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FDA OKs combination immunotherapy for first-line mesothelioma treatment
This is the first drug regimen to receive regulatory approval for mesothelioma in 16 years and only the second systemic therapy to be approved for this indication.
“Today’s approval of nivolumab plus ipilimumab provides a new treatment that has demonstrated an improvement in overall survival for patients with malignant pleural mesothelioma,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement.
“In 2004, FDA approved pemetrexed in combination with cisplatin for this indication, and now patients have an important, additional treatment option after more than a decade with only one FDA-approved drug regimen,” Dr. Pazdur added.
Improved overall survival
The approval is based on efficacy results from the CheckMate 743 trial, which compared immunotherapy with a chemotherapy regimen in a cohort of more than 600 treatment-naive patients (no systemic therapies) with unresectable mesothelioma.
Patients were randomized 1:1 to nivolumab and ipilimumab for up to 2 years (n = 303) or six cycles of combination chemotherapy with cisplatin or carboplatin plus pemetrexed (n = 302).
The study results were initially presented during the presidential symposium of the World Congress on Lung Cancer 2020.
The combined immunotherapy regimen was associated with a 26% improvement in overall survival. At 2 years, 41% of patients in the immunotherapy arm were still alive versus 27% in the chemotherapy group.
Overall, the trial demonstrated a statistically significant improvement in overall survival for patients who received nivolumab plus ipilimumab versus those treated with chemotherapy. Median overall survival was 18.1 months versus 14.1 months (hazard ratio, 0.74; P = .002).
Median progression-free survival per blinded independent central review was 6.8 months in the nivolumab plus ipilimumab arm and 7.2 months in the chemotherapy arm (HR, 1.0). The confirmed overall response rate was 40% versus 43% in the immunotherapy and chemotherapy arms, respectively.
Median response duration was 11.0 months in the nivolumab plus ipilimumab arm and 6.7 months in the chemotherapy arm. At 24 months, 32% of the immunotherapy patients were still experiencing a response, compared with 8% of those in the chemotherapy arm.
The recommended doses for unresectable malignant pleural mesothelioma are nivolumab 360 mg every 3 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.
The most common adverse reactions (incidence ≥20%) in patients receiving combination immunotherapy were fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritus.
New standard of care?
The CheckMate 743 trial “met its primary endpoint of statistically improving overall survival for the experimental arm vs chemotherapy in a prespecified interim analysis,” reported study author Paul Baas, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, at the time of its presentation.
He suggested that combination nivolumab and ipilimumab should therefore “be considered as a new standard of care.”
This article first appeared on Medscape.com.
This is the first drug regimen to receive regulatory approval for mesothelioma in 16 years and only the second systemic therapy to be approved for this indication.
“Today’s approval of nivolumab plus ipilimumab provides a new treatment that has demonstrated an improvement in overall survival for patients with malignant pleural mesothelioma,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement.
“In 2004, FDA approved pemetrexed in combination with cisplatin for this indication, and now patients have an important, additional treatment option after more than a decade with only one FDA-approved drug regimen,” Dr. Pazdur added.
Improved overall survival
The approval is based on efficacy results from the CheckMate 743 trial, which compared immunotherapy with a chemotherapy regimen in a cohort of more than 600 treatment-naive patients (no systemic therapies) with unresectable mesothelioma.
Patients were randomized 1:1 to nivolumab and ipilimumab for up to 2 years (n = 303) or six cycles of combination chemotherapy with cisplatin or carboplatin plus pemetrexed (n = 302).
The study results were initially presented during the presidential symposium of the World Congress on Lung Cancer 2020.
The combined immunotherapy regimen was associated with a 26% improvement in overall survival. At 2 years, 41% of patients in the immunotherapy arm were still alive versus 27% in the chemotherapy group.
Overall, the trial demonstrated a statistically significant improvement in overall survival for patients who received nivolumab plus ipilimumab versus those treated with chemotherapy. Median overall survival was 18.1 months versus 14.1 months (hazard ratio, 0.74; P = .002).
Median progression-free survival per blinded independent central review was 6.8 months in the nivolumab plus ipilimumab arm and 7.2 months in the chemotherapy arm (HR, 1.0). The confirmed overall response rate was 40% versus 43% in the immunotherapy and chemotherapy arms, respectively.
Median response duration was 11.0 months in the nivolumab plus ipilimumab arm and 6.7 months in the chemotherapy arm. At 24 months, 32% of the immunotherapy patients were still experiencing a response, compared with 8% of those in the chemotherapy arm.
The recommended doses for unresectable malignant pleural mesothelioma are nivolumab 360 mg every 3 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.
The most common adverse reactions (incidence ≥20%) in patients receiving combination immunotherapy were fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritus.
New standard of care?
The CheckMate 743 trial “met its primary endpoint of statistically improving overall survival for the experimental arm vs chemotherapy in a prespecified interim analysis,” reported study author Paul Baas, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, at the time of its presentation.
He suggested that combination nivolumab and ipilimumab should therefore “be considered as a new standard of care.”
This article first appeared on Medscape.com.
This is the first drug regimen to receive regulatory approval for mesothelioma in 16 years and only the second systemic therapy to be approved for this indication.
“Today’s approval of nivolumab plus ipilimumab provides a new treatment that has demonstrated an improvement in overall survival for patients with malignant pleural mesothelioma,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement.
“In 2004, FDA approved pemetrexed in combination with cisplatin for this indication, and now patients have an important, additional treatment option after more than a decade with only one FDA-approved drug regimen,” Dr. Pazdur added.
Improved overall survival
The approval is based on efficacy results from the CheckMate 743 trial, which compared immunotherapy with a chemotherapy regimen in a cohort of more than 600 treatment-naive patients (no systemic therapies) with unresectable mesothelioma.
Patients were randomized 1:1 to nivolumab and ipilimumab for up to 2 years (n = 303) or six cycles of combination chemotherapy with cisplatin or carboplatin plus pemetrexed (n = 302).
The study results were initially presented during the presidential symposium of the World Congress on Lung Cancer 2020.
The combined immunotherapy regimen was associated with a 26% improvement in overall survival. At 2 years, 41% of patients in the immunotherapy arm were still alive versus 27% in the chemotherapy group.
Overall, the trial demonstrated a statistically significant improvement in overall survival for patients who received nivolumab plus ipilimumab versus those treated with chemotherapy. Median overall survival was 18.1 months versus 14.1 months (hazard ratio, 0.74; P = .002).
Median progression-free survival per blinded independent central review was 6.8 months in the nivolumab plus ipilimumab arm and 7.2 months in the chemotherapy arm (HR, 1.0). The confirmed overall response rate was 40% versus 43% in the immunotherapy and chemotherapy arms, respectively.
Median response duration was 11.0 months in the nivolumab plus ipilimumab arm and 6.7 months in the chemotherapy arm. At 24 months, 32% of the immunotherapy patients were still experiencing a response, compared with 8% of those in the chemotherapy arm.
The recommended doses for unresectable malignant pleural mesothelioma are nivolumab 360 mg every 3 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.
The most common adverse reactions (incidence ≥20%) in patients receiving combination immunotherapy were fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritus.
New standard of care?
The CheckMate 743 trial “met its primary endpoint of statistically improving overall survival for the experimental arm vs chemotherapy in a prespecified interim analysis,” reported study author Paul Baas, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, at the time of its presentation.
He suggested that combination nivolumab and ipilimumab should therefore “be considered as a new standard of care.”
This article first appeared on Medscape.com.
Psoriasis and Psoriatic Arthritis
Psoriasis and Psoriatic Arthritis is a supplement to Dermatology News with commentary from Joel M. Gelfand, MD, MSCE and Alan Menter, MD.
- Exploring new guidelines and scientific advances
- ‘Loss-framed’ approach makes psoriasis patients more agreeable to treatment
- Topical PDE-4 inhibitor for psoriasis effective in phase 2b trial
- Biologics may delay psoriatic arthritis
- AAD-NPF releases guidelines for systemic nonbiologic treatments of psoriasis
- Specific markers detect psoriatic disease inflammation without elevated CRP
- Beyond PASI 100: Striving for molecular clearance
- Ultrasound improves specificity of psoriatic arthritis referrals
- Registry data reveal temporal relationship between psoriasis symptoms and PsA onset
- New psoriasis guidelines focus on topical and alternative treatments, and severity measures
- Psoriasis topical combination maintenance strategy hits mark at 1 year
Read the supplement.
Psoriasis and Psoriatic Arthritis is a supplement to Dermatology News with commentary from Joel M. Gelfand, MD, MSCE and Alan Menter, MD.
- Exploring new guidelines and scientific advances
- ‘Loss-framed’ approach makes psoriasis patients more agreeable to treatment
- Topical PDE-4 inhibitor for psoriasis effective in phase 2b trial
- Biologics may delay psoriatic arthritis
- AAD-NPF releases guidelines for systemic nonbiologic treatments of psoriasis
- Specific markers detect psoriatic disease inflammation without elevated CRP
- Beyond PASI 100: Striving for molecular clearance
- Ultrasound improves specificity of psoriatic arthritis referrals
- Registry data reveal temporal relationship between psoriasis symptoms and PsA onset
- New psoriasis guidelines focus on topical and alternative treatments, and severity measures
- Psoriasis topical combination maintenance strategy hits mark at 1 year
Read the supplement.
Psoriasis and Psoriatic Arthritis is a supplement to Dermatology News with commentary from Joel M. Gelfand, MD, MSCE and Alan Menter, MD.
- Exploring new guidelines and scientific advances
- ‘Loss-framed’ approach makes psoriasis patients more agreeable to treatment
- Topical PDE-4 inhibitor for psoriasis effective in phase 2b trial
- Biologics may delay psoriatic arthritis
- AAD-NPF releases guidelines for systemic nonbiologic treatments of psoriasis
- Specific markers detect psoriatic disease inflammation without elevated CRP
- Beyond PASI 100: Striving for molecular clearance
- Ultrasound improves specificity of psoriatic arthritis referrals
- Registry data reveal temporal relationship between psoriasis symptoms and PsA onset
- New psoriasis guidelines focus on topical and alternative treatments, and severity measures
- Psoriasis topical combination maintenance strategy hits mark at 1 year
Read the supplement.
Golimumab approval extended to polyarticular-course JIA and juvenile PsA
after the Food and Drug Administration approved the tumor necrosis factor inhibitor for these indications on Sept. 30, according to an announcement from its manufacturer, Janssen.
Results from the open-label, single-arm, multicenter, phase 3, GO-VIVA clinical trial formed the basis for the agency’s approval of IV golimumab. GO-VIVA was conducted in 127 patients aged 2-17 years with JIA with arthritis in five or more joints (despite receiving treatment with methotrexate for at least 2 months) as part of a postmarketing requirement under the Pediatric Research Equity Act after the intravenous formulation of the biologic was approved for adults with rheumatoid arthritis in 2013. It demonstrated that pediatric patients had a level of pharmacokinetic exposure to golimumab that was similar to what was observed in two pivotal phase 3 trials in adults with moderately to severely active RA and active PsA, as well as efficacy that was generally consistent with responses seen in adult patients with RA, the manufacturer said.
Besides RA, intravenous golimumab was previously approved for adults with PsA and ankylosing spondylitis. As opposed to the IV dosing for adults with RA, PsA, and ankylosing spondylitis at 2 mg/kg infused over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter, dosing for pediatric patients with pJIA and PsA is based on body surface area at 80 mg/m2, also given as an IV infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter.
The adverse reactions observed in GO-VIVA were consistent with the established safety profile of intravenous golimumab in adult patients with RA and PsA, according to Janssen.
The full prescribing information for intravenous golimumab can be found on the FDA website.
after the Food and Drug Administration approved the tumor necrosis factor inhibitor for these indications on Sept. 30, according to an announcement from its manufacturer, Janssen.
Results from the open-label, single-arm, multicenter, phase 3, GO-VIVA clinical trial formed the basis for the agency’s approval of IV golimumab. GO-VIVA was conducted in 127 patients aged 2-17 years with JIA with arthritis in five or more joints (despite receiving treatment with methotrexate for at least 2 months) as part of a postmarketing requirement under the Pediatric Research Equity Act after the intravenous formulation of the biologic was approved for adults with rheumatoid arthritis in 2013. It demonstrated that pediatric patients had a level of pharmacokinetic exposure to golimumab that was similar to what was observed in two pivotal phase 3 trials in adults with moderately to severely active RA and active PsA, as well as efficacy that was generally consistent with responses seen in adult patients with RA, the manufacturer said.
Besides RA, intravenous golimumab was previously approved for adults with PsA and ankylosing spondylitis. As opposed to the IV dosing for adults with RA, PsA, and ankylosing spondylitis at 2 mg/kg infused over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter, dosing for pediatric patients with pJIA and PsA is based on body surface area at 80 mg/m2, also given as an IV infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter.
The adverse reactions observed in GO-VIVA were consistent with the established safety profile of intravenous golimumab in adult patients with RA and PsA, according to Janssen.
The full prescribing information for intravenous golimumab can be found on the FDA website.
after the Food and Drug Administration approved the tumor necrosis factor inhibitor for these indications on Sept. 30, according to an announcement from its manufacturer, Janssen.
Results from the open-label, single-arm, multicenter, phase 3, GO-VIVA clinical trial formed the basis for the agency’s approval of IV golimumab. GO-VIVA was conducted in 127 patients aged 2-17 years with JIA with arthritis in five or more joints (despite receiving treatment with methotrexate for at least 2 months) as part of a postmarketing requirement under the Pediatric Research Equity Act after the intravenous formulation of the biologic was approved for adults with rheumatoid arthritis in 2013. It demonstrated that pediatric patients had a level of pharmacokinetic exposure to golimumab that was similar to what was observed in two pivotal phase 3 trials in adults with moderately to severely active RA and active PsA, as well as efficacy that was generally consistent with responses seen in adult patients with RA, the manufacturer said.
