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A patient portal for the inpatient experience
Hospitalists, nurses most impacted.
Hospitalists see patients at their most fragile – and, as a result, they have a unique opportunity to affect their health going forward.
“These moments can transform the way patients see their health and their behaviors, and any opportunity to position patients as empowered to influence their experience is one that can not be squandered,” said Timothy Huerta, PhD, MS, lead author on a study of patient portals and tablets during inpatient care.1 “In that context, hospitals have the opportunity to set expectations for engagement that can be influenced by technology. Patient portals, positioned within the inpatient setting, offer a platform to engage, empower, and educate.”
His experience – at the first and largest academic medical center to provide this technology across the entire hospital system – offers the first insight into the demands that such a process shift requires, he said. The researchers ran a 90-day pilot program giving tablets to 179 patients; subsequently, the health system committed to providing tablets for accessing inpatient portals in all seven of its hospitals. “Adopting this technology is not easy, and we continue to explore how we can use it more effectively. Our hope is that our experience can make the journey of others easier.”
Providing the technology is a necessary but insufficient component of implementation, he added. “This is not like the movie ‘Field of Dreams’ – if you build it they will come. It requires leaders to see the value proposition, champions throughout the organization to make a reality where the technology matters to the provision of care, and clinicians to see the tool as a means to a greater good.”
In hospitals, nursing staff and hospitalists are likely to be most impacted by the addition of these tools. “They will require choices – for example who will respond on what timeline to patient communication when using these tools – which requires collaboration across the institution.”
Reference
1. Huerta T, McAlearney AS, Rizer MK. “Introducing a Patient Portal and Electronic Tablets to Inpatient Care.” Ann Intern Med. 2017;167(11):816-7.
Hospitalists, nurses most impacted.
Hospitalists, nurses most impacted.
Hospitalists see patients at their most fragile – and, as a result, they have a unique opportunity to affect their health going forward.
“These moments can transform the way patients see their health and their behaviors, and any opportunity to position patients as empowered to influence their experience is one that can not be squandered,” said Timothy Huerta, PhD, MS, lead author on a study of patient portals and tablets during inpatient care.1 “In that context, hospitals have the opportunity to set expectations for engagement that can be influenced by technology. Patient portals, positioned within the inpatient setting, offer a platform to engage, empower, and educate.”
His experience – at the first and largest academic medical center to provide this technology across the entire hospital system – offers the first insight into the demands that such a process shift requires, he said. The researchers ran a 90-day pilot program giving tablets to 179 patients; subsequently, the health system committed to providing tablets for accessing inpatient portals in all seven of its hospitals. “Adopting this technology is not easy, and we continue to explore how we can use it more effectively. Our hope is that our experience can make the journey of others easier.”
Providing the technology is a necessary but insufficient component of implementation, he added. “This is not like the movie ‘Field of Dreams’ – if you build it they will come. It requires leaders to see the value proposition, champions throughout the organization to make a reality where the technology matters to the provision of care, and clinicians to see the tool as a means to a greater good.”
In hospitals, nursing staff and hospitalists are likely to be most impacted by the addition of these tools. “They will require choices – for example who will respond on what timeline to patient communication when using these tools – which requires collaboration across the institution.”
Reference
1. Huerta T, McAlearney AS, Rizer MK. “Introducing a Patient Portal and Electronic Tablets to Inpatient Care.” Ann Intern Med. 2017;167(11):816-7.
Hospitalists see patients at their most fragile – and, as a result, they have a unique opportunity to affect their health going forward.
“These moments can transform the way patients see their health and their behaviors, and any opportunity to position patients as empowered to influence their experience is one that can not be squandered,” said Timothy Huerta, PhD, MS, lead author on a study of patient portals and tablets during inpatient care.1 “In that context, hospitals have the opportunity to set expectations for engagement that can be influenced by technology. Patient portals, positioned within the inpatient setting, offer a platform to engage, empower, and educate.”
His experience – at the first and largest academic medical center to provide this technology across the entire hospital system – offers the first insight into the demands that such a process shift requires, he said. The researchers ran a 90-day pilot program giving tablets to 179 patients; subsequently, the health system committed to providing tablets for accessing inpatient portals in all seven of its hospitals. “Adopting this technology is not easy, and we continue to explore how we can use it more effectively. Our hope is that our experience can make the journey of others easier.”
Providing the technology is a necessary but insufficient component of implementation, he added. “This is not like the movie ‘Field of Dreams’ – if you build it they will come. It requires leaders to see the value proposition, champions throughout the organization to make a reality where the technology matters to the provision of care, and clinicians to see the tool as a means to a greater good.”
In hospitals, nursing staff and hospitalists are likely to be most impacted by the addition of these tools. “They will require choices – for example who will respond on what timeline to patient communication when using these tools – which requires collaboration across the institution.”
Reference
1. Huerta T, McAlearney AS, Rizer MK. “Introducing a Patient Portal and Electronic Tablets to Inpatient Care.” Ann Intern Med. 2017;167(11):816-7.
Novel blood test that predicts gestational age, fetal development, could improve prenatal care
Researchers have identified cell-free RNA transcripts obtained from a noninvasive blood test during pregnancy that can predict risk of preterm birth in addition to predicting gestational age with an accuracy similar to ultrasound, which may soon pave the way for a low-cost alternative to ultrasound for prenatal care in developing areas, according to recent results from two pilot studies.
“Our results are thus generally comparable to ultrasound measurements, can be performed throughout pregnancy, and do not require a priori physiological knowledge such as the woman’s last menstrual period,” Stephen Quake, PhD, of Stanford (Calif.) University, and his colleagues wrote in Science.
Dr. Quake and his colleagues recruited 31 women from Denmark who provided weekly blood samples (521 samples) during pregnancy up until they delivered full-term. After analyzing the cell-free RNA (cfRNA) genes, researchers found cfRNA placenta, fetal, and immune genes were highly correlated with one another. They created a random forest model based on nine cfRNA genes (CGA, CAPN6, CGB, ALPP, CSHL1, PLAC4, PSG7, PAPPA, and LGALS14) that corresponded with the placenta. They estimated that those nine genes would predict gestational age and tested the model using 306 samples from 21 women in a training cohort and validated the test using 215 samples from 10 women in a validation cohort. The blood test predicted gestational age within 14 days of delivery in 32% of cases at the second trimester (T2), 23% at the third trimester (3T), and 45% at T2 and T3, compared with a 48% with ultrasound.
In a second pilot study, Dr. Quake and his colleagues created a polymerase chain reaction panel for 38 genes identified from sequencing RNA from patients in Pennsylvania, Alabama, and Denmark, with full-term and preterm deliveries up to 2 months before labor to determine “cfRNA transcripts that might be able to discriminate a spontaneous preterm delivery from a full-term delivery.” The top seven cfRNA transcripts (CLCN3, DAPP1, PPBP, MAP3K7CL, MOB1B, RAB27B, and RGS18), when grouped in “unique combinations” of three genes, predicted 75% of preterm samples and misclassified 1 of 26 samples (4%) from Denmark and Pennsylvania; in a validated cohort of Alabama patients, the test predicted 4 of 5 preterm samples (80%) and misclassified 3 of 18 full-term samples (17%).
“These cfRNA [polymerase chain reaction]–based tests have two advantages over alternatives: broader applicability and lower cost,” Dr. Quake and his colleagues wrote. “They can be applied across the globe as a complement to or substitute for ultrasound, which can be expensive and inaccurate during the second and third trimesters.”
The authors noted a larger sample size and blinded testing on a broader patient population is needed before clinics can apply this blood test in a diagnostic or screening tool for widespread use.
Dr. Quake and three other authors have a patent application submitted by the Chan Zuckerberg Biohub relating to “noninvasive estimates of gestational age, delivery, and preterm birth.” The other authors have no relevant financial disclosures.
SOURCE: Ngo TTM et al. Science. 2018 Jun 7. doi: 10.1126/science.aar3819.
Researchers have identified cell-free RNA transcripts obtained from a noninvasive blood test during pregnancy that can predict risk of preterm birth in addition to predicting gestational age with an accuracy similar to ultrasound, which may soon pave the way for a low-cost alternative to ultrasound for prenatal care in developing areas, according to recent results from two pilot studies.
“Our results are thus generally comparable to ultrasound measurements, can be performed throughout pregnancy, and do not require a priori physiological knowledge such as the woman’s last menstrual period,” Stephen Quake, PhD, of Stanford (Calif.) University, and his colleagues wrote in Science.
Dr. Quake and his colleagues recruited 31 women from Denmark who provided weekly blood samples (521 samples) during pregnancy up until they delivered full-term. After analyzing the cell-free RNA (cfRNA) genes, researchers found cfRNA placenta, fetal, and immune genes were highly correlated with one another. They created a random forest model based on nine cfRNA genes (CGA, CAPN6, CGB, ALPP, CSHL1, PLAC4, PSG7, PAPPA, and LGALS14) that corresponded with the placenta. They estimated that those nine genes would predict gestational age and tested the model using 306 samples from 21 women in a training cohort and validated the test using 215 samples from 10 women in a validation cohort. The blood test predicted gestational age within 14 days of delivery in 32% of cases at the second trimester (T2), 23% at the third trimester (3T), and 45% at T2 and T3, compared with a 48% with ultrasound.
In a second pilot study, Dr. Quake and his colleagues created a polymerase chain reaction panel for 38 genes identified from sequencing RNA from patients in Pennsylvania, Alabama, and Denmark, with full-term and preterm deliveries up to 2 months before labor to determine “cfRNA transcripts that might be able to discriminate a spontaneous preterm delivery from a full-term delivery.” The top seven cfRNA transcripts (CLCN3, DAPP1, PPBP, MAP3K7CL, MOB1B, RAB27B, and RGS18), when grouped in “unique combinations” of three genes, predicted 75% of preterm samples and misclassified 1 of 26 samples (4%) from Denmark and Pennsylvania; in a validated cohort of Alabama patients, the test predicted 4 of 5 preterm samples (80%) and misclassified 3 of 18 full-term samples (17%).
“These cfRNA [polymerase chain reaction]–based tests have two advantages over alternatives: broader applicability and lower cost,” Dr. Quake and his colleagues wrote. “They can be applied across the globe as a complement to or substitute for ultrasound, which can be expensive and inaccurate during the second and third trimesters.”
The authors noted a larger sample size and blinded testing on a broader patient population is needed before clinics can apply this blood test in a diagnostic or screening tool for widespread use.
Dr. Quake and three other authors have a patent application submitted by the Chan Zuckerberg Biohub relating to “noninvasive estimates of gestational age, delivery, and preterm birth.” The other authors have no relevant financial disclosures.
