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Poor Quality of Cancer Content on Social Media
This transcript has been edited for clarity.
I’m delighted to talk about a very interesting topic in this commentary. This is an area that we generally don’t discuss, but it’s one that’s obviously very topical, which includes the question of social media.
The paper I’m referring to is entitled, “More Than a Song and Dance”: Exploration of Patient Perspectives and Educational Quality of Gynecologic Cancer Content on TikTok. The paper was published in Gynecologic Oncology in 2023.
They had a total of 466.7 million views. They looked at 430 of the 500 top posts that were eligible, looked at 11 central themes, did an objective analysis of educational content based on published strategy for looking at this.
What they found, unfortunately but not surprisingly, overall was that the educational quality and reliability were quite poor. They also noticed considerable differences in disparities based on racial background and really emphasized in their analysis not only how common it is for individuals to look at this content on TikTok but also concerns about what it is that the public, patients, and their families are actually seeing.
This, of course, specifically relates to gynecologic cancers, but almost certainly relates to other cancers as well. Clearly, this is a topic that needs to be discussed widely. It’s very complex and very controversial, but when you think about the information that might be provided to our patients and their families going to social media, it’s important that we understand what they’re seeing, what they’re hearing, what they’re viewing, and the impact this might have on their care and outcomes.
I encourage you to read this very interesting paper if you have an interest in this topic. Again, it was recently published in Gynecologic Oncology. I thank you for your attention.
Dr. Markman is professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California; president of Medicine & Science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline and AstraZeneca.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I’m delighted to talk about a very interesting topic in this commentary. This is an area that we generally don’t discuss, but it’s one that’s obviously very topical, which includes the question of social media.
The paper I’m referring to is entitled, “More Than a Song and Dance”: Exploration of Patient Perspectives and Educational Quality of Gynecologic Cancer Content on TikTok. The paper was published in Gynecologic Oncology in 2023.
They had a total of 466.7 million views. They looked at 430 of the 500 top posts that were eligible, looked at 11 central themes, did an objective analysis of educational content based on published strategy for looking at this.
What they found, unfortunately but not surprisingly, overall was that the educational quality and reliability were quite poor. They also noticed considerable differences in disparities based on racial background and really emphasized in their analysis not only how common it is for individuals to look at this content on TikTok but also concerns about what it is that the public, patients, and their families are actually seeing.
This, of course, specifically relates to gynecologic cancers, but almost certainly relates to other cancers as well. Clearly, this is a topic that needs to be discussed widely. It’s very complex and very controversial, but when you think about the information that might be provided to our patients and their families going to social media, it’s important that we understand what they’re seeing, what they’re hearing, what they’re viewing, and the impact this might have on their care and outcomes.
I encourage you to read this very interesting paper if you have an interest in this topic. Again, it was recently published in Gynecologic Oncology. I thank you for your attention.
Dr. Markman is professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California; president of Medicine & Science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline and AstraZeneca.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I’m delighted to talk about a very interesting topic in this commentary. This is an area that we generally don’t discuss, but it’s one that’s obviously very topical, which includes the question of social media.
The paper I’m referring to is entitled, “More Than a Song and Dance”: Exploration of Patient Perspectives and Educational Quality of Gynecologic Cancer Content on TikTok. The paper was published in Gynecologic Oncology in 2023.
They had a total of 466.7 million views. They looked at 430 of the 500 top posts that were eligible, looked at 11 central themes, did an objective analysis of educational content based on published strategy for looking at this.
What they found, unfortunately but not surprisingly, overall was that the educational quality and reliability were quite poor. They also noticed considerable differences in disparities based on racial background and really emphasized in their analysis not only how common it is for individuals to look at this content on TikTok but also concerns about what it is that the public, patients, and their families are actually seeing.
This, of course, specifically relates to gynecologic cancers, but almost certainly relates to other cancers as well. Clearly, this is a topic that needs to be discussed widely. It’s very complex and very controversial, but when you think about the information that might be provided to our patients and their families going to social media, it’s important that we understand what they’re seeing, what they’re hearing, what they’re viewing, and the impact this might have on their care and outcomes.
I encourage you to read this very interesting paper if you have an interest in this topic. Again, it was recently published in Gynecologic Oncology. I thank you for your attention.
Dr. Markman is professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California; president of Medicine & Science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline and AstraZeneca.
A version of this article appeared on Medscape.com.
CRC: Troubling Mortality Rates for a Preventable Cancer
This transcript has been edited for clarity.
The American Cancer Society has just published its cancer statistics for 2024. This is an annual report, the latest version of which has some alarming news for gastroenterologists. Usually, we think of being “number one” as a positive thing, but that’s not the case this year when it comes to the projections for colorectal cancer.
But first, let’s discuss the report’s overall findings. That decline over the past four decades is due to reductions in smoking, earlier detection, and improved screening and treatments for localized or metastatic disease. But these gains are now threatened by some offsets that we’re seeing, with increasing rates of six of the top 10 cancers in the past several years.
Increasing Rates of Gastrointestinal Cancers
The incidence rate of pancreas cancer has increased from 0.6% to 1% annually.
Pancreas cancer has a 5-year relative survival rate of 13%, which ranks as one of the three worst rates for cancers. This cancer represents a real screening challenge for us, as it typically presents asymptomatically.
Women have experienced a 2%-3% annual increase in incidence rates for liver cancer.
I suspect that this is due to cases of fibrotic liver disease resulting from viral hepatitis and metabolic liver diseases with nonalcoholic fatty liver and advanced fibrosis (F3 and F4). These cases may be carried over from before, thereby contributing to the increasing incremental cancer risk.
We can’t overlook the need for risk reduction here and should focus on applying regular screening efforts in our female patients. However, it’s also true that we require better liver cancer screening tests to accomplish that goal.
In Those Under 50, CRC the Leading Cause of Cancer Death in Men, Second in Women
I really want to focus on the news around colorectal cancer.
To put this in perspective, in the late 1990s, colorectal cancer was the fourth leading cause of death in men and women. The current report extrapolated 2024 projections using the Surveillance, Epidemiology, and End Results (SEER) database ending in 2020, which was necessary given the incremental time it takes to develop cancers. The SEER database suggests that in 2024, colorectal cancer in those younger than 50 years of age will become the number-one leading cause of cancer death in men and number-two in women. The increasing incidence of colorectal cancer in younger people is probably the result of a number of epidemiologic and other reasons.
The current report offers evidence of racial disparities in cancer mortality rates in general, which are twofold higher in Black people compared with White people, particularly for gastric cancer. There is also an evident disparity in Native Americans, who have higher rates of gastric and liver cancer. This is a reminder of the increasing need for equity to address racial disparities across these populations.
But returning to colon cancer, it’s a marked change to go from being the fourth-leading cause of cancer death in those younger than 50 years of age to being number one for men and number two for women.
Being “number one” is supposed to make you famous. This “number one,” however, should in fact be infamous. It’s a travesty, because colorectal cancer is a potentially preventable disease.
As we move into March, which happens to be Colorectal Cancer Awareness Month, hopefully this fires up some of the conversations you have with your younger at-risk population, who may be reticent or resistant to colorectal cancer screening.
We have to do better at getting this message out to that population at large. “Number one” is not where we want to be for this potentially preventable problem.
Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed ties with ISOTHRIVE and Johnson & Johnson.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
The American Cancer Society has just published its cancer statistics for 2024. This is an annual report, the latest version of which has some alarming news for gastroenterologists. Usually, we think of being “number one” as a positive thing, but that’s not the case this year when it comes to the projections for colorectal cancer.
But first, let’s discuss the report’s overall findings. That decline over the past four decades is due to reductions in smoking, earlier detection, and improved screening and treatments for localized or metastatic disease. But these gains are now threatened by some offsets that we’re seeing, with increasing rates of six of the top 10 cancers in the past several years.
Increasing Rates of Gastrointestinal Cancers
The incidence rate of pancreas cancer has increased from 0.6% to 1% annually.
Pancreas cancer has a 5-year relative survival rate of 13%, which ranks as one of the three worst rates for cancers. This cancer represents a real screening challenge for us, as it typically presents asymptomatically.
Women have experienced a 2%-3% annual increase in incidence rates for liver cancer.
I suspect that this is due to cases of fibrotic liver disease resulting from viral hepatitis and metabolic liver diseases with nonalcoholic fatty liver and advanced fibrosis (F3 and F4). These cases may be carried over from before, thereby contributing to the increasing incremental cancer risk.
We can’t overlook the need for risk reduction here and should focus on applying regular screening efforts in our female patients. However, it’s also true that we require better liver cancer screening tests to accomplish that goal.
In Those Under 50, CRC the Leading Cause of Cancer Death in Men, Second in Women
I really want to focus on the news around colorectal cancer.
To put this in perspective, in the late 1990s, colorectal cancer was the fourth leading cause of death in men and women. The current report extrapolated 2024 projections using the Surveillance, Epidemiology, and End Results (SEER) database ending in 2020, which was necessary given the incremental time it takes to develop cancers. The SEER database suggests that in 2024, colorectal cancer in those younger than 50 years of age will become the number-one leading cause of cancer death in men and number-two in women. The increasing incidence of colorectal cancer in younger people is probably the result of a number of epidemiologic and other reasons.
The current report offers evidence of racial disparities in cancer mortality rates in general, which are twofold higher in Black people compared with White people, particularly for gastric cancer. There is also an evident disparity in Native Americans, who have higher rates of gastric and liver cancer. This is a reminder of the increasing need for equity to address racial disparities across these populations.
But returning to colon cancer, it’s a marked change to go from being the fourth-leading cause of cancer death in those younger than 50 years of age to being number one for men and number two for women.
Being “number one” is supposed to make you famous. This “number one,” however, should in fact be infamous. It’s a travesty, because colorectal cancer is a potentially preventable disease.