Besides RA, intravenous golimumab was previously approved for adults with PsA and ankylosing spondylitis. As opposed to the IV dosing for adults with RA, PsA, and ankylosing spondylitis at 2 mg/kg infused over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter, dosing for pediatric patients with pJIA and PsA is based on body surface area at 80 mg/m2, also given as an IV infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter.
The adverse reactions observed in GO-VIVA were consistent with the established safety profile of intravenous golimumab in adult patients with RA and PsA, according to Janssen.
The full prescribing information for intravenous golimumab can be found on the FDA website.
Tailoring cosmetic procedures for skin of color patients minimize risks
Based on the fact that hyperpigmentation and other adverse events associated with cosmetic dermatologic procedures are relevant to skin type, not racial identification, individualized strategies to minimize the risk of potential adverse events are always appropriate, according to an expert speaking at the virtual Skin of Color Update 2020.
There are many highly effective interventions that employ lasers, chemical peels, and topical agents to achieve excellent cosmetic results in darker skin, but results are highly dependent on first understanding the relative risks and treatment goals, Cheryl Burgess, MD, president and founder of the Center for Dermatology and Dermatologic Surgery, Washington, D.C., said at the meeting.
She stressed the importance of educating patients that “all cosmetic procedures are not for skin of color.” Her approach is to engage patients on what they are trying to accomplish and then seeking a solution that tailors treatment to skin type based on the Fitzpatrick scale, the Roberts Hyperpigmentation Scale, or other guidance.
“There are so many different methods that we can use, and these are not necessarily the ones that patients have read about in a magazine,” Dr. Burgess said.
Intense pulsed laser (IPL) for hair removal is an example. This technique is not appropriate in patients with Fitzpatrick skin type IV or higher, according to Dr. Burgess, who presented a case example of a bad outcome. In this case, a patient came to her for treatment after exposure to IPL resulted in first- and second-degree burns complicated by extensive hypopigmentation.
Ultimately, the solution in this case involved more laser therapy, but this time a strategy was selected appropriate to skin of color.
“It is hard to suggest to a patient that we are going to use a laser device” when the problem was caused by a laser, Dr. Burgess observed, but properly selected lasers are effective and should be considered in patients with dark skin.
In this case, triple cream containing 6% hydroquinone was the first step towards resolving the hyperpigmentation. Jessner’s peel was also applied to increase penetration.
Laser treatment using two different types of devices was also employed: A 1,927-nm thulium-fractionated erbium glass laser and a 650-microsecond 1,064-nm Nd:YAG laser. The excellent resolution of the hyperpigmentation demonstrates that lasers are effective in dark skin when used appropriately, she noted.
Dr. Burgess emphasized that tailored therapy is not just relevant to Black patients. She cited data indicating that the proportion of multiracial individuals in the United States is increasing, and when tailoring cosmetic procedures, she recommended considering skin characteristics, not just skin color.
Relative to white skin, pigmented skin typically has greater elasticity, greater amounts of collagen, and greater oil content. Importantly, darker skin has a greater propensity to darkening as a result of injury, she said.
In a review of the hyperpigmentation process that follows injury or other insults, Dr. Burgess reported that only three occur inside the melanocyte. There are now topically applied agents to intervene at many of these steps, including hydroquinone to reduce up-regulation of tyrosinase enzymes, and cysteamine to inhibit conversion of DOPA to dopaquinone. All of these, often used in combination, offer potential benefit in skin of color.
However, “you must understand skin of color,” Dr. Burgess emphasized. For example, most hyaluronic acid dermal fillers can be considered in patients with Fitzpatrick skin types IV or higher with low risks for hypo- or hyperpigmentation, scarring, or keloid formation, but technique is important.
“There is more postinflammatory hyperpigmentation with serial or multiple puncture injection techniques” in dark skin relative to lighter skin, according to Dr. Burgess. She recommended reducing this risk with relatively slow injection times.
When in doubt about the result with any cosmetic procedure, test spots are a reasonable strategy, Dr. Burgess said. When there is concern about risk for adverse events, she recommended using low doses and longer intervals between treatments than might otherwise be considered. Patients should participate in understanding the rationale for selecting one approach over another.
It helps for patients to know that “the desired outcome may take many more sessions than what they read about in that we might have to consider conservative measures in order to ensure that we accomplish the cosmetic effect than they want,” she said.
It is critical that clinicians who perform laser or other cosmetic procedures on darker skin be aware of these precautions, agreed Eliot F. Battle Jr., MD, CEO and cofounder of Cultura Dermatology and Laser Center, Washington, D.C. “Over the past 20 years, we have improved lasers that can safely and effectively treat patients with skin of color, but we still have a way to go,” he said at the meeting. Darker skin behaves differently in response to this energy.
“The pigment in the skin of patients of color competes for the laser light, which can cause heat-related side effects, like blistering and pigmentary changes. Skin of color also has an increased incidence of scarring and unwanted pigmentary changes from laser treatments that create irritation and inflammation,” he explained.
It is important to be aware of these differences, but practitioners also “need to treat conservatively to minimize these unwanted side effects,” Dr. Battle said.
Dr. Burgess reported financial relationships with Allergan, Merz Aesthetics, Revance Therapeutics, and Galderma. Dr. Battle had no commercial disclosures.
Based on the fact that hyperpigmentation and other adverse events associated with cosmetic dermatologic procedures are relevant to skin type, not racial identification, individualized strategies to minimize the risk of potential adverse events are always appropriate, according to an expert speaking at the virtual Skin of Color Update 2020.
There are many highly effective interventions that employ lasers, chemical peels, and topical agents to achieve excellent cosmetic results in darker skin, but results are highly dependent on first understanding the relative risks and treatment goals, Cheryl Burgess, MD, president and founder of the Center for Dermatology and Dermatologic Surgery, Washington, D.C., said at the meeting.
She stressed the importance of educating patients that “all cosmetic procedures are not for skin of color.” Her approach is to engage patients on what they are trying to accomplish and then seeking a solution that tailors treatment to skin type based on the Fitzpatrick scale, the Roberts Hyperpigmentation Scale, or other guidance.
“There are so many different methods that we can use, and these are not necessarily the ones that patients have read about in a magazine,” Dr. Burgess said.
Intense pulsed laser (IPL) for hair removal is an example. This technique is not appropriate in patients with Fitzpatrick skin type IV or higher, according to Dr. Burgess, who presented a case example of a bad outcome. In this case, a patient came to her for treatment after exposure to IPL resulted in first- and second-degree burns complicated by extensive hypopigmentation.
Ultimately, the solution in this case involved more laser therapy, but this time a strategy was selected appropriate to skin of color.
“It is hard to suggest to a patient that we are going to use a laser device” when the problem was caused by a laser, Dr. Burgess observed, but properly selected lasers are effective and should be considered in patients with dark skin.
In this case, triple cream containing 6% hydroquinone was the first step towards resolving the hyperpigmentation. Jessner’s peel was also applied to increase penetration.
Laser treatment using two different types of devices was also employed: A 1,927-nm thulium-fractionated erbium glass laser and a 650-microsecond 1,064-nm Nd:YAG laser. The excellent resolution of the hyperpigmentation demonstrates that lasers are effective in dark skin when used appropriately, she noted.
Dr. Burgess emphasized that tailored therapy is not just relevant to Black patients. She cited data indicating that the proportion of multiracial individuals in the United States is increasing, and when tailoring cosmetic procedures, she recommended considering skin characteristics, not just skin color.
Relative to white skin, pigmented skin typically has greater elasticity, greater amounts of collagen, and greater oil content. Importantly, darker skin has a greater propensity to darkening as a result of injury, she said.
In a review of the hyperpigmentation process that follows injury or other insults, Dr. Burgess reported that only three occur inside the melanocyte. There are now topically applied agents to intervene at many of these steps, including hydroquinone to reduce up-regulation of tyrosinase enzymes, and cysteamine to inhibit conversion of DOPA to dopaquinone. All of these, often used in combination, offer potential benefit in skin of color.
However, “you must understand skin of color,” Dr. Burgess emphasized. For example, most hyaluronic acid dermal fillers can be considered in patients with Fitzpatrick skin types IV or higher with low risks for hypo- or hyperpigmentation, scarring, or keloid formation, but technique is important.
“There is more postinflammatory hyperpigmentation with serial or multiple puncture injection techniques” in dark skin relative to lighter skin, according to Dr. Burgess. She recommended reducing this risk with relatively slow injection times.
When in doubt about the result with any cosmetic procedure, test spots are a reasonable strategy, Dr. Burgess said. When there is concern about risk for adverse events, she recommended using low doses and longer intervals between treatments than might otherwise be considered. Patients should participate in understanding the rationale for selecting one approach over another.
It helps for patients to know that “the desired outcome may take many more sessions than what they read about in that we might have to consider conservative measures in order to ensure that we accomplish the cosmetic effect than they want,” she said.
It is critical that clinicians who perform laser or other cosmetic procedures on darker skin be aware of these precautions, agreed Eliot F. Battle Jr., MD, CEO and cofounder of Cultura Dermatology and Laser Center, Washington, D.C. “Over the past 20 years, we have improved lasers that can safely and effectively treat patients with skin of color, but we still have a way to go,” he said at the meeting. Darker skin behaves differently in response to this energy.
“The pigment in the skin of patients of color competes for the laser light, which can cause heat-related side effects, like blistering and pigmentary changes. Skin of color also has an increased incidence of scarring and unwanted pigmentary changes from laser treatments that create irritation and inflammation,” he explained.
It is important to be aware of these differences, but practitioners also “need to treat conservatively to minimize these unwanted side effects,” Dr. Battle said.
Dr. Burgess reported financial relationships with Allergan, Merz Aesthetics, Revance Therapeutics, and Galderma. Dr. Battle had no commercial disclosures.
Based on the fact that hyperpigmentation and other adverse events associated with cosmetic dermatologic procedures are relevant to skin type, not racial identification, individualized strategies to minimize the risk of potential adverse events are always appropriate, according to an expert speaking at the virtual Skin of Color Update 2020.
There are many highly effective interventions that employ lasers, chemical peels, and topical agents to achieve excellent cosmetic results in darker skin, but results are highly dependent on first understanding the relative risks and treatment goals, Cheryl Burgess, MD, president and founder of the Center for Dermatology and Dermatologic Surgery, Washington, D.C., said at the meeting.
She stressed the importance of educating patients that “all cosmetic procedures are not for skin of color.” Her approach is to engage patients on what they are trying to accomplish and then seeking a solution that tailors treatment to skin type based on the Fitzpatrick scale, the Roberts Hyperpigmentation Scale, or other guidance.
“There are so many different methods that we can use, and these are not necessarily the ones that patients have read about in a magazine,” Dr. Burgess said.
Intense pulsed laser (IPL) for hair removal is an example. This technique is not appropriate in patients with Fitzpatrick skin type IV or higher, according to Dr. Burgess, who presented a case example of a bad outcome. In this case, a patient came to her for treatment after exposure to IPL resulted in first- and second-degree burns complicated by extensive hypopigmentation.
Ultimately, the solution in this case involved more laser therapy, but this time a strategy was selected appropriate to skin of color.
“It is hard to suggest to a patient that we are going to use a laser device” when the problem was caused by a laser, Dr. Burgess observed, but properly selected lasers are effective and should be considered in patients with dark skin.
In this case, triple cream containing 6% hydroquinone was the first step towards resolving the hyperpigmentation. Jessner’s peel was also applied to increase penetration.
Laser treatment using two different types of devices was also employed: A 1,927-nm thulium-fractionated erbium glass laser and a 650-microsecond 1,064-nm Nd:YAG laser. The excellent resolution of the hyperpigmentation demonstrates that lasers are effective in dark skin when used appropriately, she noted.
Dr. Burgess emphasized that tailored therapy is not just relevant to Black patients. She cited data indicating that the proportion of multiracial individuals in the United States is increasing, and when tailoring cosmetic procedures, she recommended considering skin characteristics, not just skin color.
Relative to white skin, pigmented skin typically has greater elasticity, greater amounts of collagen, and greater oil content. Importantly, darker skin has a greater propensity to darkening as a result of injury, she said.
In a review of the hyperpigmentation process that follows injury or other insults, Dr. Burgess reported that only three occur inside the melanocyte. There are now topically applied agents to intervene at many of these steps, including hydroquinone to reduce up-regulation of tyrosinase enzymes, and cysteamine to inhibit conversion of DOPA to dopaquinone. All of these, often used in combination, offer potential benefit in skin of color.
However, “you must understand skin of color,” Dr. Burgess emphasized. For example, most hyaluronic acid dermal fillers can be considered in patients with Fitzpatrick skin types IV or higher with low risks for hypo- or hyperpigmentation, scarring, or keloid formation, but technique is important.
“There is more postinflammatory hyperpigmentation with serial or multiple puncture injection techniques” in dark skin relative to lighter skin, according to Dr. Burgess. She recommended reducing this risk with relatively slow injection times.
When in doubt about the result with any cosmetic procedure, test spots are a reasonable strategy, Dr. Burgess said. When there is concern about risk for adverse events, she recommended using low doses and longer intervals between treatments than might otherwise be considered. Patients should participate in understanding the rationale for selecting one approach over another.
It helps for patients to know that “the desired outcome may take many more sessions than what they read about in that we might have to consider conservative measures in order to ensure that we accomplish the cosmetic effect than they want,” she said.