SOURCE: Ngo TTM et al. Science. 2018 Jun 7. doi: 10.1126/science.aar3819.
Researchers have identified cell-free RNA transcripts obtained from a noninvasive blood test during pregnancy that can predict risk of preterm birth in addition to predicting gestational age with an accuracy similar to ultrasound, which may soon pave the way for a low-cost alternative to ultrasound for prenatal care in developing areas, according to recent results from two pilot studies.
“Our results are thus generally comparable to ultrasound measurements, can be performed throughout pregnancy, and do not require a priori physiological knowledge such as the woman’s last menstrual period,” Stephen Quake, PhD, of Stanford (Calif.) University, and his colleagues wrote in Science.
Dr. Quake and his colleagues recruited 31 women from Denmark who provided weekly blood samples (521 samples) during pregnancy up until they delivered full-term. After analyzing the cell-free RNA (cfRNA) genes, researchers found cfRNA placenta, fetal, and immune genes were highly correlated with one another. They created a random forest model based on nine cfRNA genes (CGA, CAPN6, CGB, ALPP, CSHL1, PLAC4, PSG7, PAPPA, and LGALS14) that corresponded with the placenta. They estimated that those nine genes would predict gestational age and tested the model using 306 samples from 21 women in a training cohort and validated the test using 215 samples from 10 women in a validation cohort. The blood test predicted gestational age within 14 days of delivery in 32% of cases at the second trimester (T2), 23% at the third trimester (3T), and 45% at T2 and T3, compared with a 48% with ultrasound.
In a second pilot study, Dr. Quake and his colleagues created a polymerase chain reaction panel for 38 genes identified from sequencing RNA from patients in Pennsylvania, Alabama, and Denmark, with full-term and preterm deliveries up to 2 months before labor to determine “cfRNA transcripts that might be able to discriminate a spontaneous preterm delivery from a full-term delivery.” The top seven cfRNA transcripts (CLCN3, DAPP1, PPBP, MAP3K7CL, MOB1B, RAB27B, and RGS18), when grouped in “unique combinations” of three genes, predicted 75% of preterm samples and misclassified 1 of 26 samples (4%) from Denmark and Pennsylvania; in a validated cohort of Alabama patients, the test predicted 4 of 5 preterm samples (80%) and misclassified 3 of 18 full-term samples (17%).
“These cfRNA [polymerase chain reaction]–based tests have two advantages over alternatives: broader applicability and lower cost,” Dr. Quake and his colleagues wrote. “They can be applied across the globe as a complement to or substitute for ultrasound, which can be expensive and inaccurate during the second and third trimesters.”
The authors noted a larger sample size and blinded testing on a broader patient population is needed before clinics can apply this blood test in a diagnostic or screening tool for widespread use.
Dr. Quake and three other authors have a patent application submitted by the Chan Zuckerberg Biohub relating to “noninvasive estimates of gestational age, delivery, and preterm birth.” The other authors have no relevant financial disclosures.
SOURCE: Ngo TTM et al. Science. 2018 Jun 7. doi: 10.1126/science.aar3819.
FROM SCIENCE
Key clinical point: Cell-free RNA transcripts identified from a single blood sample can reliably predict gestational age similar to ultrasound and can identify risk of preterm birth.
Major finding: Nine cell-free RNA transcripts predicted gestational age at an accuracy similar to ultrasound, while seven cell-free RNA transcripts predicted an increased risk of preterm birth until 2 months prior to delivery.
Study details: A pilot study of 31 pregnant women and a related pilot study of 38 women with full-term or preterm deliveries.
Disclosures: Dr. Quake and three other authors have a patent application submitted by the Chan Zuckerberg Biohub relating to “noninvasive estimates of gestational age, delivery, and preterm birth.” The other authors have no relevant financial disclosures.
Source: Ngo TTM et al. Science. 2018 Jun 7. doi: 10.1126/science.aar3819.
LLDAS shows potential as routine lupus treatment target
AMSTERDAM – The Lupus Low Disease Activity State measure of treatment response offers clinicians an attainable target for patients with systemic lupus erythematosus that correlates with a substantially reduced rate of organ damage, based on a retrospective assessment of data collected from more than 2,000 lupus patients at a single U.S. center.
The analysis showed that when patients with systemic lupus erythematosus (SLE) met the Lupus Low Disease Activity State (LLDAS) criteria at least half the time while on treatment, their overall rate of organ damage was reduced by 52%, compared with patients who never achieved LLDAS, Michelle A. Petri, MD, said at the European Congress of Rheumatology.
“LLDAS is something that anyone can use in practice,” and has the advantage of including a low steroid dose – no more than 7.5 mg prednisolone/day or an equivalent steroid – as one of its criteria, “a major bad actor” for SLE patients, Dr. Petri said in an interview. LLDAS “is absolutely ready for routine use,” although until now few clinicians have used it to monitor SLE patients, she noted.
“The LLDAS can be a useful target,” commented Ian N. Bruce, MD, professor of rheumatology at the University of Manchester (England), adding that the steroid dosage an SLE patient receives “is an important parameter to measure when assessing an SLE patient.
“It’s not far from being ready for routine use, but I’d like to see more evidence” that it’s a meaningful measure of an SLE patient’s disease status, he said in an interview.
To examine the clinical relevance of the LLDAS criteria, a five-point assessment for SLE first introduced in a 2016 report (Ann Rheum Dis. 2016 Sept;75[9]:1615-21), Dr. Petri and her associates applied it retrospectively to their records for 2,026 SLE patients in a Johns Hopkins registry. Clinicians at Johns Hopkins routinely assessed their SLE patients every 3 months and followed the patients for a median of about 10 years, and so had data from more than 81,000 patient encounters. The researchers used the longitudinal follow-up records to calculate an area under the curve for each patient that tracked their LLDAS state over time. This showed a clear dose-response relationship: The more time an SLE patient spent in LLDAS, the less organ damage they had. Patients who remained in LLDAS at least 75% of the time had a 60% reduction in cumulative organ damage, compared with patients who never achieved LLDAS, Dr. Petri said. The analysis also showed that LLDAS was substantially easier for patients to achieve than the Definitions of Remission in SLE (Ann Rheum Dis. 2017 March;76[3]:554-61). The Johns Hopkins cohort met the LLDAS definition about three times more often than they met the Definitions of Remission in SLE criteria, Dr. Petri said.
The new analysis also showed that LLDAS was especially effective in correlating with statistically significant reductions in future strokes, MI, and end-stage renal disease, though it did not significantly correlate with subsequent reductions in the incidence of cognitive impairment, deep vein thrombosis, malignancy, pulmonary fibrosis, pulmonary hypertension, or cataract development. But the strong correlation of time in LLDAS and the future rate of stroke, MI, or end-stage renal disease was very meaningful because those are the most important types of damage associated with SLE, Dr. Petri said. “LLDAS is a good treatment target as a surrogate” for future risk of SLE complications.
The study had no commercial funding, and Dr. Petri had no disclosures to report. Dr. Bruce has been a consultant to and speaker for GlaxoSmithKline, MedImmune, Pfizer, Roche, and UCB, and he has received research support from Genzyme, GlaxoSmithKline, Human Genome Sciences, Roche, and UCB.
SOURCE: Petri MA et al. Ann Rheum Dis. 2018;77(Suppl 2):111. Abstract OP0122.
AMSTERDAM – The Lupus Low Disease Activity State measure of treatment response offers clinicians an attainable target for patients with systemic lupus erythematosus that correlates with a substantially reduced rate of organ damage, based on a retrospective assessment of data collected from more than 2,000 lupus patients at a single U.S. center.
The analysis showed that when patients with systemic lupus erythematosus (SLE) met the Lupus Low Disease Activity State (LLDAS) criteria at least half the time while on treatment, their overall rate of organ damage was reduced by 52%, compared with patients who never achieved LLDAS, Michelle A. Petri, MD, said at the European Congress of Rheumatology.
“LLDAS is something that anyone can use in practice,” and has the advantage of including a low steroid dose – no more than 7.5 mg prednisolone/day or an equivalent steroid – as one of its criteria, “a major bad actor” for SLE patients, Dr. Petri said in an interview. LLDAS “is absolutely ready for routine use,” although until now few clinicians have used it to monitor SLE patients, she noted.
“The LLDAS can be a useful target,” commented Ian N. Bruce, MD, professor of rheumatology at the University of Manchester (England), adding that the steroid dosage an SLE patient receives “is an important parameter to measure when assessing an SLE patient.
“It’s not far from being ready for routine use, but I’d like to see more evidence” that it’s a meaningful measure of an SLE patient’s disease status, he said in an interview.
To examine the clinical relevance of the LLDAS criteria, a five-point assessment for SLE first introduced in a 2016 report (Ann Rheum Dis. 2016 Sept;75[9]:1615-21), Dr. Petri and her associates applied it retrospectively to their records for 2,026 SLE patients in a Johns Hopkins registry. Clinicians at Johns Hopkins routinely assessed their SLE patients every 3 months and followed the patients for a median of about 10 years, and so had data from more than 81,000 patient encounters. The researchers used the longitudinal follow-up records to calculate an area under the curve for each patient that tracked their LLDAS state over time. This showed a clear dose-response relationship: The more time an SLE patient spent in LLDAS, the less organ damage they had. Patients who remained in LLDAS at least 75% of the time had a 60% reduction in cumulative organ damage, compared with patients who never achieved LLDAS, Dr. Petri said. The analysis also showed that LLDAS was substantially easier for patients to achieve than the Definitions of Remission in SLE (Ann Rheum Dis. 2017 March;76[3]:554-61). The Johns Hopkins cohort met the LLDAS definition about three times more often than they met the Definitions of Remission in SLE criteria, Dr. Petri said.
The new analysis also showed that LLDAS was especially effective in correlating with statistically significant reductions in future strokes, MI, and end-stage renal disease, though it did not significantly correlate with subsequent reductions in the incidence of cognitive impairment, deep vein thrombosis, malignancy, pulmonary fibrosis, pulmonary hypertension, or cataract development. But the strong correlation of time in LLDAS and the future rate of stroke, MI, or end-stage renal disease was very meaningful because those are the most important types of damage associated with SLE, Dr. Petri said. “LLDAS is a good treatment target as a surrogate” for future risk of SLE complications.
The study had no commercial funding, and Dr. Petri had no disclosures to report. Dr. Bruce has been a consultant to and speaker for GlaxoSmithKline, MedImmune, Pfizer, Roche, and UCB, and he has received research support from Genzyme, GlaxoSmithKline, Human Genome Sciences, Roche, and UCB.
SOURCE: Petri MA et al. Ann Rheum Dis. 2018;77(Suppl 2):111. Abstract OP0122.
