Dear colleagues,

Colonoscopy is the bread and butter of endoscopy. Multidisciplinary updates continue to support screening colonoscopy in reducing the risk of developing colorectal cancer. But there has been debate about the best uses of resources, especially with increased recognition of colorectal cancer (CRC) in younger patients, and successive guidelines lengthening the intervals for most surveillance colonoscopy.

In particular, when do we feel comfortable recommending cessation of surveillance colonoscopy especially in those who are 75-85 years old? Routine colonoscopy remains a very low-risk procedure even in older patients with multiple comorbidities.

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven (Conn.) VA Medical Center. He is an associate editor for GI & Hepatology News.

Striking a balance: Deciding the optimal age to cease surveillance for colorectal neoplasia

BY PETR PROTIVA, MD, MPH

The appropriate age to stop surveillance for colorectal neoplasia remains uncertain. Screening for average-risk individuals is typically stopped at age 75, but personalized screening with shared decision-making may continue until age 85.¹ Evidence suggests that any survival benefit of screening past age 86 would be outweighed by the harm of screening and/or natural mortality. Nevertheless, determining the optimal age for surveillance in those with a history of neoplasia still poses some challenges. The issue is confounded as many clinicians use the terms “screening” and “surveillance” interchangeably. It should be noted that screening implies the individual is at average risk, while surveillance refers to those at elevated risk because of a personal history of colonic adenomas or cancer

Comorbidities and life expectancy

Despite recent staggering setbacks and a drop in the average life expectancy in the United States, the proportion of individuals older than 65 years old has been steadily increasing to a currently estimated 58.9 million – 16.8% of the U.S. population – and is projected to increase in the future.² However, the prevalence of comorbidities also increases with age, and these are crucial factors to weigh in the decision-making process. Severe comorbid conditions, such as chronic obstructive pulmonary disease, cirrhosis, chronic hepatitis, chronic renal failure, dementia, and congestive heart failure can limit a patient’s ability to undergo surveillance and diminish or negate its benefits. There are online tools that help clinicians estimate life expectancy and time to benefit (that is, time between the intervention and its benefit), such as the Lee or Schonberg index.³ Consensus on time to colorectal screening benefit is about 9-10 years, but may be much shorter for surveillance. Striking a balance between the potential benefits of continued surveillance and the risks and burdens imposed on older adults with limited life expectancy is essential for making well-informed decisions.
 

Age-related risk increase and risk of neoplasia in the surveillance population:

The absolute risk of developing colorectal cancer is dependent on age. In adults aged 45-49, it is 33.4/100,000, rising to 135.6 in those 70-74 years old; in persons aged 85 and older, it is 234.7/100,000.⁴ A significant challenge in determining the appropriate age to stop surveillance is the additional individual risk based on baseline polyp characteristics. It seems reasonable to treat low-risk adenomas similarly to screening and stop surveillance by 85 or 86 years old in most cases. The decision process is less clear in individuals with advanced lesions or a personal history of colon cancer. The prevalence of advanced adenomas on the baseline exam is about 15% and greater than 20% on the follow-up exam if the index adenoma(s) were at least 20 mm in diameter. For five or more adenomas at baseline, the prevalence of advanced lesions on follow-up exam is about 20%. On the other hand, a negative surveillance colonoscopy (that is, no polyps found) is associated with far fewer advanced lesions on follow-up.

Colonoscopy

The safety of colonoscopy in older adults should be considered. The colonoscopy procedure is generally very safe, but is associated with a higher risk of post-procedure complications after outpatient colonoscopy in patients 75 years and older. In addition, comorbidities such as anemia, cardiac arrhythmia, heart failure, hypertension, chronic kidney disease, liver disease, smoking history, and obesity are also risk factors. It should be noted that high-quality colonoscopy is key to the detection and full removal of neoplastic lesions and risk reduction. The inability to achieve adequate colon preparation for any reason or undertaking colonoscopy in patients at high risk for complications reduces its benefit.

Who should oversee surveillance, the primary care physician or gastroenterologist

Should a gastroenterologist oversee the decision on surveillance in older adults based on a combination of age, estimated procedure risk and benefits, patient preferences, and current guidelines? Certainly, it seems appropriate and that this is what most specialists think, according to a recent survey of gastroenterologists and primary care physicians (PCPs) on this topic.⁵ Perhaps, not surprisingly, most PCPs disagreed – PCPs are thoroughly familiar with their patients’ up-to-date comorbidities, functional status, and preferences, and they have the benefit of knowing them for a long time. They also integrate diagnostic results from multiple subspecialists, sometimes from different states. The role of PCPs is critical in centers that offer open-access colonoscopy. Gastroenterologists may be the most appropriate authority to evaluate older individuals for continued surveillance, but in most busy practices these patients are seen by mid-level practitioners. Specialists play an important role if the PCP is uncertain whether surveillance is still indicated or in older patients with a history of advanced adenoma. Therefore, the colonoscopy report or subsequent communication after pathology results are returned should include a recommendation for future surveillance and a clear provision for discontinuing the surveillance in case of future health decline.

Conclusion

Determining the optimal age to discontinue surveillance for colorectal neoplasia involves evaluating multiple factors. Although the age limit is clearer for average-risk screening and low-risk lesion surveillance, uncertainty remains for individuals with advanced neoplasia history. Significant factors in this decision-making process include subsequent neoplasia risk, comorbidities, life expectancy, and age-related risks associated with colonoscopy. Cooperation between PCPs and subspecialty physicians is essential in making surveillance decisions for older adults. PCPs are well positioned to consider detailed patient comorbidities, functional status, and patient preferences, especially with the help of online life-expectancy estimators for most elderly or comorbid patients. To assist in this process, gastroenterologists should state clearly in their procedure report and subsequent pathology letters whether surveillance is recommended and that it is conditional on future comorbidities and should be discontinued if the patient’s health significantly declines.

Dr. Protiva is associate professor of medicine, Yale University, and director of the colon cancer screening program, VA Connecticut Healthcare System, West Haven. Dr. Protiva has no relevant disclosures.

References

1. Patel SG et al. Gastroenterology. 2022;162:285-99

2. U.S. Census Bureau. Measuring America’s People, Places, and Economy

3. University of California, San Francisco. ePrognosis. 4. Siegel RL et al. CA Cancer J Clin. 2023 May-Jun;73(3):233-54.

5. Schoenborn NL et al. Am J Gastroenterol. 2023; 118(3):523-30.

The gastroenterologist should guide the decision to maintain, or halt, surveillance in older adults

BY MARIAM NAVEED, MD

Endoscopic screening and surveillance for CRC in older adults (≥ 75 years old) is a medical “gray area” that needs more high-quality data to inform clinical decision making. In the most recent 2022 clinical guideline update from the U.S. Multisociety Task Force on Colorectal Cancer, the recommendation to stop CRC screening in average risk patients older than 86 years is well supported because of colonoscopy-associated mortality risk outweighing the benefits of adenoma detection and removal. By comparison, screening recommendations for average risk individuals between 76-85 years old are ambiguous and ultimately the decision to proceed with colonoscopy in this clinical population should be individualized based on shared decision making between the provider and patient. Of note, the same guideline provides no specific guidance for ongoing surveillance in the same age group and similarly suggests a shared decision-making approach.¹

As a practicing gastroenterologist in the retirement capital of Florida, older adults comprise a large portion of my clinical practice. I have noticed several aspects unique to this demographic that merit special consideration. For example, a significant percentage of these patients are seasonal (that is, “snowbird”) patients that have multiple sets of doctors (set of physicians in their home state and another set in Florida). Consequently, fragmentation of clinical data enables opportunities for colonoscopies to be wrongly ordered (either in an inappropriate time frame and/or for inaccurate indications). In my own practice, when such a patient is referred for consideration of CRC surveillance, any/all external records must first be obtained and validated as a prerequisite for appropriate clinical counseling and informed decision-making. Additionally, consideration of periprocedural risks is particularly relevant in older adults, secondary to both the increased rate of direct complications and the likelihood of pre-existing comorbidities affecting completion of a safe colonoscopy. Factors that can be easily overlooked include higher rates of poor bowel preparation and corresponding decreased completion rates. Moreover, if the patient has a history of high-risk adenomas or worrisome family history warranting ongoing evaluation, but they also have high-risk comorbidities, I will frequently involve the patient’s cardiologist or pulmonologist to provide medical clearance prior to offering CRC screening/surveillance.

In addition to the clinical ambiguity of appropriateness of continued CRC screening/surveillance in the setting of advanced age, there is also the question of which provider is best positioned to counsel patients regarding this decision-making. Does the onus fall on the gastroenterologist (the proceduralist ultimately performing the procedure) or the PCP (who is likely more familiar with the patient’s overall health profile)? In a recent survey, more than 50% of PCPs reported feeling uncertain in their understanding of risk versus benefit stratification of continued CRC screening in older adults.² While there may be justification for both classes of providers to be involved, in my opinion, the decision to maintain or halt surveillance in older adults should be primarily guided by the gastroenterologist who is better equipped to provide individualized guidance regarding the nuanced risks of disease progression in these patients with prior history of adenomas, and who is clinically responsible for any procedure-related complications.

In an era of cost containment, insurance companies are increasingly placing barriers for approving surveillance and diagnostic colonoscopies. Thus, we need to be ever mindful of appropriately allocating resources to best benefit patients. The data on incidence of polyps and CRC in older adults is inconsistent and even difficult at times for a gastroenterologist to interpret. Therefore, in my opinion, the onus should not fall solely on the PCPs who are not routinely familiar with this information. We as gastroenterologists typically have greater domain-specific knowledge regarding current data and updated guidelines.

Gastroenterologists should wield this expertise to regulate overly liberalized recommendations for continued surveillance in fragile patients, or conversely to intervene in settings of prematurely halting surveillance in high-risk populations with appropriate life expectancy to experience disease progression. It is critical to carefully consider patient-individualized life expectancies, avoid surveillance in patients without clinically significant polyps, avoid over-weighting previous abnormal prior colonoscopies without reviewing more current procedure results, and take time to discuss patient preferences. As proceduralists, we must also be mindful of intrinsic biases towards performing surveillance in patients who are not likely to benefit from this intervention, and several studies have reported on the overuse of surveillance colonoscopies in the form of repeating surveillance earlier than recommended or in the context of limited life expectancy.³

Finally, it is necessary to emphasize that PCPs are critical allies for promoting overall patient health, especially in scenarios where recommendations to discontinue surveillance may not coincide with patient preference. It has been reported that patients usually do not consider poor overall health relevant to decisions regarding CRC surveillance (which I have also experienced to be true).⁴ In these scenarios, partnering with the PCP can be strategic, as patients may be more inclined to trust the guidance of their more familiar physician. At the end of the day, regardless of which provider takes ownership of initiating the discussion surrounding surveillance colonoscopy in older adults, communication is key between all providers and the patient to ensure optimal outcomes.

As the U.S. population continues to age, the demographic of patients aged 65 and older is projected to nearly double by 2060.⁵ Decisions regarding ongoing surveillance for CRC will continue to be frequent and increasingly relevant. The importance of studies generating high-quality data to inform appropriate guidelines specific to this population cannot be understated.

Dr. Naveed is a gastroenterologist and director of the gastroenterology and hepatology fellowship program at AdventHealth Medical Group, Altamonte Springs, Fla. Dr. Naveed had no relevant disclosures.
 

References

1. Patel SG et al. Gastroenterology. 2022 Jan;162(1):285-99.

2 Schoenborn NL et al. Am J Gastroenterol. 2023 Mar 1;118(3):523-30.

3 Calderwood AH et al. JAMA Intern Med. 2023 May 1;183(5):426-34.

4 Schoenborn NL et al. Am J Gastroenterol. 2023 Mar 1;118(3):523-30.

5 U.S. Census Bureau. Population Projections.

Dear colleagues,

Colonoscopy is the bread and butter of endoscopy. Multidisciplinary updates continue to support screening colonoscopy in reducing the risk of developing colorectal cancer. But there has been debate about the best uses of resources, especially with increased recognition of colorectal cancer (CRC) in younger patients, and successive guidelines lengthening the intervals for most surveillance colonoscopy.

In particular, when do we feel comfortable recommending cessation of surveillance colonoscopy especially in those who are 75-85 years old? Routine colonoscopy remains a very low-risk procedure even in older patients with multiple comorbidities.

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven (Conn.) VA Medical Center. He is an associate editor for GI & Hepatology News.

Striking a balance: Deciding the optimal age to cease surveillance for colorectal neoplasia

BY PETR PROTIVA, MD, MPH

The appropriate age to stop surveillance for colorectal neoplasia remains uncertain. Screening for average-risk individuals is typically stopped at age 75, but personalized screening with shared decision-making may continue until age 85.¹ Evidence suggests that any survival benefit of screening past age 86 would be outweighed by the harm of screening and/or natural mortality. Nevertheless, determining the optimal age for surveillance in those with a history of neoplasia still poses some challenges. The issue is confounded as many clinicians use the terms “screening” and “surveillance” interchangeably. It should be noted that screening implies the individual is at average risk, while surveillance refers to those at elevated risk because of a personal history of colonic adenomas or cancer

Comorbidities and life expectancy

Despite recent staggering setbacks and a drop in the average life expectancy in the United States, the proportion of individuals older than 65 years old has been steadily increasing to a currently estimated 58.9 million – 16.8% of the U.S. population – and is projected to increase in the future.² However, the prevalence of comorbidities also increases with age, and these are crucial factors to weigh in the decision-making process. Severe comorbid conditions, such as chronic obstructive pulmonary disease, cirrhosis, chronic hepatitis, chronic renal failure, dementia, and congestive heart failure can limit a patient’s ability to undergo surveillance and diminish or negate its benefits. There are online tools that help clinicians estimate life expectancy and time to benefit (that is, time between the intervention and its benefit), such as the Lee or Schonberg index.³ Consensus on time to colorectal screening benefit is about 9-10 years, but may be much shorter for surveillance. Striking a balance between the potential benefits of continued surveillance and the risks and burdens imposed on older adults with limited life expectancy is essential for making well-informed decisions.
 

Age-related risk increase and risk of neoplasia in the surveillance population:

The absolute risk of developing colorectal cancer is dependent on age. In adults aged 45-49, it is 33.4/100,000, rising to 135.6 in those 70-74 years old; in persons aged 85 and older, it is 234.7/100,000.⁴ A significant challenge in determining the appropriate age to stop surveillance is the additional individual risk based on baseline polyp characteristics. It seems reasonable to treat low-risk adenomas similarly to screening and stop surveillance by 85 or 86 years old in most cases. The decision process is less clear in individuals with advanced lesions or a personal history of colon cancer. The prevalence of advanced adenomas on the baseline exam is about 15% and greater than 20% on the follow-up exam if the index adenoma(s) were at least 20 mm in diameter. For five or more adenomas at baseline, the prevalence of advanced lesions on follow-up exam is about 20%. On the other hand, a negative surveillance colonoscopy (that is, no polyps found) is associated with far fewer advanced lesions on follow-up.

Colonoscopy

The safety of colonoscopy in older adults should be considered. The colonoscopy procedure is generally very safe, but is associated with a higher risk of post-procedure complications after outpatient colonoscopy in patients 75 years and older. In addition, comorbidities such as anemia, cardiac arrhythmia, heart failure, hypertension, chronic kidney disease, liver disease, smoking history, and obesity are also risk factors. It should be noted that high-quality colonoscopy is key to the detection and full removal of neoplastic lesions and risk reduction. The inability to achieve adequate colon preparation for any reason or undertaking colonoscopy in patients at high risk for complications reduces its benefit.

Who should oversee surveillance, the primary care physician or gastroenterologist

Should a gastroenterologist oversee the decision on surveillance in older adults based on a combination of age, estimated procedure risk and benefits, patient preferences, and current guidelines? Certainly, it seems appropriate and that this is what most specialists think, according to a recent survey of gastroenterologists and primary care physicians (PCPs) on this topic.⁵ Perhaps, not surprisingly, most PCPs disagreed – PCPs are thoroughly familiar with their patients’ up-to-date comorbidities, functional status, and preferences, and they have the benefit of knowing them for a long time. They also integrate diagnostic results from multiple subspecialists, sometimes from different states. The role of PCPs is critical in centers that offer open-access colonoscopy. Gastroenterologists may be the most appropriate authority to evaluate older individuals for continued surveillance, but in most busy practices these patients are seen by mid-level practitioners. Specialists play an important role if the PCP is uncertain whether surveillance is still indicated or in older patients with a history of advanced adenoma. Therefore, the colonoscopy report or subsequent communication after pathology results are returned should include a recommendation for future surveillance and a clear provision for discontinuing the surveillance in case of future health decline.

Conclusion

Determining the optimal age to discontinue surveillance for colorectal neoplasia involves evaluating multiple factors. Although the age limit is clearer for average-risk screening and low-risk lesion surveillance, uncertainty remains for individuals with advanced neoplasia history. Significant factors in this decision-making process include subsequent neoplasia risk, comorbidities, life expectancy, and age-related risks associated with colonoscopy. Cooperation between PCPs and subspecialty physicians is essential in making surveillance decisions for older adults. PCPs are well positioned to consider detailed patient comorbidities, functional status, and patient preferences, especially with the help of online life-expectancy estimators for most elderly or comorbid patients. To assist in this process, gastroenterologists should state clearly in their procedure report and subsequent pathology letters whether surveillance is recommended and that it is conditional on future comorbidities and should be discontinued if the patient’s health significantly declines.