It is critical that clinicians who perform laser or other cosmetic procedures on darker skin be aware of these precautions, agreed Eliot F. Battle Jr., MD, CEO and cofounder of Cultura Dermatology and Laser Center, Washington, D.C. “Over the past 20 years, we have improved lasers that can safely and effectively treat patients with skin of color, but we still have a way to go,” he said at the meeting. Darker skin behaves differently in response to this energy.
“The pigment in the skin of patients of color competes for the laser light, which can cause heat-related side effects, like blistering and pigmentary changes. Skin of color also has an increased incidence of scarring and unwanted pigmentary changes from laser treatments that create irritation and inflammation,” he explained.
It is important to be aware of these differences, but practitioners also “need to treat conservatively to minimize these unwanted side effects,” Dr. Battle said.
Dr. Burgess reported financial relationships with Allergan, Merz Aesthetics, Revance Therapeutics, and Galderma. Dr. Battle had no commercial disclosures.
FROM SOC 2020
High-dose TRT: A new standard of care for LS-SCLC?
In a phase 2 trial, the 2-year overall survival rate was 51.3% when twice-daily TRT was given at a dose of 45 Gy in 30 fractions and 75% when it was given at a dose of 60 Gy in 40 fractions in patients with LS-SCLC. The two treatment arms had similar safety and quality of life outcomes.
The higher dose “did not add toxicity,” a significant concern with higher radiation doses, said Bjorn Gronberg, MD, PhD, of the Norwegian University of Science and Technology in Trondheim, when presenting this study at the European Society for Medical Oncology Virtual Congress 2020.
However, the discussant for this study pointed out several limitations of the trial and concluded that the 45 Gy dose should remain the standard of care.
Dr. Gonberg explained that concurrent platinum/etoposide (PE) chemotherapy and TRT is the standard treatment for LS-SCLC, and the most recommended schedule for TRT is twice daily at 45 Gy in 30 fractions. He noted, however, that “there’s clearly a need for better treatment” because less than 30% of patients are cured.
“We hypothesized that increasing the dose of radiotherapy might improve survival,” he said.
Study details
Dr. Gonberg and colleagues conducted a phase 2 trial of patients with stage I-III SCLC confined to one hemithorax plus regional lymph nodes. The trial enrolled 176 patients and randomized 170 of them.
The patients received four courses of PE 3 weeks apart. For TRT, 81 patients were randomized to 45 Gy in 30 fractions, and 89 patients were randomized to 60 Gy in 40 fractions, with 10 fractions per week starting with the second PE course.
All patients who responded to chemoradiotherapy were offered prophylactic cranial irradiation at 25 Gy in 10 fractions or 30 Gy in 15 fractions.
Baseline characteristics were well balanced between the treatment arms. The median age was 65 years in both arms, and most patients were women (60.5% in the 45 Gy arm and 56% in the 60 Gy arm).
The mean number of chemotherapy courses was 3.8 in each arm, about 85% of patients received prophylactic cranial radiation, and roughly half received second-line chemotherapy. Overall, 73 patients completed TRT in the 45 Gy arm, and 81 completed TRT in the 60 Gy arm.
Efficacy
There was no significant difference in overall response rate between the treatment arms. It was 81.6% in the 45 Gy arm and 82.1% in the 60 Gy arm (P = .81).
Similarly, there was no significant difference in progression-free survival. The median progression-free survival was 11.1 months in the lower-dose arm and 18.7 months in the higher-dose arm (P = .22).
Still, there was a significant difference in overall survival between the arms. The 2-year overall survival rate was 51.3% in the lower-dose arm and 75% in the higher-dose arm (P = .002). The median overall survival was 24 months and 37.2 months, respectively (P = .034).
Discussant Corinne Faivre-Finn, MD, PhD, of the University of Manchester (England), cautioned that the lower-dose arm appeared to underperform, compared with prior research.
Additionally, “the survival curves separate at about 9 months, [with a] significant difference at 2 years, but the survival curves are coming back together at around 5 years, and that shows that there is a small difference in terms of long-term cure,” she said.
Safety
There were no significant differences in toxicity between the treatment arms.
Dr. Gronberg noted that esophagitis is considered the main dose-limiting toxicity with TRT, but there was no difference in incidence between the two arms (P = .916). Grade 3 esophagitis occurred in 18.4% of patients in the lower-dose arm and 19% of those in the higher-dose arm. There was no grade 4 esophagitis.
Rates of grade 3 and 4 neutropenic infections were higher in the lower-dose arm than in the higher-dose arm, but the difference was not statistically significant (P = .08).
There were also no significant differences in quality of life surveys that patients filled out periodically from baseline until week 52.
“Not so surprisingly,” Dr. Gronberg said, dysphagia was more common at the end of TRT. However, patients had recovered to baseline levels at week 22.
“There’s no difference in the maximum dysphagia reported between the treatment arms, but ... patients in the high-dose arm needed longer time to recover from dysphagia,” Dr. Gronberg said.
Scores for dyspnea, physical function, and global quality of life were similar between the treatment arms.
The similar toxicity between the arms “is quite puzzling,” Dr. Faivre-Finn said, given the 33% increase in radiation dose in the experimental arm. She said this “probably points out an imbalance in some of the factors” between the groups, including tumor volume and doses to organs at risk, which were not reported.
“There are some important missing data, in terms of interpretation of results,” she said.
Given the limitations, and the fact that the study population was relatively small, Dr. Faivre-Finn said “the results cannot be considered definitive and practice changing,” pending additional study.
“So my final conclusion is that twice-a-day radiotherapy at a dose of 45 Gy remains the standard of care, as recommended in the recently published ASTRO [American Society for Radiation Oncology] guidelines,” Dr. Faivre-Finn said.
The study was funded by the Norwegian Cancer Society, the Nordic Cancer Union, and the Norwegian University of Science and Technology. Dr. Gronberg disclosed relationships with Pfizer, Roche, Eli Lilly, and other companies. Dr. Faivre-Finn disclosed relationships with AstraZeneca, Merck, Pfizer, Elekta, and Boehringer Ingelheim.
SOURCE: Gronberg B et al. ESMO 2020, Abstract 1783O.
In a phase 2 trial, the 2-year overall survival rate was 51.3% when twice-daily TRT was given at a dose of 45 Gy in 30 fractions and 75% when it was given at a dose of 60 Gy in 40 fractions in patients with LS-SCLC. The two treatment arms had similar safety and quality of life outcomes.
The higher dose “did not add toxicity,” a significant concern with higher radiation doses, said Bjorn Gronberg, MD, PhD, of the Norwegian University of Science and Technology in Trondheim, when presenting this study at the European Society for Medical Oncology Virtual Congress 2020.
However, the discussant for this study pointed out several limitations of the trial and concluded that the 45 Gy dose should remain the standard of care.
Dr. Gonberg explained that concurrent platinum/etoposide (PE) chemotherapy and TRT is the standard treatment for LS-SCLC, and the most recommended schedule for TRT is twice daily at 45 Gy in 30 fractions. He noted, however, that “there’s clearly a need for better treatment” because less than 30% of patients are cured.
“We hypothesized that increasing the dose of radiotherapy might improve survival,” he said.
Study details
Dr. Gonberg and colleagues conducted a phase 2 trial of patients with stage I-III SCLC confined to one hemithorax plus regional lymph nodes. The trial enrolled 176 patients and randomized 170 of them.
The patients received four courses of PE 3 weeks apart. For TRT, 81 patients were randomized to 45 Gy in 30 fractions, and 89 patients were randomized to 60 Gy in 40 fractions, with 10 fractions per week starting with the second PE course.
All patients who responded to chemoradiotherapy were offered prophylactic cranial irradiation at 25 Gy in 10 fractions or 30 Gy in 15 fractions.
Baseline characteristics were well balanced between the treatment arms. The median age was 65 years in both arms, and most patients were women (60.5% in the 45 Gy arm and 56% in the 60 Gy arm).
The mean number of chemotherapy courses was 3.8 in each arm, about 85% of patients received prophylactic cranial radiation, and roughly half received second-line chemotherapy. Overall, 73 patients completed TRT in the 45 Gy arm, and 81 completed TRT in the 60 Gy arm.
Efficacy
There was no significant difference in overall response rate between the treatment arms. It was 81.6% in the 45 Gy arm and 82.1% in the 60 Gy arm (P = .81).
Similarly, there was no significant difference in progression-free survival. The median progression-free survival was 11.1 months in the lower-dose arm and 18.7 months in the higher-dose arm (P = .22).
Still, there was a significant difference in overall survival between the arms. The 2-year overall survival rate was 51.3% in the lower-dose arm and 75% in the higher-dose arm (P = .002). The median overall survival was 24 months and 37.2 months, respectively (P = .034).
Discussant Corinne Faivre-Finn, MD, PhD, of the University of Manchester (England), cautioned that the lower-dose arm appeared to underperform, compared with prior research.
Additionally, “the survival curves separate at about 9 months, [with a] significant difference at 2 years, but the survival curves are coming back together at around 5 years, and that shows that there is a small difference in terms of long-term cure,” she said.
Safety
There were no significant differences in toxicity between the treatment arms.
Dr. Gronberg noted that esophagitis is considered the main dose-limiting toxicity with TRT, but there was no difference in incidence between the two arms (P = .916). Grade 3 esophagitis occurred in 18.4% of patients in the lower-dose arm and 19% of those in the higher-dose arm. There was no grade 4 esophagitis.
Rates of grade 3 and 4 neutropenic infections were higher in the lower-dose arm than in the higher-dose arm, but the difference was not statistically significant (P = .08).
There were also no significant differences in quality of life surveys that patients filled out periodically from baseline until week 52.
“Not so surprisingly,” Dr. Gronberg said, dysphagia was more common at the end of TRT. However, patients had recovered to baseline levels at week 22.
“There’s no difference in the maximum dysphagia reported between the treatment arms, but ... patients in the high-dose arm needed longer time to recover from dysphagia,” Dr. Gronberg said.
Scores for dyspnea, physical function, and global quality of life were similar between the treatment arms.
The similar toxicity between the arms “is quite puzzling,” Dr. Faivre-Finn said, given the 33% increase in radiation dose in the experimental arm. She said this “probably points out an imbalance in some of the factors” between the groups, including tumor volume and doses to organs at risk, which were not reported.
“There are some important missing data, in terms of interpretation of results,” she said.
Given the limitations, and the fact that the study population was relatively small, Dr. Faivre-Finn said “the results cannot be considered definitive and practice changing,” pending additional study.
“So my final conclusion is that twice-a-day radiotherapy at a dose of 45 Gy remains the standard of care, as recommended in the recently published ASTRO [American Society for Radiation Oncology] guidelines,” Dr. Faivre-Finn said.
The study was funded by the Norwegian Cancer Society, the Nordic Cancer Union, and the Norwegian University of Science and Technology. Dr. Gronberg disclosed relationships with Pfizer, Roche, Eli Lilly, and other companies. Dr. Faivre-Finn disclosed relationships with AstraZeneca, Merck, Pfizer, Elekta, and Boehringer Ingelheim.
SOURCE: Gronberg B et al. ESMO 2020, Abstract 1783O.
In a phase 2 trial, the 2-year overall survival rate was 51.3% when twice-daily TRT was given at a dose of 45 Gy in 30 fractions and 75% when it was given at a dose of 60 Gy in 40 fractions in patients with LS-SCLC. The two treatment arms had similar safety and quality of life outcomes.
The higher dose “did not add toxicity,” a significant concern with higher radiation doses, said Bjorn Gronberg, MD, PhD, of the Norwegian University of Science and Technology in Trondheim, when presenting this study at the European Society for Medical Oncology Virtual Congress 2020.
However, the discussant for this study pointed out several limitations of the trial and concluded that the 45 Gy dose should remain the standard of care.
Dr. Gonberg explained that concurrent platinum/etoposide (PE) chemotherapy and TRT is the standard treatment for LS-SCLC, and the most recommended schedule for TRT is twice daily at 45 Gy in 30 fractions. He noted, however, that “there’s clearly a need for better treatment” because less than 30% of patients are cured.
“We hypothesized that increasing the dose of radiotherapy might improve survival,” he said.
Study details
Dr. Gonberg and colleagues conducted a phase 2 trial of patients with stage I-III SCLC confined to one hemithorax plus regional lymph nodes. The trial enrolled 176 patients and randomized 170 of them.
The patients received four courses of PE 3 weeks apart. For TRT, 81 patients were randomized to 45 Gy in 30 fractions, and 89 patients were randomized to 60 Gy in 40 fractions, with 10 fractions per week starting with the second PE course.
All patients who responded to chemoradiotherapy were offered prophylactic cranial irradiation at 25 Gy in 10 fractions or 30 Gy in 15 fractions.
Baseline characteristics were well balanced between the treatment arms. The median age was 65 years in both arms, and most patients were women (60.5% in the 45 Gy arm and 56% in the 60 Gy arm).
The mean number of chemotherapy courses was 3.8 in each arm, about 85% of patients received prophylactic cranial radiation, and roughly half received second-line chemotherapy. Overall, 73 patients completed TRT in the 45 Gy arm, and 81 completed TRT in the 60 Gy arm.
Efficacy
There was no significant difference in overall response rate between the treatment arms. It was 81.6% in the 45 Gy arm and 82.1% in the 60 Gy arm (P = .81).
Similarly, there was no significant difference in progression-free survival. The median progression-free survival was 11.1 months in the lower-dose arm and 18.7 months in the higher-dose arm (P = .22).