AMSTERDAM – The Lupus Low Disease Activity State measure of treatment response offers clinicians an attainable target for patients with systemic lupus erythematosus that correlates with a substantially reduced rate of organ damage, based on a retrospective assessment of data collected from more than 2,000 lupus patients at a single U.S. center.
The analysis showed that when patients with systemic lupus erythematosus (SLE) met the Lupus Low Disease Activity State (LLDAS) criteria at least half the time while on treatment, their overall rate of organ damage was reduced by 52%, compared with patients who never achieved LLDAS, Michelle A. Petri, MD, said at the European Congress of Rheumatology.
“LLDAS is something that anyone can use in practice,” and has the advantage of including a low steroid dose – no more than 7.5 mg prednisolone/day or an equivalent steroid – as one of its criteria, “a major bad actor” for SLE patients, Dr. Petri said in an interview. LLDAS “is absolutely ready for routine use,” although until now few clinicians have used it to monitor SLE patients, she noted.
“The LLDAS can be a useful target,” commented Ian N. Bruce, MD, professor of rheumatology at the University of Manchester (England), adding that the steroid dosage an SLE patient receives “is an important parameter to measure when assessing an SLE patient.
“It’s not far from being ready for routine use, but I’d like to see more evidence” that it’s a meaningful measure of an SLE patient’s disease status, he said in an interview.
To examine the clinical relevance of the LLDAS criteria, a five-point assessment for SLE first introduced in a 2016 report (Ann Rheum Dis. 2016 Sept;75[9]:1615-21), Dr. Petri and her associates applied it retrospectively to their records for 2,026 SLE patients in a Johns Hopkins registry. Clinicians at Johns Hopkins routinely assessed their SLE patients every 3 months and followed the patients for a median of about 10 years, and so had data from more than 81,000 patient encounters. The researchers used the longitudinal follow-up records to calculate an area under the curve for each patient that tracked their LLDAS state over time. This showed a clear dose-response relationship: The more time an SLE patient spent in LLDAS, the less organ damage they had. Patients who remained in LLDAS at least 75% of the time had a 60% reduction in cumulative organ damage, compared with patients who never achieved LLDAS, Dr. Petri said. The analysis also showed that LLDAS was substantially easier for patients to achieve than the Definitions of Remission in SLE (Ann Rheum Dis. 2017 March;76[3]:554-61). The Johns Hopkins cohort met the LLDAS definition about three times more often than they met the Definitions of Remission in SLE criteria, Dr. Petri said.
The new analysis also showed that LLDAS was especially effective in correlating with statistically significant reductions in future strokes, MI, and end-stage renal disease, though it did not significantly correlate with subsequent reductions in the incidence of cognitive impairment, deep vein thrombosis, malignancy, pulmonary fibrosis, pulmonary hypertension, or cataract development. But the strong correlation of time in LLDAS and the future rate of stroke, MI, or end-stage renal disease was very meaningful because those are the most important types of damage associated with SLE, Dr. Petri said. “LLDAS is a good treatment target as a surrogate” for future risk of SLE complications.
The study had no commercial funding, and Dr. Petri had no disclosures to report. Dr. Bruce has been a consultant to and speaker for GlaxoSmithKline, MedImmune, Pfizer, Roche, and UCB, and he has received research support from Genzyme, GlaxoSmithKline, Human Genome Sciences, Roche, and UCB.
SOURCE: Petri MA et al. Ann Rheum Dis. 2018;77(Suppl 2):111. Abstract OP0122.
REPORTING FROM THE EULAR 2018 CONGRESS
Key clinical point: The Lupus Low Disease Activity State is a good treatment target for systemic lupus erythematosus patients.
Major finding: Patients who achieved LLDAS at least half the time had 52% less organ damage than patients who never achieved LLDAS.
Study details: A review of case records from 2,026 SLE patients followed regularly at one U.S. center.
Disclosures: The study had no commercial funding, and Dr. Petri had no disclosures to report. Dr. Bruce has been a consultant to and speaker for GlaxoSmithKline, MedImmune, Pfizer, Roche, and UCB, and he has received research support from Genzyme, GlaxoSmithKline, Human Genome Sciences, Roche, and UCB.
Source: Petri MA et al. Ann Rheum Dis. 2018;77(Suppl 2):111. Abstract OP0122.
Painful Nonhealing Vulvar and Perianal Erosions
The Diagnosis: Cutaneous Crohn Disease
A punch biopsy of the vulvar skin revealed epidermal hyperplasia with moderate spongiosis and exocytosis of lymphocytes and neutrophils in the epidermis. A brisk mixed inflammatory infiltrate of epithelioid histiocytes, multinucleate foreign body-type giant cells, lymphocytes, plasma cells, neutrophils, and eosinophils in a granulomatous pattern also were present in the dermis (Figure). Periodic acid-Schiff and acid-fast bacillus stains were negative. Given the history of Crohn disease (CD) and the characteristic dermal noncaseating granulomas on histology, the patient was diagnosed with cutaneous CD.
Although the patient was offered a topical corticosteroid, she deferred topical therapy. Given the lack of response to adalimumab, the gastroenterology department switched the patient to a treatment of infliximab 5 mg/kg every 8 weeks. Azathioprine was discontinued and the patient was switched to intramuscular methotrexate 25 mg/mL weekly. Slow reepithelialization of the vulvar and perianal erosions occurred on this regimen.
Although CD has numerous cutaneous features, cutaneous CD, also known as metastatic CD, is the rarest cutaneous manifestation of CD.1 This disease process is characterized by noncaseating granulomatous cutaneous lesions that are not contiguous with the affected gastrointestinal tract.2 The pathogenesis of cutaneous CD is unknown. Young adults tend to be more predisposed to developing cutaneous CD, likely due to the age distribution of CD.3
Cutaneous CD commonly presents in patients with a well-established history of gastrointestinal CD but occasionally can be the presenting sign of CD.1 The most common sites of involvement are the legs, vulva, penis, trunk, face, and intertriginous areas. Cutaneous CD findings can be divided into 2 subgroups: genital and nongenital lesions. Genital findings involve ulceration, erythema, edema, and fissuring of the vulva, labia, clitoris, scrotum, penis, and perineum. Nongenital cutaneous manifestations include ulcers; erythematous papules, plaques, and nodules; abscesslike lesions; and lichenoid papules.4,5 The severity of cutaneous lesions does not correlate to the severity of gastrointestinal disease; however, colon involvement is more common in patients with cutaneous CD.6
Histologically, cutaneous CD presents as noncaseating granulomatous inflammation in the papillary and reticular dermis. These granulomas consist of epithelioid histiocytes and multinucleated giant cells with a lymphocytic infiltrate.5
Given the rarity of cutaneous CD, treatment approach is based on anecdotal evidence from case reports and case series. For a single lesion or localized disease, topical superpotent or intralesional steroids are recommended for initial therapy.3 Oral metronidazole also is an effective treatment and can be combined with topical or intralesional steroids.7 For disseminated disease, systemic corticosteroids have shown efficacy.3 Other reported treatment options include oral corticosteroids, sulfasalazine, azathioprine, 6-mercaptopurine, infliximab, and adalimumab. If monotherapy fails, combination therapy may be needed. Surgical debridement may be attempted if medical therapy fails but is complicated by wound dehiscence and disease recurrence.3
Although genital ulcers can be a presentation of Behçet disease and genital herpes infection, genital nodules and plaques are not typical for these 2 diseases. Also, the patient did not have oral ulcers, which is a common feature of Behçet disease. Genital sarcoidosis is extremely rare, and cutaneous CD was more likely given the patient's medical history. Finally, Jacquet dermatitis is more common in children, and patients with this condition typically have history of fecal and urinary incontinence.
- Teixeira M, Machado S, Lago P, et al. Cutaneous Crohn's disease. Int J Dermatol. 2006;45:1074-1076.
- Stingeni L, Neve D, Bassotti G, et al. Cutaneous Crohn's disease successfully treated with adalimumab [published online Sep 15, 2015]. J Eur Acad Dermatol Venerol. 2016;30:E72-E74.
- Kurtzman DJ, Jones T, Fangru L, et al. Metastatic Crohn's disease: a review and approach to therapy. J Am Acad Dermatol. 2014;71:804-813.
- Hagen JW, Swoger JM, Grandinetti LM. Cutaneous manifestations of Crohn disease. Dermatol Clin. 2015;33:417-431.
- Palamaras I, El-Jabbour J, Pietropaolo N, et al. Metastatic Crohn's disease: a review [published online June 19, 2008]. J Eur Acad Dermatol Venereol. 2008;22:1033-1043.
- Thrash B, Patel M, Shah KR, et al. Cutaneous manifestations of gastrointestinal disease, part II. J Am Acad Dermatol. 2013;68:211.e1-211.e33.
- Abide JM. Metastatic Crohn disease: clearance with metronidazole. J Am Acad Dermatol. 2011;64:448-449.
The Diagnosis: Cutaneous Crohn Disease
A punch biopsy of the vulvar skin revealed epidermal hyperplasia with moderate spongiosis and exocytosis of lymphocytes and neutrophils in the epidermis. A brisk mixed inflammatory infiltrate of epithelioid histiocytes, multinucleate foreign body-type giant cells, lymphocytes, plasma cells, neutrophils, and eosinophils in a granulomatous pattern also were present in the dermis (Figure). Periodic acid-Schiff and acid-fast bacillus stains were negative. Given the history of Crohn disease (CD) and the characteristic dermal noncaseating granulomas on histology, the patient was diagnosed with cutaneous CD.
Although the patient was offered a topical corticosteroid, she deferred topical therapy. Given the lack of response to adalimumab, the gastroenterology department switched the patient to a treatment of infliximab 5 mg/kg every 8 weeks. Azathioprine was discontinued and the patient was switched to intramuscular methotrexate 25 mg/mL weekly. Slow reepithelialization of the vulvar and perianal erosions occurred on this regimen.
