The Diagnosis: Plexiform Neurofibroma as a Manifestation of Neurofibromatosis Type I

Physical examination revealed a large 10×8-cm subcutaneous nodule that was boggy and resembled a bag of worms on palpation. It was covered by slightly hyperpigmented skin. He also had numerous (>20) café au lait spots measuring 2 to 3 cm across the body and several others on the axillae. There were no gross eye findings. Otherwise the examination was unremarkable on the rest of the body. The patient’s paternal grandfather and aunt had similar macules and multiple nodules. The patient had mild to moderate learning difficulties. He was subsequently referred for genetic and ophthalmology evaluation.

Plexiform neurofibromas are usually benign nerve sheath tumors that are elongated and are multinodular, forming when the tumor involves either multiple trunks of a plexus or multiple fascicles of a large nerve such as the sciatic. Some plexiform neurofibromas resemble a bag of worms; others produce a massive ropy enlargement of the nerve.^1,2 Plexiform neurofibromas are associated with cases of neurofibromatosis type I (NFI) and are themselves one of the diagnostic criteria for NFI.¹

Plexiform neurofibromas are benign tumors that are the result of a genetic mutation in which loss of heterozygosity occurs, as is the case with the other predominant neoplasms of NFI, that results in unrestricted cell growth.^3,4 Some patients have a loss of heterozygosity of this tumor suppression gene with overgrowth of neurofibromatosis on a Blaschko segment. One study in mouse models showed that stromal mast cells were involved in promoting inflammation and increasing tumor growth by mediation of mitogenic signals involved in vascular ingrowth, collagen deposition, and cellular proliferation.⁵ Plexiform neurofibromas are a presenting feature in 30% of NFI cases within the first year of life. They are extensive nerve sheath tumors with an unpredictable growth pattern that can involve multiple fascicles (ie, large nerves and their branches). Five percent become malignant and the transformation is often heralded by rapid growth and pain.⁶ If malignant transformation is suspected, biopsy is diagnostic. Magnetic resonance imaging with and without contrast can categorize them into 3 growth categories: superficial, displacing, and invasive.⁷ Because plexiform neurofibromas are rare tumors, it previously was common practice to delay surgical intervention until disfigurement or disability arose. Complete surgical resection at more advanced stages is nearly impossible given the networklike growth pattern that commonly encapsulates vital structures.^8,9 Therefore, surgery has been used in the past for debulking the large growths that eventually will recur. A study of 9 small superficial plexiform neurofibromas in children aged 3 to 15 years documented treatment with early surgical resection, which showed complete resection and no relapse at 4 years. This study showed a promising strategy to prevent future extension of these fast-growing tumors into vital structures.⁸ There also are current clinical trials investigating sirolimus and peginterferon alfa-2b in patients with more invasive plexiform neurofibromas that are unable to undergo surgical resection due to encapsulation or proximity to essential anatomical structures (registered at www.clinicaltrials.gov with the identifiers NCT00652990 and NCT00678951, respectively).

Pain, development of a neurologic deficit, or enlargement of a preexisting plexiform neurofibroma may signal a malignant peripheral nerve sheath tumor (MPNST) and require immediate evaluation.¹⁰ Examination by magnetic resonance imaging and positron emission tomography is useful in distinguishing benign and MPNSTs,^8,11,12 but definitive differentiation can only be made by histologic examination of the tumor. Complete surgical excision, when possible, is the only treatment that offers the possibility of cure of MPNSTs. Adjuvant chemotherapy or radiotherapy also is sometimes used, though benefit has not been clearly established.^8,9,13,14