Still, there was a significant difference in overall survival between the arms. The 2-year overall survival rate was 51.3% in the lower-dose arm and 75% in the higher-dose arm (P = .002). The median overall survival was 24 months and 37.2 months, respectively (P = .034).
Discussant Corinne Faivre-Finn, MD, PhD, of the University of Manchester (England), cautioned that the lower-dose arm appeared to underperform, compared with prior research.
Additionally, “the survival curves separate at about 9 months, [with a] significant difference at 2 years, but the survival curves are coming back together at around 5 years, and that shows that there is a small difference in terms of long-term cure,” she said.
Safety
There were no significant differences in toxicity between the treatment arms.
Dr. Gronberg noted that esophagitis is considered the main dose-limiting toxicity with TRT, but there was no difference in incidence between the two arms (P = .916). Grade 3 esophagitis occurred in 18.4% of patients in the lower-dose arm and 19% of those in the higher-dose arm. There was no grade 4 esophagitis.
Rates of grade 3 and 4 neutropenic infections were higher in the lower-dose arm than in the higher-dose arm, but the difference was not statistically significant (P = .08).
There were also no significant differences in quality of life surveys that patients filled out periodically from baseline until week 52.
“Not so surprisingly,” Dr. Gronberg said, dysphagia was more common at the end of TRT. However, patients had recovered to baseline levels at week 22.
“There’s no difference in the maximum dysphagia reported between the treatment arms, but ... patients in the high-dose arm needed longer time to recover from dysphagia,” Dr. Gronberg said.
Scores for dyspnea, physical function, and global quality of life were similar between the treatment arms.
The similar toxicity between the arms “is quite puzzling,” Dr. Faivre-Finn said, given the 33% increase in radiation dose in the experimental arm. She said this “probably points out an imbalance in some of the factors” between the groups, including tumor volume and doses to organs at risk, which were not reported.
“There are some important missing data, in terms of interpretation of results,” she said.
Given the limitations, and the fact that the study population was relatively small, Dr. Faivre-Finn said “the results cannot be considered definitive and practice changing,” pending additional study.
“So my final conclusion is that twice-a-day radiotherapy at a dose of 45 Gy remains the standard of care, as recommended in the recently published ASTRO [American Society for Radiation Oncology] guidelines,” Dr. Faivre-Finn said.
The study was funded by the Norwegian Cancer Society, the Nordic Cancer Union, and the Norwegian University of Science and Technology. Dr. Gronberg disclosed relationships with Pfizer, Roche, Eli Lilly, and other companies. Dr. Faivre-Finn disclosed relationships with AstraZeneca, Merck, Pfizer, Elekta, and Boehringer Ingelheim.
SOURCE: Gronberg B et al. ESMO 2020, Abstract 1783O.
FROM ESMO 2020
HPV vaccine shown to substantially reduce cervical cancer risk
It’s been shown that the vaccine (Gardasil) helps prevent genital warts and high-grade cervical lesions, but until now, data on the ability of the vaccine to prevent cervical cancer, although widely assumed, had been lacking.
“Our results extend [the] knowledge base by showing that quadrivalent HPV vaccination is also associated with a substantially reduced risk of invasive cervical cancer, which is the ultimate intent of HPV vaccination programs,” said investigators led by Jiayao Lei, PhD, a researcher in the department of medical epidemiology and biostatistics at the Karolinska Institute, Stockholm.
The study was published online Oct. 1 in the New England Journal of Medicine.
“This work provides evidence of actual cancer prevention,” commented Diane Harper, MD, an HPV expert and professor in the departments of family medicine and obstetrics & gynecology at the University of Michigan, Ann Arbor. She was the principal investigator on the original Gardasil trial.
This study “shows that the quadrivalent HPV vaccine provides prevention from the sexually transmitted HPV infection that actually reduces the incidence of cervical cancer in young women up to 30 years of age,” she said when approached for comment.
However, she also added a note of caution. These new results show “that vaccinated women still develop cervical cancer, but at a slower rate. This makes the connection between early-age vaccination and continued adult life screening incredibly important,” Dr. Harper said in an interview
Cervical cancer was diagnosed in 19 of the 527,871 women (0.004%) who had received at least one dose of the vaccine versus 538 among the 1,145,112 women (0.05%) who had not.
The cumulative incidence was 47 cases per 100,000 vaccinated women and 94 cases per 100,000 unvaccinated women. The cervical cancer incidence rate ratio for the comparison of vaccinated versus unvaccinated women was 0.37 (95% confidence interval, 0.21-0.57).
The risk reduction was even greater among women who had been vaccinated before the age of 17, with a cumulative incidence of 4 versus 54 cases per 100,000 for women vaccinated after age 17. The incidence rate ratio was 0.12 (95% CI, 0.00-0.34) for women who had been vaccinated before age 17 versus 0.47 (95% CI, 0.27-0.75) among those vaccinated from age 17 to 30 years.
Overall, “the risk of cervical cancer among participants who had initiated vaccination before the age of 17 years was 88% lower than among those who had never been vaccinated,” the investigators noted.
These results “support the recommendation to administer quadrivalent HPV vaccine before exposure to HPV infection to achieve the most substantial benefit,” the investigators wrote.
Details of the Swedish review
For their review, Dr. Lei and colleagues used several Swedish demographic and health registries to connect vaccination status to incident cervical cancers, using the personal identification numbers Sweden issues to residents.
Participants were followed starting either on their 10th birthday or on Jan. 1, 2006, whichever came later. They were followed until, among other things, diagnosis of invasive cervical cancer; their 31st birthday; or until Dec. 31, 2017, whichever came first.
The quadrivalent HPV vaccine, approved in Sweden in 2006, was used almost exclusively during the study period. Participants were considered vaccinated if they had received only one shot, but the investigators set out to analyze a relationship between the incidence of invasive cervical cancer and the number of shots given.
Among other things, the team controlled for age at follow-up, calendar year, county of residence, maternal disease history, and parental characteristics, including education and household income.
The investigators commented that it’s possible that HPV-vaccinated women could have been generally healthier than unvaccinated women and so would have been at lower risk for cervical cancer.
“Confounding by lifestyle and health factors in the women (such as smoking status, sexual activity, oral contraceptive use, and obesity) cannot be excluded; these factors are known to be associated with a risk of cervical cancer,” the investigators wrote.
HPV is also associated with other types of cancer, including anal and oropharyngeal cancers. But these cancers develop over a longer period than cervical cancer.
Dr. Harper noted that the “probability of HPV 16 cancer by time since infection peaks at 40 years after infection for anal cancers and nearly 50 years after infection for oropharyngeal cancers. This means that registries, such as in Sweden, for the next 40 years will record the evidence to say whether HPV vaccination lasts long enough to prevent [these] other HPV 16–associated cancers occurring at a much later time in life.”
The work was funded by the Swedish Foundation for Strategic Research, the Swedish Cancer Society, and the Swedish Research Council and by the China Scholarship Council. Dr. Lei and two other investigators reported HPV vaccine research funding from Merck, the maker of Gardasil. Harper disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
It’s been shown that the vaccine (Gardasil) helps prevent genital warts and high-grade cervical lesions, but until now, data on the ability of the vaccine to prevent cervical cancer, although widely assumed, had been lacking.
“Our results extend [the] knowledge base by showing that quadrivalent HPV vaccination is also associated with a substantially reduced risk of invasive cervical cancer, which is the ultimate intent of HPV vaccination programs,” said investigators led by Jiayao Lei, PhD, a researcher in the department of medical epidemiology and biostatistics at the Karolinska Institute, Stockholm.
The study was published online Oct. 1 in the New England Journal of Medicine.
“This work provides evidence of actual cancer prevention,” commented Diane Harper, MD, an HPV expert and professor in the departments of family medicine and obstetrics & gynecology at the University of Michigan, Ann Arbor. She was the principal investigator on the original Gardasil trial.
This study “shows that the quadrivalent HPV vaccine provides prevention from the sexually transmitted HPV infection that actually reduces the incidence of cervical cancer in young women up to 30 years of age,” she said when approached for comment.
However, she also added a note of caution. These new results show “that vaccinated women still develop cervical cancer, but at a slower rate. This makes the connection between early-age vaccination and continued adult life screening incredibly important,” Dr. Harper said in an interview
Cervical cancer was diagnosed in 19 of the 527,871 women (0.004%) who had received at least one dose of the vaccine versus 538 among the 1,145,112 women (0.05%) who had not.
The cumulative incidence was 47 cases per 100,000 vaccinated women and 94 cases per 100,000 unvaccinated women. The cervical cancer incidence rate ratio for the comparison of vaccinated versus unvaccinated women was 0.37 (95% confidence interval, 0.21-0.57).
The risk reduction was even greater among women who had been vaccinated before the age of 17, with a cumulative incidence of 4 versus 54 cases per 100,000 for women vaccinated after age 17. The incidence rate ratio was 0.12 (95% CI, 0.00-0.34) for women who had been vaccinated before age 17 versus 0.47 (95% CI, 0.27-0.75) among those vaccinated from age 17 to 30 years.
Overall, “the risk of cervical cancer among participants who had initiated vaccination before the age of 17 years was 88% lower than among those who had never been vaccinated,” the investigators noted.
These results “support the recommendation to administer quadrivalent HPV vaccine before exposure to HPV infection to achieve the most substantial benefit,” the investigators wrote.
Details of the Swedish review
For their review, Dr. Lei and colleagues used several Swedish demographic and health registries to connect vaccination status to incident cervical cancers, using the personal identification numbers Sweden issues to residents.
Participants were followed starting either on their 10th birthday or on Jan. 1, 2006, whichever came later. They were followed until, among other things, diagnosis of invasive cervical cancer; their 31st birthday; or until Dec. 31, 2017, whichever came first.
The quadrivalent HPV vaccine, approved in Sweden in 2006, was used almost exclusively during the study period. Participants were considered vaccinated if they had received only one shot, but the investigators set out to analyze a relationship between the incidence of invasive cervical cancer and the number of shots given.
Among other things, the team controlled for age at follow-up, calendar year, county of residence, maternal disease history, and parental characteristics, including education and household income.
The investigators commented that it’s possible that HPV-vaccinated women could have been generally healthier than unvaccinated women and so would have been at lower risk for cervical cancer.
“Confounding by lifestyle and health factors in the women (such as smoking status, sexual activity, oral contraceptive use, and obesity) cannot be excluded; these factors are known to be associated with a risk of cervical cancer,” the investigators wrote.
HPV is also associated with other types of cancer, including anal and oropharyngeal cancers. But these cancers develop over a longer period than cervical cancer.
Dr. Harper noted that the “probability of HPV 16 cancer by time since infection peaks at 40 years after infection for anal cancers and nearly 50 years after infection for oropharyngeal cancers. This means that registries, such as in Sweden, for the next 40 years will record the evidence to say whether HPV vaccination lasts long enough to prevent [these] other HPV 16–associated cancers occurring at a much later time in life.”
The work was funded by the Swedish Foundation for Strategic Research, the Swedish Cancer Society, and the Swedish Research Council and by the China Scholarship Council. Dr. Lei and two other investigators reported HPV vaccine research funding from Merck, the maker of Gardasil. Harper disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
It’s been shown that the vaccine (Gardasil) helps prevent genital warts and high-grade cervical lesions, but until now, data on the ability of the vaccine to prevent cervical cancer, although widely assumed, had been lacking.
“Our results extend [the] knowledge base by showing that quadrivalent HPV vaccination is also associated with a substantially reduced risk of invasive cervical cancer, which is the ultimate intent of HPV vaccination programs,” said investigators led by Jiayao Lei, PhD, a researcher in the department of medical epidemiology and biostatistics at the Karolinska Institute, Stockholm.
The study was published online Oct. 1 in the New England Journal of Medicine.
“This work provides evidence of actual cancer prevention,” commented Diane Harper, MD, an HPV expert and professor in the departments of family medicine and obstetrics & gynecology at the University of Michigan, Ann Arbor. She was the principal investigator on the original Gardasil trial.
This study “shows that the quadrivalent HPV vaccine provides prevention from the sexually transmitted HPV infection that actually reduces the incidence of cervical cancer in young women up to 30 years of age,” she said when approached for comment.
However, she also added a note of caution. These new results show “that vaccinated women still develop cervical cancer, but at a slower rate. This makes the connection between early-age vaccination and continued adult life screening incredibly important,” Dr. Harper said in an interview
Cervical cancer was diagnosed in 19 of the 527,871 women (0.004%) who had received at least one dose of the vaccine versus 538 among the 1,145,112 women (0.05%) who had not.
The cumulative incidence was 47 cases per 100,000 vaccinated women and 94 cases per 100,000 unvaccinated women. The cervical cancer incidence rate ratio for the comparison of vaccinated versus unvaccinated women was 0.37 (95% confidence interval, 0.21-0.57).
The risk reduction was even greater among women who had been vaccinated before the age of 17, with a cumulative incidence of 4 versus 54 cases per 100,000 for women vaccinated after age 17. The incidence rate ratio was 0.12 (95% CI, 0.00-0.34) for women who had been vaccinated before age 17 versus 0.47 (95% CI, 0.27-0.75) among those vaccinated from age 17 to 30 years.
Overall, “the risk of cervical cancer among participants who had initiated vaccination before the age of 17 years was 88% lower than among those who had never been vaccinated,” the investigators noted.
These results “support the recommendation to administer quadrivalent HPV vaccine before exposure to HPV infection to achieve the most substantial benefit,” the investigators wrote.
Details of the Swedish review
For their review, Dr. Lei and colleagues used several Swedish demographic and health registries to connect vaccination status to incident cervical cancers, using the personal identification numbers Sweden issues to residents.