Although CD has numerous cutaneous features, cutaneous CD, also known as metastatic CD, is the rarest cutaneous manifestation of CD.1 This disease process is characterized by noncaseating granulomatous cutaneous lesions that are not contiguous with the affected gastrointestinal tract.2 The pathogenesis of cutaneous CD is unknown. Young adults tend to be more predisposed to developing cutaneous CD, likely due to the age distribution of CD.3
Cutaneous CD commonly presents in patients with a well-established history of gastrointestinal CD but occasionally can be the presenting sign of CD.1 The most common sites of involvement are the legs, vulva, penis, trunk, face, and intertriginous areas. Cutaneous CD findings can be divided into 2 subgroups: genital and nongenital lesions. Genital findings involve ulceration, erythema, edema, and fissuring of the vulva, labia, clitoris, scrotum, penis, and perineum. Nongenital cutaneous manifestations include ulcers; erythematous papules, plaques, and nodules; abscesslike lesions; and lichenoid papules.4,5 The severity of cutaneous lesions does not correlate to the severity of gastrointestinal disease; however, colon involvement is more common in patients with cutaneous CD.6
Histologically, cutaneous CD presents as noncaseating granulomatous inflammation in the papillary and reticular dermis. These granulomas consist of epithelioid histiocytes and multinucleated giant cells with a lymphocytic infiltrate.5
Given the rarity of cutaneous CD, treatment approach is based on anecdotal evidence from case reports and case series. For a single lesion or localized disease, topical superpotent or intralesional steroids are recommended for initial therapy.3 Oral metronidazole also is an effective treatment and can be combined with topical or intralesional steroids.7 For disseminated disease, systemic corticosteroids have shown efficacy.3 Other reported treatment options include oral corticosteroids, sulfasalazine, azathioprine, 6-mercaptopurine, infliximab, and adalimumab. If monotherapy fails, combination therapy may be needed. Surgical debridement may be attempted if medical therapy fails but is complicated by wound dehiscence and disease recurrence.3
Although genital ulcers can be a presentation of Behçet disease and genital herpes infection, genital nodules and plaques are not typical for these 2 diseases. Also, the patient did not have oral ulcers, which is a common feature of Behçet disease. Genital sarcoidosis is extremely rare, and cutaneous CD was more likely given the patient's medical history. Finally, Jacquet dermatitis is more common in children, and patients with this condition typically have history of fecal and urinary incontinence.
The Diagnosis: Cutaneous Crohn Disease
A punch biopsy of the vulvar skin revealed epidermal hyperplasia with moderate spongiosis and exocytosis of lymphocytes and neutrophils in the epidermis. A brisk mixed inflammatory infiltrate of epithelioid histiocytes, multinucleate foreign body-type giant cells, lymphocytes, plasma cells, neutrophils, and eosinophils in a granulomatous pattern also were present in the dermis (Figure). Periodic acid-Schiff and acid-fast bacillus stains were negative. Given the history of Crohn disease (CD) and the characteristic dermal noncaseating granulomas on histology, the patient was diagnosed with cutaneous CD.
Although the patient was offered a topical corticosteroid, she deferred topical therapy. Given the lack of response to adalimumab, the gastroenterology department switched the patient to a treatment of infliximab 5 mg/kg every 8 weeks. Azathioprine was discontinued and the patient was switched to intramuscular methotrexate 25 mg/mL weekly. Slow reepithelialization of the vulvar and perianal erosions occurred on this regimen.
Although CD has numerous cutaneous features, cutaneous CD, also known as metastatic CD, is the rarest cutaneous manifestation of CD.1 This disease process is characterized by noncaseating granulomatous cutaneous lesions that are not contiguous with the affected gastrointestinal tract.2 The pathogenesis of cutaneous CD is unknown. Young adults tend to be more predisposed to developing cutaneous CD, likely due to the age distribution of CD.3
Cutaneous CD commonly presents in patients with a well-established history of gastrointestinal CD but occasionally can be the presenting sign of CD.1 The most common sites of involvement are the legs, vulva, penis, trunk, face, and intertriginous areas. Cutaneous CD findings can be divided into 2 subgroups: genital and nongenital lesions. Genital findings involve ulceration, erythema, edema, and fissuring of the vulva, labia, clitoris, scrotum, penis, and perineum. Nongenital cutaneous manifestations include ulcers; erythematous papules, plaques, and nodules; abscesslike lesions; and lichenoid papules.4,5 The severity of cutaneous lesions does not correlate to the severity of gastrointestinal disease; however, colon involvement is more common in patients with cutaneous CD.6
Histologically, cutaneous CD presents as noncaseating granulomatous inflammation in the papillary and reticular dermis. These granulomas consist of epithelioid histiocytes and multinucleated giant cells with a lymphocytic infiltrate.5
Given the rarity of cutaneous CD, treatment approach is based on anecdotal evidence from case reports and case series. For a single lesion or localized disease, topical superpotent or intralesional steroids are recommended for initial therapy.3 Oral metronidazole also is an effective treatment and can be combined with topical or intralesional steroids.7 For disseminated disease, systemic corticosteroids have shown efficacy.3 Other reported treatment options include oral corticosteroids, sulfasalazine, azathioprine, 6-mercaptopurine, infliximab, and adalimumab. If monotherapy fails, combination therapy may be needed. Surgical debridement may be attempted if medical therapy fails but is complicated by wound dehiscence and disease recurrence.3
Although genital ulcers can be a presentation of Behçet disease and genital herpes infection, genital nodules and plaques are not typical for these 2 diseases. Also, the patient did not have oral ulcers, which is a common feature of Behçet disease. Genital sarcoidosis is extremely rare, and cutaneous CD was more likely given the patient's medical history. Finally, Jacquet dermatitis is more common in children, and patients with this condition typically have history of fecal and urinary incontinence.
- Teixeira M, Machado S, Lago P, et al. Cutaneous Crohn's disease. Int J Dermatol. 2006;45:1074-1076.
- Stingeni L, Neve D, Bassotti G, et al. Cutaneous Crohn's disease successfully treated with adalimumab [published online Sep 15, 2015]. J Eur Acad Dermatol Venerol. 2016;30:E72-E74.
- Kurtzman DJ, Jones T, Fangru L, et al. Metastatic Crohn's disease: a review and approach to therapy. J Am Acad Dermatol. 2014;71:804-813.
- Hagen JW, Swoger JM, Grandinetti LM. Cutaneous manifestations of Crohn disease. Dermatol Clin. 2015;33:417-431.
- Palamaras I, El-Jabbour J, Pietropaolo N, et al. Metastatic Crohn's disease: a review [published online June 19, 2008]. J Eur Acad Dermatol Venereol. 2008;22:1033-1043.
- Thrash B, Patel M, Shah KR, et al. Cutaneous manifestations of gastrointestinal disease, part II. J Am Acad Dermatol. 2013;68:211.e1-211.e33.
- Abide JM. Metastatic Crohn disease: clearance with metronidazole. J Am Acad Dermatol. 2011;64:448-449.
- Teixeira M, Machado S, Lago P, et al. Cutaneous Crohn's disease. Int J Dermatol. 2006;45:1074-1076.
- Stingeni L, Neve D, Bassotti G, et al. Cutaneous Crohn's disease successfully treated with adalimumab [published online Sep 15, 2015]. J Eur Acad Dermatol Venerol. 2016;30:E72-E74.
- Kurtzman DJ, Jones T, Fangru L, et al. Metastatic Crohn's disease: a review and approach to therapy. J Am Acad Dermatol. 2014;71:804-813.
- Hagen JW, Swoger JM, Grandinetti LM. Cutaneous manifestations of Crohn disease. Dermatol Clin. 2015;33:417-431.
- Palamaras I, El-Jabbour J, Pietropaolo N, et al. Metastatic Crohn's disease: a review [published online June 19, 2008]. J Eur Acad Dermatol Venereol. 2008;22:1033-1043.
- Thrash B, Patel M, Shah KR, et al. Cutaneous manifestations of gastrointestinal disease, part II. J Am Acad Dermatol. 2013;68:211.e1-211.e33.
- Abide JM. Metastatic Crohn disease: clearance with metronidazole. J Am Acad Dermatol. 2011;64:448-449.
A 38-year-old woman with a history of Crohn disease presented with painful nonhealing vulvar and perianal erosions of 6 months' duration. The erosions developed 4 months after discontinuing adalimumab for a planned surgery. During this time, the patient also had an exacerbation of Crohn colitis and developed an anal fistula. Prior to this break in adalimumab, the patient's Crohn disease was well controlled on adalimumab 40 mg every 2 weeks, azathioprine 100 mg daily, and mesalamine 4.8 g daily. Despite restarting adalimumab and therapy with multiple antibiotics (ie, metronidazole, ciprofloxacin), the erosions persisted. On physical examination erythematous plaques and nodules were present at the vulvar (top) and perianal (bottom) skin. In addition, well-demarcated erosions measuring 20 mm and 80 mm were present on the vulvar and perianal skin, respectively. Human immunodeficiency virus screening and rapid plasma reagin were negative.
Polypoid Melanoma: An Aggressive Variant of Nodular Melanoma
To the Editor:
An 81-year-old man presented with a nodular polypoid lesion that developed on a flat lesion on the back of 2 years’ duration. The lesion grew progressively over the course of 3 months prior to presentation. The patient had a history of melanoma in situ on the forehead that was treated with conventional surgery with clear surgical margins 6 years prior to the current presentation.
On physical examination the patient had a 4×2-cm ulcerated polypoid lesion on the back. The lesion was pink with a pigmented base. Additionally, 2 pink papules with superficial telangiectases were observed around the main lesion (Figure 1).
The gross section showed an exophytic tumor largely growing above the skin surface (Figure 2). Histopathologic analysis revealed an ulcerated lesion consisting of confluent nest and sheets of epithelioid and spindle atypical cells with numerous mitotic figures and necrotic foci (Figure 3). The thickness of the lesion was 2200 µm, and the mitotic count was 28 mitoses/mm2. There also was peritumoral vascular invasion and satellite metastasis within the perilesional hypodermis measuring 0.4 mm. Immunohistochemistry staining for S-100, human melanoma black 45 (HMB-45)(Figure 4), and Melan-A was positive in neoplastic cells.
The dissemination study revealed multiple mediastinal and axillary lymphadenopathies and lesions with metastatic appearance in the brain, liver, pancreas, and muscle, together with peritoneal carcinomatosis. The patient was lost to follow-up and did not follow coadjuvant therapy with interferon alfa.
Polypoid melanoma initially was described as a type of melanoma characterized by an exophytic growth in which most of the tumor is located on the cutaneous surface, together with ulceration.1 It usually occurs in patients aged 20 to 39 years,2 and the reported incidence ranges from 1.9% to 43.3%.1 It more commonly affects mucosae, including the upper respiratory tract, esophagus, and vagina. Polypoid melanoma has a rapid progression and a poor prognosis.3 Polypoid melanoma involving the skin primarily affects the back and has a 5-year survival rate of 32% to 42%.4 Poor prognosis has been attributed to the high risk for vascular embolization under the lesion.5 Histologically, there is marked cell atypia with nuclear and cellular pleomorphism and a high mitotic count. The tumor rarely involves the reticular dermis.1,2
Polypoid melanomas are rare; however, reported frequency rates cover a wide range. These frequency rates may be due to the definition of polypoid melanoma used by the pathologist issuing the report. One of the most accepted definitions at present is a pigmented macule that progresses in months with a rapid vertical growth, invading the epidermis and the papillary dermis.2 The differential diagnosis includes pyogenic granuloma, squamous cell carcinoma, basal cell carcinoma, soft tissue sarcomas, and hemangioma.