Dr. Protiva is associate professor of medicine, Yale University, and director of the colon cancer screening program, VA Connecticut Healthcare System, West Haven. Dr. Protiva has no relevant disclosures.

References

1. Patel SG et al. Gastroenterology. 2022;162:285-99

2. U.S. Census Bureau. Measuring America’s People, Places, and Economy

3. University of California, San Francisco. ePrognosis. 4. Siegel RL et al. CA Cancer J Clin. 2023 May-Jun;73(3):233-54.

5. Schoenborn NL et al. Am J Gastroenterol. 2023; 118(3):523-30.

The gastroenterologist should guide the decision to maintain, or halt, surveillance in older adults

BY MARIAM NAVEED, MD

Endoscopic screening and surveillance for CRC in older adults (≥ 75 years old) is a medical “gray area” that needs more high-quality data to inform clinical decision making. In the most recent 2022 clinical guideline update from the U.S. Multisociety Task Force on Colorectal Cancer, the recommendation to stop CRC screening in average risk patients older than 86 years is well supported because of colonoscopy-associated mortality risk outweighing the benefits of adenoma detection and removal. By comparison, screening recommendations for average risk individuals between 76-85 years old are ambiguous and ultimately the decision to proceed with colonoscopy in this clinical population should be individualized based on shared decision making between the provider and patient. Of note, the same guideline provides no specific guidance for ongoing surveillance in the same age group and similarly suggests a shared decision-making approach.¹

As a practicing gastroenterologist in the retirement capital of Florida, older adults comprise a large portion of my clinical practice. I have noticed several aspects unique to this demographic that merit special consideration. For example, a significant percentage of these patients are seasonal (that is, “snowbird”) patients that have multiple sets of doctors (set of physicians in their home state and another set in Florida). Consequently, fragmentation of clinical data enables opportunities for colonoscopies to be wrongly ordered (either in an inappropriate time frame and/or for inaccurate indications). In my own practice, when such a patient is referred for consideration of CRC surveillance, any/all external records must first be obtained and validated as a prerequisite for appropriate clinical counseling and informed decision-making. Additionally, consideration of periprocedural risks is particularly relevant in older adults, secondary to both the increased rate of direct complications and the likelihood of pre-existing comorbidities affecting completion of a safe colonoscopy. Factors that can be easily overlooked include higher rates of poor bowel preparation and corresponding decreased completion rates. Moreover, if the patient has a history of high-risk adenomas or worrisome family history warranting ongoing evaluation, but they also have high-risk comorbidities, I will frequently involve the patient’s cardiologist or pulmonologist to provide medical clearance prior to offering CRC screening/surveillance.

In addition to the clinical ambiguity of appropriateness of continued CRC screening/surveillance in the setting of advanced age, there is also the question of which provider is best positioned to counsel patients regarding this decision-making. Does the onus fall on the gastroenterologist (the proceduralist ultimately performing the procedure) or the PCP (who is likely more familiar with the patient’s overall health profile)? In a recent survey, more than 50% of PCPs reported feeling uncertain in their understanding of risk versus benefit stratification of continued CRC screening in older adults.² While there may be justification for both classes of providers to be involved, in my opinion, the decision to maintain or halt surveillance in older adults should be primarily guided by the gastroenterologist who is better equipped to provide individualized guidance regarding the nuanced risks of disease progression in these patients with prior history of adenomas, and who is clinically responsible for any procedure-related complications.

In an era of cost containment, insurance companies are increasingly placing barriers for approving surveillance and diagnostic colonoscopies. Thus, we need to be ever mindful of appropriately allocating resources to best benefit patients. The data on incidence of polyps and CRC in older adults is inconsistent and even difficult at times for a gastroenterologist to interpret. Therefore, in my opinion, the onus should not fall solely on the PCPs who are not routinely familiar with this information. We as gastroenterologists typically have greater domain-specific knowledge regarding current data and updated guidelines.

Gastroenterologists should wield this expertise to regulate overly liberalized recommendations for continued surveillance in fragile patients, or conversely to intervene in settings of prematurely halting surveillance in high-risk populations with appropriate life expectancy to experience disease progression. It is critical to carefully consider patient-individualized life expectancies, avoid surveillance in patients without clinically significant polyps, avoid over-weighting previous abnormal prior colonoscopies without reviewing more current procedure results, and take time to discuss patient preferences. As proceduralists, we must also be mindful of intrinsic biases towards performing surveillance in patients who are not likely to benefit from this intervention, and several studies have reported on the overuse of surveillance colonoscopies in the form of repeating surveillance earlier than recommended or in the context of limited life expectancy.³

Finally, it is necessary to emphasize that PCPs are critical allies for promoting overall patient health, especially in scenarios where recommendations to discontinue surveillance may not coincide with patient preference. It has been reported that patients usually do not consider poor overall health relevant to decisions regarding CRC surveillance (which I have also experienced to be true).⁴ In these scenarios, partnering with the PCP can be strategic, as patients may be more inclined to trust the guidance of their more familiar physician. At the end of the day, regardless of which provider takes ownership of initiating the discussion surrounding surveillance colonoscopy in older adults, communication is key between all providers and the patient to ensure optimal outcomes.

As the U.S. population continues to age, the demographic of patients aged 65 and older is projected to nearly double by 2060.⁵ Decisions regarding ongoing surveillance for CRC will continue to be frequent and increasingly relevant. The importance of studies generating high-quality data to inform appropriate guidelines specific to this population cannot be understated.

Dr. Naveed is a gastroenterologist and director of the gastroenterology and hepatology fellowship program at AdventHealth Medical Group, Altamonte Springs, Fla. Dr. Naveed had no relevant disclosures.
 

References

1. Patel SG et al. Gastroenterology. 2022 Jan;162(1):285-99.

2 Schoenborn NL et al. Am J Gastroenterol. 2023 Mar 1;118(3):523-30.

3 Calderwood AH et al. JAMA Intern Med. 2023 May 1;183(5):426-34.

4 Schoenborn NL et al. Am J Gastroenterol. 2023 Mar 1;118(3):523-30.

5 U.S. Census Bureau. Population Projections.

Dear colleagues,

Colonoscopy is the bread and butter of endoscopy. Multidisciplinary updates continue to support screening colonoscopy in reducing the risk of developing colorectal cancer. But there has been debate about the best uses of resources, especially with increased recognition of colorectal cancer (CRC) in younger patients, and successive guidelines lengthening the intervals for most surveillance colonoscopy.

In particular, when do we feel comfortable recommending cessation of surveillance colonoscopy especially in those who are 75-85 years old? Routine colonoscopy remains a very low-risk procedure even in older patients with multiple comorbidities.

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven (Conn.) VA Medical Center. He is an associate editor for GI & Hepatology News.

Striking a balance: Deciding the optimal age to cease surveillance for colorectal neoplasia

BY PETR PROTIVA, MD, MPH

The appropriate age to stop surveillance for colorectal neoplasia remains uncertain. Screening for average-risk individuals is typically stopped at age 75, but personalized screening with shared decision-making may continue until age 85.¹ Evidence suggests that any survival benefit of screening past age 86 would be outweighed by the harm of screening and/or natural mortality. Nevertheless, determining the optimal age for surveillance in those with a history of neoplasia still poses some challenges. The issue is confounded as many clinicians use the terms “screening” and “surveillance” interchangeably. It should be noted that screening implies the individual is at average risk, while surveillance refers to those at elevated risk because of a personal history of colonic adenomas or cancer

Comorbidities and life expectancy

Despite recent staggering setbacks and a drop in the average life expectancy in the United States, the proportion of individuals older than 65 years old has been steadily increasing to a currently estimated 58.9 million – 16.8% of the U.S. population – and is projected to increase in the future.² However, the prevalence of comorbidities also increases with age, and these are crucial factors to weigh in the decision-making process. Severe comorbid conditions, such as chronic obstructive pulmonary disease, cirrhosis, chronic hepatitis, chronic renal failure, dementia, and congestive heart failure can limit a patient’s ability to undergo surveillance and diminish or negate its benefits. There are online tools that help clinicians estimate life expectancy and time to benefit (that is, time between the intervention and its benefit), such as the Lee or Schonberg index.³ Consensus on time to colorectal screening benefit is about 9-10 years, but may be much shorter for surveillance. Striking a balance between the potential benefits of continued surveillance and the risks and burdens imposed on older adults with limited life expectancy is essential for making well-informed decisions.
 

Age-related risk increase and risk of neoplasia in the surveillance population:

The absolute risk of developing colorectal cancer is dependent on age. In adults aged 45-49, it is 33.4/100,000, rising to 135.6 in those 70-74 years old; in persons aged 85 and older, it is 234.7/100,000.⁴ A significant challenge in determining the appropriate age to stop surveillance is the additional individual risk based on baseline polyp characteristics. It seems reasonable to treat low-risk adenomas similarly to screening and stop surveillance by 85 or 86 years old in most cases. The decision process is less clear in individuals with advanced lesions or a personal history of colon cancer. The prevalence of advanced adenomas on the baseline exam is about 15% and greater than 20% on the follow-up exam if the index adenoma(s) were at least 20 mm in diameter. For five or more adenomas at baseline, the prevalence of advanced lesions on follow-up exam is about 20%. On the other hand, a negative surveillance colonoscopy (that is, no polyps found) is associated with far fewer advanced lesions on follow-up.

Colonoscopy

The safety of colonoscopy in older adults should be considered. The colonoscopy procedure is generally very safe, but is associated with a higher risk of post-procedure complications after outpatient colonoscopy in patients 75 years and older. In addition, comorbidities such as anemia, cardiac arrhythmia, heart failure, hypertension, chronic kidney disease, liver disease, smoking history, and obesity are also risk factors. It should be noted that high-quality colonoscopy is key to the detection and full removal of neoplastic lesions and risk reduction. The inability to achieve adequate colon preparation for any reason or undertaking colonoscopy in patients at high risk for complications reduces its benefit.

Who should oversee surveillance, the primary care physician or gastroenterologist

Should a gastroenterologist oversee the decision on surveillance in older adults based on a combination of age, estimated procedure risk and benefits, patient preferences, and current guidelines? Certainly, it seems appropriate and that this is what most specialists think, according to a recent survey of gastroenterologists and primary care physicians (PCPs) on this topic.⁵ Perhaps, not surprisingly, most PCPs disagreed – PCPs are thoroughly familiar with their patients’ up-to-date comorbidities, functional status, and preferences, and they have the benefit of knowing them for a long time. They also integrate diagnostic results from multiple subspecialists, sometimes from different states. The role of PCPs is critical in centers that offer open-access colonoscopy. Gastroenterologists may be the most appropriate authority to evaluate older individuals for continued surveillance, but in most busy practices these patients are seen by mid-level practitioners. Specialists play an important role if the PCP is uncertain whether surveillance is still indicated or in older patients with a history of advanced adenoma. Therefore, the colonoscopy report or subsequent communication after pathology results are returned should include a recommendation for future surveillance and a clear provision for discontinuing the surveillance in case of future health decline.

Conclusion

Determining the optimal age to discontinue surveillance for colorectal neoplasia involves evaluating multiple factors. Although the age limit is clearer for average-risk screening and low-risk lesion surveillance, uncertainty remains for individuals with advanced neoplasia history. Significant factors in this decision-making process include subsequent neoplasia risk, comorbidities, life expectancy, and age-related risks associated with colonoscopy. Cooperation between PCPs and subspecialty physicians is essential in making surveillance decisions for older adults. PCPs are well positioned to consider detailed patient comorbidities, functional status, and patient preferences, especially with the help of online life-expectancy estimators for most elderly or comorbid patients. To assist in this process, gastroenterologists should state clearly in their procedure report and subsequent pathology letters whether surveillance is recommended and that it is conditional on future comorbidities and should be discontinued if the patient’s health significantly declines.

Dr. Protiva is associate professor of medicine, Yale University, and director of the colon cancer screening program, VA Connecticut Healthcare System, West Haven. Dr. Protiva has no relevant disclosures.

References

1. Patel SG et al. Gastroenterology. 2022;162:285-99

2. U.S. Census Bureau. Measuring America’s People, Places, and Economy

3. University of California, San Francisco. ePrognosis. 4. Siegel RL et al. CA Cancer J Clin. 2023 May-Jun;73(3):233-54.

5. Schoenborn NL et al. Am J Gastroenterol. 2023; 118(3):523-30.

The gastroenterologist should guide the decision to maintain, or halt, surveillance in older adults

BY MARIAM NAVEED, MD

Endoscopic screening and surveillance for CRC in older adults (≥ 75 years old) is a medical “gray area” that needs more high-quality data to inform clinical decision making. In the most recent 2022 clinical guideline update from the U.S. Multisociety Task Force on Colorectal Cancer, the recommendation to stop CRC screening in average risk patients older than 86 years is well supported because of colonoscopy-associated mortality risk outweighing the benefits of adenoma detection and removal. By comparison, screening recommendations for average risk individuals between 76-85 years old are ambiguous and ultimately the decision to proceed with colonoscopy in this clinical population should be individualized based on shared decision making between the provider and patient. Of note, the same guideline provides no specific guidance for ongoing surveillance in the same age group and similarly suggests a shared decision-making approach.¹

As a practicing gastroenterologist in the retirement capital of Florida, older adults comprise a large portion of my clinical practice. I have noticed several aspects unique to this demographic that merit special consideration. For example, a significant percentage of these patients are seasonal (that is, “snowbird”) patients that have multiple sets of doctors (set of physicians in their home state and another set in Florida). Consequently, fragmentation of clinical data enables opportunities for colonoscopies to be wrongly ordered (either in an inappropriate time frame and/or for inaccurate indications). In my own practice, when such a patient is referred for consideration of CRC surveillance, any/all external records must first be obtained and validated as a prerequisite for appropriate clinical counseling and informed decision-making. Additionally, consideration of periprocedural risks is particularly relevant in older adults, secondary to both the increased rate of direct complications and the likelihood of pre-existing comorbidities affecting completion of a safe colonoscopy. Factors that can be easily overlooked include higher rates of poor bowel preparation and corresponding decreased completion rates. Moreover, if the patient has a history of high-risk adenomas or worrisome family history warranting ongoing evaluation, but they also have high-risk comorbidities, I will frequently involve the patient’s cardiologist or pulmonologist to provide medical clearance prior to offering CRC screening/surveillance.

In addition to the clinical ambiguity of appropriateness of continued CRC screening/surveillance in the setting of advanced age, there is also the question of which provider is best positioned to counsel patients regarding this decision-making. Does the onus fall on the gastroenterologist (the proceduralist ultimately performing the procedure) or the PCP (who is likely more familiar with the patient’s overall health profile)? In a recent survey, more than 50% of PCPs reported feeling uncertain in their understanding of risk versus benefit stratification of continued CRC screening in older adults.² While there may be justification for both classes of providers to be involved, in my opinion, the decision to maintain or halt surveillance in older adults should be primarily guided by the gastroenterologist who is better equipped to provide individualized guidance regarding the nuanced risks of disease progression in these patients with prior history of adenomas, and who is clinically responsible for any procedure-related complications.

In an era of cost containment, insurance companies are increasingly placing barriers for approving surveillance and diagnostic colonoscopies. Thus, we need to be ever mindful of appropriately allocating resources to best benefit patients. The data on incidence of polyps and CRC in older adults is inconsistent and even difficult at times for a gastroenterologist to interpret. Therefore, in my opinion, the onus should not fall solely on the PCPs who are not routinely familiar with this information. We as gastroenterologists typically have greater domain-specific knowledge regarding current data and updated guidelines.

Gastroenterologists should wield this expertise to regulate overly liberalized recommendations for continued surveillance in fragile patients, or conversely to intervene in settings of prematurely halting surveillance in high-risk populations with appropriate life expectancy to experience disease progression. It is critical to carefully consider patient-individualized life expectancies, avoid surveillance in patients without clinically significant polyps, avoid over-weighting previous abnormal prior colonoscopies without reviewing more current procedure results, and take time to discuss patient preferences. As proceduralists, we must also be mindful of intrinsic biases towards performing surveillance in patients who are not likely to benefit from this intervention, and several studies have reported on the overuse of surveillance colonoscopies in the form of repeating surveillance earlier than recommended or in the context of limited life expectancy.³

Finally, it is necessary to emphasize that PCPs are critical allies for promoting overall patient health, especially in scenarios where recommendations to discontinue surveillance may not coincide with patient preference. It has been reported that patients usually do not consider poor overall health relevant to decisions regarding CRC surveillance (which I have also experienced to be true).⁴ In these scenarios, partnering with the PCP can be strategic, as patients may be more inclined to trust the guidance of their more familiar physician. At the end of the day, regardless of which provider takes ownership of initiating the discussion surrounding surveillance colonoscopy in older adults, communication is key between all providers and the patient to ensure optimal outcomes.

As the U.S. population continues to age, the demographic of patients aged 65 and older is projected to nearly double by 2060.⁵ Decisions regarding ongoing surveillance for CRC will continue to be frequent and increasingly relevant. The importance of studies generating high-quality data to inform appropriate guidelines specific to this population cannot be understated.

Dr. Naveed is a gastroenterologist and director of the gastroenterology and hepatology fellowship program at AdventHealth Medical Group, Altamonte Springs, Fla. Dr. Naveed had no relevant disclosures.
 