Participants were followed starting either on their 10th birthday or on Jan. 1, 2006, whichever came later. They were followed until, among other things, diagnosis of invasive cervical cancer; their 31st birthday; or until Dec. 31, 2017, whichever came first.
The quadrivalent HPV vaccine, approved in Sweden in 2006, was used almost exclusively during the study period. Participants were considered vaccinated if they had received only one shot, but the investigators set out to analyze a relationship between the incidence of invasive cervical cancer and the number of shots given.
Among other things, the team controlled for age at follow-up, calendar year, county of residence, maternal disease history, and parental characteristics, including education and household income.
The investigators commented that it’s possible that HPV-vaccinated women could have been generally healthier than unvaccinated women and so would have been at lower risk for cervical cancer.
“Confounding by lifestyle and health factors in the women (such as smoking status, sexual activity, oral contraceptive use, and obesity) cannot be excluded; these factors are known to be associated with a risk of cervical cancer,” the investigators wrote.
HPV is also associated with other types of cancer, including anal and oropharyngeal cancers. But these cancers develop over a longer period than cervical cancer.
Dr. Harper noted that the “probability of HPV 16 cancer by time since infection peaks at 40 years after infection for anal cancers and nearly 50 years after infection for oropharyngeal cancers. This means that registries, such as in Sweden, for the next 40 years will record the evidence to say whether HPV vaccination lasts long enough to prevent [these] other HPV 16–associated cancers occurring at a much later time in life.”
The work was funded by the Swedish Foundation for Strategic Research, the Swedish Cancer Society, and the Swedish Research Council and by the China Scholarship Council. Dr. Lei and two other investigators reported HPV vaccine research funding from Merck, the maker of Gardasil. Harper disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Real-world safety, efficacy found for fecal transplants
Fecal microbiota transplantation (FMT) appears safe and effective as a treatment for most Clostridioides difficile infections as it is currently being administered, researchers say.
“We actually didn’t see any infections that were definitely transmissible via fecal transplant,” Colleen Kelly, MD, an associate professor of medicine at Brown University, Providence, R.I., said in an interview.
The findings, published online Oct. 1 in the journal Gastroenterology, come from the American Gastroenterological Association (AGA) NIH-funded FMT National Registry and could allay concerns about a treatment that has yet to gain full approval by the Food and Drug Administration, despite successful clinical trials.
C. diff infections are common and increasing in the United States, often can’t be cured with conventional treatments such as antibiotics, and can be deadly.
Transplanting fecal matter from a donor to the patient appears to work by restoring beneficial microorganisms to the patient’s gut. The procedure is also under investigation for a wide range of other ailments, from irritable bowel syndrome to mood disorders.
But much remains unknown. Researchers have counted a thousand bacterial species along with viruses, bacteriophages, archaea, and fungi in the human gut that interact in complex ways, not all of them beneficial.
The FDA has not enforced regulations that would prohibit the procedure, but in March, it warned about infections with enteropathogenic Escherichia coli and Shiga toxin–producing E. coli following fecal transplants.
As a result of these reports, and the theoretical risk of spreading SARS-CoV-2, OpenBiome, the largest stool bank in the United States, has suspended shipments except for emergency orders, and asked clinicians to quarantine any of its products they already have on hand.
In the meantime, long-term effects of the treatment have not been well documented. And clinical trials have excluded patients who might benefit, such as those who have been immunocompromised or have inflammatory bowel disease.
National registry follows patients outside clinical trials
To better understand how patients fare outside these trials, AGA and other organizations developed a national registry, funded by a grant from the National Institute of Allergy and Infectious Diseases.
The current report summarizes results on 259 patients enrolled between Dec. 5, 2017, and Sept. 2, 2019 at 20 sites.
At baseline, 44% of these patients suffered moderate and 36% mild C. diff infections. The duration of the diagnosis ranged from less than 1 week to 9 years, with a median duration of 20 weeks. They ranged from 1 to 15 episodes with a mean of 3.5.
Almost all had received vancomycin, and 62% had at least two courses. About 40% had received metronidazole and 28% had received fidaxomicin.
Almost all participants received stool from an unknown donor, mostly from stool banks, with OpenBiome accounting for 67%. About 85% of the transplants were administered through colonoscopy and 6% by upper endoscopy.
Out of 222 patients who returned for a 1-month follow-up, 90% met the investigators’ definition of cure: resolution of diarrhea without need for further anti–C. diff therapy. About 98% received only one transplant. An intent to treat analysis produced a cure rate of 86%.
Results were good in patients with comorbidities, including 12% who had irritable bowel syndrome, 9% who had ulcerative colitis, and 7% who had Crohn’s disease, Dr. Kelly said. “I hope everybody sees the importance of it. In these patients that are more complicated, who may have underlying comorbidities, who may not have been in the clinical trials, it looks effective in that group, and also incredibly safe.”
She added that the risk of transmitting SARS-CoV-2 is minor. “I think it would be a very, very unlikely way for someone to get a respiratory pathogen.”
Of the 112 participants who were cured at 1 month and returned for follow-up after 6 months, 4 developed recurrent C. diff infection. Eleven patients who were not cured in the first month returned after 6 months. Of these, seven were reported cured at this later follow-up.
Three complications occurred as result of the procedure: one colonoscopic perforation and two episodes of gastrointestinal bleeding.
About 45% of participants reported at least one symptom, with diarrhea not related to C. difficile the most common, followed by abdominal pain, bloating, and constipation.
Eleven patients suffered infections, including two which the investigators thought might be related to the procedure: Bacteroides fragilis in one participant with severe diarrhea, and enteropathogenic E. coli in another with loose stools. Other infections included four urinary tract infections, three cases of pneumonia, one E. coli bacteremia and one tooth infection.
Within a month of the procedure, 27 patients were hospitalized, with 3 of these cases considered possibly related to the procedure.
Findings may not apply to all clinical settings
Vincent B. Young, MD, PhD, a professor of medicine and infectious diseases at the University of Michigan, Ann Arbor, pointed out that the findings might not apply to all clinical settings. The participating clinicians were almost all gastroenterologists working in academic centers.
“Most of them are not Joe Doctor at the doctor’s office,” said Dr. Young, who was not involved with the study. Clinicians in other specialties, such as infectious diseases, might be more inclined to administer fecal transplants through capsules rather than colonoscopies.
And he added that the study does not address effects of the transplant that might develop over years. “Some people talk about how changes in the microbiota lead to increased risk for long-term complications, things like cancer or heart disease. You’re not going to see those in 6 months.”
Also, the study didn’t yield any findings on indications other than C. diff. “In no way, shape, or form does it mean you can use it for autism, depression, heart disease, or [irritable bowel syndrome],” he said.
Still, he said, the study “confirms the fact that fecal cell transplantation is an effective treatment for recurrent C. diff infection when administered as they administered it.”
The National Institute of Allergy and Infectious Diseases funded the registry. Dr. Kelly reported a relationship with Finch Therapeutics. Dr. Young reports financial relationships with Vedanta Biosciences and Bio-K+.
This story was updated on Oct. 4, 2020.
A version of this article originally appeared on Medscape.com.
Fecal microbiota transplantation (FMT) appears safe and effective as a treatment for most Clostridioides difficile infections as it is currently being administered, researchers say.
“We actually didn’t see any infections that were definitely transmissible via fecal transplant,” Colleen Kelly, MD, an associate professor of medicine at Brown University, Providence, R.I., said in an interview.
The findings, published online Oct. 1 in the journal Gastroenterology, come from the American Gastroenterological Association (AGA) NIH-funded FMT National Registry and could allay concerns about a treatment that has yet to gain full approval by the Food and Drug Administration, despite successful clinical trials.
C. diff infections are common and increasing in the United States, often can’t be cured with conventional treatments such as antibiotics, and can be deadly.
Transplanting fecal matter from a donor to the patient appears to work by restoring beneficial microorganisms to the patient’s gut. The procedure is also under investigation for a wide range of other ailments, from irritable bowel syndrome to mood disorders.
But much remains unknown. Researchers have counted a thousand bacterial species along with viruses, bacteriophages, archaea, and fungi in the human gut that interact in complex ways, not all of them beneficial.
The FDA has not enforced regulations that would prohibit the procedure, but in March, it warned about infections with enteropathogenic Escherichia coli and Shiga toxin–producing E. coli following fecal transplants.
As a result of these reports, and the theoretical risk of spreading SARS-CoV-2, OpenBiome, the largest stool bank in the United States, has suspended shipments except for emergency orders, and asked clinicians to quarantine any of its products they already have on hand.
In the meantime, long-term effects of the treatment have not been well documented. And clinical trials have excluded patients who might benefit, such as those who have been immunocompromised or have inflammatory bowel disease.
National registry follows patients outside clinical trials
To better understand how patients fare outside these trials, AGA and other organizations developed a national registry, funded by a grant from the National Institute of Allergy and Infectious Diseases.
The current report summarizes results on 259 patients enrolled between Dec. 5, 2017, and Sept. 2, 2019 at 20 sites.
At baseline, 44% of these patients suffered moderate and 36% mild C. diff infections. The duration of the diagnosis ranged from less than 1 week to 9 years, with a median duration of 20 weeks. They ranged from 1 to 15 episodes with a mean of 3.5.
Almost all had received vancomycin, and 62% had at least two courses. About 40% had received metronidazole and 28% had received fidaxomicin.
Almost all participants received stool from an unknown donor, mostly from stool banks, with OpenBiome accounting for 67%. About 85% of the transplants were administered through colonoscopy and 6% by upper endoscopy.
Out of 222 patients who returned for a 1-month follow-up, 90% met the investigators’ definition of cure: resolution of diarrhea without need for further anti–C. diff therapy. About 98% received only one transplant. An intent to treat analysis produced a cure rate of 86%.
Results were good in patients with comorbidities, including 12% who had irritable bowel syndrome, 9% who had ulcerative colitis, and 7% who had Crohn’s disease, Dr. Kelly said. “I hope everybody sees the importance of it. In these patients that are more complicated, who may have underlying comorbidities, who may not have been in the clinical trials, it looks effective in that group, and also incredibly safe.”
She added that the risk of transmitting SARS-CoV-2 is minor. “I think it would be a very, very unlikely way for someone to get a respiratory pathogen.”
Of the 112 participants who were cured at 1 month and returned for follow-up after 6 months, 4 developed recurrent C. diff infection. Eleven patients who were not cured in the first month returned after 6 months. Of these, seven were reported cured at this later follow-up.
Three complications occurred as result of the procedure: one colonoscopic perforation and two episodes of gastrointestinal bleeding.
About 45% of participants reported at least one symptom, with diarrhea not related to C. difficile the most common, followed by abdominal pain, bloating, and constipation.
Eleven patients suffered infections, including two which the investigators thought might be related to the procedure: Bacteroides fragilis in one participant with severe diarrhea, and enteropathogenic E. coli in another with loose stools. Other infections included four urinary tract infections, three cases of pneumonia, one E. coli bacteremia and one tooth infection.
Within a month of the procedure, 27 patients were hospitalized, with 3 of these cases considered possibly related to the procedure.
Findings may not apply to all clinical settings
Vincent B. Young, MD, PhD, a professor of medicine and infectious diseases at the University of Michigan, Ann Arbor, pointed out that the findings might not apply to all clinical settings. The participating clinicians were almost all gastroenterologists working in academic centers.
“Most of them are not Joe Doctor at the doctor’s office,” said Dr. Young, who was not involved with the study. Clinicians in other specialties, such as infectious diseases, might be more inclined to administer fecal transplants through capsules rather than colonoscopies.
And he added that the study does not address effects of the transplant that might develop over years. “Some people talk about how changes in the microbiota lead to increased risk for long-term complications, things like cancer or heart disease. You’re not going to see those in 6 months.”
Also, the study didn’t yield any findings on indications other than C. diff. “In no way, shape, or form does it mean you can use it for autism, depression, heart disease, or [irritable bowel syndrome],” he said.
Still, he said, the study “confirms the fact that fecal cell transplantation is an effective treatment for recurrent C. diff infection when administered as they administered it.”
The National Institute of Allergy and Infectious Diseases funded the registry. Dr. Kelly reported a relationship with Finch Therapeutics. Dr. Young reports financial relationships with Vedanta Biosciences and Bio-K+.
This story was updated on Oct. 4, 2020.
A version of this article originally appeared on Medscape.com.
Fecal microbiota transplantation (FMT) appears safe and effective as a treatment for most Clostridioides difficile infections as it is currently being administered, researchers say.
“We actually didn’t see any infections that were definitely transmissible via fecal transplant,” Colleen Kelly, MD, an associate professor of medicine at Brown University, Providence, R.I., said in an interview.
The findings, published online Oct. 1 in the journal Gastroenterology, come from the American Gastroenterological Association (AGA) NIH-funded FMT National Registry and could allay concerns about a treatment that has yet to gain full approval by the Food and Drug Administration, despite successful clinical trials.
C. diff infections are common and increasing in the United States, often can’t be cured with conventional treatments such as antibiotics, and can be deadly.
Transplanting fecal matter from a donor to the patient appears to work by restoring beneficial microorganisms to the patient’s gut. The procedure is also under investigation for a wide range of other ailments, from irritable bowel syndrome to mood disorders.
But much remains unknown. Researchers have counted a thousand bacterial species along with viruses, bacteriophages, archaea, and fungi in the human gut that interact in complex ways, not all of them beneficial.
The FDA has not enforced regulations that would prohibit the procedure, but in March, it warned about infections with enteropathogenic Escherichia coli and Shiga toxin–producing E. coli following fecal transplants.