Although our patient had a history of melanoma and the polypoid lesion developed from a flat lesion, he was late to seek medical care. The diagnosis of melanoma is made on increasingly smaller lesions with better prognosis, but there still are reports of larger melanomas. This case highlights the role dermatologists serve in the education of patients on their diagnoses and risk factors so that we may be able to diagnose non–life-threatening small lesions. It is important to remember this morphologic variety of melanoma and highlight its rapid progression and poor prognosis.
- Knezević F, Duancić V, Sitić S, et al. Histological types of polypoid cutaneous melanoma II. Coll Antropol. 2007;31:1049-1053.
- Dini M, Quercioli F, Caldarella V, et al. Head and neck polypoid melanoma. J Craniofac Surg. 2012;23:E23-E25.
- Plotnick H, Rachmaninoff N, VandenBerg HJ Jr. Polypoid melanoma: a virulent variant of nodular melanoma. report of three cases and literature review. J Am Acad Dermatol. 1990;23(5, pt 1):880-884.
- Manci EA, Balch CM, Murad TM, et al. Polypoid melanoma, a virulent variant of the nodular growth pattern. Am J Clin Pathol. 1981;75:810-815.
- De Giorgi V, Massi D, Gerlini G, et al. Immediate local and regional recurrence after the excision of a polypoid melanoma: tumor dormancy or tumor activation? Dermatol Surg. 2003;29:664-667.
To the Editor:
An 81-year-old man presented with a nodular polypoid lesion that developed on a flat lesion on the back of 2 years’ duration. The lesion grew progressively over the course of 3 months prior to presentation. The patient had a history of melanoma in situ on the forehead that was treated with conventional surgery with clear surgical margins 6 years prior to the current presentation.
On physical examination the patient had a 4×2-cm ulcerated polypoid lesion on the back. The lesion was pink with a pigmented base. Additionally, 2 pink papules with superficial telangiectases were observed around the main lesion (Figure 1).
The gross section showed an exophytic tumor largely growing above the skin surface (Figure 2). Histopathologic analysis revealed an ulcerated lesion consisting of confluent nest and sheets of epithelioid and spindle atypical cells with numerous mitotic figures and necrotic foci (Figure 3). The thickness of the lesion was 2200 µm, and the mitotic count was 28 mitoses/mm2. There also was peritumoral vascular invasion and satellite metastasis within the perilesional hypodermis measuring 0.4 mm. Immunohistochemistry staining for S-100, human melanoma black 45 (HMB-45)(Figure 4), and Melan-A was positive in neoplastic cells.
The dissemination study revealed multiple mediastinal and axillary lymphadenopathies and lesions with metastatic appearance in the brain, liver, pancreas, and muscle, together with peritoneal carcinomatosis. The patient was lost to follow-up and did not follow coadjuvant therapy with interferon alfa.
Polypoid melanoma initially was described as a type of melanoma characterized by an exophytic growth in which most of the tumor is located on the cutaneous surface, together with ulceration.1 It usually occurs in patients aged 20 to 39 years,2 and the reported incidence ranges from 1.9% to 43.3%.1 It more commonly affects mucosae, including the upper respiratory tract, esophagus, and vagina. Polypoid melanoma has a rapid progression and a poor prognosis.3 Polypoid melanoma involving the skin primarily affects the back and has a 5-year survival rate of 32% to 42%.4 Poor prognosis has been attributed to the high risk for vascular embolization under the lesion.5 Histologically, there is marked cell atypia with nuclear and cellular pleomorphism and a high mitotic count. The tumor rarely involves the reticular dermis.1,2
Polypoid melanomas are rare; however, reported frequency rates cover a wide range. These frequency rates may be due to the definition of polypoid melanoma used by the pathologist issuing the report. One of the most accepted definitions at present is a pigmented macule that progresses in months with a rapid vertical growth, invading the epidermis and the papillary dermis.2 The differential diagnosis includes pyogenic granuloma, squamous cell carcinoma, basal cell carcinoma, soft tissue sarcomas, and hemangioma.
Although our patient had a history of melanoma and the polypoid lesion developed from a flat lesion, he was late to seek medical care. The diagnosis of melanoma is made on increasingly smaller lesions with better prognosis, but there still are reports of larger melanomas. This case highlights the role dermatologists serve in the education of patients on their diagnoses and risk factors so that we may be able to diagnose non–life-threatening small lesions. It is important to remember this morphologic variety of melanoma and highlight its rapid progression and poor prognosis.
To the Editor:
An 81-year-old man presented with a nodular polypoid lesion that developed on a flat lesion on the back of 2 years’ duration. The lesion grew progressively over the course of 3 months prior to presentation. The patient had a history of melanoma in situ on the forehead that was treated with conventional surgery with clear surgical margins 6 years prior to the current presentation.
On physical examination the patient had a 4×2-cm ulcerated polypoid lesion on the back. The lesion was pink with a pigmented base. Additionally, 2 pink papules with superficial telangiectases were observed around the main lesion (Figure 1).
The gross section showed an exophytic tumor largely growing above the skin surface (Figure 2). Histopathologic analysis revealed an ulcerated lesion consisting of confluent nest and sheets of epithelioid and spindle atypical cells with numerous mitotic figures and necrotic foci (Figure 3). The thickness of the lesion was 2200 µm, and the mitotic count was 28 mitoses/mm2. There also was peritumoral vascular invasion and satellite metastasis within the perilesional hypodermis measuring 0.4 mm. Immunohistochemistry staining for S-100, human melanoma black 45 (HMB-45)(Figure 4), and Melan-A was positive in neoplastic cells.
The dissemination study revealed multiple mediastinal and axillary lymphadenopathies and lesions with metastatic appearance in the brain, liver, pancreas, and muscle, together with peritoneal carcinomatosis. The patient was lost to follow-up and did not follow coadjuvant therapy with interferon alfa.
Polypoid melanoma initially was described as a type of melanoma characterized by an exophytic growth in which most of the tumor is located on the cutaneous surface, together with ulceration.1 It usually occurs in patients aged 20 to 39 years,2 and the reported incidence ranges from 1.9% to 43.3%.1 It more commonly affects mucosae, including the upper respiratory tract, esophagus, and vagina. Polypoid melanoma has a rapid progression and a poor prognosis.3 Polypoid melanoma involving the skin primarily affects the back and has a 5-year survival rate of 32% to 42%.4 Poor prognosis has been attributed to the high risk for vascular embolization under the lesion.5 Histologically, there is marked cell atypia with nuclear and cellular pleomorphism and a high mitotic count. The tumor rarely involves the reticular dermis.1,2
Polypoid melanomas are rare; however, reported frequency rates cover a wide range. These frequency rates may be due to the definition of polypoid melanoma used by the pathologist issuing the report. One of the most accepted definitions at present is a pigmented macule that progresses in months with a rapid vertical growth, invading the epidermis and the papillary dermis.2 The differential diagnosis includes pyogenic granuloma, squamous cell carcinoma, basal cell carcinoma, soft tissue sarcomas, and hemangioma.
Although our patient had a history of melanoma and the polypoid lesion developed from a flat lesion, he was late to seek medical care. The diagnosis of melanoma is made on increasingly smaller lesions with better prognosis, but there still are reports of larger melanomas. This case highlights the role dermatologists serve in the education of patients on their diagnoses and risk factors so that we may be able to diagnose non–life-threatening small lesions. It is important to remember this morphologic variety of melanoma and highlight its rapid progression and poor prognosis.
- Knezević F, Duancić V, Sitić S, et al. Histological types of polypoid cutaneous melanoma II. Coll Antropol. 2007;31:1049-1053.
- Dini M, Quercioli F, Caldarella V, et al. Head and neck polypoid melanoma. J Craniofac Surg. 2012;23:E23-E25.
- Plotnick H, Rachmaninoff N, VandenBerg HJ Jr. Polypoid melanoma: a virulent variant of nodular melanoma. report of three cases and literature review. J Am Acad Dermatol. 1990;23(5, pt 1):880-884.
- Manci EA, Balch CM, Murad TM, et al. Polypoid melanoma, a virulent variant of the nodular growth pattern. Am J Clin Pathol. 1981;75:810-815.
- De Giorgi V, Massi D, Gerlini G, et al. Immediate local and regional recurrence after the excision of a polypoid melanoma: tumor dormancy or tumor activation? Dermatol Surg. 2003;29:664-667.
- Knezević F, Duancić V, Sitić S, et al. Histological types of polypoid cutaneous melanoma II. Coll Antropol. 2007;31:1049-1053.
- Dini M, Quercioli F, Caldarella V, et al. Head and neck polypoid melanoma. J Craniofac Surg. 2012;23:E23-E25.
- Plotnick H, Rachmaninoff N, VandenBerg HJ Jr. Polypoid melanoma: a virulent variant of nodular melanoma. report of three cases and literature review. J Am Acad Dermatol. 1990;23(5, pt 1):880-884.
- Manci EA, Balch CM, Murad TM, et al. Polypoid melanoma, a virulent variant of the nodular growth pattern. Am J Clin Pathol. 1981;75:810-815.
- De Giorgi V, Massi D, Gerlini G, et al. Immediate local and regional recurrence after the excision of a polypoid melanoma: tumor dormancy or tumor activation? Dermatol Surg. 2003;29:664-667.
Practice Points
- The differential diagnosis of polypoid melanoma includes pyogenic granuloma and squamous cell carcinoma.
- Polypoid melanoma has a poor prognosis because of its thickness and ulceration at the time of diagnosis and the risk of vascular embolization.
Baricitinib shows potential as lupus treatment
AMSTERDAM – A significantly higher proportion of patients with lupus experienced improvements in joint and skin symptoms if they were treated with baricitinib (Olumiant) than if they received placebo in a phase 2 trial.
The primary endpoint of arthritis or rash resolution as measured by the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) was met by approximately 67% of patients who were treated with 4 mg baricitinib once daily and by around 53% of patients given a matching placebo (P less than .05).
With no new safety concerns, these findings suggest that baricitinib could be of benefit in patients with SLE and further study is warranted in a phase 3 trial, said the presenting study investigator Daniel J. Wallace, MD, at the European Congress of Rheumatology. Dr. Wallace is the associate director of the Rheumatology Fellowship Program at Cedars-Sinai Medical Center, Los Angeles.
Baricitinib is already approved for use as a treatment for RA in more than 40 countries. On June 1, Eli Lilly announced that the Food and Drug Administration had given the green light for its use in RA in the United States, but only at a dose of 2 mg once daily, whereas a 2-mg and 4-mg once-daily dose is approved in most other countries.