References

1. Patel SG et al. Gastroenterology. 2022 Jan;162(1):285-99.

2 Schoenborn NL et al. Am J Gastroenterol. 2023 Mar 1;118(3):523-30.

3 Calderwood AH et al. JAMA Intern Med. 2023 May 1;183(5):426-34.

4 Schoenborn NL et al. Am J Gastroenterol. 2023 Mar 1;118(3):523-30.

5 U.S. Census Bureau. Population Projections.

At first, the prospect of starting a new novel practice was daunting, said Russ Arjal, MD, AGAF, a gastroenterologist in San Luis Obispo, Calif., who in 2021 launched Telebelly Health, a virtual care gastroenterology clinic that partners with health systems to offer GI care services throughout the country.

Dr. Arjal, who as a cofounder of Telebelly Health also serves as chief medical officer and president of the practice, previously served as vice president of Puget Sound Gastroenterology and practiced in the Seattle area for 13 years. He served as vice president of clinical affairs for Gastro Health, the nation’s second-largest gastroenterology group, which acquired the Puget Sound practice in 2019. But then in 2021, he founded Telebelly with Sheri Rudberg, MBA, JD, who serves as CEO of the business; Alex Brown, who leads product development; and Nakort Valles, who serves as the company’s chief technology officer.

Building a new business whose goal is to transform GI health care delivery has been his biggest challenge to date. “I am proud of Telebelly because its goals are goals we all share, which is to try to get people in the door and take good care of them,” Dr. Arjal said.

Through virtual care clinics like Telebelly Health, patients can see a provider who is affiliated with a practice, even if the provider is in another state provided he or she is licensed in the patient’s home state. Some states have passed legislation to permanently allow out-of-state physicians to practice telehealth in their state if they follow the state’s requirements. In some states, that may amount to accepting an out-of-state medical license or requiring out-of-state clinicians to pass an exam.

Telebelly Health has served thousands of patients since September when the practice was launched. “We are scaling pretty quickly and will be doubling the number of providers in the next couple of months,” Dr. Arjal said.

In this Q&A, he talks more about his new business venture and his vision for the future of medicine.

Question: Why did you choose GI?

Answer: I wanted to do something that was cognitive where I interacted with and really got to know patients. I also wanted to be a proceduralist. I never wanted to be a surgeon – I knew that wasn’t for me. I fell in love with GI the first year in med school. I thought the pathology was interesting, and what GIs did in the acute setting as well as the outpatient setting was compelling.



Q. What achievement are you most proud of?

A. Prior to Telebelly, I led a large regional GI group in a competitive marketplace. Now, with Telebelly, building a team with a vision to transform the space has been the biggest challenge I have taken on. It’s still a work in progress, but we’ve had a great start. Starting a company wasn’t easy. It was something that I didn’t know a lot about, so I had to take a fair bit of risk. I wasn’t sure if I had it in me at the beginning. It’s not something I’d ever done before, so I was testing myself. I am proud that we were able to launch the company and have successfully scaled it. It’s been more successful than I expected.



Q. Describe your biggest practice-related challenge and what you are doing to address it.

A. Access to care. I think it’s very hard to see somebody with GI expertise and it certainly got worse during the pandemic. In my previous role, we used advanced practice providers. We tried to implement technology, sometimes effectively, sometimes not. But in general, we wanted to try to increase the supply of providers and compress these patient journeys to get people in the door. But that’s still a very difficult challenge we’re all trying to solve.



Q. What teacher or mentor had the greatest impact on you?

A. I would say two: James Trotter, MD, a hepatologist at the University of Colorado where I trained. He had a terrific impact in the sense that he was 100% focused on patients and got to know them as people. This taught me what it meant to be a clinician that was sort of a humanist. He cared so much for his patients that I still think about what Jim would do in a room today, 15 years after I finished my fellowship.

When I started my first job at Puget Sound Gastroenterology in the Seattle area, Robin Sloane, MD, was one of the senior partners of the group. I had a lot to learn after finishing fellowship. He was wonderful and gracious and really taught me a ton about the practical aspects of medicine. I felt this was an extension of my training in that he was a real clinician who really cared deeply for his patients. If I hadn’t met those two, my career and maybe my view of just what I did day-to-day would be different. They were both very, very impactful for me.



Q. Outside of teachers and mentors, who has had the strongest influence on your life?

A. Two people: my mother and my wife. My mother was a single parent and we were immigrants to the country. She was an ambitious woman who didn’t let anything stop her. I certainly learned a ton about resilience, work ethic. She’s somebody who always treated people well. My wife also supported and believed in me, and without her, I would not have had the courage to start a company.



Q. Describe a scene of your vision for the future.

A. I think we need to change our mindset in terms of how we interact with patients. I think there’s going to be a lot of clinical testing that is performed away from the physician’s office. It’s going to become more democratized and more decentralized. And I think in the future, patients will have more agency in how they interact with the system. I think artificial intelligence will potentially augment all of this as well. We’ll have patients who are more engaged, have more choice and easier access to expert care. They’ll come in with more information on their hands and they won’t have to wait as long. I think the wait times to get to a GI clinic now are way too long.

What I’d also like to see are providers spending more time doing things that they’re trained to do rather than documentation, summarizing data, and dealing with administrative headaches. I think almost everybody has that goal, but I think that’s achievable.

I want providers to have an iron man or iron woman suit when they see a patient, to have more data at their fingertips, to spend more time with the patients and have smarter visits.



Q. What did you fear most early in your career?

A. Failure for the most part, and comfort. For a long time, I wanted to start a company and change the space. Fear of failure has been ingrained in me and I think that’s true for a lot of physicians. I had always been a perfectionist.



Q. What gives you the most joy in your day-to-day practice?

A. Seeing patients is by far the thing I enjoy most. I don’t love documenting or digging up information, but I like getting to know folks. In general, I’m a social person and my outpatient clinic gives me the most joy, probably more than anything else.

Q. How do you stay current with advances in your field?

A. I’m curious about all new things, so I stay current through traditional means: I go to conferences regularly, I take postgraduate courses, I listen to podcasts, talk to colleagues, and read journals on a regular basis. But there are a lot of adjacent sources I pay attention to as well, such as nonmedical journals and nonmedical podcasts. I talk to folks outside the space and try to learn from them as well.



Q. What habits have you established that have benefited your career?

A. I do the same thing every day before my clinic days or my endoscopy days. I make reading a part of each day so I can slow down and be more present. Every day I try not to perform just what I do workwise, but I try to find some balance either with my family, or through exercise. I think I’ve been pretty good at separating work life from personal life.
 

Lightning round questions

Texting or talking? Talking.

Favorite junk food? Peanut butter M&Ms.

How many cups of coffee do you drink per day? Three.

If you weren’t a gastroenterologist, what would you be? Venture capitalist.

Introvert or extrovert? Both.

At first, the prospect of starting a new novel practice was daunting, said Russ Arjal, MD, AGAF, a gastroenterologist in San Luis Obispo, Calif., who in 2021 launched Telebelly Health, a virtual care gastroenterology clinic that partners with health systems to offer GI care services throughout the country.

Dr. Arjal, who as a cofounder of Telebelly Health also serves as chief medical officer and president of the practice, previously served as vice president of Puget Sound Gastroenterology and practiced in the Seattle area for 13 years. He served as vice president of clinical affairs for Gastro Health, the nation’s second-largest gastroenterology group, which acquired the Puget Sound practice in 2019. But then in 2021, he founded Telebelly with Sheri Rudberg, MBA, JD, who serves as CEO of the business; Alex Brown, who leads product development; and Nakort Valles, who serves as the company’s chief technology officer.

Building a new business whose goal is to transform GI health care delivery has been his biggest challenge to date. “I am proud of Telebelly because its goals are goals we all share, which is to try to get people in the door and take good care of them,” Dr. Arjal said.

Through virtual care clinics like Telebelly Health, patients can see a provider who is affiliated with a practice, even if the provider is in another state provided he or she is licensed in the patient’s home state. Some states have passed legislation to permanently allow out-of-state physicians to practice telehealth in their state if they follow the state’s requirements. In some states, that may amount to accepting an out-of-state medical license or requiring out-of-state clinicians to pass an exam.

Telebelly Health has served thousands of patients since September when the practice was launched. “We are scaling pretty quickly and will be doubling the number of providers in the next couple of months,” Dr. Arjal said.

In this Q&A, he talks more about his new business venture and his vision for the future of medicine.

Question: Why did you choose GI?

Answer: I wanted to do something that was cognitive where I interacted with and really got to know patients. I also wanted to be a proceduralist. I never wanted to be a surgeon – I knew that wasn’t for me. I fell in love with GI the first year in med school. I thought the pathology was interesting, and what GIs did in the acute setting as well as the outpatient setting was compelling.



Q. What achievement are you most proud of?

A. Prior to Telebelly, I led a large regional GI group in a competitive marketplace. Now, with Telebelly, building a team with a vision to transform the space has been the biggest challenge I have taken on. It’s still a work in progress, but we’ve had a great start. Starting a company wasn’t easy. It was something that I didn’t know a lot about, so I had to take a fair bit of risk. I wasn’t sure if I had it in me at the beginning. It’s not something I’d ever done before, so I was testing myself. I am proud that we were able to launch the company and have successfully scaled it. It’s been more successful than I expected.



Q. Describe your biggest practice-related challenge and what you are doing to address it.

A. Access to care. I think it’s very hard to see somebody with GI expertise and it certainly got worse during the pandemic. In my previous role, we used advanced practice providers. We tried to implement technology, sometimes effectively, sometimes not. But in general, we wanted to try to increase the supply of providers and compress these patient journeys to get people in the door. But that’s still a very difficult challenge we’re all trying to solve.



Q. What teacher or mentor had the greatest impact on you?

A. I would say two: James Trotter, MD, a hepatologist at the University of Colorado where I trained. He had a terrific impact in the sense that he was 100% focused on patients and got to know them as people. This taught me what it meant to be a clinician that was sort of a humanist. He cared so much for his patients that I still think about what Jim would do in a room today, 15 years after I finished my fellowship.

When I started my first job at Puget Sound Gastroenterology in the Seattle area, Robin Sloane, MD, was one of the senior partners of the group. I had a lot to learn after finishing fellowship. He was wonderful and gracious and really taught me a ton about the practical aspects of medicine. I felt this was an extension of my training in that he was a real clinician who really cared deeply for his patients. If I hadn’t met those two, my career and maybe my view of just what I did day-to-day would be different. They were both very, very impactful for me.



Q. Outside of teachers and mentors, who has had the strongest influence on your life?

A. Two people: my mother and my wife. My mother was a single parent and we were immigrants to the country. She was an ambitious woman who didn’t let anything stop her. I certainly learned a ton about resilience, work ethic. She’s somebody who always treated people well. My wife also supported and believed in me, and without her, I would not have had the courage to start a company.



Q. Describe a scene of your vision for the future.

A. I think we need to change our mindset in terms of how we interact with patients. I think there’s going to be a lot of clinical testing that is performed away from the physician’s office. It’s going to become more democratized and more decentralized. And I think in the future, patients will have more agency in how they interact with the system. I think artificial intelligence will potentially augment all of this as well. We’ll have patients who are more engaged, have more choice and easier access to expert care. They’ll come in with more information on their hands and they won’t have to wait as long. I think the wait times to get to a GI clinic now are way too long.

What I’d also like to see are providers spending more time doing things that they’re trained to do rather than documentation, summarizing data, and dealing with administrative headaches. I think almost everybody has that goal, but I think that’s achievable.

I want providers to have an iron man or iron woman suit when they see a patient, to have more data at their fingertips, to spend more time with the patients and have smarter visits.



Q. What did you fear most early in your career?

A. Failure for the most part, and comfort. For a long time, I wanted to start a company and change the space. Fear of failure has been ingrained in me and I think that’s true for a lot of physicians. I had always been a perfectionist.



Q. What gives you the most joy in your day-to-day practice?

A. Seeing patients is by far the thing I enjoy most. I don’t love documenting or digging up information, but I like getting to know folks. In general, I’m a social person and my outpatient clinic gives me the most joy, probably more than anything else.

Q. How do you stay current with advances in your field?

A. I’m curious about all new things, so I stay current through traditional means: I go to conferences regularly, I take postgraduate courses, I listen to podcasts, talk to colleagues, and read journals on a regular basis. But there are a lot of adjacent sources I pay attention to as well, such as nonmedical journals and nonmedical podcasts. I talk to folks outside the space and try to learn from them as well.



Q. What habits have you established that have benefited your career?

A. I do the same thing every day before my clinic days or my endoscopy days. I make reading a part of each day so I can slow down and be more present. Every day I try not to perform just what I do workwise, but I try to find some balance either with my family, or through exercise. I think I’ve been pretty good at separating work life from personal life.
 

Lightning round questions

Texting or talking? Talking.

Favorite junk food? Peanut butter M&Ms.

How many cups of coffee do you drink per day? Three.

If you weren’t a gastroenterologist, what would you be? Venture capitalist.

Introvert or extrovert? Both.

At first, the prospect of starting a new novel practice was daunting, said Russ Arjal, MD, AGAF, a gastroenterologist in San Luis Obispo, Calif., who in 2021 launched Telebelly Health, a virtual care gastroenterology clinic that partners with health systems to offer GI care services throughout the country.

Dr. Arjal, who as a cofounder of Telebelly Health also serves as chief medical officer and president of the practice, previously served as vice president of Puget Sound Gastroenterology and practiced in the Seattle area for 13 years. He served as vice president of clinical affairs for Gastro Health, the nation’s second-largest gastroenterology group, which acquired the Puget Sound practice in 2019. But then in 2021, he founded Telebelly with Sheri Rudberg, MBA, JD, who serves as CEO of the business; Alex Brown, who leads product development; and Nakort Valles, who serves as the company’s chief technology officer.

Building a new business whose goal is to transform GI health care delivery has been his biggest challenge to date. “I am proud of Telebelly because its goals are goals we all share, which is to try to get people in the door and take good care of them,” Dr. Arjal said.

Through virtual care clinics like Telebelly Health, patients can see a provider who is affiliated with a practice, even if the provider is in another state provided he or she is licensed in the patient’s home state. Some states have passed legislation to permanently allow out-of-state physicians to practice telehealth in their state if they follow the state’s requirements. In some states, that may amount to accepting an out-of-state medical license or requiring out-of-state clinicians to pass an exam.

Telebelly Health has served thousands of patients since September when the practice was launched. “We are scaling pretty quickly and will be doubling the number of providers in the next couple of months,” Dr. Arjal said.

In this Q&A, he talks more about his new business venture and his vision for the future of medicine.

Question: Why did you choose GI?

Answer: I wanted to do something that was cognitive where I interacted with and really got to know patients. I also wanted to be a proceduralist. I never wanted to be a surgeon – I knew that wasn’t for me. I fell in love with GI the first year in med school. I thought the pathology was interesting, and what GIs did in the acute setting as well as the outpatient setting was compelling.



Q. What achievement are you most proud of?

A. Prior to Telebelly, I led a large regional GI group in a competitive marketplace. Now, with Telebelly, building a team with a vision to transform the space has been the biggest challenge I have taken on. It’s still a work in progress, but we’ve had a great start. Starting a company wasn’t easy. It was something that I didn’t know a lot about, so I had to take a fair bit of risk. I wasn’t sure if I had it in me at the beginning. It’s not something I’d ever done before, so I was testing myself. I am proud that we were able to launch the company and have successfully scaled it. It’s been more successful than I expected.



Q. Describe your biggest practice-related challenge and what you are doing to address it.

A. Access to care. I think it’s very hard to see somebody with GI expertise and it certainly got worse during the pandemic. In my previous role, we used advanced practice providers. We tried to implement technology, sometimes effectively, sometimes not. But in general, we wanted to try to increase the supply of providers and compress these patient journeys to get people in the door. But that’s still a very difficult challenge we’re all trying to solve.



Q. What teacher or mentor had the greatest impact on you?

A. I would say two: James Trotter, MD, a hepatologist at the University of Colorado where I trained. He had a terrific impact in the sense that he was 100% focused on patients and got to know them as people. This taught me what it meant to be a clinician that was sort of a humanist. He cared so much for his patients that I still think about what Jim would do in a room today, 15 years after I finished my fellowship.

When I started my first job at Puget Sound Gastroenterology in the Seattle area, Robin Sloane, MD, was one of the senior partners of the group. I had a lot to learn after finishing fellowship. He was wonderful and gracious and really taught me a ton about the practical aspects of medicine. I felt this was an extension of my training in that he was a real clinician who really cared deeply for his patients. If I hadn’t met those two, my career and maybe my view of just what I did day-to-day would be different. They were both very, very impactful for me.



Q. Outside of teachers and mentors, who has had the strongest influence on your life?

A. Two people: my mother and my wife. My mother was a single parent and we were immigrants to the country. She was an ambitious woman who didn’t let anything stop her. I certainly learned a ton about resilience, work ethic. She’s somebody who always treated people well. My wife also supported and believed in me, and without her, I would not have had the courage to start a company.



Q. Describe a scene of your vision for the future.

A. I think we need to change our mindset in terms of how we interact with patients. I think there’s going to be a lot of clinical testing that is performed away from the physician’s office. It’s going to become more democratized and more decentralized. And I think in the future, patients will have more agency in how they interact with the system. I think artificial intelligence will potentially augment all of this as well. We’ll have patients who are more engaged, have more choice and easier access to expert care. They’ll come in with more information on their hands and they won’t have to wait as long. I think the wait times to get to a GI clinic now are way too long.