Death certificate and population-based studies have shown that approximately 10% of patients with NFI have a reduced life expectancy due to MPNSTs; indeed, these tumors arising from plexiform neurofibromas are the main cause of death in adults with NFI. In 2003, Mautner et al⁷ studied 50 individuals with NFI. The objective was to establish magnetic resonance imaging criteria for MPNST and to test their usefulness in detecting early malignant change in plexiform neurofibromas. This study found that MPNST in patients with NFI frequently showed inhomogeneous contrast enhancement. This inhomogeneity was due to necrosis and hemorrhage, as shown by macroscopic and histologic analysis of amputated limbs in 2 patients within the study. The investigators found it to be possible to detect malignant transformation at an early stage in patients with no overt clinical signs of progression.⁷ Careful follow-up will determine how frequently early malignancy can be detected and if it is worthwhile carrying out magnetic resonance imaging at defined intervals.^2,7,10,15,16

The Diagnosis: Plexiform Neurofibroma as a Manifestation of Neurofibromatosis Type I

Physical examination revealed a large 10×8-cm subcutaneous nodule that was boggy and resembled a bag of worms on palpation. It was covered by slightly hyperpigmented skin. He also had numerous (>20) café au lait spots measuring 2 to 3 cm across the body and several others on the axillae. There were no gross eye findings. Otherwise the examination was unremarkable on the rest of the body. The patient’s paternal grandfather and aunt had similar macules and multiple nodules. The patient had mild to moderate learning difficulties. He was subsequently referred for genetic and ophthalmology evaluation.

Plexiform neurofibromas are usually benign nerve sheath tumors that are elongated and are multinodular, forming when the tumor involves either multiple trunks of a plexus or multiple fascicles of a large nerve such as the sciatic. Some plexiform neurofibromas resemble a bag of worms; others produce a massive ropy enlargement of the nerve.^1,2 Plexiform neurofibromas are associated with cases of neurofibromatosis type I (NFI) and are themselves one of the diagnostic criteria for NFI.¹

Plexiform neurofibromas are benign tumors that are the result of a genetic mutation in which loss of heterozygosity occurs, as is the case with the other predominant neoplasms of NFI, that results in unrestricted cell growth.^3,4 Some patients have a loss of heterozygosity of this tumor suppression gene with overgrowth of neurofibromatosis on a Blaschko segment. One study in mouse models showed that stromal mast cells were involved in promoting inflammation and increasing tumor growth by mediation of mitogenic signals involved in vascular ingrowth, collagen deposition, and cellular proliferation.⁵ Plexiform neurofibromas are a presenting feature in 30% of NFI cases within the first year of life. They are extensive nerve sheath tumors with an unpredictable growth pattern that can involve multiple fascicles (ie, large nerves and their branches). Five percent become malignant and the transformation is often heralded by rapid growth and pain.⁶ If malignant transformation is suspected, biopsy is diagnostic. Magnetic resonance imaging with and without contrast can categorize them into 3 growth categories: superficial, displacing, and invasive.⁷ Because plexiform neurofibromas are rare tumors, it previously was common practice to delay surgical intervention until disfigurement or disability arose. Complete surgical resection at more advanced stages is nearly impossible given the networklike growth pattern that commonly encapsulates vital structures.^8,9 Therefore, surgery has been used in the past for debulking the large growths that eventually will recur. A study of 9 small superficial plexiform neurofibromas in children aged 3 to 15 years documented treatment with early surgical resection, which showed complete resection and no relapse at 4 years. This study showed a promising strategy to prevent future extension of these fast-growing tumors into vital structures.⁸ There also are current clinical trials investigating sirolimus and peginterferon alfa-2b in patients with more invasive plexiform neurofibromas that are unable to undergo surgical resection due to encapsulation or proximity to essential anatomical structures (registered at www.clinicaltrials.gov with the identifiers NCT00652990 and NCT00678951, respectively).