As a result of these reports, and the theoretical risk of spreading SARS-CoV-2, OpenBiome, the largest stool bank in the United States, has suspended shipments except for emergency orders, and asked clinicians to quarantine any of its products they already have on hand.
In the meantime, long-term effects of the treatment have not been well documented. And clinical trials have excluded patients who might benefit, such as those who have been immunocompromised or have inflammatory bowel disease.
National registry follows patients outside clinical trials
To better understand how patients fare outside these trials, AGA and other organizations developed a national registry, funded by a grant from the National Institute of Allergy and Infectious Diseases.
The current report summarizes results on 259 patients enrolled between Dec. 5, 2017, and Sept. 2, 2019 at 20 sites.
At baseline, 44% of these patients suffered moderate and 36% mild C. diff infections. The duration of the diagnosis ranged from less than 1 week to 9 years, with a median duration of 20 weeks. They ranged from 1 to 15 episodes with a mean of 3.5.
Almost all had received vancomycin, and 62% had at least two courses. About 40% had received metronidazole and 28% had received fidaxomicin.
Almost all participants received stool from an unknown donor, mostly from stool banks, with OpenBiome accounting for 67%. About 85% of the transplants were administered through colonoscopy and 6% by upper endoscopy.
Out of 222 patients who returned for a 1-month follow-up, 90% met the investigators’ definition of cure: resolution of diarrhea without need for further anti–C. diff therapy. About 98% received only one transplant. An intent to treat analysis produced a cure rate of 86%.
Results were good in patients with comorbidities, including 12% who had irritable bowel syndrome, 9% who had ulcerative colitis, and 7% who had Crohn’s disease, Dr. Kelly said. “I hope everybody sees the importance of it. In these patients that are more complicated, who may have underlying comorbidities, who may not have been in the clinical trials, it looks effective in that group, and also incredibly safe.”
She added that the risk of transmitting SARS-CoV-2 is minor. “I think it would be a very, very unlikely way for someone to get a respiratory pathogen.”
Of the 112 participants who were cured at 1 month and returned for follow-up after 6 months, 4 developed recurrent C. diff infection. Eleven patients who were not cured in the first month returned after 6 months. Of these, seven were reported cured at this later follow-up.
Three complications occurred as result of the procedure: one colonoscopic perforation and two episodes of gastrointestinal bleeding.
About 45% of participants reported at least one symptom, with diarrhea not related to C. difficile the most common, followed by abdominal pain, bloating, and constipation.
Eleven patients suffered infections, including two which the investigators thought might be related to the procedure: Bacteroides fragilis in one participant with severe diarrhea, and enteropathogenic E. coli in another with loose stools. Other infections included four urinary tract infections, three cases of pneumonia, one E. coli bacteremia and one tooth infection.
Within a month of the procedure, 27 patients were hospitalized, with 3 of these cases considered possibly related to the procedure.
Findings may not apply to all clinical settings
Vincent B. Young, MD, PhD, a professor of medicine and infectious diseases at the University of Michigan, Ann Arbor, pointed out that the findings might not apply to all clinical settings. The participating clinicians were almost all gastroenterologists working in academic centers.
“Most of them are not Joe Doctor at the doctor’s office,” said Dr. Young, who was not involved with the study. Clinicians in other specialties, such as infectious diseases, might be more inclined to administer fecal transplants through capsules rather than colonoscopies.
And he added that the study does not address effects of the transplant that might develop over years. “Some people talk about how changes in the microbiota lead to increased risk for long-term complications, things like cancer or heart disease. You’re not going to see those in 6 months.”
Also, the study didn’t yield any findings on indications other than C. diff. “In no way, shape, or form does it mean you can use it for autism, depression, heart disease, or [irritable bowel syndrome],” he said.
Still, he said, the study “confirms the fact that fecal cell transplantation is an effective treatment for recurrent C. diff infection when administered as they administered it.”
The National Institute of Allergy and Infectious Diseases funded the registry. Dr. Kelly reported a relationship with Finch Therapeutics. Dr. Young reports financial relationships with Vedanta Biosciences and Bio-K+.
This story was updated on Oct. 4, 2020.
A version of this article originally appeared on Medscape.com.
Mental illness tied to increased mortality in COVID-19
A psychiatric diagnosis for patients hospitalized with COVID-19 is linked to a significantly increased risk for death, new research shows.
Investigators found that patients who were hospitalized with COVID-19 and who had been diagnosed with a psychiatric disorder had a 50% increased risk for a COVID-related death in comparison with COVID-19 patients who had not received a psychiatric diagnosis.
“Pay attention and potentially address/treat a prior psychiatric diagnosis if a patient is hospitalized for COVID-19, as this risk factor can impact the patient’s outcome – death – while in the hospital,” lead investigator Luming Li, MD, assistant professor of psychiatry and associate medical director of quality improvement, Yale New Haven Psychiatric Hospital, New Haven, Conn., said in an interview.
The study was published Sept. 30 in JAMA Network Open.
Negative impact
“We were interested to learn more about the impact of psychiatric diagnoses on COVID-19 mortality, as prior large cohort studies included neurological and other medical conditions but did not assess for a priori psychiatric diagnoses,” said Dr. Li.
“We know from the literature that prior psychiatric diagnoses can have a negative impact on the outcomes of medical conditions, and therefore we tested our hypothesis on a cohort of patients who were hospitalized with COVID-19,” she added.
To investigate, the researchers analyzed data on 1,685 patients hospitalized with COVID-19 between Feb. 15 and April 25, 2020, and whose cases were followed to May 27, 2020. The patients (mean age, 65.2 years; 52.6% men) were drawn from the Yale New Haven Health System.
The median follow-up period was 8 days (interquartile range, 4-16 days) .
Of these patients, 28% had received a psychiatric diagnosis prior to hospitalization. (i.e., cancer, cerebrovascular disease, heart failure, diabetes, kidney disease, liver disease, MI, and/or HIV).
Psychiatric diagnoses were defined in accordance with ICD codes that included mental and behavioral health, Alzheimer’s disease, and self-injury.
Vulnerability to stress
In the unadjusted model, the risk for COVID-19–related hospital death was greater for those who had received any psychiatric diagnosis, compared with those had not (hazard ratio, 2.3; 95% CI, 1.8-2.9; P < .001).
In the adjusted model that controlled for demographic characteristics, other medical comorbidities, and hospital location, the mortality risk somewhat decreased but still remained significantly higher (HR, 1.5; 95% CI, 1.1-1.9; P = .003).
Dr. Li noted a number of factors that might account for the higher mortality rate among psychiatric patients who had COVID-19 in comparison with COVD-19 patients who did not have a psychiatric disorder. These included “potential inflammatory and stress responses that the body experiences related to prior psychiatric conditions,” she said.
Having been previously diagnosed with a psychiatric disorder may also “reflect existing neurochemical differences, compared to those who do not have a prior psychiatric diagnosis, [and] these differences may make the population with the prior psychiatric diagnosis more vulnerable to respond to an acute stressor such as COVID-19,” she said.
Quality care
Harold Pincus, MD, professor and vice chair of the department of psychiatry at Columbia University, New York, said it “adds to the fairly well-known and well-established phenomenon that people with mental illnesses have a high risk of all sorts of morbidity and mortality for non–mental health conditions.”
The researchers “adjusted for various expected [mortality] risks that would be independent of the presence of COVID-19,” so “there was something else going on associated with mortality,” said Dr. Pincus, who is also codirector of the Irving Institute for Clinical and Translation Research. He was not involved with the study.
Beyond the possibility of “some basic immunologic process affected by the presence of a mental disorder,” it is possible that the vulnerability is “related to access to quality care for the comorbid general condition that is not being effectively treated,” he said.
“The take-home message is that people with mental disorders are at higher risk for death, and we need to make sure that, irrespective of COVID-19, they get adequate preventive and chronic-disease care, which would be the most effective way to intervene and protect the impact of a serious disease like COVID-19,” he noted. This would include being appropriately vaccinated and receiving preventive healthcare to reduce smoking and encourage weight loss.
No source of funding for the study was provided. Dr. Li reported receiving grants from a Health and Aging Policy Fellowship during the conduct of the study. Dr. Pincus reported no relevant financial relationships.
A psychiatric diagnosis for patients hospitalized with COVID-19 is linked to a significantly increased risk for death, new research shows.
Investigators found that patients who were hospitalized with COVID-19 and who had been diagnosed with a psychiatric disorder had a 50% increased risk for a COVID-related death in comparison with COVID-19 patients who had not received a psychiatric diagnosis.
“Pay attention and potentially address/treat a prior psychiatric diagnosis if a patient is hospitalized for COVID-19, as this risk factor can impact the patient’s outcome – death – while in the hospital,” lead investigator Luming Li, MD, assistant professor of psychiatry and associate medical director of quality improvement, Yale New Haven Psychiatric Hospital, New Haven, Conn., said in an interview.
The study was published Sept. 30 in JAMA Network Open.
Negative impact
“We were interested to learn more about the impact of psychiatric diagnoses on COVID-19 mortality, as prior large cohort studies included neurological and other medical conditions but did not assess for a priori psychiatric diagnoses,” said Dr. Li.
“We know from the literature that prior psychiatric diagnoses can have a negative impact on the outcomes of medical conditions, and therefore we tested our hypothesis on a cohort of patients who were hospitalized with COVID-19,” she added.
To investigate, the researchers analyzed data on 1,685 patients hospitalized with COVID-19 between Feb. 15 and April 25, 2020, and whose cases were followed to May 27, 2020. The patients (mean age, 65.2 years; 52.6% men) were drawn from the Yale New Haven Health System.
The median follow-up period was 8 days (interquartile range, 4-16 days) .
Of these patients, 28% had received a psychiatric diagnosis prior to hospitalization. (i.e., cancer, cerebrovascular disease, heart failure, diabetes, kidney disease, liver disease, MI, and/or HIV).
Psychiatric diagnoses were defined in accordance with ICD codes that included mental and behavioral health, Alzheimer’s disease, and self-injury.
Vulnerability to stress
In the unadjusted model, the risk for COVID-19–related hospital death was greater for those who had received any psychiatric diagnosis, compared with those had not (hazard ratio, 2.3; 95% CI, 1.8-2.9; P < .001).
In the adjusted model that controlled for demographic characteristics, other medical comorbidities, and hospital location, the mortality risk somewhat decreased but still remained significantly higher (HR, 1.5; 95% CI, 1.1-1.9; P = .003).
Dr. Li noted a number of factors that might account for the higher mortality rate among psychiatric patients who had COVID-19 in comparison with COVD-19 patients who did not have a psychiatric disorder. These included “potential inflammatory and stress responses that the body experiences related to prior psychiatric conditions,” she said.
Having been previously diagnosed with a psychiatric disorder may also “reflect existing neurochemical differences, compared to those who do not have a prior psychiatric diagnosis, [and] these differences may make the population with the prior psychiatric diagnosis more vulnerable to respond to an acute stressor such as COVID-19,” she said.
Quality care
Harold Pincus, MD, professor and vice chair of the department of psychiatry at Columbia University, New York, said it “adds to the fairly well-known and well-established phenomenon that people with mental illnesses have a high risk of all sorts of morbidity and mortality for non–mental health conditions.”
The researchers “adjusted for various expected [mortality] risks that would be independent of the presence of COVID-19,” so “there was something else going on associated with mortality,” said Dr. Pincus, who is also codirector of the Irving Institute for Clinical and Translation Research. He was not involved with the study.
Beyond the possibility of “some basic immunologic process affected by the presence of a mental disorder,” it is possible that the vulnerability is “related to access to quality care for the comorbid general condition that is not being effectively treated,” he said.
“The take-home message is that people with mental disorders are at higher risk for death, and we need to make sure that, irrespective of COVID-19, they get adequate preventive and chronic-disease care, which would be the most effective way to intervene and protect the impact of a serious disease like COVID-19,” he noted. This would include being appropriately vaccinated and receiving preventive healthcare to reduce smoking and encourage weight loss.
No source of funding for the study was provided. Dr. Li reported receiving grants from a Health and Aging Policy Fellowship during the conduct of the study. Dr. Pincus reported no relevant financial relationships.
A psychiatric diagnosis for patients hospitalized with COVID-19 is linked to a significantly increased risk for death, new research shows.
Investigators found that patients who were hospitalized with COVID-19 and who had been diagnosed with a psychiatric disorder had a 50% increased risk for a COVID-related death in comparison with COVID-19 patients who had not received a psychiatric diagnosis.
“Pay attention and potentially address/treat a prior psychiatric diagnosis if a patient is hospitalized for COVID-19, as this risk factor can impact the patient’s outcome – death – while in the hospital,” lead investigator Luming Li, MD, assistant professor of psychiatry and associate medical director of quality improvement, Yale New Haven Psychiatric Hospital, New Haven, Conn., said in an interview.
The study was published Sept. 30 in JAMA Network Open.
Negative impact
“We were interested to learn more about the impact of psychiatric diagnoses on COVID-19 mortality, as prior large cohort studies included neurological and other medical conditions but did not assess for a priori psychiatric diagnoses,” said Dr. Li.
“We know from the literature that prior psychiatric diagnoses can have a negative impact on the outcomes of medical conditions, and therefore we tested our hypothesis on a cohort of patients who were hospitalized with COVID-19,” she added.
To investigate, the researchers analyzed data on 1,685 patients hospitalized with COVID-19 between Feb. 15 and April 25, 2020, and whose cases were followed to May 27, 2020. The patients (mean age, 65.2 years; 52.6% men) were drawn from the Yale New Haven Health System.
The median follow-up period was 8 days (interquartile range, 4-16 days) .