Data from the phase 2 trial presented by Dr. Wallace did include a 2-mg dose arm, but the difference in treatment response rates versus placebo was not statistically significant.
“I think the placebo response is mainly inflated by the use of corticosteroids,” said Dr. Dörner, professor of medicine at Charité–Universitätsmedizin Berlin. “If one would have applied a steroid tapering regimen, I would have expected a larger effect size, and possibly also the 2-mg [dose] be more effective as compared to placebo.” This is something to consider when moving into a phase 3 trial, he suggested.
For inclusion in the phase 2 trial, patients had to meet the following criteria: Be positive for antinuclear antibodies and/or a positive anti-dsDNA test, have a SLEDAI-2K clinical score of 4 or more, and have active SLEDAI arthritis and/or rash. Patients with severe active lupus nephritis or CNS involvement were excluded.
The mean age of patients was around 44 years, and as might be expected, the study population was predominantly female (99%). Around two-thirds of patients were white, 19% were of Asian descent, and the rest were designated as “other”. The average time to SLE onset was 9.7 years in the placebo group and just over 11 years in the baricitinib arms, with similar SLEDAI-2K scores of about 8-9, about 7-8 tender joints, and about five swollen joints at baseline.
A number of other secondary endpoints were also met by the 4 mg baricitinib group, Dr. Wallace reported. This included the relatively new Lupus Low Disease Activity State, he said, which was met by 38% (n = 27) of patients treated with 4 mg baricitinib, 33% (n = 35) treated with 2 mg baricitinib, and 26% (n = 27) of those given placebo (P less than .05 for the 4-mg dose vs. placebo). There were also numerically fewer SLE flares, including fewer severe flares.
“Some of the other outcomes demonstrated statistical significance: Physician Global Assessment, tender joint count, worst joint pain, and worst pain on a numeric rating scale,” Dr. Wallace said. A trend towards improvement was seen in the swollen joint count, with modest improvement in fatigue.
Treatment-emergent adverse events were seen in around 71%-73% of patients given baricitinib and 65% of patients given placebo. Most were mild or moderate in nature, but serious adverse events did occur in approximately 10% of patients who received baricitinib and in 4% of those who received placebo.
What’s noteworthy, Dr. Dörner said during a press briefing, is the very low rate of venous thromboembolism seen in the trial. “We’d have expected to see more deep vein thrombosis,” he said. Only one case occurred, in a patent taking the 4-mg dose, but this patient had preexisting antiphospholipid antibodies.
Additionally, although the percentage of patients with serious infections was slightly higher in the 2 and 4 mg baricitinib arms than for placebo (1.9% and 5.8% vs. 1%, respectively) “this is what we expect for lupus patients,” Dr. Dörner said. Furthermore, herpes zoster infection, which is very often reactivated in lupus because of the disease or its treatment, was only reported in one patient in the placebo group and in one patient in the 4 mg group.
“I think there is a very promising outlook, at least for the 4-mg dose of baricitinib,” Dr. Dörner said. “There have been no new safety or tolerability issues when compared to the RA population, and we’re looking forward to seeing subsequent studies in this [SLE] patient population where we have a need for more efficacious therapies.”
The study was funded by Eli Lilly. Dr. Dörner was part of the trial’s steering committee and has acted as a consultant for Eli Lilly. He has also received grant or research support from Roche/Chugai, Janssen, and Sanofi-Aventis; consulted for AbbVie, Celgene, Roche, UCB, Merck Sharp & Dohme, Pfizer/Hospira, and Novartis; and he is part of the speakers bureaus for Amgen, Celgene, and Biogen. Dr. Wallace has acted as a consultant for Eli Lilly, as well as EMD Serono, Pfizer, and GlaxoSmithKline.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SOURCE: Wallace DJ et al. Ann Rheum Dis. 2018;77(Suppl 2):59. Abstract OP0019.
AMSTERDAM – A significantly higher proportion of patients with lupus experienced improvements in joint and skin symptoms if they were treated with baricitinib (Olumiant) than if they received placebo in a phase 2 trial.
The primary endpoint of arthritis or rash resolution as measured by the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) was met by approximately 67% of patients who were treated with 4 mg baricitinib once daily and by around 53% of patients given a matching placebo (P less than .05).
With no new safety concerns, these findings suggest that baricitinib could be of benefit in patients with SLE and further study is warranted in a phase 3 trial, said the presenting study investigator Daniel J. Wallace, MD, at the European Congress of Rheumatology. Dr. Wallace is the associate director of the Rheumatology Fellowship Program at Cedars-Sinai Medical Center, Los Angeles.
Baricitinib is already approved for use as a treatment for RA in more than 40 countries. On June 1, Eli Lilly announced that the Food and Drug Administration had given the green light for its use in RA in the United States, but only at a dose of 2 mg once daily, whereas a 2-mg and 4-mg once-daily dose is approved in most other countries.
Data from the phase 2 trial presented by Dr. Wallace did include a 2-mg dose arm, but the difference in treatment response rates versus placebo was not statistically significant.
“I think the placebo response is mainly inflated by the use of corticosteroids,” said Dr. Dörner, professor of medicine at Charité–Universitätsmedizin Berlin. “If one would have applied a steroid tapering regimen, I would have expected a larger effect size, and possibly also the 2-mg [dose] be more effective as compared to placebo.” This is something to consider when moving into a phase 3 trial, he suggested.
For inclusion in the phase 2 trial, patients had to meet the following criteria: Be positive for antinuclear antibodies and/or a positive anti-dsDNA test, have a SLEDAI-2K clinical score of 4 or more, and have active SLEDAI arthritis and/or rash. Patients with severe active lupus nephritis or CNS involvement were excluded.
The mean age of patients was around 44 years, and as might be expected, the study population was predominantly female (99%). Around two-thirds of patients were white, 19% were of Asian descent, and the rest were designated as “other”. The average time to SLE onset was 9.7 years in the placebo group and just over 11 years in the baricitinib arms, with similar SLEDAI-2K scores of about 8-9, about 7-8 tender joints, and about five swollen joints at baseline.
A number of other secondary endpoints were also met by the 4 mg baricitinib group, Dr. Wallace reported. This included the relatively new Lupus Low Disease Activity State, he said, which was met by 38% (n = 27) of patients treated with 4 mg baricitinib, 33% (n = 35) treated with 2 mg baricitinib, and 26% (n = 27) of those given placebo (P less than .05 for the 4-mg dose vs. placebo). There were also numerically fewer SLE flares, including fewer severe flares.
“Some of the other outcomes demonstrated statistical significance: Physician Global Assessment, tender joint count, worst joint pain, and worst pain on a numeric rating scale,” Dr. Wallace said. A trend towards improvement was seen in the swollen joint count, with modest improvement in fatigue.
Treatment-emergent adverse events were seen in around 71%-73% of patients given baricitinib and 65% of patients given placebo. Most were mild or moderate in nature, but serious adverse events did occur in approximately 10% of patients who received baricitinib and in 4% of those who received placebo.
What’s noteworthy, Dr. Dörner said during a press briefing, is the very low rate of venous thromboembolism seen in the trial. “We’d have expected to see more deep vein thrombosis,” he said. Only one case occurred, in a patent taking the 4-mg dose, but this patient had preexisting antiphospholipid antibodies.
Additionally, although the percentage of patients with serious infections was slightly higher in the 2 and 4 mg baricitinib arms than for placebo (1.9% and 5.8% vs. 1%, respectively) “this is what we expect for lupus patients,” Dr. Dörner said. Furthermore, herpes zoster infection, which is very often reactivated in lupus because of the disease or its treatment, was only reported in one patient in the placebo group and in one patient in the 4 mg group.
“I think there is a very promising outlook, at least for the 4-mg dose of baricitinib,” Dr. Dörner said. “There have been no new safety or tolerability issues when compared to the RA population, and we’re looking forward to seeing subsequent studies in this [SLE] patient population where we have a need for more efficacious therapies.”
The study was funded by Eli Lilly. Dr. Dörner was part of the trial’s steering committee and has acted as a consultant for Eli Lilly. He has also received grant or research support from Roche/Chugai, Janssen, and Sanofi-Aventis; consulted for AbbVie, Celgene, Roche, UCB, Merck Sharp & Dohme, Pfizer/Hospira, and Novartis; and he is part of the speakers bureaus for Amgen, Celgene, and Biogen. Dr. Wallace has acted as a consultant for Eli Lilly, as well as EMD Serono, Pfizer, and GlaxoSmithKline.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SOURCE: Wallace DJ et al. Ann Rheum Dis. 2018;77(Suppl 2):59. Abstract OP0019.
AMSTERDAM – A significantly higher proportion of patients with lupus experienced improvements in joint and skin symptoms if they were treated with baricitinib (Olumiant) than if they received placebo in a phase 2 trial.
The primary endpoint of arthritis or rash resolution as measured by the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) was met by approximately 67% of patients who were treated with 4 mg baricitinib once daily and by around 53% of patients given a matching placebo (P less than .05).
With no new safety concerns, these findings suggest that baricitinib could be of benefit in patients with SLE and further study is warranted in a phase 3 trial, said the presenting study investigator Daniel J. Wallace, MD, at the European Congress of Rheumatology. Dr. Wallace is the associate director of the Rheumatology Fellowship Program at Cedars-Sinai Medical Center, Los Angeles.
Baricitinib is already approved for use as a treatment for RA in more than 40 countries. On June 1, Eli Lilly announced that the Food and Drug Administration had given the green light for its use in RA in the United States, but only at a dose of 2 mg once daily, whereas a 2-mg and 4-mg once-daily dose is approved in most other countries.
Data from the phase 2 trial presented by Dr. Wallace did include a 2-mg dose arm, but the difference in treatment response rates versus placebo was not statistically significant.
“I think the placebo response is mainly inflated by the use of corticosteroids,” said Dr. Dörner, professor of medicine at Charité–Universitätsmedizin Berlin. “If one would have applied a steroid tapering regimen, I would have expected a larger effect size, and possibly also the 2-mg [dose] be more effective as compared to placebo.” This is something to consider when moving into a phase 3 trial, he suggested.
For inclusion in the phase 2 trial, patients had to meet the following criteria: Be positive for antinuclear antibodies and/or a positive anti-dsDNA test, have a SLEDAI-2K clinical score of 4 or more, and have active SLEDAI arthritis and/or rash. Patients with severe active lupus nephritis or CNS involvement were excluded.
The mean age of patients was around 44 years, and as might be expected, the study population was predominantly female (99%). Around two-thirds of patients were white, 19% were of Asian descent, and the rest were designated as “other”. The average time to SLE onset was 9.7 years in the placebo group and just over 11 years in the baricitinib arms, with similar SLEDAI-2K scores of about 8-9, about 7-8 tender joints, and about five swollen joints at baseline.