What I’d also like to see are providers spending more time doing things that they’re trained to do rather than documentation, summarizing data, and dealing with administrative headaches. I think almost everybody has that goal, but I think that’s achievable.

I want providers to have an iron man or iron woman suit when they see a patient, to have more data at their fingertips, to spend more time with the patients and have smarter visits.



Q. What did you fear most early in your career?

A. Failure for the most part, and comfort. For a long time, I wanted to start a company and change the space. Fear of failure has been ingrained in me and I think that’s true for a lot of physicians. I had always been a perfectionist.



Q. What gives you the most joy in your day-to-day practice?

A. Seeing patients is by far the thing I enjoy most. I don’t love documenting or digging up information, but I like getting to know folks. In general, I’m a social person and my outpatient clinic gives me the most joy, probably more than anything else.

Q. How do you stay current with advances in your field?

A. I’m curious about all new things, so I stay current through traditional means: I go to conferences regularly, I take postgraduate courses, I listen to podcasts, talk to colleagues, and read journals on a regular basis. But there are a lot of adjacent sources I pay attention to as well, such as nonmedical journals and nonmedical podcasts. I talk to folks outside the space and try to learn from them as well.



Q. What habits have you established that have benefited your career?

A. I do the same thing every day before my clinic days or my endoscopy days. I make reading a part of each day so I can slow down and be more present. Every day I try not to perform just what I do workwise, but I try to find some balance either with my family, or through exercise. I think I’ve been pretty good at separating work life from personal life.
 

Lightning round questions

Texting or talking? Talking.

Favorite junk food? Peanut butter M&Ms.

How many cups of coffee do you drink per day? Three.

If you weren’t a gastroenterologist, what would you be? Venture capitalist.

Introvert or extrovert? Both.

Transcatheter aortic valve implantation/replacement (TAVI/TAVR) is typically the domain of cardiac surgeons and interventional cardiologists.

In the United Kingdom, John Steele, an advanced nurse practitioner (ANP) at Glenfield Hospital, part of the University Hospitals of Leicester NHS Trust (UHL), was congratulated on Twitter as “the first nurse-ANP who has performed the whole TAVI procedure as the first operator – true transformation addressing NHS needs.”

Could it happen in the U.S.?

Could a U.S.-based nurse practitioner perform TAVR? Possibly. Should they? No, says Andrew M. Goldsweig, MD, chair of the U.S. Society for Cardiovascular Angiography and Interventions Structural Heart Council. “Experienced nurse practitioners who have participated as secondary operators in many TAVR procedures and have observed the primary physician operators likely know the technical steps involved in an uncomplicated transfemoral TAVR procedure,” he told this news organization.

“However, a physician’s depth and breadth of training are absolutely required both to recognize and to address any periprocedural issues,” said Dr. Goldsweig, who is also director of the cardiac catheterization laboratory and director of cardiovascular clinical research at Baystate Medical Center in Springfield, Mass.
 

What it takes to do TAVR

Transcatheter aortic valves were first approved by the FDA in 2011 for use in patients with severe, inoperable, aortic stenosis. The procedure is now increasingly used as an alternative to surgical AVR in intermediate- and low-risk patients and has a longer history in Europe.

Dr. Goldsweig notes that “TAVR is a complex procedure with many potential challenges. Physicians are trained to diagnose and manage vascular access complications, heart failure and respiratory complications, rhythm disturbances, stroke, paravalvular leak, valve malpositioning/embolization, cardiogenic shock, and any other issues that may arise in the peri-TAVR period.

“Physicians can perform vascular imaging and interventions, transition to alternative access, manage intubation and ventilation, facilitate embolectomy, place a pacemaker, close a paravalvular leak, capture a misplaced valve, deploy mechanical circulatory support, and perform other diagnostic and interventional procedures as necessary that are required for TAVR operators and vastly exceed the training and scope of a nurse practitioner.”

The 2023 ACC/AHA/SCAI advanced training statement on interventional cardiology defines select competencies for interventional cardiologists who choose to focus their career on peripheral, vascular, or structural heart interventions.

In a recent article in Structural Heart, Dr. Goldsweig and colleagues write, “Training in SHD [structural heart disease] has historically been fragmented and informal. Current modes of SHD training include unaccredited fellowship training, industry-sponsored forums and device-specific training, and training through on-site proctorship.”

Such programs have grown “exponentially,” they write, “despite the conspicuous absence of formalized training requirements.”

In response to the John Steele uproar, the British Cardiovascular Intervention Society posted a statement on its website, noting, “As medicine has changed so there has increasingly been a role for allied health practitioners with advanced skills to take on responsibilities that were previously considered to be the domain of doctors ...

“TAVI procedures however carry a mortality risk, and the responsibility for undertaking a successful TAVI procedure will always lie with a Cardiologist who has had the breadth of training to manage the various complications that may occur during or after a procedure. This requires years of training, and there is no short-cut, or substitute.”

The BCIS promises a statement “later in the year [on] the expected training route for undertaking TAVI and other structural heart procedures.”
 

Why it matters: Scope creep

Despite the current upheaval, it’s not the first time that a nurse in the United Kingdom has performed a procedure normally performed by a medical doctor. A 3-year-old Reddit post on r/JuniorDoctorsUK points to a 2017 Guardian article titled, “Meet the nurse who will soon perform surgery on patients alone.” Although the “surgical care practitioner” seems to be performing within the scope of her practice, people responding to the post say it’s an example of “mid-level [scope] creep.”

More recently, a Reddit post in the same group points to a congratulatory post for a “nurse-led radial access.” One person commented, “Today they do the access. Tomorrow they do the full diagnostic. Day after they do the pressure wire. Next week they do the PCI [percutaneous coronary intervention].”

Broadly, “scope creep” refers to scope-of-practice expansions, but not turf wars, according to Rebekah Bernard, MD, a family physician in Fort Myers, Fla., who cowrote, “Patients at Risk: The Rise of the Nurse Practitioner and Physician Assistant in Healthcare,” with Niran Al-Agba, MD, a pediatrician in Silverdale, Wash.

The reasons behind U.K. scope creep aren’t clear. Some believe it’s money. Some say the system is broken and that doctors are being exploited.

In relation to the NP-TAVI case, the British Junior Cardiologist Association commented that it reflects a lack of support and advocacy for medical/surgical trainees who need the training opportunities that are going instead to allied health professionals.

In the United States, scope creep is being taken seriously (some may say too seriously) by the American Medical Association. The AMA is lobbying to stop “inappropriate scope expansions,” bolstered by its AMA Scope of Practice Partnership.

Pointing to a scope creep video produced by the AMA, one JuniorDoctorsUK Reddit post asks, “why isn’t the BMA doing anything similar?”
 

Time for a rethink?

Back to Glenfield Hospital. Not only has Cardiology Glenfield deleted the controversial tweet; it is now is backtracking on its congratulations to ANP Steele, tweeting, “We want to make clear that the lead operator for the procedure was a consultant structural interventionist. However, we are looking into the circumstances, including a review of clinical governance.” From the responses, few clinicians are buying that explanation.

In response to a request for a comment from Glenfield, Andrew Furlong, UHL medical director, reiterated to this news organization through communications manager Gareth Duggan, “We are investigating the circumstances of the procedure with our cardiology team and reviewing our governance processes.”

Dr. Goldsweig participated in a past speaking engagement for Edwards Lifesciences.

A version of this article originally appeared on Medscape.com.

Transcatheter aortic valve implantation/replacement (TAVI/TAVR) is typically the domain of cardiac surgeons and interventional cardiologists.

In the United Kingdom, John Steele, an advanced nurse practitioner (ANP) at Glenfield Hospital, part of the University Hospitals of Leicester NHS Trust (UHL), was congratulated on Twitter as “the first nurse-ANP who has performed the whole TAVI procedure as the first operator – true transformation addressing NHS needs.”

Could it happen in the U.S.?

Could a U.S.-based nurse practitioner perform TAVR? Possibly. Should they? No, says Andrew M. Goldsweig, MD, chair of the U.S. Society for Cardiovascular Angiography and Interventions Structural Heart Council. “Experienced nurse practitioners who have participated as secondary operators in many TAVR procedures and have observed the primary physician operators likely know the technical steps involved in an uncomplicated transfemoral TAVR procedure,” he told this news organization.

“However, a physician’s depth and breadth of training are absolutely required both to recognize and to address any periprocedural issues,” said Dr. Goldsweig, who is also director of the cardiac catheterization laboratory and director of cardiovascular clinical research at Baystate Medical Center in Springfield, Mass.
 

What it takes to do TAVR

Transcatheter aortic valves were first approved by the FDA in 2011 for use in patients with severe, inoperable, aortic stenosis. The procedure is now increasingly used as an alternative to surgical AVR in intermediate- and low-risk patients and has a longer history in Europe.

Dr. Goldsweig notes that “TAVR is a complex procedure with many potential challenges. Physicians are trained to diagnose and manage vascular access complications, heart failure and respiratory complications, rhythm disturbances, stroke, paravalvular leak, valve malpositioning/embolization, cardiogenic shock, and any other issues that may arise in the peri-TAVR period.

“Physicians can perform vascular imaging and interventions, transition to alternative access, manage intubation and ventilation, facilitate embolectomy, place a pacemaker, close a paravalvular leak, capture a misplaced valve, deploy mechanical circulatory support, and perform other diagnostic and interventional procedures as necessary that are required for TAVR operators and vastly exceed the training and scope of a nurse practitioner.”

The 2023 ACC/AHA/SCAI advanced training statement on interventional cardiology defines select competencies for interventional cardiologists who choose to focus their career on peripheral, vascular, or structural heart interventions.

In a recent article in Structural Heart, Dr. Goldsweig and colleagues write, “Training in SHD [structural heart disease] has historically been fragmented and informal. Current modes of SHD training include unaccredited fellowship training, industry-sponsored forums and device-specific training, and training through on-site proctorship.”

Such programs have grown “exponentially,” they write, “despite the conspicuous absence of formalized training requirements.”

In response to the John Steele uproar, the British Cardiovascular Intervention Society posted a statement on its website, noting, “As medicine has changed so there has increasingly been a role for allied health practitioners with advanced skills to take on responsibilities that were previously considered to be the domain of doctors ...

“TAVI procedures however carry a mortality risk, and the responsibility for undertaking a successful TAVI procedure will always lie with a Cardiologist who has had the breadth of training to manage the various complications that may occur during or after a procedure. This requires years of training, and there is no short-cut, or substitute.”

The BCIS promises a statement “later in the year [on] the expected training route for undertaking TAVI and other structural heart procedures.”
 

Why it matters: Scope creep

Despite the current upheaval, it’s not the first time that a nurse in the United Kingdom has performed a procedure normally performed by a medical doctor. A 3-year-old Reddit post on r/JuniorDoctorsUK points to a 2017 Guardian article titled, “Meet the nurse who will soon perform surgery on patients alone.” Although the “surgical care practitioner” seems to be performing within the scope of her practice, people responding to the post say it’s an example of “mid-level [scope] creep.”

More recently, a Reddit post in the same group points to a congratulatory post for a “nurse-led radial access.” One person commented, “Today they do the access. Tomorrow they do the full diagnostic. Day after they do the pressure wire. Next week they do the PCI [percutaneous coronary intervention].”

Broadly, “scope creep” refers to scope-of-practice expansions, but not turf wars, according to Rebekah Bernard, MD, a family physician in Fort Myers, Fla., who cowrote, “Patients at Risk: The Rise of the Nurse Practitioner and Physician Assistant in Healthcare,” with Niran Al-Agba, MD, a pediatrician in Silverdale, Wash.

The reasons behind U.K. scope creep aren’t clear. Some believe it’s money. Some say the system is broken and that doctors are being exploited.

In relation to the NP-TAVI case, the British Junior Cardiologist Association commented that it reflects a lack of support and advocacy for medical/surgical trainees who need the training opportunities that are going instead to allied health professionals.

In the United States, scope creep is being taken seriously (some may say too seriously) by the American Medical Association. The AMA is lobbying to stop “inappropriate scope expansions,” bolstered by its AMA Scope of Practice Partnership.

Pointing to a scope creep video produced by the AMA, one JuniorDoctorsUK Reddit post asks, “why isn’t the BMA doing anything similar?”
 

Time for a rethink?

Back to Glenfield Hospital. Not only has Cardiology Glenfield deleted the controversial tweet; it is now is backtracking on its congratulations to ANP Steele, tweeting, “We want to make clear that the lead operator for the procedure was a consultant structural interventionist. However, we are looking into the circumstances, including a review of clinical governance.” From the responses, few clinicians are buying that explanation.

In response to a request for a comment from Glenfield, Andrew Furlong, UHL medical director, reiterated to this news organization through communications manager Gareth Duggan, “We are investigating the circumstances of the procedure with our cardiology team and reviewing our governance processes.”

Dr. Goldsweig participated in a past speaking engagement for Edwards Lifesciences.

A version of this article originally appeared on Medscape.com.

Transcatheter aortic valve implantation/replacement (TAVI/TAVR) is typically the domain of cardiac surgeons and interventional cardiologists.

In the United Kingdom, John Steele, an advanced nurse practitioner (ANP) at Glenfield Hospital, part of the University Hospitals of Leicester NHS Trust (UHL), was congratulated on Twitter as “the first nurse-ANP who has performed the whole TAVI procedure as the first operator – true transformation addressing NHS needs.”

Could it happen in the U.S.?

Could a U.S.-based nurse practitioner perform TAVR? Possibly. Should they? No, says Andrew M. Goldsweig, MD, chair of the U.S. Society for Cardiovascular Angiography and Interventions Structural Heart Council. “Experienced nurse practitioners who have participated as secondary operators in many TAVR procedures and have observed the primary physician operators likely know the technical steps involved in an uncomplicated transfemoral TAVR procedure,” he told this news organization.

“However, a physician’s depth and breadth of training are absolutely required both to recognize and to address any periprocedural issues,” said Dr. Goldsweig, who is also director of the cardiac catheterization laboratory and director of cardiovascular clinical research at Baystate Medical Center in Springfield, Mass.
 

What it takes to do TAVR

Transcatheter aortic valves were first approved by the FDA in 2011 for use in patients with severe, inoperable, aortic stenosis. The procedure is now increasingly used as an alternative to surgical AVR in intermediate- and low-risk patients and has a longer history in Europe.

Dr. Goldsweig notes that “TAVR is a complex procedure with many potential challenges. Physicians are trained to diagnose and manage vascular access complications, heart failure and respiratory complications, rhythm disturbances, stroke, paravalvular leak, valve malpositioning/embolization, cardiogenic shock, and any other issues that may arise in the peri-TAVR period.

“Physicians can perform vascular imaging and interventions, transition to alternative access, manage intubation and ventilation, facilitate embolectomy, place a pacemaker, close a paravalvular leak, capture a misplaced valve, deploy mechanical circulatory support, and perform other diagnostic and interventional procedures as necessary that are required for TAVR operators and vastly exceed the training and scope of a nurse practitioner.”

The 2023 ACC/AHA/SCAI advanced training statement on interventional cardiology defines select competencies for interventional cardiologists who choose to focus their career on peripheral, vascular, or structural heart interventions.

In a recent article in Structural Heart, Dr. Goldsweig and colleagues write, “Training in SHD [structural heart disease] has historically been fragmented and informal. Current modes of SHD training include unaccredited fellowship training, industry-sponsored forums and device-specific training, and training through on-site proctorship.”

Such programs have grown “exponentially,” they write, “despite the conspicuous absence of formalized training requirements.”

In response to the John Steele uproar, the British Cardiovascular Intervention Society posted a statement on its website, noting, “As medicine has changed so there has increasingly been a role for allied health practitioners with advanced skills to take on responsibilities that were previously considered to be the domain of doctors ...

“TAVI procedures however carry a mortality risk, and the responsibility for undertaking a successful TAVI procedure will always lie with a Cardiologist who has had the breadth of training to manage the various complications that may occur during or after a procedure. This requires years of training, and there is no short-cut, or substitute.”

The BCIS promises a statement “later in the year [on] the expected training route for undertaking TAVI and other structural heart procedures.”
 

Why it matters: Scope creep

Despite the current upheaval, it’s not the first time that a nurse in the United Kingdom has performed a procedure normally performed by a medical doctor. A 3-year-old Reddit post on r/JuniorDoctorsUK points to a 2017 Guardian article titled, “Meet the nurse who will soon perform surgery on patients alone.” Although the “surgical care practitioner” seems to be performing within the scope of her practice, people responding to the post say it’s an example of “mid-level [scope] creep.”

More recently, a Reddit post in the same group points to a congratulatory post for a “nurse-led radial access.” One person commented, “Today they do the access. Tomorrow they do the full diagnostic. Day after they do the pressure wire. Next week they do the PCI [percutaneous coronary intervention].”

Broadly, “scope creep” refers to scope-of-practice expansions, but not turf wars, according to Rebekah Bernard, MD, a family physician in Fort Myers, Fla., who cowrote, “Patients at Risk: The Rise of the Nurse Practitioner and Physician Assistant in Healthcare,” with Niran Al-Agba, MD, a pediatrician in Silverdale, Wash.

The reasons behind U.K. scope creep aren’t clear. Some believe it’s money. Some say the system is broken and that doctors are being exploited.

In relation to the NP-TAVI case, the British Junior Cardiologist Association commented that it reflects a lack of support and advocacy for medical/surgical trainees who need the training opportunities that are going instead to allied health professionals.