As we move into March, which happens to be Colorectal Cancer Awareness Month, hopefully this fires up some of the conversations you have with your younger at-risk population, who may be reticent or resistant to colorectal cancer screening.
We have to do better at getting this message out to that population at large. “Number one” is not where we want to be for this potentially preventable problem.
Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed ties with ISOTHRIVE and Johnson & Johnson.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
The American Cancer Society has just published its cancer statistics for 2024. This is an annual report, the latest version of which has some alarming news for gastroenterologists. Usually, we think of being “number one” as a positive thing, but that’s not the case this year when it comes to the projections for colorectal cancer.
But first, let’s discuss the report’s overall findings. That decline over the past four decades is due to reductions in smoking, earlier detection, and improved screening and treatments for localized or metastatic disease. But these gains are now threatened by some offsets that we’re seeing, with increasing rates of six of the top 10 cancers in the past several years.
Increasing Rates of Gastrointestinal Cancers
The incidence rate of pancreas cancer has increased from 0.6% to 1% annually.
Pancreas cancer has a 5-year relative survival rate of 13%, which ranks as one of the three worst rates for cancers. This cancer represents a real screening challenge for us, as it typically presents asymptomatically.
Women have experienced a 2%-3% annual increase in incidence rates for liver cancer.
I suspect that this is due to cases of fibrotic liver disease resulting from viral hepatitis and metabolic liver diseases with nonalcoholic fatty liver and advanced fibrosis (F3 and F4). These cases may be carried over from before, thereby contributing to the increasing incremental cancer risk.
We can’t overlook the need for risk reduction here and should focus on applying regular screening efforts in our female patients. However, it’s also true that we require better liver cancer screening tests to accomplish that goal.
In Those Under 50, CRC the Leading Cause of Cancer Death in Men, Second in Women
I really want to focus on the news around colorectal cancer.
To put this in perspective, in the late 1990s, colorectal cancer was the fourth leading cause of death in men and women. The current report extrapolated 2024 projections using the Surveillance, Epidemiology, and End Results (SEER) database ending in 2020, which was necessary given the incremental time it takes to develop cancers. The SEER database suggests that in 2024, colorectal cancer in those younger than 50 years of age will become the number-one leading cause of cancer death in men and number-two in women. The increasing incidence of colorectal cancer in younger people is probably the result of a number of epidemiologic and other reasons.
The current report offers evidence of racial disparities in cancer mortality rates in general, which are twofold higher in Black people compared with White people, particularly for gastric cancer. There is also an evident disparity in Native Americans, who have higher rates of gastric and liver cancer. This is a reminder of the increasing need for equity to address racial disparities across these populations.
But returning to colon cancer, it’s a marked change to go from being the fourth-leading cause of cancer death in those younger than 50 years of age to being number one for men and number two for women.
Being “number one” is supposed to make you famous. This “number one,” however, should in fact be infamous. It’s a travesty, because colorectal cancer is a potentially preventable disease.
As we move into March, which happens to be Colorectal Cancer Awareness Month, hopefully this fires up some of the conversations you have with your younger at-risk population, who may be reticent or resistant to colorectal cancer screening.
We have to do better at getting this message out to that population at large. “Number one” is not where we want to be for this potentially preventable problem.
Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed ties with ISOTHRIVE and Johnson & Johnson.
A version of this article appeared on Medscape.com.
The Daycare Petri Dish
I can’t remember where I heard it. Maybe I made it up myself. But, one definition of a family is a group of folks with whom you share your genes and germs. In that same vein, one could define daycare as a group of germ-sharing children. Of course that’s news to almost no one. Parents who decide, or are forced, to send their children to daycare expect that those children will get more colds, “stomach flu,” and ear infections than the children who spend their days in isolation at home. Everyone from the pediatrician to the little old lady next door has warned parents of the inevitable reality of daycare. Of course there are upsides that parents can cling to, including increased socialization and the hope that getting sick young will build a more robust immunity in the long run.
However, there has been little research exploring the nuances of the germ sharing that we all know is happening in these and other social settings.
A team of evolutionary biologists at Harvard is working to better define the “social microbiome” and its “role in individuals’ susceptibility to, and resilience against, both communicable and noncommunicable diseases.” These researchers point out that while we harbor our own unique collection of microbes, we share those with the microbiomes of the people with whom we interact socially. They report that studies by other investigators have shown that residents of a household share a significant proportion of their gastrointestinal flora. There are other studies that have shown that villages can be identified by their own social biome. There are few social settings more intimately involved in microbe sharing than daycares. I have a friends who calls them “petri dishes.”
The biologists point out that antibiotic-resistant microbes can become part of an individual’s microbiome and can be shared with other individuals in their social group, who can then go on and share them in a different social environment. Imagine there is one popular physician in a community whose sense of antibiotic stewardship is, shall we say, somewhat lacking. By inappropriately prescribing antibiotics to a child or two in a daycare, he may be altering the social biome in that daycare, which could then jeopardize the health of all the children and eventually their own home-based social biomes, that may include an immune deficient individual.
The researchers also remind us that different cultures and countries may have different antibiotic usage patterns. Does this mean I am taking a risk by traveling in these “culture-dependent transmission landscapes”? Am I more likely to encounter an antibiotic-resistant microbe when I am visiting a country whose healthcare providers are less prudent prescribers?
However, as these evolutionary biologists point out, not all shared microbes are bad. There is some evidence in animals that individuals can share microbes that have been found to “increase resilience against colitis or improve their responsiveness to cancer therapy.” If a microbe can contribute to a disease that was once considered to be “noncommunicable,” we may need to redefine “communicable” in the light this more nuanced view of the social biome.
It became standard practice during the COVID pandemic to test dormitory and community sewage water to determine the level of infection. Can sewage water be used as a proxy for a social biome? If a parent is lucky enough to have a choice of daycares, would knowing each facility’s biome, as reflected in an analysis of its sewage effluent, help him or her decide? Should a daycare ask for a stool sample from each child before accepting him or her? Seems like this would raise some privacy issues, not to mention the logistical messiness of the process. As we learn more about social biomes, can we imagine a time when a daycare or country or region might proudly advertise itself as having the healthiest spectrum of microbes in its sewage system?
Communal living certainly has its benefits, not just for children but also adults as we realize how loneliness is eating its way into our society. However,
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
I can’t remember where I heard it. Maybe I made it up myself. But, one definition of a family is a group of folks with whom you share your genes and germs. In that same vein, one could define daycare as a group of germ-sharing children. Of course that’s news to almost no one. Parents who decide, or are forced, to send their children to daycare expect that those children will get more colds, “stomach flu,” and ear infections than the children who spend their days in isolation at home. Everyone from the pediatrician to the little old lady next door has warned parents of the inevitable reality of daycare. Of course there are upsides that parents can cling to, including increased socialization and the hope that getting sick young will build a more robust immunity in the long run.
However, there has been little research exploring the nuances of the germ sharing that we all know is happening in these and other social settings.
A team of evolutionary biologists at Harvard is working to better define the “social microbiome” and its “role in individuals’ susceptibility to, and resilience against, both communicable and noncommunicable diseases.” These researchers point out that while we harbor our own unique collection of microbes, we share those with the microbiomes of the people with whom we interact socially. They report that studies by other investigators have shown that residents of a household share a significant proportion of their gastrointestinal flora. There are other studies that have shown that villages can be identified by their own social biome. There are few social settings more intimately involved in microbe sharing than daycares. I have a friends who calls them “petri dishes.”
The biologists point out that antibiotic-resistant microbes can become part of an individual’s microbiome and can be shared with other individuals in their social group, who can then go on and share them in a different social environment. Imagine there is one popular physician in a community whose sense of antibiotic stewardship is, shall we say, somewhat lacking. By inappropriately prescribing antibiotics to a child or two in a daycare, he may be altering the social biome in that daycare, which could then jeopardize the health of all the children and eventually their own home-based social biomes, that may include an immune deficient individual.
The researchers also remind us that different cultures and countries may have different antibiotic usage patterns. Does this mean I am taking a risk by traveling in these “culture-dependent transmission landscapes”? Am I more likely to encounter an antibiotic-resistant microbe when I am visiting a country whose healthcare providers are less prudent prescribers?
However, as these evolutionary biologists point out, not all shared microbes are bad. There is some evidence in animals that individuals can share microbes that have been found to “increase resilience against colitis or improve their responsiveness to cancer therapy.” If a microbe can contribute to a disease that was once considered to be “noncommunicable,” we may need to redefine “communicable” in the light this more nuanced view of the social biome.
It became standard practice during the COVID pandemic to test dormitory and community sewage water to determine the level of infection. Can sewage water be used as a proxy for a social biome? If a parent is lucky enough to have a choice of daycares, would knowing each facility’s biome, as reflected in an analysis of its sewage effluent, help him or her decide? Should a daycare ask for a stool sample from each child before accepting him or her? Seems like this would raise some privacy issues, not to mention the logistical messiness of the process. As we learn more about social biomes, can we imagine a time when a daycare or country or region might proudly advertise itself as having the healthiest spectrum of microbes in its sewage system?
Communal living certainly has its benefits, not just for children but also adults as we realize how loneliness is eating its way into our society. However,
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
I can’t remember where I heard it. Maybe I made it up myself. But, one definition of a family is a group of folks with whom you share your genes and germs. In that same vein, one could define daycare as a group of germ-sharing children. Of course that’s news to almost no one. Parents who decide, or are forced, to send their children to daycare expect that those children will get more colds, “stomach flu,” and ear infections than the children who spend their days in isolation at home. Everyone from the pediatrician to the little old lady next door has warned parents of the inevitable reality of daycare. Of course there are upsides that parents can cling to, including increased socialization and the hope that getting sick young will build a more robust immunity in the long run.
However, there has been little research exploring the nuances of the germ sharing that we all know is happening in these and other social settings.
