If nonabsorbable suture materials are used, nylon and prolene should be avoided since they tend to tear through the oral mucosa. Soft or braided silk are good choices, she said, and sutures can come out in 5-7 days.

Absorbable sutures have the advantage of not requiring removal, but they can be more irritating to the surrounding mucosa. Chromic or fast gut are the choices here, said Dr. Fazel. Whether absorbable or nonabsorbable sutures are placed, the size should be 4-0 or 5-0, she said.
 

Postoperative care, complications, and the limits of the dermatologist

Postoperatively, patients should know that swelling is to be expected, especially with procedures like minor salivary gland biopsies that involve the lip. Icing 15 minutes per hour for the first few hours will help with swelling; wound care is optimized with gentle salt water rinses. A bland diet that avoids acidic, spicy, and excessively hot foods and beverages will minimize wound irritation. Foods with sharp edges like chips, crackers, and nuts can actually catch sutures and cause pain and bleeding, so these too should be avoided.

As with dental work, care should be taken with eating or drinking until anesthesia has worn off, which may take up to 3 hours. Patients should also be cautioned that sutures are likely to come out prematurely just because of the mobility of the structures of the mouth with normal activities such as eating and talking.

Should a wound infection occur, said Dr. Fazel, it’s likely that mixed aerobic and anaerobic bacteria are to blame; accordingly, broad-spectrum beta-lactam antibiotics can be a good first-line course. More severe infections are more likely to have an anaerobic or gram-negative etiology; metronidazole is a reasonable choice for anaerobic coverage, she noted. The life-threatening complication not to miss is cellulitis of the floor of the mouth, or Ludwig angina. The swelling results in superior and posterior displacement of the tongue, obstructing the upper airway, so any patient suspected of having Ludwig angina needs emergent evaluation and treatment.

When should a dermatologist consider referral to an otolaryngologist rather than diving into a biopsy in the dermatology clinic? If the area of concern is on the posterior third of the tongue, access without special tools or higher levels of anesthesia becomes tricky, Dr. Fazel pointed out. The posterior hard palate, the soft palate, and the floor of the mouth are also regions best left to otolaryngologists, she said.

[email protected]