In the United States, scope creep is being taken seriously (some may say too seriously) by the American Medical Association. The AMA is lobbying to stop “inappropriate scope expansions,” bolstered by its AMA Scope of Practice Partnership.

Pointing to a scope creep video produced by the AMA, one JuniorDoctorsUK Reddit post asks, “why isn’t the BMA doing anything similar?”
 

Time for a rethink?

Back to Glenfield Hospital. Not only has Cardiology Glenfield deleted the controversial tweet; it is now is backtracking on its congratulations to ANP Steele, tweeting, “We want to make clear that the lead operator for the procedure was a consultant structural interventionist. However, we are looking into the circumstances, including a review of clinical governance.” From the responses, few clinicians are buying that explanation.

In response to a request for a comment from Glenfield, Andrew Furlong, UHL medical director, reiterated to this news organization through communications manager Gareth Duggan, “We are investigating the circumstances of the procedure with our cardiology team and reviewing our governance processes.”

Dr. Goldsweig participated in a past speaking engagement for Edwards Lifesciences.

A version of this article originally appeared on Medscape.com.

The Diagnosis: Cutaneous Metastasis

A shave biopsy of the lip revealed a diffuse cellular infiltrate filling the superficial and deep dermis (Figure 1A). Morphologically, the cells had abundant clear cytoplasm with eccentrically located, pleomorphic, hyperchromatic nuclei with occasional prominent nucleoli (Figure 1B). The cells stained positive for AE1/ AE3 on immunohistochemistry (Figure 2). A punch biopsy of the nodule in the right axillary vault revealed a morphologically similar proliferation of cells. A colonoscopy revealed a completely obstructing circumferential mass in the distal ascending colon. A biopsy of the mass confirmed invasive adenocarcinoma, supporting a diagnosis of cutaneous metastases from adenocarcinoma of the colon. The patient underwent resection of the lip tumor and started multiagent chemotherapy for his newly diagnosed stage IV adenocarcinoma of the colon. The patient died, despite therapy.

Cutaneous metastasis from solid malignancies is uncommon, as only 1.3% of them exhibit cutaneous manifestations at presentation.¹ Cutaneous metastasis from signet ring cell adenocarcinoma (SRCA) of the colon is uncommon, and cutaneous metastasis of colorectal SRCA rarely precedes the diagnosis of the primary lesion.² Among the colorectal cancers that metastasize to the skin, metastasis to the face occurs in only 0.5% of patients.³

Signet ring cell adenocarcinomas are poorly differentiated adenocarcinomas histologically characterized by the neoplastic cells’ circular to ovoid appearance with a flattened top.^4,5 This distinctive shape is from the displacement of the nucleus to the periphery of the cell due to the accumulation of intracytoplasmic mucin.⁴ Classically, malignancies are characterized as an SRCA if more than 50% of the cells have a signet ring cell morphology; if the signet ring cells comprise less than 50% of the neoplasm, the tumor is designated as an adenocarcinoma with signet ring morphology.⁴ The most common cause of cutaneous metastasis with signet ring morphology is gastric cancer, while colorectal carcinoma is less common.1 Colorectal SRCAs usually are found in the right colon or the rectum in comparison to other colonic sites.⁶

Clinically, cutaneous metastasis can present in a variety of ways. The most common presentation is nodular lesions that may coalesce to become zosteriform in configuration or lesions that mimic inflammatory dermatoses.⁷ Cutaneous metastasis is more common in breast and lung cancer, and when it occurs secondary to colorectal cancer, cutaneous metastasis rarely predates the detection of the primary neoplasm.²

The clinical appearance of metastasis is not specific and can mimic many entities⁸; therefore, a high index of suspicion must be employed when managing patients, even those without a history of internal malignancy. In our patient, the smooth nodular lesion appeared similar to a basal cell carcinoma; however, basal cell carcinomas appear more pearly, and arborizing telangiectasia often is seen.⁹ Merkel cell carcinoma is common on sundamaged skin of the head and neck but clinically appears more violaceous than the lesion seen in our patient.¹⁰ Paracoccidioidomycosis may form ulcerated papulonodules or plaques, especially around the nose and mouth. In many of these cases, lesions develop from contiguous lesions of the oral mucosa; therefore, the presence of oral lesions will help distinguish this infectious entity from cutaneous metastasis. Multiple lesions usually are identified when there is hematogenous dissemination.¹¹ Mycosis fungoides is a subtype of cutaneous T-cell lymphoma and is characterized by multiple patches, plaques, and nodules on sun-protected areas. Involvement of the head and neck is not common, except in the folliculotropic subtype, which has a separate and distinct clinical morphology.¹²

The development of signet ring morphology from an adenocarcinoma can be attributed to the activation of phosphatidylinositol 3-kinase (PI3K), which leads to downstream activation of mitogen-activated protein kinase (MAPK) and the subsequent loss of intercellular tight junctions. The mucin 4 gene, MUC4, also is upregulated by PI3K activation and possesses antiapoptotic and mitogenic effects in addition to its mucin secretory function.¹³

The neoplastic cells in SRCAs stain positive for mucicarmine, Alcian blue, and periodic acid–Schiff, which highlights the mucinous component of the cells.⁷ Immunohistochemical stains with CK7, CK20, AE1/AE3, and epithelial membrane antigen can be implemented to confirm an epithelial origin of the primary cancer.^7,13 CK20 is a low-molecular-weight cytokeratin normally expressed by Merkel cells and by the epithelium of the gastrointestinal tract and urothelium, whereas CK7 expression typically is expressed in the lungs, ovaries, endometrium, and breasts, but not in the lower gastrointestinal tract.¹⁴ Differentiating primary cutaneous adenocarcinoma from cutaneous metastasis can be accomplished with a thorough clinical history; however, p63 positivity supports a primary cutaneous lesion and may be useful in certain situations.⁷ CDX2 stains can be utilized to aid in localizing the primary neoplasm when it is unknown, and when positive, it suggests a lower gastrointestinal tract origin. However, special AT-rich sequence-binding protein 2 (SATB2) recently has been proposed as a replacement immunohistochemical marker for CDX2, as it has greater specificity for SRCA of the lower gastrointestinal tract.¹⁵ Benign entities with signet ring cell morphology are difficult to distinguish from SRCA; however, malignant lesions are more likely to demonstrate an infiltrative growth pattern, frequent mitotic figures, and apoptosis. Immunohistochemistry also can be utilized to support the diagnosis of benign proliferation with signet ring morphology, as benign lesions often will demonstrate E-cadherin positivity and negativity for p53 and Ki-67.¹³

Cutaneous metastasis usually correlates to advanced disease and generally indicates a worse prognosis.¹³ Signet ring cell morphology in both gastric and colorectal cancer portends a poor prognosis, and there is a lower overall survival in patients with these malignancies compared to cancers of the same organ with non–signet ring cell morphology.^4,8

The Diagnosis: Cutaneous Metastasis

A shave biopsy of the lip revealed a diffuse cellular infiltrate filling the superficial and deep dermis (Figure 1A). Morphologically, the cells had abundant clear cytoplasm with eccentrically located, pleomorphic, hyperchromatic nuclei with occasional prominent nucleoli (Figure 1B). The cells stained positive for AE1/ AE3 on immunohistochemistry (Figure 2). A punch biopsy of the nodule in the right axillary vault revealed a morphologically similar proliferation of cells. A colonoscopy revealed a completely obstructing circumferential mass in the distal ascending colon. A biopsy of the mass confirmed invasive adenocarcinoma, supporting a diagnosis of cutaneous metastases from adenocarcinoma of the colon. The patient underwent resection of the lip tumor and started multiagent chemotherapy for his newly diagnosed stage IV adenocarcinoma of the colon. The patient died, despite therapy.

Cutaneous metastasis from solid malignancies is uncommon, as only 1.3% of them exhibit cutaneous manifestations at presentation.¹ Cutaneous metastasis from signet ring cell adenocarcinoma (SRCA) of the colon is uncommon, and cutaneous metastasis of colorectal SRCA rarely precedes the diagnosis of the primary lesion.² Among the colorectal cancers that metastasize to the skin, metastasis to the face occurs in only 0.5% of patients.³

Signet ring cell adenocarcinomas are poorly differentiated adenocarcinomas histologically characterized by the neoplastic cells’ circular to ovoid appearance with a flattened top.^4,5 This distinctive shape is from the displacement of the nucleus to the periphery of the cell due to the accumulation of intracytoplasmic mucin.⁴ Classically, malignancies are characterized as an SRCA if more than 50% of the cells have a signet ring cell morphology; if the signet ring cells comprise less than 50% of the neoplasm, the tumor is designated as an adenocarcinoma with signet ring morphology.⁴ The most common cause of cutaneous metastasis with signet ring morphology is gastric cancer, while colorectal carcinoma is less common.1 Colorectal SRCAs usually are found in the right colon or the rectum in comparison to other colonic sites.⁶

Clinically, cutaneous metastasis can present in a variety of ways. The most common presentation is nodular lesions that may coalesce to become zosteriform in configuration or lesions that mimic inflammatory dermatoses.⁷ Cutaneous metastasis is more common in breast and lung cancer, and when it occurs secondary to colorectal cancer, cutaneous metastasis rarely predates the detection of the primary neoplasm.²

The clinical appearance of metastasis is not specific and can mimic many entities⁸; therefore, a high index of suspicion must be employed when managing patients, even those without a history of internal malignancy. In our patient, the smooth nodular lesion appeared similar to a basal cell carcinoma; however, basal cell carcinomas appear more pearly, and arborizing telangiectasia often is seen.⁹ Merkel cell carcinoma is common on sundamaged skin of the head and neck but clinically appears more violaceous than the lesion seen in our patient.¹⁰ Paracoccidioidomycosis may form ulcerated papulonodules or plaques, especially around the nose and mouth. In many of these cases, lesions develop from contiguous lesions of the oral mucosa; therefore, the presence of oral lesions will help distinguish this infectious entity from cutaneous metastasis. Multiple lesions usually are identified when there is hematogenous dissemination.¹¹ Mycosis fungoides is a subtype of cutaneous T-cell lymphoma and is characterized by multiple patches, plaques, and nodules on sun-protected areas. Involvement of the head and neck is not common, except in the folliculotropic subtype, which has a separate and distinct clinical morphology.¹²

The development of signet ring morphology from an adenocarcinoma can be attributed to the activation of phosphatidylinositol 3-kinase (PI3K), which leads to downstream activation of mitogen-activated protein kinase (MAPK) and the subsequent loss of intercellular tight junctions. The mucin 4 gene, MUC4, also is upregulated by PI3K activation and possesses antiapoptotic and mitogenic effects in addition to its mucin secretory function.¹³

The neoplastic cells in SRCAs stain positive for mucicarmine, Alcian blue, and periodic acid–Schiff, which highlights the mucinous component of the cells.⁷ Immunohistochemical stains with CK7, CK20, AE1/AE3, and epithelial membrane antigen can be implemented to confirm an epithelial origin of the primary cancer.^7,13 CK20 is a low-molecular-weight cytokeratin normally expressed by Merkel cells and by the epithelium of the gastrointestinal tract and urothelium, whereas CK7 expression typically is expressed in the lungs, ovaries, endometrium, and breasts, but not in the lower gastrointestinal tract.¹⁴ Differentiating primary cutaneous adenocarcinoma from cutaneous metastasis can be accomplished with a thorough clinical history; however, p63 positivity supports a primary cutaneous lesion and may be useful in certain situations.⁷ CDX2 stains can be utilized to aid in localizing the primary neoplasm when it is unknown, and when positive, it suggests a lower gastrointestinal tract origin. However, special AT-rich sequence-binding protein 2 (SATB2) recently has been proposed as a replacement immunohistochemical marker for CDX2, as it has greater specificity for SRCA of the lower gastrointestinal tract.¹⁵ Benign entities with signet ring cell morphology are difficult to distinguish from SRCA; however, malignant lesions are more likely to demonstrate an infiltrative growth pattern, frequent mitotic figures, and apoptosis. Immunohistochemistry also can be utilized to support the diagnosis of benign proliferation with signet ring morphology, as benign lesions often will demonstrate E-cadherin positivity and negativity for p53 and Ki-67.¹³

Cutaneous metastasis usually correlates to advanced disease and generally indicates a worse prognosis.¹³ Signet ring cell morphology in both gastric and colorectal cancer portends a poor prognosis, and there is a lower overall survival in patients with these malignancies compared to cancers of the same organ with non–signet ring cell morphology.^4,8

The Diagnosis: Cutaneous Metastasis

A shave biopsy of the lip revealed a diffuse cellular infiltrate filling the superficial and deep dermis (Figure 1A). Morphologically, the cells had abundant clear cytoplasm with eccentrically located, pleomorphic, hyperchromatic nuclei with occasional prominent nucleoli (Figure 1B). The cells stained positive for AE1/ AE3 on immunohistochemistry (Figure 2). A punch biopsy of the nodule in the right axillary vault revealed a morphologically similar proliferation of cells. A colonoscopy revealed a completely obstructing circumferential mass in the distal ascending colon. A biopsy of the mass confirmed invasive adenocarcinoma, supporting a diagnosis of cutaneous metastases from adenocarcinoma of the colon. The patient underwent resection of the lip tumor and started multiagent chemotherapy for his newly diagnosed stage IV adenocarcinoma of the colon. The patient died, despite therapy.

Cutaneous metastasis from solid malignancies is uncommon, as only 1.3% of them exhibit cutaneous manifestations at presentation.¹ Cutaneous metastasis from signet ring cell adenocarcinoma (SRCA) of the colon is uncommon, and cutaneous metastasis of colorectal SRCA rarely precedes the diagnosis of the primary lesion.² Among the colorectal cancers that metastasize to the skin, metastasis to the face occurs in only 0.5% of patients.³

Signet ring cell adenocarcinomas are poorly differentiated adenocarcinomas histologically characterized by the neoplastic cells’ circular to ovoid appearance with a flattened top.^4,5 This distinctive shape is from the displacement of the nucleus to the periphery of the cell due to the accumulation of intracytoplasmic mucin.⁴ Classically, malignancies are characterized as an SRCA if more than 50% of the cells have a signet ring cell morphology; if the signet ring cells comprise less than 50% of the neoplasm, the tumor is designated as an adenocarcinoma with signet ring morphology.⁴ The most common cause of cutaneous metastasis with signet ring morphology is gastric cancer, while colorectal carcinoma is less common.1 Colorectal SRCAs usually are found in the right colon or the rectum in comparison to other colonic sites.⁶

Clinically, cutaneous metastasis can present in a variety of ways. The most common presentation is nodular lesions that may coalesce to become zosteriform in configuration or lesions that mimic inflammatory dermatoses.⁷ Cutaneous metastasis is more common in breast and lung cancer, and when it occurs secondary to colorectal cancer, cutaneous metastasis rarely predates the detection of the primary neoplasm.²

The clinical appearance of metastasis is not specific and can mimic many entities⁸; therefore, a high index of suspicion must be employed when managing patients, even those without a history of internal malignancy. In our patient, the smooth nodular lesion appeared similar to a basal cell carcinoma; however, basal cell carcinomas appear more pearly, and arborizing telangiectasia often is seen.⁹ Merkel cell carcinoma is common on sundamaged skin of the head and neck but clinically appears more violaceous than the lesion seen in our patient.¹⁰ Paracoccidioidomycosis may form ulcerated papulonodules or plaques, especially around the nose and mouth. In many of these cases, lesions develop from contiguous lesions of the oral mucosa; therefore, the presence of oral lesions will help distinguish this infectious entity from cutaneous metastasis. Multiple lesions usually are identified when there is hematogenous dissemination.¹¹ Mycosis fungoides is a subtype of cutaneous T-cell lymphoma and is characterized by multiple patches, plaques, and nodules on sun-protected areas. Involvement of the head and neck is not common, except in the folliculotropic subtype, which has a separate and distinct clinical morphology.¹²

The development of signet ring morphology from an adenocarcinoma can be attributed to the activation of phosphatidylinositol 3-kinase (PI3K), which leads to downstream activation of mitogen-activated protein kinase (MAPK) and the subsequent loss of intercellular tight junctions. The mucin 4 gene, MUC4, also is upregulated by PI3K activation and possesses antiapoptotic and mitogenic effects in addition to its mucin secretory function.¹³

The neoplastic cells in SRCAs stain positive for mucicarmine, Alcian blue, and periodic acid–Schiff, which highlights the mucinous component of the cells.⁷ Immunohistochemical stains with CK7, CK20, AE1/AE3, and epithelial membrane antigen can be implemented to confirm an epithelial origin of the primary cancer.^7,13 CK20 is a low-molecular-weight cytokeratin normally expressed by Merkel cells and by the epithelium of the gastrointestinal tract and urothelium, whereas CK7 expression typically is expressed in the lungs, ovaries, endometrium, and breasts, but not in the lower gastrointestinal tract.¹⁴ Differentiating primary cutaneous adenocarcinoma from cutaneous metastasis can be accomplished with a thorough clinical history; however, p63 positivity supports a primary cutaneous lesion and may be useful in certain situations.⁷ CDX2 stains can be utilized to aid in localizing the primary neoplasm when it is unknown, and when positive, it suggests a lower gastrointestinal tract origin. However, special AT-rich sequence-binding protein 2 (SATB2) recently has been proposed as a replacement immunohistochemical marker for CDX2, as it has greater specificity for SRCA of the lower gastrointestinal tract.¹⁵ Benign entities with signet ring cell morphology are difficult to distinguish from SRCA; however, malignant lesions are more likely to demonstrate an infiltrative growth pattern, frequent mitotic figures, and apoptosis. Immunohistochemistry also can be utilized to support the diagnosis of benign proliferation with signet ring morphology, as benign lesions often will demonstrate E-cadherin positivity and negativity for p53 and Ki-67.¹³

Cutaneous metastasis usually correlates to advanced disease and generally indicates a worse prognosis.¹³ Signet ring cell morphology in both gastric and colorectal cancer portends a poor prognosis, and there is a lower overall survival in patients with these malignancies compared to cancers of the same organ with non–signet ring cell morphology.^4,8

Opioids do not relieve acute low back or neck pain in the short term and lead to worse outcomes in the long term, results of the first randomized controlled trial testing the efficacy and safety of a short course of opioids for acute nonspecific low back/neck pain suggest.