A team of evolutionary biologists at Harvard is working to better define the “social microbiome” and its “role in individuals’ susceptibility to, and resilience against, both communicable and noncommunicable diseases.” These researchers point out that while we harbor our own unique collection of microbes, we share those with the microbiomes of the people with whom we interact socially. They report that studies by other investigators have shown that residents of a household share a significant proportion of their gastrointestinal flora. There are other studies that have shown that villages can be identified by their own social biome. There are few social settings more intimately involved in microbe sharing than daycares. I have a friends who calls them “petri dishes.”
The biologists point out that antibiotic-resistant microbes can become part of an individual’s microbiome and can be shared with other individuals in their social group, who can then go on and share them in a different social environment. Imagine there is one popular physician in a community whose sense of antibiotic stewardship is, shall we say, somewhat lacking. By inappropriately prescribing antibiotics to a child or two in a daycare, he may be altering the social biome in that daycare, which could then jeopardize the health of all the children and eventually their own home-based social biomes, that may include an immune deficient individual.
The researchers also remind us that different cultures and countries may have different antibiotic usage patterns. Does this mean I am taking a risk by traveling in these “culture-dependent transmission landscapes”? Am I more likely to encounter an antibiotic-resistant microbe when I am visiting a country whose healthcare providers are less prudent prescribers?
However, as these evolutionary biologists point out, not all shared microbes are bad. There is some evidence in animals that individuals can share microbes that have been found to “increase resilience against colitis or improve their responsiveness to cancer therapy.” If a microbe can contribute to a disease that was once considered to be “noncommunicable,” we may need to redefine “communicable” in the light this more nuanced view of the social biome.
It became standard practice during the COVID pandemic to test dormitory and community sewage water to determine the level of infection. Can sewage water be used as a proxy for a social biome? If a parent is lucky enough to have a choice of daycares, would knowing each facility’s biome, as reflected in an analysis of its sewage effluent, help him or her decide? Should a daycare ask for a stool sample from each child before accepting him or her? Seems like this would raise some privacy issues, not to mention the logistical messiness of the process. As we learn more about social biomes, can we imagine a time when a daycare or country or region might proudly advertise itself as having the healthiest spectrum of microbes in its sewage system?
Communal living certainly has its benefits, not just for children but also adults as we realize how loneliness is eating its way into our society. However,
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
Updated Clinical Guidelines for the Treatment of Acne Vulgaris
In January 2024, the American Academy of Dermatology released updated clinical guidelines for the treatment of acne. These guidelines include 18 evidence-based recommendations.
As primary care physicians, we commonly encounter acne vulgaris in our practices. While it may not be a life-threatening condition, it deeply affects the quality of life for many who suffer from it. It can be accompanied by stigmatization and bullying and can affect a person’s self-esteem; it can lead to suicidal ideation. It is important to treat it and know when to refer to a dermatologist.
According to the AAD, acne is the most common skin condition, affecting 50 million Americans annually. It can occur at any stage in life, often starting during puberty. It is so common that at least 85% of people between the ages of 12 and 24 experience at least mild acne.
The guidelines stress using multimodal therapies combining multiple mechanisms of action. For example, they show strong evidence for using topical retinoids with topical benzoyl peroxide or topical retinoids with topical antibiotics. They recommend against using oral antibiotics, except in severe cases, to prevent antibiotic resistance. The strongest evidence regarding antibiotics shows doxycycline or minocycline to be the most effective for treating acne and these can be combined with topical medications.
These guidelines also include isotretinoin to be used for severe acne patients, who are defined as “patients with psychosocial burden or scarring.” They recommend monitoring liver function and lipids as good practice and mandatory pregnancy prevention. These guidelines find no conclusive evidence for physical modalities such as lesion extraction, chemical peels, use of laser and light-based devices, microneedling, use of radiofrequency devices, and photodynamic therapy.
A conditional recommendation is given for the use of combined oral contraception pills and spironolactone. The AAD advises considering the risks of these agents along with other conditions present that they may be useful for.
In primary care, we see many complicated patients and often acne is not considered a serious condition. However, it can be as life-altering to the patient as other chronic diseases such as rheumatoid arthritis. We need to know the appropriate management of acne and start following the evidence-based guidelines. Acne needs follow-up as close as for other chronic diseases. We need to be able to assess the severity of disease and the effectiveness of treatments we have prescribed.
Some patients may be embarrassed to start the discussion about acne. If the patient doesn’t initiate the discussion, we should in an empathetic way. Acne is one of those diseases that doesn’t need any diagnostic tests to discover as it is readily apparent right in front of us.
Some patients may not be bothered by it, but for others, it may be ruining their lives, and they just don’t feel comfortable starting the conversation. Offering them a treatment will alleviate their disease but may also change their lives for the better.
Acne is also one of those conditions that has a host of misinformation and myths surrounding it. These myths range from dietary recommendations to hygiene and many others. As physicians, we need to educate ourselves about these myths and misconceptions. Patients will have questions regarding them and we need to be able to give them answers to their questions. We also shouldn’t give out misinformation ourselves. The evidence around acne treatment is readily available.
Given the availability of multiple acne therapies, shared-decision making is important. We need to discuss options with the patients and devise the best treatment regimen for them. If our therapies are not getting the results we would like, we need to consider referring the patient to a dermatologist.
We need to remember that acne is not just a cosmetic disease. It affects the lives of those suffering from it and we need to address it like any other chronic disease.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J.
In January 2024, the American Academy of Dermatology released updated clinical guidelines for the treatment of acne. These guidelines include 18 evidence-based recommendations.
As primary care physicians, we commonly encounter acne vulgaris in our practices. While it may not be a life-threatening condition, it deeply affects the quality of life for many who suffer from it. It can be accompanied by stigmatization and bullying and can affect a person’s self-esteem; it can lead to suicidal ideation. It is important to treat it and know when to refer to a dermatologist.
According to the AAD, acne is the most common skin condition, affecting 50 million Americans annually. It can occur at any stage in life, often starting during puberty. It is so common that at least 85% of people between the ages of 12 and 24 experience at least mild acne.
The guidelines stress using multimodal therapies combining multiple mechanisms of action. For example, they show strong evidence for using topical retinoids with topical benzoyl peroxide or topical retinoids with topical antibiotics. They recommend against using oral antibiotics, except in severe cases, to prevent antibiotic resistance. The strongest evidence regarding antibiotics shows doxycycline or minocycline to be the most effective for treating acne and these can be combined with topical medications.
These guidelines also include isotretinoin to be used for severe acne patients, who are defined as “patients with psychosocial burden or scarring.” They recommend monitoring liver function and lipids as good practice and mandatory pregnancy prevention. These guidelines find no conclusive evidence for physical modalities such as lesion extraction, chemical peels, use of laser and light-based devices, microneedling, use of radiofrequency devices, and photodynamic therapy.
A conditional recommendation is given for the use of combined oral contraception pills and spironolactone. The AAD advises considering the risks of these agents along with other conditions present that they may be useful for.
In primary care, we see many complicated patients and often acne is not considered a serious condition. However, it can be as life-altering to the patient as other chronic diseases such as rheumatoid arthritis. We need to know the appropriate management of acne and start following the evidence-based guidelines. Acne needs follow-up as close as for other chronic diseases. We need to be able to assess the severity of disease and the effectiveness of treatments we have prescribed.
Some patients may be embarrassed to start the discussion about acne. If the patient doesn’t initiate the discussion, we should in an empathetic way. Acne is one of those diseases that doesn’t need any diagnostic tests to discover as it is readily apparent right in front of us.
Some patients may not be bothered by it, but for others, it may be ruining their lives, and they just don’t feel comfortable starting the conversation. Offering them a treatment will alleviate their disease but may also change their lives for the better.
Acne is also one of those conditions that has a host of misinformation and myths surrounding it. These myths range from dietary recommendations to hygiene and many others. As physicians, we need to educate ourselves about these myths and misconceptions. Patients will have questions regarding them and we need to be able to give them answers to their questions. We also shouldn’t give out misinformation ourselves. The evidence around acne treatment is readily available.
Given the availability of multiple acne therapies, shared-decision making is important. We need to discuss options with the patients and devise the best treatment regimen for them. If our therapies are not getting the results we would like, we need to consider referring the patient to a dermatologist.
We need to remember that acne is not just a cosmetic disease. It affects the lives of those suffering from it and we need to address it like any other chronic disease.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J.
In January 2024, the American Academy of Dermatology released updated clinical guidelines for the treatment of acne. These guidelines include 18 evidence-based recommendations.
As primary care physicians, we commonly encounter acne vulgaris in our practices. While it may not be a life-threatening condition, it deeply affects the quality of life for many who suffer from it. It can be accompanied by stigmatization and bullying and can affect a person’s self-esteem; it can lead to suicidal ideation. It is important to treat it and know when to refer to a dermatologist.
According to the AAD, acne is the most common skin condition, affecting 50 million Americans annually. It can occur at any stage in life, often starting during puberty. It is so common that at least 85% of people between the ages of 12 and 24 experience at least mild acne.
The guidelines stress using multimodal therapies combining multiple mechanisms of action. For example, they show strong evidence for using topical retinoids with topical benzoyl peroxide or topical retinoids with topical antibiotics. They recommend against using oral antibiotics, except in severe cases, to prevent antibiotic resistance. The strongest evidence regarding antibiotics shows doxycycline or minocycline to be the most effective for treating acne and these can be combined with topical medications.
These guidelines also include isotretinoin to be used for severe acne patients, who are defined as “patients with psychosocial burden or scarring.” They recommend monitoring liver function and lipids as good practice and mandatory pregnancy prevention. These guidelines find no conclusive evidence for physical modalities such as lesion extraction, chemical peels, use of laser and light-based devices, microneedling, use of radiofrequency devices, and photodynamic therapy.