Of these patients, 28% had received a psychiatric diagnosis prior to hospitalization. (i.e., cancer, cerebrovascular disease, heart failure, diabetes, kidney disease, liver disease, MI, and/or HIV).
Psychiatric diagnoses were defined in accordance with ICD codes that included mental and behavioral health, Alzheimer’s disease, and self-injury.
Vulnerability to stress
In the unadjusted model, the risk for COVID-19–related hospital death was greater for those who had received any psychiatric diagnosis, compared with those had not (hazard ratio, 2.3; 95% CI, 1.8-2.9; P < .001).
In the adjusted model that controlled for demographic characteristics, other medical comorbidities, and hospital location, the mortality risk somewhat decreased but still remained significantly higher (HR, 1.5; 95% CI, 1.1-1.9; P = .003).
Dr. Li noted a number of factors that might account for the higher mortality rate among psychiatric patients who had COVID-19 in comparison with COVD-19 patients who did not have a psychiatric disorder. These included “potential inflammatory and stress responses that the body experiences related to prior psychiatric conditions,” she said.
Having been previously diagnosed with a psychiatric disorder may also “reflect existing neurochemical differences, compared to those who do not have a prior psychiatric diagnosis, [and] these differences may make the population with the prior psychiatric diagnosis more vulnerable to respond to an acute stressor such as COVID-19,” she said.
Quality care
Harold Pincus, MD, professor and vice chair of the department of psychiatry at Columbia University, New York, said it “adds to the fairly well-known and well-established phenomenon that people with mental illnesses have a high risk of all sorts of morbidity and mortality for non–mental health conditions.”
The researchers “adjusted for various expected [mortality] risks that would be independent of the presence of COVID-19,” so “there was something else going on associated with mortality,” said Dr. Pincus, who is also codirector of the Irving Institute for Clinical and Translation Research. He was not involved with the study.
Beyond the possibility of “some basic immunologic process affected by the presence of a mental disorder,” it is possible that the vulnerability is “related to access to quality care for the comorbid general condition that is not being effectively treated,” he said.
“The take-home message is that people with mental disorders are at higher risk for death, and we need to make sure that, irrespective of COVID-19, they get adequate preventive and chronic-disease care, which would be the most effective way to intervene and protect the impact of a serious disease like COVID-19,” he noted. This would include being appropriately vaccinated and receiving preventive healthcare to reduce smoking and encourage weight loss.
No source of funding for the study was provided. Dr. Li reported receiving grants from a Health and Aging Policy Fellowship during the conduct of the study. Dr. Pincus reported no relevant financial relationships.
Highlights in Disease-Modifying Therapies From ECTRIMS2020
Dr Patricia Coyle from Stony Brook University Medical Center in New York highlights new data on disease-modifying therapies (DMTs) from the 8th Joint ACTRIMS-ECTRIMS Meeting, MSVirtual2020.
Focusing on relapsing-remitting multiple sclerosis (RRMS), Dr Coyle discusses new research that further explores the efficacy and rebound effects of DMTs, 24 of which are approved in the United States for this patient population.
She reports on results from a database study comparing DMTs vs moderate-efficacy drugs and escalating treatment in the first-line setting, a cohort of pediatric patients receiving adult-approved teriflunomide, and an exploration of fingolimod rebound syndrome.
INFORMATION FROM INDUSTRY
Resources
Have You Seen the Head-to-Head Efficacy Data for ZEPOSIA® (ozanimod)?
Clinical Trial Safety Findings for an S1P Therapy
Discover How to Start Appropriate Patients on an S1P
US-ZEP-20-0997 10/20
Patricia K. Coyle, MD, Professor, Interim Chair, Director, Multiple Sclerosis Comprehensive Care Center, Department of Neurology, Stony Brook University Medical Center, Stony Brook, New York
Dr Patricia Coyle from Stony Brook University Medical Center in New York highlights new data on disease-modifying therapies (DMTs) from the 8th Joint ACTRIMS-ECTRIMS Meeting, MSVirtual2020.
Focusing on relapsing-remitting multiple sclerosis (RRMS), Dr Coyle discusses new research that further explores the efficacy and rebound effects of DMTs, 24 of which are approved in the United States for this patient population.
She reports on results from a database study comparing DMTs vs moderate-efficacy drugs and escalating treatment in the first-line setting, a cohort of pediatric patients receiving adult-approved teriflunomide, and an exploration of fingolimod rebound syndrome.
INFORMATION FROM INDUSTRY
Resources
Have You Seen the Head-to-Head Efficacy Data for ZEPOSIA® (ozanimod)?
Clinical Trial Safety Findings for an S1P Therapy
Discover How to Start Appropriate Patients on an S1P
US-ZEP-20-0997 10/20
Patricia K. Coyle, MD, Professor, Interim Chair, Director, Multiple Sclerosis Comprehensive Care Center, Department of Neurology, Stony Brook University Medical Center, Stony Brook, New York
Dr Patricia Coyle from Stony Brook University Medical Center in New York highlights new data on disease-modifying therapies (DMTs) from the 8th Joint ACTRIMS-ECTRIMS Meeting, MSVirtual2020.
Focusing on relapsing-remitting multiple sclerosis (RRMS), Dr Coyle discusses new research that further explores the efficacy and rebound effects of DMTs, 24 of which are approved in the United States for this patient population.
She reports on results from a database study comparing DMTs vs moderate-efficacy drugs and escalating treatment in the first-line setting, a cohort of pediatric patients receiving adult-approved teriflunomide, and an exploration of fingolimod rebound syndrome.
INFORMATION FROM INDUSTRY
Resources
Have You Seen the Head-to-Head Efficacy Data for ZEPOSIA® (ozanimod)?
Clinical Trial Safety Findings for an S1P Therapy
Discover How to Start Appropriate Patients on an S1P
US-ZEP-20-0997 10/20
Patricia K. Coyle, MD, Professor, Interim Chair, Director, Multiple Sclerosis Comprehensive Care Center, Department of Neurology, Stony Brook University Medical Center, Stony Brook, New York
Endoscopic drainage of pancreatic fluid collections
Pancreatic fluid collections (PFCs) are common after acute pancreatitis but almost always resolve spontaneously. Persistent collections that cause symptoms, become infected, and/or compress vital structures require treatment. Open surgery had traditionally been considered the standard method for this indication;1 Given its inherently less invasive nature, endoscopic transmural drainage (ETMD) has become a mainstay of this step-up philosophy – it is now the dominant strategy for pseudocyst drainage and, on the basis of emerging randomized trial data, compares very favorably with surgery for the treatment of walled-off necrosis (WON).
According to the step-up approach, the initial treatment of symptomatic and/or infected collections that are within 4 weeks of an attack of pancreatitis involves conservative management because the wall of the collection is typically immature; the systemic inflammation may be significantly exacerbated by definitive drainage, particularly surgery. In this early phase, failure of conservative management is addressed by percutaneous catheter placement, stepping up to a minimally invasive operation if the response to percutaneous drainage and antibiotics is insufficient.
Collections that are at least 4 weeks from the onset of acute pancreatitis are considered mature and termed pseudocysts or WONs depending on whether they contain pure fluid or necrotic tissue. In this phase, endoscopic treatment plays a primary management role because these collections are generally adherent to the stomach or duodenal wall and their capsule is organized enough to withstand endoscopic intervention. If treatment can be held off until this phase, then percutaneous and surgical drainage can often be avoided.
In practice, the 4-week rule holds true for most, but not all, PFCs. ETMD can be performed in some particularly mature collections prior to 4 weeks if the indication is strong and the collection appears to have a mature wall. However, the potential for cyst wall perforation is higher and should be considered in the risk-benefit discussion. Conversely, some collections beyond 4 weeks lack an adequately organized wall and require additional time for maturation.
While endoscopic drainage of pseudocysts has essentially supplanted surgery, the management of WON is more complex and remains multidisciplinary. Two recent randomized trials demonstrated no difference in major complications and/or death between a surgical and endoscopic step-up strategy for WON.2,3 Rates of pancreatic fistulae, hospital stay, and overall treatment costs, however, favored endoscopy. Nevertheless, defining the ideal strategy for many of these patients with complexity requires multidisciplinary discussion. Surgery continues to play a primary role in several scenarios, including collections that are not close to the upper GI tract, those that are particularly complex and extend caudally, and situations in which the endoscopic progress is too slow.
The three most important questions when deciding to embark on ETMD are: (1) whether drainage is indicated (that is, is the patient symptomatic or is there evidence that the PFC is infected?), (2) whether the wall of the collection is adequately mature and apposed to the GI tract wall; and (3) whether the collection contains necrosis? This last question has critical implications in the technical approach to drainage. While CT scan with IV contrast is accurate for assessing wall maturity, it is inadequate to evaluate the presence or quantity of necrosum. Transabdominal ultrasound, endoscopic ultrasound, and MRI (on a T2 sequence) are all superior for this purpose. MRI has the additional benefit of assessing the pancreatic duct integrity, which may influence subsequent management.
Pseudocysts can be managed by cyst-gastrostomy or cyst-duodenostomy alone, whereas most WONs require the additional step of endoscopic necrosectomy – the process of entering the cyst cavity to mechanically debride necrotic tissue. Because of a higher rate of technical success, endoscopic ultrasound–directed creation of the transmural drainage pathway has become standard practice. In addition, it is likely safer, allowing for the identification and avoidance of interceding vessels and other vital structures. The role of endoscopic retrograde cholangiopancreatography with pancreatic stent placement as primary therapy for PFCs is limited to the drainage of small collections (<5 cm), for which it is the preferred treatment strategy. It is as effective as ETMD, which may not be feasible or safe for small PFCs.
Plastic double-pigtail stents have traditionally been used to maintain the transmural tract for both pseudocyst and WON. Recently, however, metallic stents have become more popular. Fully covered biliary self-expanding metallic stents (SEMS) are easier to place, have a larger lumen, and are associated with improved outcomes, compared with plastic stents in observational studies of pseudocyst drainage. Lumen-apposing metallic stents (LAMS) have become the preferred prosthesis for WON drainage given the ability to near-simultaneously establish access and deploy the stent, as well as their much larger caliber lumen which permits seamless entry into the cavity with an endoscope. Based on ease and efficiency of use, LAMS are also commonly employed for pseudocyst drainage, although entry into the cavity is unnecessary.
Plastic stents have been shown to be more cost effective than LAMS for pseudocyst drainage, although the economics around biliary SEMS in this context have not been explored. Robust comparative effectiveness data defining the optimal prostheses for pseudocysts are needed. The literature comparing LAMS to plastic stents for the management of WON is mixed. Studies have shown LAMS to be more cost effective, but a small randomized trial demonstrated no difference in clinical success or in the number of procedures to achieve WON resolution.4 We generally favor LAMS for WON since large-caliber balloon dilation of the tract seems safer within the lumen of the LAMS (which could seal small perforations and tamponade bleeding vessels) than within a freshly created tract.
Secondary infection of the cavity, usually because of stent occlusion, and bleeding are the most common complications of ETMD. Even in the absence of stent occlusion, contamination of the collection after ETMD is ubiquitous and, as such, we prescribe prophylactic antibiotics for 1-2 weeks after the procedure, although this practice is not evidence based. Hemorrhage appears to be increasing in frequency with the diffusion of LAMS; this has been postulated to be due to particularly rapid cyst cavity collapse resulting in erosion of the stent into contralateral cyst wall vessels. CT angiography followed by an embolization procedure for a possible pseudoaneurysm is the mainstay of treatment. Serious venous bleeding is more challenging to address because angiographic options are limited.
Despite tremendous recent advances, several important controversies in the endoscopic management of PFCs persist. The optimal prosthesis, the importance of first-session endoscopic necroscopy (compared with stepping up to endoscopic necroscopy only if necessary), the roles of adjunctive drain placement and chemical debridement (such as hydrogen peroxide), the need for concomitant pancreatic stent placement, and the preferred long-term management of a disconnected pancreatic duct are areas for which additional research is sorely needed. We further discuss these questions and many additional technical considerations pertaining to endoscopic drainage in a recent review.5
In summary, endoscopic transmural drainage of mature PFCs is effective and safe. Existing evidence supports its use as the favored treatment modality in appropriate candidates and has rendered it a mainstay of the therapeutic armamentarium for this disease. Further studies are needed to address critical unanswered questions and to develop a uniform endoscopic management paradigm.
References
1. van Santvoort HC et al. N Engl J Med. 2010;362(16):1491-502.
2. van Brunschot S et al. Lancet. 2018;391(10115):51-8.
3. Bang JY et al. Gastroenterology. 2019;156(4):1027-40.
4. Bang JY et al. Gut. 2019;68(7):1200-9.
5. Elmunzer BJ. Clin Gastroenterol Hepatol. 2018;16(12):1851-63.
Dr. Moran is assistant professor of medicine, division of gastroenterology and hepatology, Medical University of South Carolina, Charleston; Dr. Elmunzer is the Peter Cotton Professor of Medicine and Endoscopic Innovation, division of gastroenterology and hepatology, Medical University of South Carolina. The authors have no conflicts of interest pertaining to this review.
Pancreatic fluid collections (PFCs) are common after acute pancreatitis but almost always resolve spontaneously. Persistent collections that cause symptoms, become infected, and/or compress vital structures require treatment. Open surgery had traditionally been considered the standard method for this indication;1 Given its inherently less invasive nature, endoscopic transmural drainage (ETMD) has become a mainstay of this step-up philosophy – it is now the dominant strategy for pseudocyst drainage and, on the basis of emerging randomized trial data, compares very favorably with surgery for the treatment of walled-off necrosis (WON).