After 6 weeks, there was no significant difference in pain scores of patients who took opioids, compared with those who took placebo. After 1 year, patients given the placebo had slightly lower pain scores. Also, patients using opioids were at greater risk of opioid misuse after 1 year.

This is a “landmark” trial with “practice-changing” results, senior author Christine Lin, PhD, with the University of Sydney, told this news organization.

“Before this trial, we did not have good evidence on whether opioids were effective for acute low back pain or neck pain, yet opioids were one of the most commonly used medicines for these conditions,” Dr. Lin explained.

On the basis of these results, “opioids should not be recommended at all for acute low back pain and neck pain,” Dr. Lin said.

Results of the OPAL study were published online  in The Lancet.
 

Rigorous trial

The trial was conducted in 157 primary care or emergency department sites in Australia and involved 347 adults who had been experiencing low back pain, neck pain, or both for 12 weeks or less.

They were randomly allocated (1:1) to receive guideline-recommended care (reassurance and advice to stay active) plus an opioid (oxycodone up to 20 mg daily) or identical placebo for up to 6 weeks. Naloxone was provided to help prevent opioid-induced constipation and improve blinding.

The primary outcome was pain severity at 6 weeks, measured with the pain severity subscale of the Brief Pain Inventory (10-point scale).

After 6 weeks, opioid therapy offered no more relief for acute back/neck pain or functional improvement than placebo.

The mean pain score at 6 weeks was 2.78 in the opioid group, versus 2.25 in the placebo group (adjusted mean difference, 0.53; 95% confidence interval, –0.00 to 1.07; P = .051). At 1 year, mean pain scores in the placebo group were slightly lower than in the opioid group (1.8 vs. 2.4).

In addition, there was a doubling of the risk of opioid misuse at 1 year among patients randomly allocated to receive opioid therapy for 6 weeks, compared with those allocated to receive placebo for 6 weeks.

At 1 year, 24 (20%) of 123 of the patients who received opioids were at risk of misuse, as indicated by the Current Opioid Misuse Measure scale, compared with 13 (10%) of 128 patients in the placebo group (P = .049). The COMM is a widely used measure of current aberrant drug-related behavior among patients with chronic pain who are being prescribed opioid therapy.
 

Results raise ‘serious questions’

“I believe the findings of the study will need to be disseminated to the doctors and patients, so they receive this latest evidence on opioids,” Dr. Lin said in an interview.

“We need to reassure doctors and patients that most people with acute low back pain and neck pain recover well with time (usually by 6 weeks), so management is simple – staying active, avoiding bed rest, and, if necessary, using a heat pack for short term pain relief. If drugs are required, consider anti-inflammatory drugs,” Dr. Lin added.

The authors of a linked comment say the OPAL trial “raises serious questions about the use of opioid therapy for acute low back and neck pain.”

Mark Sullivan, MD, PhD, and Jane Ballantyne, MD, with the University of Washington, Seattle, note that current clinical guidelines recommend opioids for patients with acute back and neck pain when other drug treatments fail or are contraindicated.

“As many as two-thirds of patients might receive an opioid when presenting for care of back or neck pain. It is time to re-examine these guidelines and these practices,” Dr. Sullivan and Dr. Ballantyne conclude.

Funding for the OPAL study was provided by the National Health and Medical Research Council, the University of Sydney Faculty of Medicine and Health, and SafeWork SA. The study authors have disclosed no relevant financial relationships. Dr. Sullivan and Dr. Ballantyne are board members (unpaid) of Physicians for Responsible Opioid Prescribing and have been paid consultants in opioid litigation.

A version of this article originally appeared on Medscape.com.

Opioids do not relieve acute low back or neck pain in the short term and lead to worse outcomes in the long term, results of the first randomized controlled trial testing the efficacy and safety of a short course of opioids for acute nonspecific low back/neck pain suggest.

After 6 weeks, there was no significant difference in pain scores of patients who took opioids, compared with those who took placebo. After 1 year, patients given the placebo had slightly lower pain scores. Also, patients using opioids were at greater risk of opioid misuse after 1 year.

This is a “landmark” trial with “practice-changing” results, senior author Christine Lin, PhD, with the University of Sydney, told this news organization.

“Before this trial, we did not have good evidence on whether opioids were effective for acute low back pain or neck pain, yet opioids were one of the most commonly used medicines for these conditions,” Dr. Lin explained.

On the basis of these results, “opioids should not be recommended at all for acute low back pain and neck pain,” Dr. Lin said.

Results of the OPAL study were published online  in The Lancet.
 

Rigorous trial

The trial was conducted in 157 primary care or emergency department sites in Australia and involved 347 adults who had been experiencing low back pain, neck pain, or both for 12 weeks or less.

They were randomly allocated (1:1) to receive guideline-recommended care (reassurance and advice to stay active) plus an opioid (oxycodone up to 20 mg daily) or identical placebo for up to 6 weeks. Naloxone was provided to help prevent opioid-induced constipation and improve blinding.

The primary outcome was pain severity at 6 weeks, measured with the pain severity subscale of the Brief Pain Inventory (10-point scale).

After 6 weeks, opioid therapy offered no more relief for acute back/neck pain or functional improvement than placebo.

The mean pain score at 6 weeks was 2.78 in the opioid group, versus 2.25 in the placebo group (adjusted mean difference, 0.53; 95% confidence interval, –0.00 to 1.07; P = .051). At 1 year, mean pain scores in the placebo group were slightly lower than in the opioid group (1.8 vs. 2.4).

In addition, there was a doubling of the risk of opioid misuse at 1 year among patients randomly allocated to receive opioid therapy for 6 weeks, compared with those allocated to receive placebo for 6 weeks.

At 1 year, 24 (20%) of 123 of the patients who received opioids were at risk of misuse, as indicated by the Current Opioid Misuse Measure scale, compared with 13 (10%) of 128 patients in the placebo group (P = .049). The COMM is a widely used measure of current aberrant drug-related behavior among patients with chronic pain who are being prescribed opioid therapy.
 

Results raise ‘serious questions’

“I believe the findings of the study will need to be disseminated to the doctors and patients, so they receive this latest evidence on opioids,” Dr. Lin said in an interview.

“We need to reassure doctors and patients that most people with acute low back pain and neck pain recover well with time (usually by 6 weeks), so management is simple – staying active, avoiding bed rest, and, if necessary, using a heat pack for short term pain relief. If drugs are required, consider anti-inflammatory drugs,” Dr. Lin added.

The authors of a linked comment say the OPAL trial “raises serious questions about the use of opioid therapy for acute low back and neck pain.”

Mark Sullivan, MD, PhD, and Jane Ballantyne, MD, with the University of Washington, Seattle, note that current clinical guidelines recommend opioids for patients with acute back and neck pain when other drug treatments fail or are contraindicated.

“As many as two-thirds of patients might receive an opioid when presenting for care of back or neck pain. It is time to re-examine these guidelines and these practices,” Dr. Sullivan and Dr. Ballantyne conclude.

Funding for the OPAL study was provided by the National Health and Medical Research Council, the University of Sydney Faculty of Medicine and Health, and SafeWork SA. The study authors have disclosed no relevant financial relationships. Dr. Sullivan and Dr. Ballantyne are board members (unpaid) of Physicians for Responsible Opioid Prescribing and have been paid consultants in opioid litigation.

A version of this article originally appeared on Medscape.com.

Opioids do not relieve acute low back or neck pain in the short term and lead to worse outcomes in the long term, results of the first randomized controlled trial testing the efficacy and safety of a short course of opioids for acute nonspecific low back/neck pain suggest.

After 6 weeks, there was no significant difference in pain scores of patients who took opioids, compared with those who took placebo. After 1 year, patients given the placebo had slightly lower pain scores. Also, patients using opioids were at greater risk of opioid misuse after 1 year.

This is a “landmark” trial with “practice-changing” results, senior author Christine Lin, PhD, with the University of Sydney, told this news organization.

“Before this trial, we did not have good evidence on whether opioids were effective for acute low back pain or neck pain, yet opioids were one of the most commonly used medicines for these conditions,” Dr. Lin explained.

On the basis of these results, “opioids should not be recommended at all for acute low back pain and neck pain,” Dr. Lin said.

Results of the OPAL study were published online  in The Lancet.
 

Rigorous trial

The trial was conducted in 157 primary care or emergency department sites in Australia and involved 347 adults who had been experiencing low back pain, neck pain, or both for 12 weeks or less.

They were randomly allocated (1:1) to receive guideline-recommended care (reassurance and advice to stay active) plus an opioid (oxycodone up to 20 mg daily) or identical placebo for up to 6 weeks. Naloxone was provided to help prevent opioid-induced constipation and improve blinding.

The primary outcome was pain severity at 6 weeks, measured with the pain severity subscale of the Brief Pain Inventory (10-point scale).

After 6 weeks, opioid therapy offered no more relief for acute back/neck pain or functional improvement than placebo.

The mean pain score at 6 weeks was 2.78 in the opioid group, versus 2.25 in the placebo group (adjusted mean difference, 0.53; 95% confidence interval, –0.00 to 1.07; P = .051). At 1 year, mean pain scores in the placebo group were slightly lower than in the opioid group (1.8 vs. 2.4).

In addition, there was a doubling of the risk of opioid misuse at 1 year among patients randomly allocated to receive opioid therapy for 6 weeks, compared with those allocated to receive placebo for 6 weeks.

At 1 year, 24 (20%) of 123 of the patients who received opioids were at risk of misuse, as indicated by the Current Opioid Misuse Measure scale, compared with 13 (10%) of 128 patients in the placebo group (P = .049). The COMM is a widely used measure of current aberrant drug-related behavior among patients with chronic pain who are being prescribed opioid therapy.
 

Results raise ‘serious questions’

“I believe the findings of the study will need to be disseminated to the doctors and patients, so they receive this latest evidence on opioids,” Dr. Lin said in an interview.

“We need to reassure doctors and patients that most people with acute low back pain and neck pain recover well with time (usually by 6 weeks), so management is simple – staying active, avoiding bed rest, and, if necessary, using a heat pack for short term pain relief. If drugs are required, consider anti-inflammatory drugs,” Dr. Lin added.

The authors of a linked comment say the OPAL trial “raises serious questions about the use of opioid therapy for acute low back and neck pain.”

Mark Sullivan, MD, PhD, and Jane Ballantyne, MD, with the University of Washington, Seattle, note that current clinical guidelines recommend opioids for patients with acute back and neck pain when other drug treatments fail or are contraindicated.

“As many as two-thirds of patients might receive an opioid when presenting for care of back or neck pain. It is time to re-examine these guidelines and these practices,” Dr. Sullivan and Dr. Ballantyne conclude.

Funding for the OPAL study was provided by the National Health and Medical Research Council, the University of Sydney Faculty of Medicine and Health, and SafeWork SA. The study authors have disclosed no relevant financial relationships. Dr. Sullivan and Dr. Ballantyne are board members (unpaid) of Physicians for Responsible Opioid Prescribing and have been paid consultants in opioid litigation.

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration approved the gene therapy valoctocogene roxaparvovec (Roctavian, BioMarin) for adults with severe hemophilia A.

Valoctocogene roxaparvovec, a one-time, single-dose IV infusion, is the first gene therapy approved in the United States for severe hemophilia A and will cost around $2.9 million. BioMarin has said the price tag reflects “the possibility of freedom from years” of infusions, which come to about $800,000 each year.

However, last December, the Institute for Clinical and Economic Review (ICER) set the upper bounds for the gene therapy at about $1.96 million. The extent to which the gene therapy will provide freedom from infusions, for how long, and in which patients are not completely understood.

Hemophilia A is caused by a mutation in the gene that produces a protein called coagulation factor VIII, which is essential for blood clotting. Valoctocogene roxaparvovec delivers a functional gene to liver cells via an adeno-associated virus serotype 5; the gene instructs the cells to make the missing clotting factor.

“Adults with severe hemophilia A face a lifelong burden, with frequent infusions and a high risk of health complications, including uncontrolled bleeding and irreversible joint damage,” Steven Pipe, MD, professor of pediatrics and pathology at the University of Michigan, Ann Arbor, and an investigator for the phase 3 study that led to the approval, said in a statement. The approval of valoctocogene roxaparvovec “has the potential to transform the way we treat adults based on years of bleed control following a single, one-time infusion.”

About 6,500 U.S. adults live with severe hemophilia A, and BioMarin said it anticipates approximately 2,500 will be eligible to receive the gene therapy following the approval. The U.S. indication is limited to patients without a history of factor VIII inhibitors and without detectable antibodies to the adeno-associated virus serotype 5.

Last August, the European Medicines Agency authorized the gene therapy for use in Europe, but according to Forbes and PharmaPhorum, uptake in Europe has been delayed because of reimbursement issues, given the cost of treatment and clinical uncertainties.

Data to date, however, are promising for most patients. Approval was based on BioMarin’s open-label, single-arm GENEr8-1 study in 134 men with severe congenital hemophilia A. Patients received a single infusion of 6 x 10¹³ vector genomes per kilogram.

Among the 132 patients available for 2-year evaluation, median factor VIII activity was in the range for mild hemophilia (6%-39% of normal) with an 84.5% reduction in bleeding events from baseline.

More than 80% of participants had no bleeding events requiring treatment, and there was a 98% reduction from baseline in mean use of exogenous factor VIII.

Overall, at 2 years, only 4.5% of patients had factor VIII activity consistent with severe hemophilia A; 9.1% had activity consistent with moderate disease; 59.8% had activity consistent with mild disease, and 26.5% had activity in the normal range above 40 IU/dL.

Trial investigators estimated that the typical half-life of the transgene-derived factor VIII production system is 123 weeks.

Among the six men who resumed prophylaxis, most had fewer bleeding events than when they were on prophylaxis before the infusion. All patients developed antibodies to the virus delivery vector, precluding retreatment.

Elevated alanine aminotransferase levels were the most common adverse event, occurring in 88.8% of patients, who were treated with immunosuppressants for a median of 33 weeks. Elevations persisted at 2 years in 29% of patients.

The other most common adverse events were headache (38.1%), nausea (37.3%), and increases in aspartate aminotransferase (35.1%).

A version of this article first appeared on Medscape.com.

The Food and Drug Administration approved the gene therapy valoctocogene roxaparvovec (Roctavian, BioMarin) for adults with severe hemophilia A.

Valoctocogene roxaparvovec, a one-time, single-dose IV infusion, is the first gene therapy approved in the United States for severe hemophilia A and will cost around $2.9 million. BioMarin has said the price tag reflects “the possibility of freedom from years” of infusions, which come to about $800,000 each year.

However, last December, the Institute for Clinical and Economic Review (ICER) set the upper bounds for the gene therapy at about $1.96 million. The extent to which the gene therapy will provide freedom from infusions, for how long, and in which patients are not completely understood.

Hemophilia A is caused by a mutation in the gene that produces a protein called coagulation factor VIII, which is essential for blood clotting. Valoctocogene roxaparvovec delivers a functional gene to liver cells via an adeno-associated virus serotype 5; the gene instructs the cells to make the missing clotting factor.

“Adults with severe hemophilia A face a lifelong burden, with frequent infusions and a high risk of health complications, including uncontrolled bleeding and irreversible joint damage,” Steven Pipe, MD, professor of pediatrics and pathology at the University of Michigan, Ann Arbor, and an investigator for the phase 3 study that led to the approval, said in a statement. The approval of valoctocogene roxaparvovec “has the potential to transform the way we treat adults based on years of bleed control following a single, one-time infusion.”

About 6,500 U.S. adults live with severe hemophilia A, and BioMarin said it anticipates approximately 2,500 will be eligible to receive the gene therapy following the approval. The U.S. indication is limited to patients without a history of factor VIII inhibitors and without detectable antibodies to the adeno-associated virus serotype 5.

Last August, the European Medicines Agency authorized the gene therapy for use in Europe, but according to Forbes and PharmaPhorum, uptake in Europe has been delayed because of reimbursement issues, given the cost of treatment and clinical uncertainties.

Data to date, however, are promising for most patients. Approval was based on BioMarin’s open-label, single-arm GENEr8-1 study in 134 men with severe congenital hemophilia A. Patients received a single infusion of 6 x 10¹³ vector genomes per kilogram.

Among the 132 patients available for 2-year evaluation, median factor VIII activity was in the range for mild hemophilia (6%-39% of normal) with an 84.5% reduction in bleeding events from baseline.

More than 80% of participants had no bleeding events requiring treatment, and there was a 98% reduction from baseline in mean use of exogenous factor VIII.