A number of other secondary endpoints were also met by the 4 mg baricitinib group, Dr. Wallace reported. This included the relatively new Lupus Low Disease Activity State, he said, which was met by 38% (n = 27) of patients treated with 4 mg baricitinib, 33% (n = 35) treated with 2 mg baricitinib, and 26% (n = 27) of those given placebo (P less than .05 for the 4-mg dose vs. placebo). There were also numerically fewer SLE flares, including fewer severe flares.
“Some of the other outcomes demonstrated statistical significance: Physician Global Assessment, tender joint count, worst joint pain, and worst pain on a numeric rating scale,” Dr. Wallace said. A trend towards improvement was seen in the swollen joint count, with modest improvement in fatigue.
Treatment-emergent adverse events were seen in around 71%-73% of patients given baricitinib and 65% of patients given placebo. Most were mild or moderate in nature, but serious adverse events did occur in approximately 10% of patients who received baricitinib and in 4% of those who received placebo.
What’s noteworthy, Dr. Dörner said during a press briefing, is the very low rate of venous thromboembolism seen in the trial. “We’d have expected to see more deep vein thrombosis,” he said. Only one case occurred, in a patent taking the 4-mg dose, but this patient had preexisting antiphospholipid antibodies.
Additionally, although the percentage of patients with serious infections was slightly higher in the 2 and 4 mg baricitinib arms than for placebo (1.9% and 5.8% vs. 1%, respectively) “this is what we expect for lupus patients,” Dr. Dörner said. Furthermore, herpes zoster infection, which is very often reactivated in lupus because of the disease or its treatment, was only reported in one patient in the placebo group and in one patient in the 4 mg group.
“I think there is a very promising outlook, at least for the 4-mg dose of baricitinib,” Dr. Dörner said. “There have been no new safety or tolerability issues when compared to the RA population, and we’re looking forward to seeing subsequent studies in this [SLE] patient population where we have a need for more efficacious therapies.”
The study was funded by Eli Lilly. Dr. Dörner was part of the trial’s steering committee and has acted as a consultant for Eli Lilly. He has also received grant or research support from Roche/Chugai, Janssen, and Sanofi-Aventis; consulted for AbbVie, Celgene, Roche, UCB, Merck Sharp & Dohme, Pfizer/Hospira, and Novartis; and he is part of the speakers bureaus for Amgen, Celgene, and Biogen. Dr. Wallace has acted as a consultant for Eli Lilly, as well as EMD Serono, Pfizer, and GlaxoSmithKline.
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SOURCE: Wallace DJ et al. Ann Rheum Dis. 2018;77(Suppl 2):59. Abstract OP0019.
REPORTING FROM THE EULAR 2018 CONGRESS
Key clinical point: Baricitinib at 4 mg was associated with significant clinical improvements versus placebo and had an acceptable safety and tolerability profile.
Major finding: A higher percentage of patients receiving 4 mg of baricitinib than those receiving placebo achieved the primary endpoint of arthritis and/or rash remission as defined by the Systemic Lupus Erythematosus Disease Activity Index 2000 at week 24 (P less than .05).
Study details: A phase 2, multinational, double-blind, placebo-controlled, parallel group study of once-daily, oral baricitinib (2 mg and 4 mg) in 314 patients with SLE receiving standard therapy.
Disclosures: The study was funded by Eli Lilly. Dr. Dörner was part of the trial’s steering committee and has acted as a consultant for Eli Lilly. He has also received grant or research support from Roche/Chugai, Janssen, and Sanofi-Aventis; consulted for AbbVie, Celgene, Roche, UCB, Merck Sharp & Dohme, Pfizer/Hospira, and Novartis; and he is part of the speakers bureaus for Amgen, Celgene, and Biogen. Dr. Wallace has acted as a consultant for Eli Lilly, as well as EMD Serono, Pfizer, and GlaxoSmithKline.
Source: Wallace DJ et al. Ann Rheum Dis. 2018;77(Suppl 2):59. Abstract OP0019.
Honors Committee Accepting Nominations for Prestigious ACS Awards
The American College of Surgeons (ACS) Honors Committee is soliciting nominations for several prestigious awards and honors. These include the Distinguished Service Award; the Rodman E. and Thomas G. Sheen Award; the Jacobson Innovation Award; the Lifetime Achievement Award; candidates for Honorary Fellowship (from countries outside of the U.S. and Canada); and potential innovative speakers for the Martin Memorial Lecture, delivered at the Opening Ceremony of the annual ACS Clinical Congress.
Nominations are accepted all year long; however, Honorary Fellowship nominees are selected each October for induction at the following year’s Clinical Congress.
Visit the Honors Committee web page at www.facs.org/about-acs/governance/acs-committees/honors-committee for additional details about the criteria for nominations. Specific questions may be directed to Donna Coulombe, Honors Committee Staff Liaison, at [email protected] or 312-202-5203.
The American College of Surgeons (ACS) Honors Committee is soliciting nominations for several prestigious awards and honors. These include the Distinguished Service Award; the Rodman E. and Thomas G. Sheen Award; the Jacobson Innovation Award; the Lifetime Achievement Award; candidates for Honorary Fellowship (from countries outside of the U.S. and Canada); and potential innovative speakers for the Martin Memorial Lecture, delivered at the Opening Ceremony of the annual ACS Clinical Congress.
Nominations are accepted all year long; however, Honorary Fellowship nominees are selected each October for induction at the following year’s Clinical Congress.
Visit the Honors Committee web page at www.facs.org/about-acs/governance/acs-committees/honors-committee for additional details about the criteria for nominations. Specific questions may be directed to Donna Coulombe, Honors Committee Staff Liaison, at [email protected] or 312-202-5203.
The American College of Surgeons (ACS) Honors Committee is soliciting nominations for several prestigious awards and honors. These include the Distinguished Service Award; the Rodman E. and Thomas G. Sheen Award; the Jacobson Innovation Award; the Lifetime Achievement Award; candidates for Honorary Fellowship (from countries outside of the U.S. and Canada); and potential innovative speakers for the Martin Memorial Lecture, delivered at the Opening Ceremony of the annual ACS Clinical Congress.
Nominations are accepted all year long; however, Honorary Fellowship nominees are selected each October for induction at the following year’s Clinical Congress.
Visit the Honors Committee web page at www.facs.org/about-acs/governance/acs-committees/honors-committee for additional details about the criteria for nominations. Specific questions may be directed to Donna Coulombe, Honors Committee Staff Liaison, at [email protected] or 312-202-5203.
PU-H71 receives orphan drug designation for myelofibrosis
The US Food and Drug Administration (FDA) has granted orphan drug designation to PU-H71 to treat patients with myelofibrosis.
The drug specifically targets the epichaperome, a network of high-molecular-weight complexes found in multiple diseases, including cancer and neurologic disorders. These complexes enhance cellular survival, irrespective of tissue of origin or genetic background.
According to research published in Nature Reviews Cancer, Pu-H71 interferes with the epichaperome function in diseases and does not affect normal cells.
PU-H71 is being evaluated in a phase 1b trial in myelofibrosis and advanced metastatic breast cancer.
“In myelofibrosis, the epichaperome plays a central role in optimizing the JAK-STAT pathway,” said Srdan Verstovsek, MD, PhD, “allowing JAK2 to form dimers that evade inhibition with a JAK2 inhibitor such as ruxolitinib.”
“By inhibiting epichaperome function and breaking this mechanism, we believe PU-H71 can increase anti-cancer activity of JAK2 inhibitors,” he said. Dr Verstovsek, of the MD Anderson Cancer Center in Houston, Texas, is lead clinical research advisor for the phase 1b myelofibrosis study.
Phase 1b Study (NCT01393509)
This is a multicenter study designed to assess the safety, tolerability, pharmacokinetic and preliminary efficacy of PU-H71 in patients taking concomitant ruxolitinib.
The safety expansion phase of the trial is open for accrual only to patients with myeloproliferative neoplasms (MPNs).
These patients must have been on ruxolitinib for at least 3 months, be on a stable dose for at least 1 month prior to enrollment and be taking at least 5 mg twice daily.
Patients must have persistent disease manifestations, despite ruxolitinib therapy. These include persistent splenomegaly, abnormal blood counts, persistent constitutional symptoms, residual fibrosis in bone marrow (2+ or greater), or measurable allele burden as evidenced by clonal JAK2 or MPL mutation.
Samus Therapeutics, the developer of PU-H71, announced, simultaneously with the orphan drug designation, the dosing of the first patient in the phase 1b myelofibrosis study.
“Targeting the epichaperome offers an exciting new avenue for treating myelofibrosis and related diseases,” Dr Verstovsek said.
“I look forward to seeing how the combination of these therapies can affect outcomes in patients for whom this resistance is associated with poor prognoses.”
The US Food and Drug Administration (FDA) has granted orphan drug designation to PU-H71 to treat patients with myelofibrosis.
The drug specifically targets the epichaperome, a network of high-molecular-weight complexes found in multiple diseases, including cancer and neurologic disorders. These complexes enhance cellular survival, irrespective of tissue of origin or genetic background.
According to research published in Nature Reviews Cancer, Pu-H71 interferes with the epichaperome function in diseases and does not affect normal cells.
PU-H71 is being evaluated in a phase 1b trial in myelofibrosis and advanced metastatic breast cancer.
“In myelofibrosis, the epichaperome plays a central role in optimizing the JAK-STAT pathway,” said Srdan Verstovsek, MD, PhD, “allowing JAK2 to form dimers that evade inhibition with a JAK2 inhibitor such as ruxolitinib.”
“By inhibiting epichaperome function and breaking this mechanism, we believe PU-H71 can increase anti-cancer activity of JAK2 inhibitors,” he said. Dr Verstovsek, of the MD Anderson Cancer Center in Houston, Texas, is lead clinical research advisor for the phase 1b myelofibrosis study.
Phase 1b Study (NCT01393509)
This is a multicenter study designed to assess the safety, tolerability, pharmacokinetic and preliminary efficacy of PU-H71 in patients taking concomitant ruxolitinib.
The safety expansion phase of the trial is open for accrual only to patients with myeloproliferative neoplasms (MPNs).
These patients must have been on ruxolitinib for at least 3 months, be on a stable dose for at least 1 month prior to enrollment and be taking at least 5 mg twice daily.
Patients must have persistent disease manifestations, despite ruxolitinib therapy. These include persistent splenomegaly, abnormal blood counts, persistent constitutional symptoms, residual fibrosis in bone marrow (2+ or greater), or measurable allele burden as evidenced by clonal JAK2 or MPL mutation.