A conditional recommendation is given for the use of combined oral contraception pills and spironolactone. The AAD advises considering the risks of these agents along with other conditions present that they may be useful for.
In primary care, we see many complicated patients and often acne is not considered a serious condition. However, it can be as life-altering to the patient as other chronic diseases such as rheumatoid arthritis. We need to know the appropriate management of acne and start following the evidence-based guidelines. Acne needs follow-up as close as for other chronic diseases. We need to be able to assess the severity of disease and the effectiveness of treatments we have prescribed.
Some patients may be embarrassed to start the discussion about acne. If the patient doesn’t initiate the discussion, we should in an empathetic way. Acne is one of those diseases that doesn’t need any diagnostic tests to discover as it is readily apparent right in front of us.
Some patients may not be bothered by it, but for others, it may be ruining their lives, and they just don’t feel comfortable starting the conversation. Offering them a treatment will alleviate their disease but may also change their lives for the better.
Acne is also one of those conditions that has a host of misinformation and myths surrounding it. These myths range from dietary recommendations to hygiene and many others. As physicians, we need to educate ourselves about these myths and misconceptions. Patients will have questions regarding them and we need to be able to give them answers to their questions. We also shouldn’t give out misinformation ourselves. The evidence around acne treatment is readily available.
Given the availability of multiple acne therapies, shared-decision making is important. We need to discuss options with the patients and devise the best treatment regimen for them. If our therapies are not getting the results we would like, we need to consider referring the patient to a dermatologist.
We need to remember that acne is not just a cosmetic disease. It affects the lives of those suffering from it and we need to address it like any other chronic disease.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J.
Unleashing Our Immune Response to Quash Cancer
This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”
It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.
Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.
Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.
And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.
As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.
Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.
An Ever-Expanding Armamentarium
Immune Checkpoint Inhibitors
The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.
But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.
Therapeutic Cancer Vaccines
There are many therapeutic cancer vaccines in the works, as reviewed in depth here.
Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.
An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.
Antibody-Drug Conjugates (ADC)
There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.
A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.
This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.
Oncolytic Viruses
Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.
After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.
Engineering T Cells (Chimeric Antigen Receptor [CAR-T])
As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.
As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.
Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.
Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.
Summary
Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.
Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.
Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.
Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.
Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.
A version of this article appeared on Medscape.com.
This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”
It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.
Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.
Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.
And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.
As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.
Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.
An Ever-Expanding Armamentarium
Immune Checkpoint Inhibitors
The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.
But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.
Therapeutic Cancer Vaccines
There are many therapeutic cancer vaccines in the works, as reviewed in depth here.
Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.
An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.
Antibody-Drug Conjugates (ADC)
There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.
A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.
This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.
Oncolytic Viruses
Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.
After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.
Engineering T Cells (Chimeric Antigen Receptor [CAR-T])
As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.
As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.
Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.
Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.
Summary
Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.
Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.
Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.
Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.
Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.
A version of this article appeared on Medscape.com.
This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”
It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.
Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.
Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.
And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.
As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.
Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.
An Ever-Expanding Armamentarium
Immune Checkpoint Inhibitors
The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.
But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.
Therapeutic Cancer Vaccines
There are many therapeutic cancer vaccines in the works, as reviewed in depth here.
Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.
An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.
Antibody-Drug Conjugates (ADC)
There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.
A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.
This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.
Oncolytic Viruses
Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.
After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.
Engineering T Cells (Chimeric Antigen Receptor [CAR-T])
As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.
As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.
Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.
Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.
Summary
Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.
Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.
Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.
Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.
Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.
A version of this article appeared on Medscape.com.
Kimchi: Not Magically Protective Against Weight Gain
How much of societal diet-related scientific illiteracy can be blamed on the publication decisions of medical journals around food studies?
That was the question I pondered when reading “Association between kimchi consumption and obesity based on BMI and abdominal obesity in Korean adults: a cross-sectional analysis of the Health Examinees study,” recently published in BMJ Open. Although I will get to the study particulars momentarily, that it’s 2024 and journals are still publishing cross-sectional studies of the impact of a single food’s subjectively reported consumption on health outcomes is mind boggling.
You might wonder why I wasn’t mind boggled by the authors rather than the journal — but the authors’ interest in publishing a study on kimchi’s supposed impact on obesity is an easy thing to explain, in that the study was funded by the World Institute of Kimchi, where two of its four authors are employed.
You might also wonder why I wasn’t mind boggled by media running with this story — but the media’s job is to capture eyeballs, and who doesn’t love a good magic food story, doubly so for one involving obesity and one with a study backing it up?
Back to this World Institute of Kimchi project looking at kimchi intake on obesity rates. No doubt if I worked for the World Institute of Kimchi, I would want kimchi to be shown to be somehow magically protective against weight gain. So how might I go about exploring that?
Well, I could look to the data from the Health Examinees (HEXA) Study. The HEXA study was a cross-sectional look at South Koreans; included in their data collection was a 106-item food frequency questionnaire (FFQ).
That questionnaire looked at 106 food items — yep, you guessed it, explicitly including kimchi. Not included in this FFQ, though, were prepared foods, meaning that it was unable to measure seasonings, spices, or cooking oils. Also perhaps problematic is that no doubt most of us consume more than 106 total food items in our diets. Perhaps this is why the validation study of HEXA’s food item–based FFQ found that it had “relatively low validity” when compared against 12-day food diaries and why its creators themselves report it to be in their study’s conclusion only “reasonably acceptable” to apply to a population. But yes, kimchi!
So for the sake of this exercise, though, let’s assume that instead of only a reasonably acceptable FFQ with low validity, the FFQ was fantastic and its data robust. How great then is kimchi at preventing obesity? Certainly, the media report it’s pretty darn good. Here’s a smattering from the literal dozens of headlines of stories covering this paper:
Eating kimchi every day could help stave off weight gain, new study says — NBC News
Eating kimchi every day may prevent weight gain, research suggests — Sky News
Want to avoid piling on the pounds? Try kimchi for breakfast — The Telegraph
But when we turn to the paper itself, suddenly things aren’t so clear.
According to the paper, men who reported eating two to three servings of kimchi per day were found to have lower rates of obesity, whereas men who reported eating three to five servings of kimchi per day were not. But these are overlapping groups! Also found was that men consuming more than five servings of kimchi per day have higher rates of obesity. When taken together, these findings do not demonstrate a statistically significant trend of kimchi intake on obesity in men. Whereas in women, things are worse in that the more kimchi reportedly consumed, the more obesity, in a trend that did (just) reach statistical significance.
So even if we pretend the FFQs were robust enough to make conclusions about a single food’s impact on obesity, and we pretend there was a well-described, plausible mechanistic reason to believe same (there isn’t), and we pretend that this particular FFQ had better than “relatively low validity,” there is no conclusion here to be drawn about kimchi’s impact on obesity.
What we can conclude is that when it comes to publishing papers purporting to find the impact of single foods on obesity, journals will still happily publish them and their publication will lead to hyperbolic headlines and stories, which in turn reinforce the scientifically illiterate notion that the highly complex multifactorial problem of obesity boils down to simple food choices, which in turn keeps weight loss grifters everywhere in business while fueling societal weight bias.
Dr. Freedhoff is Associate Professor, Department of Family Medicine, University of Ottawa; Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He disclosed ties with Bariatric Medical Institute, Constant Health, and Novo Nordisk.
A version of this article appeared on Medscape.com.
How much of societal diet-related scientific illiteracy can be blamed on the publication decisions of medical journals around food studies?
That was the question I pondered when reading “Association between kimchi consumption and obesity based on BMI and abdominal obesity in Korean adults: a cross-sectional analysis of the Health Examinees study,” recently published in BMJ Open. Although I will get to the study particulars momentarily, that it’s 2024 and journals are still publishing cross-sectional studies of the impact of a single food’s subjectively reported consumption on health outcomes is mind boggling.
You might wonder why I wasn’t mind boggled by the authors rather than the journal — but the authors’ interest in publishing a study on kimchi’s supposed impact on obesity is an easy thing to explain, in that the study was funded by the World Institute of Kimchi, where two of its four authors are employed.
You might also wonder why I wasn’t mind boggled by media running with this story — but the media’s job is to capture eyeballs, and who doesn’t love a good magic food story, doubly so for one involving obesity and one with a study backing it up?
Back to this World Institute of Kimchi project looking at kimchi intake on obesity rates. No doubt if I worked for the World Institute of Kimchi, I would want kimchi to be shown to be somehow magically protective against weight gain. So how might I go about exploring that?
Well, I could look to the data from the Health Examinees (HEXA) Study. The HEXA study was a cross-sectional look at South Koreans; included in their data collection was a 106-item food frequency questionnaire (FFQ).
That questionnaire looked at 106 food items — yep, you guessed it, explicitly including kimchi. Not included in this FFQ, though, were prepared foods, meaning that it was unable to measure seasonings, spices, or cooking oils. Also perhaps problematic is that no doubt most of us consume more than 106 total food items in our diets. Perhaps this is why the validation study of HEXA’s food item–based FFQ found that it had “relatively low validity” when compared against 12-day food diaries and why its creators themselves report it to be in their study’s conclusion only “reasonably acceptable” to apply to a population. But yes, kimchi!
So for the sake of this exercise, though, let’s assume that instead of only a reasonably acceptable FFQ with low validity, the FFQ was fantastic and its data robust. How great then is kimchi at preventing obesity? Certainly, the media report it’s pretty darn good. Here’s a smattering from the literal dozens of headlines of stories covering this paper:
Eating kimchi every day could help stave off weight gain, new study says — NBC News
Eating kimchi every day may prevent weight gain, research suggests — Sky News
Want to avoid piling on the pounds? Try kimchi for breakfast — The Telegraph
But when we turn to the paper itself, suddenly things aren’t so clear.