Overall, at 2 years, only 4.5% of patients had factor VIII activity consistent with severe hemophilia A; 9.1% had activity consistent with moderate disease; 59.8% had activity consistent with mild disease, and 26.5% had activity in the normal range above 40 IU/dL.

Trial investigators estimated that the typical half-life of the transgene-derived factor VIII production system is 123 weeks.

Among the six men who resumed prophylaxis, most had fewer bleeding events than when they were on prophylaxis before the infusion. All patients developed antibodies to the virus delivery vector, precluding retreatment.

Elevated alanine aminotransferase levels were the most common adverse event, occurring in 88.8% of patients, who were treated with immunosuppressants for a median of 33 weeks. Elevations persisted at 2 years in 29% of patients.

The other most common adverse events were headache (38.1%), nausea (37.3%), and increases in aspartate aminotransferase (35.1%).

A version of this article first appeared on Medscape.com.

The Food and Drug Administration approved the gene therapy valoctocogene roxaparvovec (Roctavian, BioMarin) for adults with severe hemophilia A.

Valoctocogene roxaparvovec, a one-time, single-dose IV infusion, is the first gene therapy approved in the United States for severe hemophilia A and will cost around $2.9 million. BioMarin has said the price tag reflects “the possibility of freedom from years” of infusions, which come to about $800,000 each year.

However, last December, the Institute for Clinical and Economic Review (ICER) set the upper bounds for the gene therapy at about $1.96 million. The extent to which the gene therapy will provide freedom from infusions, for how long, and in which patients are not completely understood.

Hemophilia A is caused by a mutation in the gene that produces a protein called coagulation factor VIII, which is essential for blood clotting. Valoctocogene roxaparvovec delivers a functional gene to liver cells via an adeno-associated virus serotype 5; the gene instructs the cells to make the missing clotting factor.

“Adults with severe hemophilia A face a lifelong burden, with frequent infusions and a high risk of health complications, including uncontrolled bleeding and irreversible joint damage,” Steven Pipe, MD, professor of pediatrics and pathology at the University of Michigan, Ann Arbor, and an investigator for the phase 3 study that led to the approval, said in a statement. The approval of valoctocogene roxaparvovec “has the potential to transform the way we treat adults based on years of bleed control following a single, one-time infusion.”

About 6,500 U.S. adults live with severe hemophilia A, and BioMarin said it anticipates approximately 2,500 will be eligible to receive the gene therapy following the approval. The U.S. indication is limited to patients without a history of factor VIII inhibitors and without detectable antibodies to the adeno-associated virus serotype 5.

Last August, the European Medicines Agency authorized the gene therapy for use in Europe, but according to Forbes and PharmaPhorum, uptake in Europe has been delayed because of reimbursement issues, given the cost of treatment and clinical uncertainties.

Data to date, however, are promising for most patients. Approval was based on BioMarin’s open-label, single-arm GENEr8-1 study in 134 men with severe congenital hemophilia A. Patients received a single infusion of 6 x 10¹³ vector genomes per kilogram.

Among the 132 patients available for 2-year evaluation, median factor VIII activity was in the range for mild hemophilia (6%-39% of normal) with an 84.5% reduction in bleeding events from baseline.

More than 80% of participants had no bleeding events requiring treatment, and there was a 98% reduction from baseline in mean use of exogenous factor VIII.

Overall, at 2 years, only 4.5% of patients had factor VIII activity consistent with severe hemophilia A; 9.1% had activity consistent with moderate disease; 59.8% had activity consistent with mild disease, and 26.5% had activity in the normal range above 40 IU/dL.

Trial investigators estimated that the typical half-life of the transgene-derived factor VIII production system is 123 weeks.

Among the six men who resumed prophylaxis, most had fewer bleeding events than when they were on prophylaxis before the infusion. All patients developed antibodies to the virus delivery vector, precluding retreatment.

Elevated alanine aminotransferase levels were the most common adverse event, occurring in 88.8% of patients, who were treated with immunosuppressants for a median of 33 weeks. Elevations persisted at 2 years in 29% of patients.

The other most common adverse events were headache (38.1%), nausea (37.3%), and increases in aspartate aminotransferase (35.1%).

A version of this article first appeared on Medscape.com.

The effectiveness and safety of biosimilars for psoriasis appear to be similar to the originator biologics, reported the authors of a review of studies comparing the two.

“This systematic review found that there was no clinically or statistically significant difference in the efficacy and safety between biosimilars and originators of adalimumab, etanercept, infliximab, and ustekinumab for the treatment of psoriasis,” senior study author and clinical lecturer Zenas Z. N. Yiu, MBChB, PhD, and his colleagues at the University of Manchester, England, wrote in JAMA Dermatology.“The biosimilars evaluated in this study could be considered alongside originators for biologic-naive patients to improve the accessibility of biological treatments,” they added. “Switching patients currently on originators to biosimilars could be considered where clinically appropriate to reduce treatment costs.”

Biologics versus biosimilars

In contrast to most chemically synthesized drugs, biologics are created from living organisms, and they have complex structures that can vary slightly from batch to batch, Luigi Naldi, MD, director of the department of dermatology of Ospedale San Bortolo, Vicenza, Italy, and Antonio Addis, PharmD, researcher in the department of epidemiology, Regione Lazio, in Rome, wrote in an accompanying editorial.

Once the patent on the “originator” biologic expires, U.S. and European regulators allow other manufacturers to develop similar molecules – biosimilars – through an abbreviated approval process. If the results of a limited number of equivalence or noninferiority clinical trials are acceptable, registration for all the indications of the originator is allowed for its biosimilars. Referring to the expense of biologics, Dr. Naldi and Dr. Addis noted that in the United States, “biologics comprise less than 3% of the volume of drugs on the market, but account for more than one-third of all drug spending.”

Systematic review

Dr. Yiu and his colleagues queried standard medical research databases in August 2022, and included 14 randomized clinical trials (10 adalimumab, 2 etanercept, 1 infliximab, and 1 ustekinumab) and 3 cohort studies (1 adalimumab, 1 etanercept, 1 infliximab and etanercept) in their review.

Twelve trials compared biosimilars vs. originators in originator-naive patients, and 11 trials compared switching from originators to biosimilars vs. continuous treatment with the originator.

The researchers found the following:

At week 16, mean PASI75 (Psoriasis Area and Severity Index) response rates ranges from 60.7% to 90.6% for adalimumab biosimilars, vs. 61.5% to 91.7% for the originator. Mean PASI75 responses for the two etanercept biosimilars were 56.1% and 76.7% vs. 55.5% and 73.4% for the originator. In the ustekinumab study, mean PASI75 responses were 86.1% for the biosimilar vs. 84.0% for the originator.

At week 52, mean PASI75 responses were between 86.3% and 92.8% for adalimumab biosimilars vs. 84.9% and 93.9% for the originator. In the one comparison of an etanercept biosimilar, mean PAS175 responses were 80.9% for the biosimilar vs. 82.9% for the originator.

In studies involving patients switching from the originator to a biosimilar vs. continuing treatment with the originator, 32-week response rates ranged from 87.0% to 91.3% for adalimumab biosimilars and from 88.2% to 93.2% for the originator. In the one ustekinumab study, the 32-week mean PASI75 response was 92.6% after switching from the originator to a biosimilar vs. 92.9% with continuous treatment with the originator.

At week 52, mean PASI75 responses to adalimumab were between 84.2% and 94.8% for patients who switched to biosimilars and between 88.1% and 93.9% for those who stayed on the originator.

At week 52, in all the randomized trials, the incidence of adverse events and serious adverse events among those who switched to the biosimilar and those who continued with the originator were similar. Two cohort studies showed similar safety outcomes between originators and biosimilars, but one reported more adverse events in patients who switched to adalimumab biosimilars (P = .04).

Three clinical trials showed low risk for bias, 11 had moderate risk, and all cohort studies had moderate to high risk for bias.

Experts weigh in

Asked to comment on the study, Steven R. Feldman, MD, PhD, professor of dermatology at Wake Forest University, Winston-Salem, N.C., told this news organization that he expects that the results will affect patient care.

However, he added, “I believe the decision of whether to use a biosimilar instead of the originator biologic may be more in the hands of the insurers than in the hands of physicians and patients.

“Biologics for psoriasis are so complicated that even the originator products vary from batch to batch. A biosimilar is basically like another batch of the innovative product,” explained Dr. Feldman, who was not involved in the study. “If we’re comfortable with patients being on different batches of the innovator product, we probably should be comfortable with them being on a biosimilar, as we have more evidence for the similarity of the biosimilar than we do for the current batch of the originator product.”

Aída Lugo-Somolinos, MD, professor of dermatology and director of the Contact Dermatitis Clinic at the University of North Carolina, Chapel Hill, said that “biologics have become the treatment of choice for moderate to severe psoriasis, and the use of biosimilars may be an alternative to reduce psoriasis treatment costs.

“Unfortunately, this study included a comparison of the existing biosimilars, which are drugs that are not the first line of treatment for psoriasis any longer,” added Dr. Lugo-Somolinos, who was not involved in the study.

Neil J. Korman, MD, PhD, professor of dermatology and codirector of the Skin Study Center at Case Western Reserve University, Cleveland, said the study was an important systematic review.

“This is a very timely publication because in the United States, several biosimilars are reaching the market in 2023,” he said. “The costs of the originator biologics are extraordinarily high, and the promise of biosimilars is that their costs will be significantly lower.”

Because all the studies were short term, Dr. Korman, who was not involved in the study, joins the study authors in recommending further related research into the long-term safety and efficacy of these agents.

Dr. Feldman, as well as one study author and one editorial author, reported relevant relationships with various pharmaceutical companies, including those that develop biosimilars. The remaining study authors, as well as Dr. Lugo-Somolinos and Dr. Korman, reported no relevant relationships. The study was funded by the Psoriasis Association and supported by the NIHR (National Institute for Health and Care Research) Manchester Biomedical Research Centre. All outside experts commented by email.

The effectiveness and safety of biosimilars for psoriasis appear to be similar to the originator biologics, reported the authors of a review of studies comparing the two.

“This systematic review found that there was no clinically or statistically significant difference in the efficacy and safety between biosimilars and originators of adalimumab, etanercept, infliximab, and ustekinumab for the treatment of psoriasis,” senior study author and clinical lecturer Zenas Z. N. Yiu, MBChB, PhD, and his colleagues at the University of Manchester, England, wrote in JAMA Dermatology.“The biosimilars evaluated in this study could be considered alongside originators for biologic-naive patients to improve the accessibility of biological treatments,” they added. “Switching patients currently on originators to biosimilars could be considered where clinically appropriate to reduce treatment costs.”

Biologics versus biosimilars

In contrast to most chemically synthesized drugs, biologics are created from living organisms, and they have complex structures that can vary slightly from batch to batch, Luigi Naldi, MD, director of the department of dermatology of Ospedale San Bortolo, Vicenza, Italy, and Antonio Addis, PharmD, researcher in the department of epidemiology, Regione Lazio, in Rome, wrote in an accompanying editorial.

Once the patent on the “originator” biologic expires, U.S. and European regulators allow other manufacturers to develop similar molecules – biosimilars – through an abbreviated approval process. If the results of a limited number of equivalence or noninferiority clinical trials are acceptable, registration for all the indications of the originator is allowed for its biosimilars. Referring to the expense of biologics, Dr. Naldi and Dr. Addis noted that in the United States, “biologics comprise less than 3% of the volume of drugs on the market, but account for more than one-third of all drug spending.”

Systematic review

Dr. Yiu and his colleagues queried standard medical research databases in August 2022, and included 14 randomized clinical trials (10 adalimumab, 2 etanercept, 1 infliximab, and 1 ustekinumab) and 3 cohort studies (1 adalimumab, 1 etanercept, 1 infliximab and etanercept) in their review.

Twelve trials compared biosimilars vs. originators in originator-naive patients, and 11 trials compared switching from originators to biosimilars vs. continuous treatment with the originator.

The researchers found the following:

At week 16, mean PASI75 (Psoriasis Area and Severity Index) response rates ranges from 60.7% to 90.6% for adalimumab biosimilars, vs. 61.5% to 91.7% for the originator. Mean PASI75 responses for the two etanercept biosimilars were 56.1% and 76.7% vs. 55.5% and 73.4% for the originator. In the ustekinumab study, mean PASI75 responses were 86.1% for the biosimilar vs. 84.0% for the originator.

At week 52, mean PASI75 responses were between 86.3% and 92.8% for adalimumab biosimilars vs. 84.9% and 93.9% for the originator. In the one comparison of an etanercept biosimilar, mean PAS175 responses were 80.9% for the biosimilar vs. 82.9% for the originator.

In studies involving patients switching from the originator to a biosimilar vs. continuing treatment with the originator, 32-week response rates ranged from 87.0% to 91.3% for adalimumab biosimilars and from 88.2% to 93.2% for the originator. In the one ustekinumab study, the 32-week mean PASI75 response was 92.6% after switching from the originator to a biosimilar vs. 92.9% with continuous treatment with the originator.

At week 52, mean PASI75 responses to adalimumab were between 84.2% and 94.8% for patients who switched to biosimilars and between 88.1% and 93.9% for those who stayed on the originator.

At week 52, in all the randomized trials, the incidence of adverse events and serious adverse events among those who switched to the biosimilar and those who continued with the originator were similar. Two cohort studies showed similar safety outcomes between originators and biosimilars, but one reported more adverse events in patients who switched to adalimumab biosimilars (P = .04).

Three clinical trials showed low risk for bias, 11 had moderate risk, and all cohort studies had moderate to high risk for bias.

Experts weigh in

Asked to comment on the study, Steven R. Feldman, MD, PhD, professor of dermatology at Wake Forest University, Winston-Salem, N.C., told this news organization that he expects that the results will affect patient care.

However, he added, “I believe the decision of whether to use a biosimilar instead of the originator biologic may be more in the hands of the insurers than in the hands of physicians and patients.

“Biologics for psoriasis are so complicated that even the originator products vary from batch to batch. A biosimilar is basically like another batch of the innovative product,” explained Dr. Feldman, who was not involved in the study. “If we’re comfortable with patients being on different batches of the innovator product, we probably should be comfortable with them being on a biosimilar, as we have more evidence for the similarity of the biosimilar than we do for the current batch of the originator product.”

Aída Lugo-Somolinos, MD, professor of dermatology and director of the Contact Dermatitis Clinic at the University of North Carolina, Chapel Hill, said that “biologics have become the treatment of choice for moderate to severe psoriasis, and the use of biosimilars may be an alternative to reduce psoriasis treatment costs.

“Unfortunately, this study included a comparison of the existing biosimilars, which are drugs that are not the first line of treatment for psoriasis any longer,” added Dr. Lugo-Somolinos, who was not involved in the study.

Neil J. Korman, MD, PhD, professor of dermatology and codirector of the Skin Study Center at Case Western Reserve University, Cleveland, said the study was an important systematic review.

“This is a very timely publication because in the United States, several biosimilars are reaching the market in 2023,” he said. “The costs of the originator biologics are extraordinarily high, and the promise of biosimilars is that their costs will be significantly lower.”

Because all the studies were short term, Dr. Korman, who was not involved in the study, joins the study authors in recommending further related research into the long-term safety and efficacy of these agents.

Dr. Feldman, as well as one study author and one editorial author, reported relevant relationships with various pharmaceutical companies, including those that develop biosimilars. The remaining study authors, as well as Dr. Lugo-Somolinos and Dr. Korman, reported no relevant relationships. The study was funded by the Psoriasis Association and supported by the NIHR (National Institute for Health and Care Research) Manchester Biomedical Research Centre. All outside experts commented by email.

The effectiveness and safety of biosimilars for psoriasis appear to be similar to the originator biologics, reported the authors of a review of studies comparing the two.

“This systematic review found that there was no clinically or statistically significant difference in the efficacy and safety between biosimilars and originators of adalimumab, etanercept, infliximab, and ustekinumab for the treatment of psoriasis,” senior study author and clinical lecturer Zenas Z. N. Yiu, MBChB, PhD, and his colleagues at the University of Manchester, England, wrote in JAMA Dermatology.“The biosimilars evaluated in this study could be considered alongside originators for biologic-naive patients to improve the accessibility of biological treatments,” they added. “Switching patients currently on originators to biosimilars could be considered where clinically appropriate to reduce treatment costs.”

Biologics versus biosimilars

In contrast to most chemically synthesized drugs, biologics are created from living organisms, and they have complex structures that can vary slightly from batch to batch, Luigi Naldi, MD, director of the department of dermatology of Ospedale San Bortolo, Vicenza, Italy, and Antonio Addis, PharmD, researcher in the department of epidemiology, Regione Lazio, in Rome, wrote in an accompanying editorial.

Once the patent on the “originator” biologic expires, U.S. and European regulators allow other manufacturers to develop similar molecules – biosimilars – through an abbreviated approval process. If the results of a limited number of equivalence or noninferiority clinical trials are acceptable, registration for all the indications of the originator is allowed for its biosimilars. Referring to the expense of biologics, Dr. Naldi and Dr. Addis noted that in the United States, “biologics comprise less than 3% of the volume of drugs on the market, but account for more than one-third of all drug spending.”

Systematic review

Dr. Yiu and his colleagues queried standard medical research databases in August 2022, and included 14 randomized clinical trials (10 adalimumab, 2 etanercept, 1 infliximab, and 1 ustekinumab) and 3 cohort studies (1 adalimumab, 1 etanercept, 1 infliximab and etanercept) in their review.