According to the step-up approach, the initial treatment of symptomatic and/or infected collections that are within 4 weeks of an attack of pancreatitis involves conservative management because the wall of the collection is typically immature; the systemic inflammation may be significantly exacerbated by definitive drainage, particularly surgery. In this early phase, failure of conservative management is addressed by percutaneous catheter placement, stepping up to a minimally invasive operation if the response to percutaneous drainage and antibiotics is insufficient.
Collections that are at least 4 weeks from the onset of acute pancreatitis are considered mature and termed pseudocysts or WONs depending on whether they contain pure fluid or necrotic tissue. In this phase, endoscopic treatment plays a primary management role because these collections are generally adherent to the stomach or duodenal wall and their capsule is organized enough to withstand endoscopic intervention. If treatment can be held off until this phase, then percutaneous and surgical drainage can often be avoided.
In practice, the 4-week rule holds true for most, but not all, PFCs. ETMD can be performed in some particularly mature collections prior to 4 weeks if the indication is strong and the collection appears to have a mature wall. However, the potential for cyst wall perforation is higher and should be considered in the risk-benefit discussion. Conversely, some collections beyond 4 weeks lack an adequately organized wall and require additional time for maturation.
While endoscopic drainage of pseudocysts has essentially supplanted surgery, the management of WON is more complex and remains multidisciplinary. Two recent randomized trials demonstrated no difference in major complications and/or death between a surgical and endoscopic step-up strategy for WON.2,3 Rates of pancreatic fistulae, hospital stay, and overall treatment costs, however, favored endoscopy. Nevertheless, defining the ideal strategy for many of these patients with complexity requires multidisciplinary discussion. Surgery continues to play a primary role in several scenarios, including collections that are not close to the upper GI tract, those that are particularly complex and extend caudally, and situations in which the endoscopic progress is too slow.
The three most important questions when deciding to embark on ETMD are: (1) whether drainage is indicated (that is, is the patient symptomatic or is there evidence that the PFC is infected?), (2) whether the wall of the collection is adequately mature and apposed to the GI tract wall; and (3) whether the collection contains necrosis? This last question has critical implications in the technical approach to drainage. While CT scan with IV contrast is accurate for assessing wall maturity, it is inadequate to evaluate the presence or quantity of necrosum. Transabdominal ultrasound, endoscopic ultrasound, and MRI (on a T2 sequence) are all superior for this purpose. MRI has the additional benefit of assessing the pancreatic duct integrity, which may influence subsequent management.
Pseudocysts can be managed by cyst-gastrostomy or cyst-duodenostomy alone, whereas most WONs require the additional step of endoscopic necrosectomy – the process of entering the cyst cavity to mechanically debride necrotic tissue. Because of a higher rate of technical success, endoscopic ultrasound–directed creation of the transmural drainage pathway has become standard practice. In addition, it is likely safer, allowing for the identification and avoidance of interceding vessels and other vital structures. The role of endoscopic retrograde cholangiopancreatography with pancreatic stent placement as primary therapy for PFCs is limited to the drainage of small collections (<5 cm), for which it is the preferred treatment strategy. It is as effective as ETMD, which may not be feasible or safe for small PFCs.
Plastic double-pigtail stents have traditionally been used to maintain the transmural tract for both pseudocyst and WON. Recently, however, metallic stents have become more popular. Fully covered biliary self-expanding metallic stents (SEMS) are easier to place, have a larger lumen, and are associated with improved outcomes, compared with plastic stents in observational studies of pseudocyst drainage. Lumen-apposing metallic stents (LAMS) have become the preferred prosthesis for WON drainage given the ability to near-simultaneously establish access and deploy the stent, as well as their much larger caliber lumen which permits seamless entry into the cavity with an endoscope. Based on ease and efficiency of use, LAMS are also commonly employed for pseudocyst drainage, although entry into the cavity is unnecessary.
Plastic stents have been shown to be more cost effective than LAMS for pseudocyst drainage, although the economics around biliary SEMS in this context have not been explored. Robust comparative effectiveness data defining the optimal prostheses for pseudocysts are needed. The literature comparing LAMS to plastic stents for the management of WON is mixed. Studies have shown LAMS to be more cost effective, but a small randomized trial demonstrated no difference in clinical success or in the number of procedures to achieve WON resolution.4 We generally favor LAMS for WON since large-caliber balloon dilation of the tract seems safer within the lumen of the LAMS (which could seal small perforations and tamponade bleeding vessels) than within a freshly created tract.
Secondary infection of the cavity, usually because of stent occlusion, and bleeding are the most common complications of ETMD. Even in the absence of stent occlusion, contamination of the collection after ETMD is ubiquitous and, as such, we prescribe prophylactic antibiotics for 1-2 weeks after the procedure, although this practice is not evidence based. Hemorrhage appears to be increasing in frequency with the diffusion of LAMS; this has been postulated to be due to particularly rapid cyst cavity collapse resulting in erosion of the stent into contralateral cyst wall vessels. CT angiography followed by an embolization procedure for a possible pseudoaneurysm is the mainstay of treatment. Serious venous bleeding is more challenging to address because angiographic options are limited.
Despite tremendous recent advances, several important controversies in the endoscopic management of PFCs persist. The optimal prosthesis, the importance of first-session endoscopic necroscopy (compared with stepping up to endoscopic necroscopy only if necessary), the roles of adjunctive drain placement and chemical debridement (such as hydrogen peroxide), the need for concomitant pancreatic stent placement, and the preferred long-term management of a disconnected pancreatic duct are areas for which additional research is sorely needed. We further discuss these questions and many additional technical considerations pertaining to endoscopic drainage in a recent review.5
In summary, endoscopic transmural drainage of mature PFCs is effective and safe. Existing evidence supports its use as the favored treatment modality in appropriate candidates and has rendered it a mainstay of the therapeutic armamentarium for this disease. Further studies are needed to address critical unanswered questions and to develop a uniform endoscopic management paradigm.
References
1. van Santvoort HC et al. N Engl J Med. 2010;362(16):1491-502.
2. van Brunschot S et al. Lancet. 2018;391(10115):51-8.
3. Bang JY et al. Gastroenterology. 2019;156(4):1027-40.
4. Bang JY et al. Gut. 2019;68(7):1200-9.
5. Elmunzer BJ. Clin Gastroenterol Hepatol. 2018;16(12):1851-63.
Dr. Moran is assistant professor of medicine, division of gastroenterology and hepatology, Medical University of South Carolina, Charleston; Dr. Elmunzer is the Peter Cotton Professor of Medicine and Endoscopic Innovation, division of gastroenterology and hepatology, Medical University of South Carolina. The authors have no conflicts of interest pertaining to this review.
Pancreatic fluid collections (PFCs) are common after acute pancreatitis but almost always resolve spontaneously. Persistent collections that cause symptoms, become infected, and/or compress vital structures require treatment. Open surgery had traditionally been considered the standard method for this indication;1 Given its inherently less invasive nature, endoscopic transmural drainage (ETMD) has become a mainstay of this step-up philosophy – it is now the dominant strategy for pseudocyst drainage and, on the basis of emerging randomized trial data, compares very favorably with surgery for the treatment of walled-off necrosis (WON).
According to the step-up approach, the initial treatment of symptomatic and/or infected collections that are within 4 weeks of an attack of pancreatitis involves conservative management because the wall of the collection is typically immature; the systemic inflammation may be significantly exacerbated by definitive drainage, particularly surgery. In this early phase, failure of conservative management is addressed by percutaneous catheter placement, stepping up to a minimally invasive operation if the response to percutaneous drainage and antibiotics is insufficient.
Collections that are at least 4 weeks from the onset of acute pancreatitis are considered mature and termed pseudocysts or WONs depending on whether they contain pure fluid or necrotic tissue. In this phase, endoscopic treatment plays a primary management role because these collections are generally adherent to the stomach or duodenal wall and their capsule is organized enough to withstand endoscopic intervention. If treatment can be held off until this phase, then percutaneous and surgical drainage can often be avoided.
In practice, the 4-week rule holds true for most, but not all, PFCs. ETMD can be performed in some particularly mature collections prior to 4 weeks if the indication is strong and the collection appears to have a mature wall. However, the potential for cyst wall perforation is higher and should be considered in the risk-benefit discussion. Conversely, some collections beyond 4 weeks lack an adequately organized wall and require additional time for maturation.
While endoscopic drainage of pseudocysts has essentially supplanted surgery, the management of WON is more complex and remains multidisciplinary. Two recent randomized trials demonstrated no difference in major complications and/or death between a surgical and endoscopic step-up strategy for WON.2,3 Rates of pancreatic fistulae, hospital stay, and overall treatment costs, however, favored endoscopy. Nevertheless, defining the ideal strategy for many of these patients with complexity requires multidisciplinary discussion. Surgery continues to play a primary role in several scenarios, including collections that are not close to the upper GI tract, those that are particularly complex and extend caudally, and situations in which the endoscopic progress is too slow.
The three most important questions when deciding to embark on ETMD are: (1) whether drainage is indicated (that is, is the patient symptomatic or is there evidence that the PFC is infected?), (2) whether the wall of the collection is adequately mature and apposed to the GI tract wall; and (3) whether the collection contains necrosis? This last question has critical implications in the technical approach to drainage. While CT scan with IV contrast is accurate for assessing wall maturity, it is inadequate to evaluate the presence or quantity of necrosum. Transabdominal ultrasound, endoscopic ultrasound, and MRI (on a T2 sequence) are all superior for this purpose. MRI has the additional benefit of assessing the pancreatic duct integrity, which may influence subsequent management.
Pseudocysts can be managed by cyst-gastrostomy or cyst-duodenostomy alone, whereas most WONs require the additional step of endoscopic necrosectomy – the process of entering the cyst cavity to mechanically debride necrotic tissue. Because of a higher rate of technical success, endoscopic ultrasound–directed creation of the transmural drainage pathway has become standard practice. In addition, it is likely safer, allowing for the identification and avoidance of interceding vessels and other vital structures. The role of endoscopic retrograde cholangiopancreatography with pancreatic stent placement as primary therapy for PFCs is limited to the drainage of small collections (<5 cm), for which it is the preferred treatment strategy. It is as effective as ETMD, which may not be feasible or safe for small PFCs.
Plastic double-pigtail stents have traditionally been used to maintain the transmural tract for both pseudocyst and WON. Recently, however, metallic stents have become more popular. Fully covered biliary self-expanding metallic stents (SEMS) are easier to place, have a larger lumen, and are associated with improved outcomes, compared with plastic stents in observational studies of pseudocyst drainage. Lumen-apposing metallic stents (LAMS) have become the preferred prosthesis for WON drainage given the ability to near-simultaneously establish access and deploy the stent, as well as their much larger caliber lumen which permits seamless entry into the cavity with an endoscope. Based on ease and efficiency of use, LAMS are also commonly employed for pseudocyst drainage, although entry into the cavity is unnecessary.
Plastic stents have been shown to be more cost effective than LAMS for pseudocyst drainage, although the economics around biliary SEMS in this context have not been explored. Robust comparative effectiveness data defining the optimal prostheses for pseudocysts are needed. The literature comparing LAMS to plastic stents for the management of WON is mixed. Studies have shown LAMS to be more cost effective, but a small randomized trial demonstrated no difference in clinical success or in the number of procedures to achieve WON resolution.4 We generally favor LAMS for WON since large-caliber balloon dilation of the tract seems safer within the lumen of the LAMS (which could seal small perforations and tamponade bleeding vessels) than within a freshly created tract.
Secondary infection of the cavity, usually because of stent occlusion, and bleeding are the most common complications of ETMD. Even in the absence of stent occlusion, contamination of the collection after ETMD is ubiquitous and, as such, we prescribe prophylactic antibiotics for 1-2 weeks after the procedure, although this practice is not evidence based. Hemorrhage appears to be increasing in frequency with the diffusion of LAMS; this has been postulated to be due to particularly rapid cyst cavity collapse resulting in erosion of the stent into contralateral cyst wall vessels. CT angiography followed by an embolization procedure for a possible pseudoaneurysm is the mainstay of treatment. Serious venous bleeding is more challenging to address because angiographic options are limited.
Despite tremendous recent advances, several important controversies in the endoscopic management of PFCs persist. The optimal prosthesis, the importance of first-session endoscopic necroscopy (compared with stepping up to endoscopic necroscopy only if necessary), the roles of adjunctive drain placement and chemical debridement (such as hydrogen peroxide), the need for concomitant pancreatic stent placement, and the preferred long-term management of a disconnected pancreatic duct are areas for which additional research is sorely needed. We further discuss these questions and many additional technical considerations pertaining to endoscopic drainage in a recent review.5
In summary, endoscopic transmural drainage of mature PFCs is effective and safe. Existing evidence supports its use as the favored treatment modality in appropriate candidates and has rendered it a mainstay of the therapeutic armamentarium for this disease. Further studies are needed to address critical unanswered questions and to develop a uniform endoscopic management paradigm.
References
1. van Santvoort HC et al. N Engl J Med. 2010;362(16):1491-502.
2. van Brunschot S et al. Lancet. 2018;391(10115):51-8.
3. Bang JY et al. Gastroenterology. 2019;156(4):1027-40.
4. Bang JY et al. Gut. 2019;68(7):1200-9.
5. Elmunzer BJ. Clin Gastroenterol Hepatol. 2018;16(12):1851-63.
Dr. Moran is assistant professor of medicine, division of gastroenterology and hepatology, Medical University of South Carolina, Charleston; Dr. Elmunzer is the Peter Cotton Professor of Medicine and Endoscopic Innovation, division of gastroenterology and hepatology, Medical University of South Carolina. The authors have no conflicts of interest pertaining to this review.