According to the paper, men who reported eating two to three servings of kimchi per day were found to have lower rates of obesity, whereas men who reported eating three to five servings of kimchi per day were not. But these are overlapping groups! Also found was that men consuming more than five servings of kimchi per day have higher rates of obesity. When taken together, these findings do not demonstrate a statistically significant trend of kimchi intake on obesity in men. Whereas in women, things are worse in that the more kimchi reportedly consumed, the more obesity, in a trend that did (just) reach statistical significance.
So even if we pretend the FFQs were robust enough to make conclusions about a single food’s impact on obesity, and we pretend there was a well-described, plausible mechanistic reason to believe same (there isn’t), and we pretend that this particular FFQ had better than “relatively low validity,” there is no conclusion here to be drawn about kimchi’s impact on obesity.
What we can conclude is that when it comes to publishing papers purporting to find the impact of single foods on obesity, journals will still happily publish them and their publication will lead to hyperbolic headlines and stories, which in turn reinforce the scientifically illiterate notion that the highly complex multifactorial problem of obesity boils down to simple food choices, which in turn keeps weight loss grifters everywhere in business while fueling societal weight bias.
Dr. Freedhoff is Associate Professor, Department of Family Medicine, University of Ottawa; Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He disclosed ties with Bariatric Medical Institute, Constant Health, and Novo Nordisk.
A version of this article appeared on Medscape.com.
How much of societal diet-related scientific illiteracy can be blamed on the publication decisions of medical journals around food studies?
That was the question I pondered when reading “Association between kimchi consumption and obesity based on BMI and abdominal obesity in Korean adults: a cross-sectional analysis of the Health Examinees study,” recently published in BMJ Open. Although I will get to the study particulars momentarily, that it’s 2024 and journals are still publishing cross-sectional studies of the impact of a single food’s subjectively reported consumption on health outcomes is mind boggling.
You might wonder why I wasn’t mind boggled by the authors rather than the journal — but the authors’ interest in publishing a study on kimchi’s supposed impact on obesity is an easy thing to explain, in that the study was funded by the World Institute of Kimchi, where two of its four authors are employed.
You might also wonder why I wasn’t mind boggled by media running with this story — but the media’s job is to capture eyeballs, and who doesn’t love a good magic food story, doubly so for one involving obesity and one with a study backing it up?
Back to this World Institute of Kimchi project looking at kimchi intake on obesity rates. No doubt if I worked for the World Institute of Kimchi, I would want kimchi to be shown to be somehow magically protective against weight gain. So how might I go about exploring that?
Well, I could look to the data from the Health Examinees (HEXA) Study. The HEXA study was a cross-sectional look at South Koreans; included in their data collection was a 106-item food frequency questionnaire (FFQ).
That questionnaire looked at 106 food items — yep, you guessed it, explicitly including kimchi. Not included in this FFQ, though, were prepared foods, meaning that it was unable to measure seasonings, spices, or cooking oils. Also perhaps problematic is that no doubt most of us consume more than 106 total food items in our diets. Perhaps this is why the validation study of HEXA’s food item–based FFQ found that it had “relatively low validity” when compared against 12-day food diaries and why its creators themselves report it to be in their study’s conclusion only “reasonably acceptable” to apply to a population. But yes, kimchi!
So for the sake of this exercise, though, let’s assume that instead of only a reasonably acceptable FFQ with low validity, the FFQ was fantastic and its data robust. How great then is kimchi at preventing obesity? Certainly, the media report it’s pretty darn good. Here’s a smattering from the literal dozens of headlines of stories covering this paper:
Eating kimchi every day could help stave off weight gain, new study says — NBC News
Eating kimchi every day may prevent weight gain, research suggests — Sky News
Want to avoid piling on the pounds? Try kimchi for breakfast — The Telegraph
But when we turn to the paper itself, suddenly things aren’t so clear.
According to the paper, men who reported eating two to three servings of kimchi per day were found to have lower rates of obesity, whereas men who reported eating three to five servings of kimchi per day were not. But these are overlapping groups! Also found was that men consuming more than five servings of kimchi per day have higher rates of obesity. When taken together, these findings do not demonstrate a statistically significant trend of kimchi intake on obesity in men. Whereas in women, things are worse in that the more kimchi reportedly consumed, the more obesity, in a trend that did (just) reach statistical significance.
So even if we pretend the FFQs were robust enough to make conclusions about a single food’s impact on obesity, and we pretend there was a well-described, plausible mechanistic reason to believe same (there isn’t), and we pretend that this particular FFQ had better than “relatively low validity,” there is no conclusion here to be drawn about kimchi’s impact on obesity.
What we can conclude is that when it comes to publishing papers purporting to find the impact of single foods on obesity, journals will still happily publish them and their publication will lead to hyperbolic headlines and stories, which in turn reinforce the scientifically illiterate notion that the highly complex multifactorial problem of obesity boils down to simple food choices, which in turn keeps weight loss grifters everywhere in business while fueling societal weight bias.
Dr. Freedhoff is Associate Professor, Department of Family Medicine, University of Ottawa; Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He disclosed ties with Bariatric Medical Institute, Constant Health, and Novo Nordisk.
A version of this article appeared on Medscape.com.
Long-Term Follow-Up Emphasizes HPV Vaccination Importance
This transcript has been edited for clarity.
I want to briefly discuss a critically important topic that cannot be overly emphasized. It is the relevance, the importance, the benefits, and the outcome of HPV vaccination.
The paper I’m referring to was published in Pediatrics in October 2023. It’s titled, “Ten-Year Follow-up of 9-Valent Human Papillomavirus Vaccine: Immunogenicity, Effectiveness, and Safety.”
Let me emphasize that we’re talking about a 10-year follow-up. In this particular paper and analysis, 301 boys — I emphasize boys — were included and 971 girls at 40 different sites in 13 countries, who received the 9-valent vaccine, which includes HPV 16, 18, and seven other types.
Most importantly, there was not a single case. Not one. Let me repeat this: There was not a single case of high-grade intraepithelial neoplasia, or worse, or condyloma in either males or females. There was not a single case in over 1000 individuals with a follow-up of more than 10 years.
It is difficult to overstate the magnitude of the benefit associated with HPV vaccination for our children and young adults on their risk of developing highly relevant, life-changing, potentially deadly cancers.
For those of you who are interested in this topic — which should include almost all of you, if not all of you — I encourage you to read this very important follow-up paper, again, demonstrating the simple, overwhelming magnitude of the benefit of HPV vaccination. I thank you for your attention.
Dr. Markman is a professor in the department of medical oncology and therapeutics research, City of Hope, Duarte, California, and president of medicine and science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline; AstraZeneca.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I want to briefly discuss a critically important topic that cannot be overly emphasized. It is the relevance, the importance, the benefits, and the outcome of HPV vaccination.
The paper I’m referring to was published in Pediatrics in October 2023. It’s titled, “Ten-Year Follow-up of 9-Valent Human Papillomavirus Vaccine: Immunogenicity, Effectiveness, and Safety.”
Let me emphasize that we’re talking about a 10-year follow-up. In this particular paper and analysis, 301 boys — I emphasize boys — were included and 971 girls at 40 different sites in 13 countries, who received the 9-valent vaccine, which includes HPV 16, 18, and seven other types.
Most importantly, there was not a single case. Not one. Let me repeat this: There was not a single case of high-grade intraepithelial neoplasia, or worse, or condyloma in either males or females. There was not a single case in over 1000 individuals with a follow-up of more than 10 years.
It is difficult to overstate the magnitude of the benefit associated with HPV vaccination for our children and young adults on their risk of developing highly relevant, life-changing, potentially deadly cancers.
For those of you who are interested in this topic — which should include almost all of you, if not all of you — I encourage you to read this very important follow-up paper, again, demonstrating the simple, overwhelming magnitude of the benefit of HPV vaccination. I thank you for your attention.
Dr. Markman is a professor in the department of medical oncology and therapeutics research, City of Hope, Duarte, California, and president of medicine and science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline; AstraZeneca.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I want to briefly discuss a critically important topic that cannot be overly emphasized. It is the relevance, the importance, the benefits, and the outcome of HPV vaccination.
The paper I’m referring to was published in Pediatrics in October 2023. It’s titled, “Ten-Year Follow-up of 9-Valent Human Papillomavirus Vaccine: Immunogenicity, Effectiveness, and Safety.”
Let me emphasize that we’re talking about a 10-year follow-up. In this particular paper and analysis, 301 boys — I emphasize boys — were included and 971 girls at 40 different sites in 13 countries, who received the 9-valent vaccine, which includes HPV 16, 18, and seven other types.
Most importantly, there was not a single case. Not one. Let me repeat this: There was not a single case of high-grade intraepithelial neoplasia, or worse, or condyloma in either males or females. There was not a single case in over 1000 individuals with a follow-up of more than 10 years.
It is difficult to overstate the magnitude of the benefit associated with HPV vaccination for our children and young adults on their risk of developing highly relevant, life-changing, potentially deadly cancers.
For those of you who are interested in this topic — which should include almost all of you, if not all of you — I encourage you to read this very important follow-up paper, again, demonstrating the simple, overwhelming magnitude of the benefit of HPV vaccination. I thank you for your attention.
Dr. Markman is a professor in the department of medical oncology and therapeutics research, City of Hope, Duarte, California, and president of medicine and science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline; AstraZeneca.
A version of this article appeared on Medscape.com.
Physicians as First Responders II
I recently wrote about a fledgling program here in Maine in which some emergency room physicians were being outfitted with equipment and communications gear that would allow them to respond on the fly to emergencies in the field when they weren’t working in the hospital. I questioned the rationale of using in-house personnel, already in short supply, for the few situations in which trained EMT personnel would usually be called. At the same time, I promised to return to the broader subject of the role of physicians as first responders in a future letter. And, here it is.
Have you ever been on a plane or at a large public gathering and the public addressed system crackled, “Is there a doctor on board” or in the audience? Or have you been on the highway and come upon a fresh accident in which it appears that there may have been injuries? Or at a youth soccer game in which a player has been injured and is still on the ground?