Twelve trials compared biosimilars vs. originators in originator-naive patients, and 11 trials compared switching from originators to biosimilars vs. continuous treatment with the originator.

The researchers found the following:

At week 16, mean PASI75 (Psoriasis Area and Severity Index) response rates ranges from 60.7% to 90.6% for adalimumab biosimilars, vs. 61.5% to 91.7% for the originator. Mean PASI75 responses for the two etanercept biosimilars were 56.1% and 76.7% vs. 55.5% and 73.4% for the originator. In the ustekinumab study, mean PASI75 responses were 86.1% for the biosimilar vs. 84.0% for the originator.

At week 52, mean PASI75 responses were between 86.3% and 92.8% for adalimumab biosimilars vs. 84.9% and 93.9% for the originator. In the one comparison of an etanercept biosimilar, mean PAS175 responses were 80.9% for the biosimilar vs. 82.9% for the originator.

In studies involving patients switching from the originator to a biosimilar vs. continuing treatment with the originator, 32-week response rates ranged from 87.0% to 91.3% for adalimumab biosimilars and from 88.2% to 93.2% for the originator. In the one ustekinumab study, the 32-week mean PASI75 response was 92.6% after switching from the originator to a biosimilar vs. 92.9% with continuous treatment with the originator.

At week 52, mean PASI75 responses to adalimumab were between 84.2% and 94.8% for patients who switched to biosimilars and between 88.1% and 93.9% for those who stayed on the originator.

At week 52, in all the randomized trials, the incidence of adverse events and serious adverse events among those who switched to the biosimilar and those who continued with the originator were similar. Two cohort studies showed similar safety outcomes between originators and biosimilars, but one reported more adverse events in patients who switched to adalimumab biosimilars (P = .04).

Three clinical trials showed low risk for bias, 11 had moderate risk, and all cohort studies had moderate to high risk for bias.

Experts weigh in

Asked to comment on the study, Steven R. Feldman, MD, PhD, professor of dermatology at Wake Forest University, Winston-Salem, N.C., told this news organization that he expects that the results will affect patient care.

However, he added, “I believe the decision of whether to use a biosimilar instead of the originator biologic may be more in the hands of the insurers than in the hands of physicians and patients.

“Biologics for psoriasis are so complicated that even the originator products vary from batch to batch. A biosimilar is basically like another batch of the innovative product,” explained Dr. Feldman, who was not involved in the study. “If we’re comfortable with patients being on different batches of the innovator product, we probably should be comfortable with them being on a biosimilar, as we have more evidence for the similarity of the biosimilar than we do for the current batch of the originator product.”

Aída Lugo-Somolinos, MD, professor of dermatology and director of the Contact Dermatitis Clinic at the University of North Carolina, Chapel Hill, said that “biologics have become the treatment of choice for moderate to severe psoriasis, and the use of biosimilars may be an alternative to reduce psoriasis treatment costs.

“Unfortunately, this study included a comparison of the existing biosimilars, which are drugs that are not the first line of treatment for psoriasis any longer,” added Dr. Lugo-Somolinos, who was not involved in the study.

Neil J. Korman, MD, PhD, professor of dermatology and codirector of the Skin Study Center at Case Western Reserve University, Cleveland, said the study was an important systematic review.

“This is a very timely publication because in the United States, several biosimilars are reaching the market in 2023,” he said. “The costs of the originator biologics are extraordinarily high, and the promise of biosimilars is that their costs will be significantly lower.”

Because all the studies were short term, Dr. Korman, who was not involved in the study, joins the study authors in recommending further related research into the long-term safety and efficacy of these agents.

Dr. Feldman, as well as one study author and one editorial author, reported relevant relationships with various pharmaceutical companies, including those that develop biosimilars. The remaining study authors, as well as Dr. Lugo-Somolinos and Dr. Korman, reported no relevant relationships. The study was funded by the Psoriasis Association and supported by the NIHR (National Institute for Health and Care Research) Manchester Biomedical Research Centre. All outside experts commented by email.

The Food and Drug Administration recently released final guidance on a voluntary pilot program to help reduce the risks associated with certain diagnostic biomarker tests used to guide cancer treatment decisions for patients.

These laboratory-developed tests were designed to detect cancer biomarkers to help clinicians find the most appropriate cancer treatments for their patients. But the agency explained it has “become increasingly concerned that some tests made by laboratories and not authorized by the FDA may not provide accurate and reliable test results or perform as well as FDA-authorized tests.”

Currently, in most circumstances, an in vitro companion diagnostic would be granted marketing authorization alongside the approval of a corresponding cancer therapy. Under limited circumstances, however, the FDA may decide to approve a cancer therapy that requires a diagnostic test, which has not yet received marketing authorization. In these instances, “the benefits from the use of the therapeutic product are so pronounced as to outweigh the risks from the lack of an [in vitro companion diagnostic] with marketing authorization,” the FDA explained in 2014 in a guidance titled, In Vitro Companion Diagnostic Devices .

The new pilot program now aims to “address concerns and questions around the use of unauthorized diagnostics” and help improve cancer care for patients, Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a press announcement.

The voluntary program will seek to provide greater transparency surrounding performance recommendations for these diagnostic tests. More specifically, the FDA will ask drug manufacturers to provide performance information for tests used to enroll patients in clinical trials that support drug approval. The agency will assess the performance information and establish the minimum performance criteria recommended for similar tests used to select cancer treatments for patients. The results, posted to the FDA’s website, may be used by laboratories to guide their development of diagnostic tests.

The FDA plans to evaluate no more than nine drug sponsors for the pilot program. This initial phase of the program is anticipated to last up to a year.

“We believe this guidance and the launch of the pilot program are important steps toward addressing safety risks posed by the use of poorly performing laboratory developed tests,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, said in a statement.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration recently released final guidance on a voluntary pilot program to help reduce the risks associated with certain diagnostic biomarker tests used to guide cancer treatment decisions for patients.

These laboratory-developed tests were designed to detect cancer biomarkers to help clinicians find the most appropriate cancer treatments for their patients. But the agency explained it has “become increasingly concerned that some tests made by laboratories and not authorized by the FDA may not provide accurate and reliable test results or perform as well as FDA-authorized tests.”

Currently, in most circumstances, an in vitro companion diagnostic would be granted marketing authorization alongside the approval of a corresponding cancer therapy. Under limited circumstances, however, the FDA may decide to approve a cancer therapy that requires a diagnostic test, which has not yet received marketing authorization. In these instances, “the benefits from the use of the therapeutic product are so pronounced as to outweigh the risks from the lack of an [in vitro companion diagnostic] with marketing authorization,” the FDA explained in 2014 in a guidance titled, In Vitro Companion Diagnostic Devices .

The new pilot program now aims to “address concerns and questions around the use of unauthorized diagnostics” and help improve cancer care for patients, Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a press announcement.

The voluntary program will seek to provide greater transparency surrounding performance recommendations for these diagnostic tests. More specifically, the FDA will ask drug manufacturers to provide performance information for tests used to enroll patients in clinical trials that support drug approval. The agency will assess the performance information and establish the minimum performance criteria recommended for similar tests used to select cancer treatments for patients. The results, posted to the FDA’s website, may be used by laboratories to guide their development of diagnostic tests.

The FDA plans to evaluate no more than nine drug sponsors for the pilot program. This initial phase of the program is anticipated to last up to a year.

“We believe this guidance and the launch of the pilot program are important steps toward addressing safety risks posed by the use of poorly performing laboratory developed tests,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, said in a statement.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration recently released final guidance on a voluntary pilot program to help reduce the risks associated with certain diagnostic biomarker tests used to guide cancer treatment decisions for patients.

These laboratory-developed tests were designed to detect cancer biomarkers to help clinicians find the most appropriate cancer treatments for their patients. But the agency explained it has “become increasingly concerned that some tests made by laboratories and not authorized by the FDA may not provide accurate and reliable test results or perform as well as FDA-authorized tests.”

Currently, in most circumstances, an in vitro companion diagnostic would be granted marketing authorization alongside the approval of a corresponding cancer therapy. Under limited circumstances, however, the FDA may decide to approve a cancer therapy that requires a diagnostic test, which has not yet received marketing authorization. In these instances, “the benefits from the use of the therapeutic product are so pronounced as to outweigh the risks from the lack of an [in vitro companion diagnostic] with marketing authorization,” the FDA explained in 2014 in a guidance titled, In Vitro Companion Diagnostic Devices .

The new pilot program now aims to “address concerns and questions around the use of unauthorized diagnostics” and help improve cancer care for patients, Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a press announcement.

The voluntary program will seek to provide greater transparency surrounding performance recommendations for these diagnostic tests. More specifically, the FDA will ask drug manufacturers to provide performance information for tests used to enroll patients in clinical trials that support drug approval. The agency will assess the performance information and establish the minimum performance criteria recommended for similar tests used to select cancer treatments for patients. The results, posted to the FDA’s website, may be used by laboratories to guide their development of diagnostic tests.

The FDA plans to evaluate no more than nine drug sponsors for the pilot program. This initial phase of the program is anticipated to last up to a year.

“We believe this guidance and the launch of the pilot program are important steps toward addressing safety risks posed by the use of poorly performing laboratory developed tests,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, said in a statement.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved Suflave, a new low-volume, lemon-lime flavored liquid osmotic laxative for colonoscopy preparation in adults, the manufacturer, Sebela Pharmaceuticals, has announced.

Suflave comes in a carton containing two bottles and two flavor packets. Each bottle contains 178.7 g polyethylene glycol 3350, 7.3 g sodium sulfate, 1.12 g potassium chloride, 0.9 g magnesium sulfate, and 0.5 g sodium chloride. One bottle and one flavor packet are equivalent to one dose.

Administration of both doses is required for a complete preparation for colonoscopy. After each dose, an additional 16 ounces of water must be consumed. 

In a clinical trial, 94% of patients achieved successful bowel cleansing with Suflave, the company said in a news release.

Most patients reported that Suflave tastes like a sports drink and described the taste as “neutral to very pleasant.” Most patients also reported that Suflave was “tolerable to very easy” to consume and indicated they would request it for a subsequent colonoscopy.

“Patients frequently struggle with the taste and volume of traditional bowel preparations – and fear related to the preparation can also negatively affect patient willingness to undergo follow-up colonoscopy if it is indicated,” Douglas K. Rex, MD, gastroenterologist and distinguished professor emeritus at Indiana University, Indianapolis, said in the release.

“I believe the palatable lemon-lime flavor of Suflave will be a welcomed option for patients – reducing preparation hesitancy and giving more people the chance to feel comfortable during preparation and getting a successful and effective procedure,” Dr. Rex added.

Suflave will be available by prescription to patients in the United States in early August.

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration has approved Suflave, a new low-volume, lemon-lime flavored liquid osmotic laxative for colonoscopy preparation in adults, the manufacturer, Sebela Pharmaceuticals, has announced.

Suflave comes in a carton containing two bottles and two flavor packets. Each bottle contains 178.7 g polyethylene glycol 3350, 7.3 g sodium sulfate, 1.12 g potassium chloride, 0.9 g magnesium sulfate, and 0.5 g sodium chloride. One bottle and one flavor packet are equivalent to one dose.

Administration of both doses is required for a complete preparation for colonoscopy. After each dose, an additional 16 ounces of water must be consumed. 

In a clinical trial, 94% of patients achieved successful bowel cleansing with Suflave, the company said in a news release.

Most patients reported that Suflave tastes like a sports drink and described the taste as “neutral to very pleasant.” Most patients also reported that Suflave was “tolerable to very easy” to consume and indicated they would request it for a subsequent colonoscopy.

“Patients frequently struggle with the taste and volume of traditional bowel preparations – and fear related to the preparation can also negatively affect patient willingness to undergo follow-up colonoscopy if it is indicated,” Douglas K. Rex, MD, gastroenterologist and distinguished professor emeritus at Indiana University, Indianapolis, said in the release.

“I believe the palatable lemon-lime flavor of Suflave will be a welcomed option for patients – reducing preparation hesitancy and giving more people the chance to feel comfortable during preparation and getting a successful and effective procedure,” Dr. Rex added.

Suflave will be available by prescription to patients in the United States in early August.

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration has approved Suflave, a new low-volume, lemon-lime flavored liquid osmotic laxative for colonoscopy preparation in adults, the manufacturer, Sebela Pharmaceuticals, has announced.

Suflave comes in a carton containing two bottles and two flavor packets. Each bottle contains 178.7 g polyethylene glycol 3350, 7.3 g sodium sulfate, 1.12 g potassium chloride, 0.9 g magnesium sulfate, and 0.5 g sodium chloride. One bottle and one flavor packet are equivalent to one dose.

Administration of both doses is required for a complete preparation for colonoscopy. After each dose, an additional 16 ounces of water must be consumed. 

In a clinical trial, 94% of patients achieved successful bowel cleansing with Suflave, the company said in a news release.

Most patients reported that Suflave tastes like a sports drink and described the taste as “neutral to very pleasant.” Most patients also reported that Suflave was “tolerable to very easy” to consume and indicated they would request it for a subsequent colonoscopy.

“Patients frequently struggle with the taste and volume of traditional bowel preparations – and fear related to the preparation can also negatively affect patient willingness to undergo follow-up colonoscopy if it is indicated,” Douglas K. Rex, MD, gastroenterologist and distinguished professor emeritus at Indiana University, Indianapolis, said in the release.

“I believe the palatable lemon-lime flavor of Suflave will be a welcomed option for patients – reducing preparation hesitancy and giving more people the chance to feel comfortable during preparation and getting a successful and effective procedure,” Dr. Rex added.

Suflave will be available by prescription to patients in the United States in early August.

A version of this article originally appeared on Medscape.com.

The World Health Organization is set to list the artificial sweetener aspartame as a possible carcinogen.

The move, reported by multiple media sources, is expected during a July 14 meeting of WHO research experts – the International Agency for Research on Cancer. Reuters cited two unnamed sources “with knowledge of the process,” noting that aspartame is one of the world’s most commonly used sweeteners. 

Aspartame is 200 times sweeter than sugar and was first approved by the Food and Drug Administration in 1974 for use as a tabletop sweetener and in chewing gum and cold breakfast cereals, as well as instant coffee, gelatins, puddings and fillings, and dairy products. Up to 95% of carbonated soft drinks that have a sweetener use aspartame, and the substance is often added by consumers to beverages (it’s the blue packet of sweetener in the array of packets that appear on diner and restaurant tables),  The Washington Post  reported. 

The WHO currently lists 126 agents as known to be carcinogenic to humans, ranging from alcohol and tobacco to outdoor air pollution. The WHO also lists 94 agents as “probably” carcinogenic to humans and 322 agents as “possibly” carcinogenic to humans. Aspartame would join the “possibly” group, which includes gasoline engine exhaust and working as a dry cleaner.

Earlier this year, the WHO warned that people should not use nonsugar sweeteners to control their weight because of potential health risks. 
 

A version of this article originally appeared on WebMD.com.

The World Health Organization is set to list the artificial sweetener aspartame as a possible carcinogen.

The move, reported by multiple media sources, is expected during a July 14 meeting of WHO research experts – the International Agency for Research on Cancer. Reuters cited two unnamed sources “with knowledge of the process,” noting that aspartame is one of the world’s most commonly used sweeteners. 

Aspartame is 200 times sweeter than sugar and was first approved by the Food and Drug Administration in 1974 for use as a tabletop sweetener and in chewing gum and cold breakfast cereals, as well as instant coffee, gelatins, puddings and fillings, and dairy products. Up to 95% of carbonated soft drinks that have a sweetener use aspartame, and the substance is often added by consumers to beverages (it’s the blue packet of sweetener in the array of packets that appear on diner and restaurant tables),  The Washington Post  reported. 

The WHO currently lists 126 agents as known to be carcinogenic to humans, ranging from alcohol and tobacco to outdoor air pollution. The WHO also lists 94 agents as “probably” carcinogenic to humans and 322 agents as “possibly” carcinogenic to humans. Aspartame would join the “possibly” group, which includes gasoline engine exhaust and working as a dry cleaner.

Earlier this year, the WHO warned that people should not use nonsugar sweeteners to control their weight because of potential health risks. 
 

A version of this article originally appeared on WebMD.com.

The World Health Organization is set to list the artificial sweetener aspartame as a possible carcinogen.

The move, reported by multiple media sources, is expected during a July 14 meeting of WHO research experts – the International Agency for Research on Cancer. Reuters cited two unnamed sources “with knowledge of the process,” noting that aspartame is one of the world’s most commonly used sweeteners. 

Aspartame is 200 times sweeter than sugar and was first approved by the Food and Drug Administration in 1974 for use as a tabletop sweetener and in chewing gum and cold breakfast cereals, as well as instant coffee, gelatins, puddings and fillings, and dairy products. Up to 95% of carbonated soft drinks that have a sweetener use aspartame, and the substance is often added by consumers to beverages (it’s the blue packet of sweetener in the array of packets that appear on diner and restaurant tables),  The Washington Post  reported. 

The WHO currently lists 126 agents as known to be carcinogenic to humans, ranging from alcohol and tobacco to outdoor air pollution. The WHO also lists 94 agents as “probably” carcinogenic to humans and 322 agents as “possibly” carcinogenic to humans. Aspartame would join the “possibly” group, which includes gasoline engine exhaust and working as a dry cleaner.

Earlier this year, the WHO warned that people should not use nonsugar sweeteners to control their weight because of potential health risks. 
 

A version of this article originally appeared on WebMD.com.