Samus Therapeutics, the developer of PU-H71, announced, simultaneously with the orphan drug designation, the dosing of the first patient in the phase 1b myelofibrosis study.
“Targeting the epichaperome offers an exciting new avenue for treating myelofibrosis and related diseases,” Dr Verstovsek said.
“I look forward to seeing how the combination of these therapies can affect outcomes in patients for whom this resistance is associated with poor prognoses.”
The US Food and Drug Administration (FDA) has granted orphan drug designation to PU-H71 to treat patients with myelofibrosis.
The drug specifically targets the epichaperome, a network of high-molecular-weight complexes found in multiple diseases, including cancer and neurologic disorders. These complexes enhance cellular survival, irrespective of tissue of origin or genetic background.
According to research published in Nature Reviews Cancer, Pu-H71 interferes with the epichaperome function in diseases and does not affect normal cells.
PU-H71 is being evaluated in a phase 1b trial in myelofibrosis and advanced metastatic breast cancer.
“In myelofibrosis, the epichaperome plays a central role in optimizing the JAK-STAT pathway,” said Srdan Verstovsek, MD, PhD, “allowing JAK2 to form dimers that evade inhibition with a JAK2 inhibitor such as ruxolitinib.”
“By inhibiting epichaperome function and breaking this mechanism, we believe PU-H71 can increase anti-cancer activity of JAK2 inhibitors,” he said. Dr Verstovsek, of the MD Anderson Cancer Center in Houston, Texas, is lead clinical research advisor for the phase 1b myelofibrosis study.
Phase 1b Study (NCT01393509)
This is a multicenter study designed to assess the safety, tolerability, pharmacokinetic and preliminary efficacy of PU-H71 in patients taking concomitant ruxolitinib.
The safety expansion phase of the trial is open for accrual only to patients with myeloproliferative neoplasms (MPNs).
These patients must have been on ruxolitinib for at least 3 months, be on a stable dose for at least 1 month prior to enrollment and be taking at least 5 mg twice daily.
Patients must have persistent disease manifestations, despite ruxolitinib therapy. These include persistent splenomegaly, abnormal blood counts, persistent constitutional symptoms, residual fibrosis in bone marrow (2+ or greater), or measurable allele burden as evidenced by clonal JAK2 or MPL mutation.
Samus Therapeutics, the developer of PU-H71, announced, simultaneously with the orphan drug designation, the dosing of the first patient in the phase 1b myelofibrosis study.
“Targeting the epichaperome offers an exciting new avenue for treating myelofibrosis and related diseases,” Dr Verstovsek said.
“I look forward to seeing how the combination of these therapies can affect outcomes in patients for whom this resistance is associated with poor prognoses.”
NAPRC Awards accredited John Muir Health Rectal Cancer Program
The National Accreditation Program for Rectal Cancer (NAPRC), recently launched by the American College of Surgeons (ACS), has awarded its first accreditation to the John Muir Health Rectal Cancer Program, Walnut Creek and Concord, CA. To earn the voluntary accreditation, the John Muir Health Rectal Cancer Program met 19 standards, including the establishment of a rectal cancer multidisciplinary team (RC-MDT) with clinical representatives from surgery, pathology, radiology, radiation oncology, and medical oncology.
Thirteen of those standards address clinical services that the program was required to provide, including carcinoembryonic antigen testing and magnetic resonance and computed tomography imaging for cancer staging, and ensuring a process whereby the patient starts treatment within a defined time frame. One of the most important clinical standards requires all rectal cancer patients to be present at both pre- and post-treatment RC-MDT meetings.
“When a cancer center achieves this type of specialized accreditation, it means that their rectal cancer patients will receive streamlined, modern evaluation and treatment for the disease. Compliance with our standards will assure optimal care for these patients,” said David P. Winchester, MD, FACS, Medical Director of ACS Cancer Programs.
The NAPRC was developed through a collaboration between the Optimizing the Surgical Treatment of Rectal Cancer Consortium and the ACS Commission on Cancer. It is based on successful international models that emphasize program structure, patient care processes, performance improvement, and performance measures. Its goal is to ensure that rectal cancer patients receive appropriate care using a multidisciplinary approach.
Read more in the ACS press release at www.facs.org/media/press-releases/2018/naprc052218. For more information about the program and instructions on how to apply for accreditation, visit the NAPRC website at www.facs.org/quality-programs/cancer/naprc, or contact [email protected].
The National Accreditation Program for Rectal Cancer (NAPRC), recently launched by the American College of Surgeons (ACS), has awarded its first accreditation to the John Muir Health Rectal Cancer Program, Walnut Creek and Concord, CA. To earn the voluntary accreditation, the John Muir Health Rectal Cancer Program met 19 standards, including the establishment of a rectal cancer multidisciplinary team (RC-MDT) with clinical representatives from surgery, pathology, radiology, radiation oncology, and medical oncology.
Thirteen of those standards address clinical services that the program was required to provide, including carcinoembryonic antigen testing and magnetic resonance and computed tomography imaging for cancer staging, and ensuring a process whereby the patient starts treatment within a defined time frame. One of the most important clinical standards requires all rectal cancer patients to be present at both pre- and post-treatment RC-MDT meetings.
“When a cancer center achieves this type of specialized accreditation, it means that their rectal cancer patients will receive streamlined, modern evaluation and treatment for the disease. Compliance with our standards will assure optimal care for these patients,” said David P. Winchester, MD, FACS, Medical Director of ACS Cancer Programs.
The NAPRC was developed through a collaboration between the Optimizing the Surgical Treatment of Rectal Cancer Consortium and the ACS Commission on Cancer. It is based on successful international models that emphasize program structure, patient care processes, performance improvement, and performance measures. Its goal is to ensure that rectal cancer patients receive appropriate care using a multidisciplinary approach.
Read more in the ACS press release at www.facs.org/media/press-releases/2018/naprc052218. For more information about the program and instructions on how to apply for accreditation, visit the NAPRC website at www.facs.org/quality-programs/cancer/naprc, or contact [email protected].
The National Accreditation Program for Rectal Cancer (NAPRC), recently launched by the American College of Surgeons (ACS), has awarded its first accreditation to the John Muir Health Rectal Cancer Program, Walnut Creek and Concord, CA. To earn the voluntary accreditation, the John Muir Health Rectal Cancer Program met 19 standards, including the establishment of a rectal cancer multidisciplinary team (RC-MDT) with clinical representatives from surgery, pathology, radiology, radiation oncology, and medical oncology.
Thirteen of those standards address clinical services that the program was required to provide, including carcinoembryonic antigen testing and magnetic resonance and computed tomography imaging for cancer staging, and ensuring a process whereby the patient starts treatment within a defined time frame. One of the most important clinical standards requires all rectal cancer patients to be present at both pre- and post-treatment RC-MDT meetings.
“When a cancer center achieves this type of specialized accreditation, it means that their rectal cancer patients will receive streamlined, modern evaluation and treatment for the disease. Compliance with our standards will assure optimal care for these patients,” said David P. Winchester, MD, FACS, Medical Director of ACS Cancer Programs.
The NAPRC was developed through a collaboration between the Optimizing the Surgical Treatment of Rectal Cancer Consortium and the ACS Commission on Cancer. It is based on successful international models that emphasize program structure, patient care processes, performance improvement, and performance measures. Its goal is to ensure that rectal cancer patients receive appropriate care using a multidisciplinary approach.
Read more in the ACS press release at www.facs.org/media/press-releases/2018/naprc052218. For more information about the program and instructions on how to apply for accreditation, visit the NAPRC website at www.facs.org/quality-programs/cancer/naprc, or contact [email protected].
NCDB-Sourced Study Focuses on Post-Treatment Surveillance for Colorectal Cancer Patients
The first findings from a collaborative study within the American College of Surgeons (ACS) Cancer Programs—and published earlier this week in the Journal of the American Medical Association (JAMA)—showed no significant association between frequency of surveillance testing and the time to detection of recurrence for colorectal cancer patients.
The study is an effort of the ACS Clinical Research Program and the Commission on Cancer and uses data from the National Cancer Database (NCDB), which is jointly sponsored by the ACS and the American Cancer Society. It focuses on post-treatment surveillance for breast, colon, and lung cancers and was funded by the Patient-Centered Outcomes Research Institute.
This portion of the study included more than 8,500 patients and was the first of eight manuscripts accepted for publication from a larger study conducted in 2015. The corresponding author is George J. Chang, MD, FACS, chief, section of colon and rectal surgery; professor of surgical oncology and health services research; and director of clinical operations, minimally invasive and new technologies in oncologic surgery program, University of Texas MD Anderson Cancer Center, Houston.
View the full text article on the JAMA website at https://jamanetwork.com/journals/jama/fullarticle/2681746/.
The first findings from a collaborative study within the American College of Surgeons (ACS) Cancer Programs—and published earlier this week in the Journal of the American Medical Association (JAMA)—showed no significant association between frequency of surveillance testing and the time to detection of recurrence for colorectal cancer patients.
The study is an effort of the ACS Clinical Research Program and the Commission on Cancer and uses data from the National Cancer Database (NCDB), which is jointly sponsored by the ACS and the American Cancer Society. It focuses on post-treatment surveillance for breast, colon, and lung cancers and was funded by the Patient-Centered Outcomes Research Institute.
This portion of the study included more than 8,500 patients and was the first of eight manuscripts accepted for publication from a larger study conducted in 2015. The corresponding author is George J. Chang, MD, FACS, chief, section of colon and rectal surgery; professor of surgical oncology and health services research; and director of clinical operations, minimally invasive and new technologies in oncologic surgery program, University of Texas MD Anderson Cancer Center, Houston.
View the full text article on the JAMA website at https://jamanetwork.com/journals/jama/fullarticle/2681746/.
The first findings from a collaborative study within the American College of Surgeons (ACS) Cancer Programs—and published earlier this week in the Journal of the American Medical Association (JAMA)—showed no significant association between frequency of surveillance testing and the time to detection of recurrence for colorectal cancer patients.
The study is an effort of the ACS Clinical Research Program and the Commission on Cancer and uses data from the National Cancer Database (NCDB), which is jointly sponsored by the ACS and the American Cancer Society. It focuses on post-treatment surveillance for breast, colon, and lung cancers and was funded by the Patient-Centered Outcomes Research Institute.
This portion of the study included more than 8,500 patients and was the first of eight manuscripts accepted for publication from a larger study conducted in 2015. The corresponding author is George J. Chang, MD, FACS, chief, section of colon and rectal surgery; professor of surgical oncology and health services research; and director of clinical operations, minimally invasive and new technologies in oncologic surgery program, University of Texas MD Anderson Cancer Center, Houston.
View the full text article on the JAMA website at https://jamanetwork.com/journals/jama/fullarticle/2681746/.