How do you usually respond in situations like this? Do you immediately identify yourself as a physician? Or, do you routinely shy away from involvement? What thoughts run through your head?
Do you feel your training and experience with emergencies is so outdated that you doubt you could be of any assistance? Has your practice become so specialized that you aren’t comfortable with anything outside of your specialty? Maybe getting involved is likely to throw your already tight travel schedule into disarray? Or are you afraid that should something go wrong while you were helping out you could be sued?
Keeping in mind that I am a retired septuagenarian pediatrician more than a decade removed from active practice, I would describe my usual response to these situations as “attentive hovering.” I position myself to have a good view of the victim and watch to see if there are any other responders. Either because of their personality or their experience, often there is someone who steps forward to help. Trained EMTs seem to have no hesitancy going into action. If I sense things aren’t going well, or the victim is a child, I will identify myself as a retired pediatrician and offer my assistance. Even if the response given by others seems appropriate, I may still eventually identify myself, maybe to lend an air of legitimacy to the process.
What are the roots of my hesitancy? I have found that I generally have little to add when there is a trained first responder on hand. They have been-there-and-done-that far more recently than I have. They know how to stabilize potential or obvious fractures. They know how to position the victim for transport. Even when I am in an environment where my medical background is already known, I yield to the more recently experienced first responders.
I don’t particularly worry about being sued. Every state has Good Samaritan laws. Although the laws vary from state to state, here in Maine I feel comfortable with the good sense of my fellow citizens. I understand if you live or practice in a more litigious environment you may be more concerned. On an airplane there is the Aviation Medical Assistant Act, which became law in 1998, and provides us with some extra protection.
What if there is a situation in which even with my outdated skills I seem to be the only show in town? Fortunately, that situation hasn’t occurred for me in quite a few years, but the odds are that one might occur. In almost 1 out of 600 airline flights, there is an inflight emergency. I tend to hang out with other septuagenarians and octogenarians doing active things. And I frequent youth athletic events where there is unlikely to be a first responder assigned to the event.
Should I be doing more to update my skills? It’s been a while since I refreshed by CPR techniques. I can’t recall the last time I handled a defibrillator. Should I be learning more about exsanguination prevention techniques?
Every so often there are some rumblings to mandate that all physicians should be required to update these first responder skills to maintain their license or certification. That wouldn’t cover those of us who are retired or who no longer practice medicine. And, I’m not sure we need to add another layer to the system. I think there are enough of us out there who would like to add ourselves to the first responder population, maybe not as fully trained experts but as folks who would like to be more ready to help by updating old or seldom-used skills.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
I recently wrote about a fledgling program here in Maine in which some emergency room physicians were being outfitted with equipment and communications gear that would allow them to respond on the fly to emergencies in the field when they weren’t working in the hospital. I questioned the rationale of using in-house personnel, already in short supply, for the few situations in which trained EMT personnel would usually be called. At the same time, I promised to return to the broader subject of the role of physicians as first responders in a future letter. And, here it is.
Have you ever been on a plane or at a large public gathering and the public addressed system crackled, “Is there a doctor on board” or in the audience? Or have you been on the highway and come upon a fresh accident in which it appears that there may have been injuries? Or at a youth soccer game in which a player has been injured and is still on the ground?
How do you usually respond in situations like this? Do you immediately identify yourself as a physician? Or, do you routinely shy away from involvement? What thoughts run through your head?
Do you feel your training and experience with emergencies is so outdated that you doubt you could be of any assistance? Has your practice become so specialized that you aren’t comfortable with anything outside of your specialty? Maybe getting involved is likely to throw your already tight travel schedule into disarray? Or are you afraid that should something go wrong while you were helping out you could be sued?
Keeping in mind that I am a retired septuagenarian pediatrician more than a decade removed from active practice, I would describe my usual response to these situations as “attentive hovering.” I position myself to have a good view of the victim and watch to see if there are any other responders. Either because of their personality or their experience, often there is someone who steps forward to help. Trained EMTs seem to have no hesitancy going into action. If I sense things aren’t going well, or the victim is a child, I will identify myself as a retired pediatrician and offer my assistance. Even if the response given by others seems appropriate, I may still eventually identify myself, maybe to lend an air of legitimacy to the process.
What are the roots of my hesitancy? I have found that I generally have little to add when there is a trained first responder on hand. They have been-there-and-done-that far more recently than I have. They know how to stabilize potential or obvious fractures. They know how to position the victim for transport. Even when I am in an environment where my medical background is already known, I yield to the more recently experienced first responders.
I don’t particularly worry about being sued. Every state has Good Samaritan laws. Although the laws vary from state to state, here in Maine I feel comfortable with the good sense of my fellow citizens. I understand if you live or practice in a more litigious environment you may be more concerned. On an airplane there is the Aviation Medical Assistant Act, which became law in 1998, and provides us with some extra protection.
What if there is a situation in which even with my outdated skills I seem to be the only show in town? Fortunately, that situation hasn’t occurred for me in quite a few years, but the odds are that one might occur. In almost 1 out of 600 airline flights, there is an inflight emergency. I tend to hang out with other septuagenarians and octogenarians doing active things. And I frequent youth athletic events where there is unlikely to be a first responder assigned to the event.
Should I be doing more to update my skills? It’s been a while since I refreshed by CPR techniques. I can’t recall the last time I handled a defibrillator. Should I be learning more about exsanguination prevention techniques?
Every so often there are some rumblings to mandate that all physicians should be required to update these first responder skills to maintain their license or certification. That wouldn’t cover those of us who are retired or who no longer practice medicine. And, I’m not sure we need to add another layer to the system. I think there are enough of us out there who would like to add ourselves to the first responder population, maybe not as fully trained experts but as folks who would like to be more ready to help by updating old or seldom-used skills.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
I recently wrote about a fledgling program here in Maine in which some emergency room physicians were being outfitted with equipment and communications gear that would allow them to respond on the fly to emergencies in the field when they weren’t working in the hospital. I questioned the rationale of using in-house personnel, already in short supply, for the few situations in which trained EMT personnel would usually be called. At the same time, I promised to return to the broader subject of the role of physicians as first responders in a future letter. And, here it is.
Have you ever been on a plane or at a large public gathering and the public addressed system crackled, “Is there a doctor on board” or in the audience? Or have you been on the highway and come upon a fresh accident in which it appears that there may have been injuries? Or at a youth soccer game in which a player has been injured and is still on the ground?
How do you usually respond in situations like this? Do you immediately identify yourself as a physician? Or, do you routinely shy away from involvement? What thoughts run through your head?
Do you feel your training and experience with emergencies is so outdated that you doubt you could be of any assistance? Has your practice become so specialized that you aren’t comfortable with anything outside of your specialty? Maybe getting involved is likely to throw your already tight travel schedule into disarray? Or are you afraid that should something go wrong while you were helping out you could be sued?
Keeping in mind that I am a retired septuagenarian pediatrician more than a decade removed from active practice, I would describe my usual response to these situations as “attentive hovering.” I position myself to have a good view of the victim and watch to see if there are any other responders. Either because of their personality or their experience, often there is someone who steps forward to help. Trained EMTs seem to have no hesitancy going into action. If I sense things aren’t going well, or the victim is a child, I will identify myself as a retired pediatrician and offer my assistance. Even if the response given by others seems appropriate, I may still eventually identify myself, maybe to lend an air of legitimacy to the process.
What are the roots of my hesitancy? I have found that I generally have little to add when there is a trained first responder on hand. They have been-there-and-done-that far more recently than I have. They know how to stabilize potential or obvious fractures. They know how to position the victim for transport. Even when I am in an environment where my medical background is already known, I yield to the more recently experienced first responders.
I don’t particularly worry about being sued. Every state has Good Samaritan laws. Although the laws vary from state to state, here in Maine I feel comfortable with the good sense of my fellow citizens. I understand if you live or practice in a more litigious environment you may be more concerned. On an airplane there is the Aviation Medical Assistant Act, which became law in 1998, and provides us with some extra protection.
What if there is a situation in which even with my outdated skills I seem to be the only show in town? Fortunately, that situation hasn’t occurred for me in quite a few years, but the odds are that one might occur. In almost 1 out of 600 airline flights, there is an inflight emergency. I tend to hang out with other septuagenarians and octogenarians doing active things. And I frequent youth athletic events where there is unlikely to be a first responder assigned to the event.
Should I be doing more to update my skills? It’s been a while since I refreshed by CPR techniques. I can’t recall the last time I handled a defibrillator. Should I be learning more about exsanguination prevention techniques?
Every so often there are some rumblings to mandate that all physicians should be required to update these first responder skills to maintain their license or certification. That wouldn’t cover those of us who are retired or who no longer practice medicine. And, I’m not sure we need to add another layer to the system. I think there are enough of us out there who would like to add ourselves to the first responder population, maybe not as fully trained experts but as folks who would like to be more ready to help by updating old or seldom-used skills.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
Healing From Trauma
“You’ll never walk alone.” — Nettie Fowler, Carousel
A few winters ago, a young man and his fiancée were driving on the 91 freeway in southern California during a torrential downpour when their Honda Civic hydroplaned, slamming into the jersey barrier. They were both unhurt. Unsure what to do next, they made the catastrophic decision to exit the vehicle. As the man walked around the back of the car he was nearly hit by a black sedan sliding out of control trying to avoid them. When he came around the car, his fiancé was nowhere to be found. She had been struck at highway speed and lay crushed under the sedan hundreds of feet away.
I know this poor man because he was referred to me. Not as a dermatologist, but as a fellow human healing from trauma. On January 1, 2019, at about 9:30 PM, while we were home together, my beloved wife of 24 years took her own life. Even 5 years on it is difficult to believe that she isn’t proofing this paragraph like she had done for every one of my Derm News columns for years. We had been together since teenagers and had lived a joy-filled life. There isn’t any medical reason to share. But that day I joined the community of those who have carried unbearable heaviness of grief and survived. Sometimes others seek me out for help.
At first, my instinct was to guide them, to give advice, to tell them what to do and where to go. But I’ve learned that people in this dark valley don’t need a guide. They need someone to accompany them. To walk with them for a few minutes on their lonely journey. I recently read David Brooks’s new book, How to Know a Person. I’ve been a fan of his since he joined the New York Times in 2003 and have read almost everything he’s written. I sometimes even imagine how he might approach a column whenever I’m stuck (thank you, David). His The Road to Character book is in my canon of literature for self-growth. This latest book is an interesting digression from that central theme. He argues that our society is in acute need of forming better connections and that an important way we can be moral is to learn, and to practice, how to know each other. He shares an emotional experience of losing a close friend to suicide and writes a poignant explanation of what it means to accompany someone in need. It particularly resonated with me. We are doctors and are wired to find the source of a problem, like quickly rotating through the 4X, 10X, 40X on a microscope. Once identified, we spend most of our time creating and explaining treatments. I see how this makes me a great dermatologist but just an average human.
Brooks tells the story of a woman with a brain tumor who often finds herself on the ground surrounded by well-meaning people trying to help. She explains later that what she really needs in those moments is just for someone to get on the ground and lie with her. To accompany her.
Having crossed the midpoint of life, I see with the benefit of perspective how suffering has afforded me wisdom: I am more sensitive and attuned to others. It also gave me credibility: I know how it feels to walk life’s loneliest journey. I’ve also learned to make myself vulnerable for someone to share their story with me. I won’t be afraid to hear the details. I won’t judge them for weeping too little or for sobbing too much. I don’t answer whys. I won’t say what they should do next. But for a few minutes I can walk beside them as a person who cares.
I do not try to remember the hours and days after Susan’s death, but one moment stands out and makes my eyes well when I think of it. That following day my dear brother flew across the country on the next flight out. I was sitting in a psychiatry waiting room when he came down the hall with his luggage in tow. He hugged me as only a brother could, then looked me in my eyes, which were bloodshot from tears just as his were, and he said, “We’re going to be OK.” And with that he walked with me into the office.
We physicians are blessed to have so many intimate human interactions. This book reminded me that sometimes my most important job is not to be the optimized doctor, but just a good human walking alongside.
I have no conflict of interest and purchased these books.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at [email protected].
“You’ll never walk alone.” — Nettie Fowler, Carousel
A few winters ago, a young man and his fiancée were driving on the 91 freeway in southern California during a torrential downpour when their Honda Civic hydroplaned, slamming into the jersey barrier. They were both unhurt. Unsure what to do next, they made the catastrophic decision to exit the vehicle. As the man walked around the back of the car he was nearly hit by a black sedan sliding out of control trying to avoid them. When he came around the car, his fiancé was nowhere to be found. She had been struck at highway speed and lay crushed under the sedan hundreds of feet away.
I know this poor man because he was referred to me. Not as a dermatologist, but as a fellow human healing from trauma. On January 1, 2019, at about 9:30 PM, while we were home together, my beloved wife of 24 years took her own life. Even 5 years on it is difficult to believe that she isn’t proofing this paragraph like she had done for every one of my Derm News columns for years. We had been together since teenagers and had lived a joy-filled life. There isn’t any medical reason to share. But that day I joined the community of those who have carried unbearable heaviness of grief and survived. Sometimes others seek me out for help.
At first, my instinct was to guide them, to give advice, to tell them what to do and where to go. But I’ve learned that people in this dark valley don’t need a guide. They need someone to accompany them. To walk with them for a few minutes on their lonely journey. I recently read David Brooks’s new book, How to Know a Person. I’ve been a fan of his since he joined the New York Times in 2003 and have read almost everything he’s written. I sometimes even imagine how he might approach a column whenever I’m stuck (thank you, David). His The Road to Character book is in my canon of literature for self-growth. This latest book is an interesting digression from that central theme. He argues that our society is in acute need of forming better connections and that an important way we can be moral is to learn, and to practice, how to know each other. He shares an emotional experience of losing a close friend to suicide and writes a poignant explanation of what it means to accompany someone in need. It particularly resonated with me. We are doctors and are wired to find the source of a problem, like quickly rotating through the 4X, 10X, 40X on a microscope. Once identified, we spend most of our time creating and explaining treatments. I see how this makes me a great dermatologist but just an average human.
Brooks tells the story of a woman with a brain tumor who often finds herself on the ground surrounded by well-meaning people trying to help. She explains later that what she really needs in those moments is just for someone to get on the ground and lie with her. To accompany her.
Having crossed the midpoint of life, I see with the benefit of perspective how suffering has afforded me wisdom: I am more sensitive and attuned to others. It also gave me credibility: I know how it feels to walk life’s loneliest journey. I’ve also learned to make myself vulnerable for someone to share their story with me. I won’t be afraid to hear the details. I won’t judge them for weeping too little or for sobbing too much. I don’t answer whys. I won’t say what they should do next. But for a few minutes I can walk beside them as a person who cares.
I do not try to remember the hours and days after Susan’s death, but one moment stands out and makes my eyes well when I think of it. That following day my dear brother flew across the country on the next flight out. I was sitting in a psychiatry waiting room when he came down the hall with his luggage in tow. He hugged me as only a brother could, then looked me in my eyes, which were bloodshot from tears just as his were, and he said, “We’re going to be OK.” And with that he walked with me into the office.
We physicians are blessed to have so many intimate human interactions. This book reminded me that sometimes my most important job is not to be the optimized doctor, but just a good human walking alongside.
I have no conflict of interest and purchased these books.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at [email protected].
“You’ll never walk alone.” — Nettie Fowler, Carousel
A few winters ago, a young man and his fiancée were driving on the 91 freeway in southern California during a torrential downpour when their Honda Civic hydroplaned, slamming into the jersey barrier. They were both unhurt. Unsure what to do next, they made the catastrophic decision to exit the vehicle. As the man walked around the back of the car he was nearly hit by a black sedan sliding out of control trying to avoid them. When he came around the car, his fiancé was nowhere to be found. She had been struck at highway speed and lay crushed under the sedan hundreds of feet away.
I know this poor man because he was referred to me. Not as a dermatologist, but as a fellow human healing from trauma. On January 1, 2019, at about 9:30 PM, while we were home together, my beloved wife of 24 years took her own life. Even 5 years on it is difficult to believe that she isn’t proofing this paragraph like she had done for every one of my Derm News columns for years. We had been together since teenagers and had lived a joy-filled life. There isn’t any medical reason to share. But that day I joined the community of those who have carried unbearable heaviness of grief and survived. Sometimes others seek me out for help.
At first, my instinct was to guide them, to give advice, to tell them what to do and where to go. But I’ve learned that people in this dark valley don’t need a guide. They need someone to accompany them. To walk with them for a few minutes on their lonely journey. I recently read David Brooks’s new book, How to Know a Person. I’ve been a fan of his since he joined the New York Times in 2003 and have read almost everything he’s written. I sometimes even imagine how he might approach a column whenever I’m stuck (thank you, David). His The Road to Character book is in my canon of literature for self-growth. This latest book is an interesting digression from that central theme. He argues that our society is in acute need of forming better connections and that an important way we can be moral is to learn, and to practice, how to know each other. He shares an emotional experience of losing a close friend to suicide and writes a poignant explanation of what it means to accompany someone in need. It particularly resonated with me. We are doctors and are wired to find the source of a problem, like quickly rotating through the 4X, 10X, 40X on a microscope. Once identified, we spend most of our time creating and explaining treatments. I see how this makes me a great dermatologist but just an average human.
Brooks tells the story of a woman with a brain tumor who often finds herself on the ground surrounded by well-meaning people trying to help. She explains later that what she really needs in those moments is just for someone to get on the ground and lie with her. To accompany her.
Having crossed the midpoint of life, I see with the benefit of perspective how suffering has afforded me wisdom: I am more sensitive and attuned to others. It also gave me credibility: I know how it feels to walk life’s loneliest journey. I’ve also learned to make myself vulnerable for someone to share their story with me. I won’t be afraid to hear the details. I won’t judge them for weeping too little or for sobbing too much. I don’t answer whys. I won’t say what they should do next. But for a few minutes I can walk beside them as a person who cares.
I do not try to remember the hours and days after Susan’s death, but one moment stands out and makes my eyes well when I think of it. That following day my dear brother flew across the country on the next flight out. I was sitting in a psychiatry waiting room when he came down the hall with his luggage in tow. He hugged me as only a brother could, then looked me in my eyes, which were bloodshot from tears just as his were, and he said, “We’re going to be OK.” And with that he walked with me into the office.
We physicians are blessed to have so many intimate human interactions. This book reminded me that sometimes my most important job is not to be the optimized doctor, but just a good human walking alongside.
I have no conflict of interest and purchased these books.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at [email protected].
A 74-year-old White male presented with a 1-year history of depigmented patches on the hands, arms, and face, as well as white eyelashes and eyebrows
This patient showed no evidence of recurrence in the scar where the melanoma was excised, and had no enlarged lymph nodes on palpation. His complete blood count and liver function tests were normal. A positron emission tomography (PET) scan was ordered by Dr. Nasser that revealed hypermetabolic right paratracheal, right hilar, and subcarinal lymph nodes, highly suspicious for malignant lymph nodes. The patient was referred to oncology for metastatic melanoma treatment and has been doing well on ipilimumab and nivolumab.
Vitiligo is an autoimmune condition characterized by the progressive destruction of melanocytes resulting in hypopigmentation or depigmentation of the skin. Vitiligo has been associated with cutaneous melanoma. Melanoma-associated leukoderma occurs in a portion of patients with melanoma and is correlated with a favorable prognosis. Additionally, leukoderma has been described as a side effect of melanoma treatment itself. However, cases such as this one have also been reported of vitiligo-like depigmentation presenting prior to the diagnosis of metastatic melanoma.
Melanoma, like vitiligo, is considered highly immunogenic, and cytotoxic T lymphocytes (CTLs) can recognize antigens in melanoma. Furthermore, studies have shown a vitiligo-like halo around melanoma tumors, likely caused by T-cell recruitment, and this may lead to tumor destruction, but rarely total clearance. It seems that the CTL infiltrate in both diseases is similar, but regulatory T cells are decreased in vitiligo, whereas they are present in melanomas and may contribute to the immunosuppressive tumor microenvironment found at the margin of these lesions.
Leukoderma is also associated with melanoma immunotherapy which may be described as drug-induced leukoderma. Additionally, the frequency of recognition of melanoma cells by CTLs leading to hypopigmentation appears to be higher in those with metastatic disease. High immune infiltrate with CTLs and interferon-gamma (IFN-gamma) expression by type 1 T helper cells is associated with favorable prognosis. Immunotherapy with checkpoint inhibitors has shown promise in treatment augmentation for melanoma, but not all patients fully respond to therapy. Nonetheless, development of leukoderma with these treatments has been significantly associated with good therapeutic response. Depigmentation of hair and retinal epithelium has also been reported. However, drug-induced leukoderma and vitiligo seem to have clinical and biological differences, including family history of disease and serum chemokine levels. Vaccines are in production to aid in the treatment of melanoma, but researchers must first identify the appropriate antigen(s) to include.
Conversely, vitiligo-like depigmentation has been reported as a harbinger of metastatic melanoma. Patients with previous excision of primary melanoma have presented months or years later with depigmentation and, upon further evaluation, have been diagnosed with metastatic melanoma. The prevalence of depigmentation in melanoma patients is about 3%-6%, and is estimated to be 7-10 times more common in those with melanoma than in the general population. In most cases, hypopigmentation follows the diagnosis of melanoma, with an average of 4.8 years after the initial diagnosis and 1-2 years after lymph node or distant metastases. It is unclear whether hypopigmentation occurs before or after the growth of metastatic lesions, but this clinical finding in a patient with previous melanoma may serve as an important clue to conduct further investigation for metastasis.
This case and the photos were submitted by Lucas Shapiro, BS, of Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Florida, and Natalie Y. Nasser, MD, Kaiser Permanente Riverside Medical Center; Riverside, California. The column was edited by Donna Bilu Martin, MD.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
References
Cerci FB et al. Cutis. 2017 Jun;99(6):E1-E2. PMID: 28686764.
Cho EA et al. Ann Dermatol. 2009 May;21(2):178-181.
Failla CM et al. Int J Mol Sci. 2019 Nov 15;20(22):5731.
This patient showed no evidence of recurrence in the scar where the melanoma was excised, and had no enlarged lymph nodes on palpation. His complete blood count and liver function tests were normal. A positron emission tomography (PET) scan was ordered by Dr. Nasser that revealed hypermetabolic right paratracheal, right hilar, and subcarinal lymph nodes, highly suspicious for malignant lymph nodes. The patient was referred to oncology for metastatic melanoma treatment and has been doing well on ipilimumab and nivolumab.
Vitiligo is an autoimmune condition characterized by the progressive destruction of melanocytes resulting in hypopigmentation or depigmentation of the skin. Vitiligo has been associated with cutaneous melanoma. Melanoma-associated leukoderma occurs in a portion of patients with melanoma and is correlated with a favorable prognosis. Additionally, leukoderma has been described as a side effect of melanoma treatment itself. However, cases such as this one have also been reported of vitiligo-like depigmentation presenting prior to the diagnosis of metastatic melanoma.
Melanoma, like vitiligo, is considered highly immunogenic, and cytotoxic T lymphocytes (CTLs) can recognize antigens in melanoma. Furthermore, studies have shown a vitiligo-like halo around melanoma tumors, likely caused by T-cell recruitment, and this may lead to tumor destruction, but rarely total clearance. It seems that the CTL infiltrate in both diseases is similar, but regulatory T cells are decreased in vitiligo, whereas they are present in melanomas and may contribute to the immunosuppressive tumor microenvironment found at the margin of these lesions.
Leukoderma is also associated with melanoma immunotherapy which may be described as drug-induced leukoderma. Additionally, the frequency of recognition of melanoma cells by CTLs leading to hypopigmentation appears to be higher in those with metastatic disease. High immune infiltrate with CTLs and interferon-gamma (IFN-gamma) expression by type 1 T helper cells is associated with favorable prognosis. Immunotherapy with checkpoint inhibitors has shown promise in treatment augmentation for melanoma, but not all patients fully respond to therapy. Nonetheless, development of leukoderma with these treatments has been significantly associated with good therapeutic response. Depigmentation of hair and retinal epithelium has also been reported. However, drug-induced leukoderma and vitiligo seem to have clinical and biological differences, including family history of disease and serum chemokine levels. Vaccines are in production to aid in the treatment of melanoma, but researchers must first identify the appropriate antigen(s) to include.
Conversely, vitiligo-like depigmentation has been reported as a harbinger of metastatic melanoma. Patients with previous excision of primary melanoma have presented months or years later with depigmentation and, upon further evaluation, have been diagnosed with metastatic melanoma. The prevalence of depigmentation in melanoma patients is about 3%-6%, and is estimated to be 7-10 times more common in those with melanoma than in the general population. In most cases, hypopigmentation follows the diagnosis of melanoma, with an average of 4.8 years after the initial diagnosis and 1-2 years after lymph node or distant metastases. It is unclear whether hypopigmentation occurs before or after the growth of metastatic lesions, but this clinical finding in a patient with previous melanoma may serve as an important clue to conduct further investigation for metastasis.
This case and the photos were submitted by Lucas Shapiro, BS, of Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Florida, and Natalie Y. Nasser, MD, Kaiser Permanente Riverside Medical Center; Riverside, California. The column was edited by Donna Bilu Martin, MD.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
References
Cerci FB et al. Cutis. 2017 Jun;99(6):E1-E2. PMID: 28686764.
Cho EA et al. Ann Dermatol. 2009 May;21(2):178-181.
Failla CM et al. Int J Mol Sci. 2019 Nov 15;20(22):5731.
This patient showed no evidence of recurrence in the scar where the melanoma was excised, and had no enlarged lymph nodes on palpation. His complete blood count and liver function tests were normal. A positron emission tomography (PET) scan was ordered by Dr. Nasser that revealed hypermetabolic right paratracheal, right hilar, and subcarinal lymph nodes, highly suspicious for malignant lymph nodes. The patient was referred to oncology for metastatic melanoma treatment and has been doing well on ipilimumab and nivolumab.
Vitiligo is an autoimmune condition characterized by the progressive destruction of melanocytes resulting in hypopigmentation or depigmentation of the skin. Vitiligo has been associated with cutaneous melanoma. Melanoma-associated leukoderma occurs in a portion of patients with melanoma and is correlated with a favorable prognosis. Additionally, leukoderma has been described as a side effect of melanoma treatment itself. However, cases such as this one have also been reported of vitiligo-like depigmentation presenting prior to the diagnosis of metastatic melanoma.
Melanoma, like vitiligo, is considered highly immunogenic, and cytotoxic T lymphocytes (CTLs) can recognize antigens in melanoma. Furthermore, studies have shown a vitiligo-like halo around melanoma tumors, likely caused by T-cell recruitment, and this may lead to tumor destruction, but rarely total clearance. It seems that the CTL infiltrate in both diseases is similar, but regulatory T cells are decreased in vitiligo, whereas they are present in melanomas and may contribute to the immunosuppressive tumor microenvironment found at the margin of these lesions.
Leukoderma is also associated with melanoma immunotherapy which may be described as drug-induced leukoderma. Additionally, the frequency of recognition of melanoma cells by CTLs leading to hypopigmentation appears to be higher in those with metastatic disease. High immune infiltrate with CTLs and interferon-gamma (IFN-gamma) expression by type 1 T helper cells is associated with favorable prognosis. Immunotherapy with checkpoint inhibitors has shown promise in treatment augmentation for melanoma, but not all patients fully respond to therapy. Nonetheless, development of leukoderma with these treatments has been significantly associated with good therapeutic response. Depigmentation of hair and retinal epithelium has also been reported. However, drug-induced leukoderma and vitiligo seem to have clinical and biological differences, including family history of disease and serum chemokine levels. Vaccines are in production to aid in the treatment of melanoma, but researchers must first identify the appropriate antigen(s) to include.
Conversely, vitiligo-like depigmentation has been reported as a harbinger of metastatic melanoma. Patients with previous excision of primary melanoma have presented months or years later with depigmentation and, upon further evaluation, have been diagnosed with metastatic melanoma. The prevalence of depigmentation in melanoma patients is about 3%-6%, and is estimated to be 7-10 times more common in those with melanoma than in the general population. In most cases, hypopigmentation follows the diagnosis of melanoma, with an average of 4.8 years after the initial diagnosis and 1-2 years after lymph node or distant metastases. It is unclear whether hypopigmentation occurs before or after the growth of metastatic lesions, but this clinical finding in a patient with previous melanoma may serve as an important clue to conduct further investigation for metastasis.
This case and the photos were submitted by Lucas Shapiro, BS, of Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Florida, and Natalie Y. Nasser, MD, Kaiser Permanente Riverside Medical Center; Riverside, California. The column was edited by Donna Bilu Martin, MD.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
References
Cerci FB et al. Cutis. 2017 Jun;99(6):E1-E2. PMID: 28686764.
Cho EA et al. Ann Dermatol. 2009 May;21(2):178-181.
Failla CM et al. Int J Mol Sci. 2019 Nov 15;20(22):5731.