Pain, development of a neurologic deficit, or enlargement of a preexisting plexiform neurofibroma may signal a malignant peripheral nerve sheath tumor (MPNST) and require immediate evaluation.¹⁰ Examination by magnetic resonance imaging and positron emission tomography is useful in distinguishing benign and MPNSTs,^8,11,12 but definitive differentiation can only be made by histologic examination of the tumor. Complete surgical excision, when possible, is the only treatment that offers the possibility of cure of MPNSTs. Adjuvant chemotherapy or radiotherapy also is sometimes used, though benefit has not been clearly established.^8,9,13,14

Death certificate and population-based studies have shown that approximately 10% of patients with NFI have a reduced life expectancy due to MPNSTs; indeed, these tumors arising from plexiform neurofibromas are the main cause of death in adults with NFI. In 2003, Mautner et al⁷ studied 50 individuals with NFI. The objective was to establish magnetic resonance imaging criteria for MPNST and to test their usefulness in detecting early malignant change in plexiform neurofibromas. This study found that MPNST in patients with NFI frequently showed inhomogeneous contrast enhancement. This inhomogeneity was due to necrosis and hemorrhage, as shown by macroscopic and histologic analysis of amputated limbs in 2 patients within the study. The investigators found it to be possible to detect malignant transformation at an early stage in patients with no overt clinical signs of progression.⁷ Careful follow-up will determine how frequently early malignancy can be detected and if it is worthwhile carrying out magnetic resonance imaging at defined intervals.^2,7,10,15,16

The Diagnosis: Plexiform Neurofibroma as a Manifestation of Neurofibromatosis Type I

Physical examination revealed a large 10×8-cm subcutaneous nodule that was boggy and resembled a bag of worms on palpation. It was covered by slightly hyperpigmented skin. He also had numerous (>20) café au lait spots measuring 2 to 3 cm across the body and several others on the axillae. There were no gross eye findings. Otherwise the examination was unremarkable on the rest of the body. The patient’s paternal grandfather and aunt had similar macules and multiple nodules. The patient had mild to moderate learning difficulties. He was subsequently referred for genetic and ophthalmology evaluation.

Plexiform neurofibromas are usually benign nerve sheath tumors that are elongated and are multinodular, forming when the tumor involves either multiple trunks of a plexus or multiple fascicles of a large nerve such as the sciatic. Some plexiform neurofibromas resemble a bag of worms; others produce a massive ropy enlargement of the nerve.^1,2 Plexiform neurofibromas are associated with cases of neurofibromatosis type I (NFI) and are themselves one of the diagnostic criteria for NFI.¹

Plexiform neurofibromas are benign tumors that are the result of a genetic mutation in which loss of heterozygosity occurs, as is the case with the other predominant neoplasms of NFI, that results in unrestricted cell growth.^3,4 Some patients have a loss of heterozygosity of this tumor suppression gene with overgrowth of neurofibromatosis on a Blaschko segment. One study in mouse models showed that stromal mast cells were involved in promoting inflammation and increasing tumor growth by mediation of mitogenic signals involved in vascular ingrowth, collagen deposition, and cellular proliferation.⁵ Plexiform neurofibromas are a presenting feature in 30% of NFI cases within the first year of life. They are extensive nerve sheath tumors with an unpredictable growth pattern that can involve multiple fascicles (ie, large nerves and their branches). Five percent become malignant and the transformation is often heralded by rapid growth and pain.⁶ If malignant transformation is suspected, biopsy is diagnostic. Magnetic resonance imaging with and without contrast can categorize them into 3 growth categories: superficial, displacing, and invasive.⁷ Because plexiform neurofibromas are rare tumors, it previously was common practice to delay surgical intervention until disfigurement or disability arose. Complete surgical resection at more advanced stages is nearly impossible given the networklike growth pattern that commonly encapsulates vital structures.^8,9 Therefore, surgery has been used in the past for debulking the large growths that eventually will recur. A study of 9 small superficial plexiform neurofibromas in children aged 3 to 15 years documented treatment with early surgical resection, which showed complete resection and no relapse at 4 years. This study showed a promising strategy to prevent future extension of these fast-growing tumors into vital structures.⁸ There also are current clinical trials investigating sirolimus and peginterferon alfa-2b in patients with more invasive plexiform neurofibromas that are unable to undergo surgical resection due to encapsulation or proximity to essential anatomical structures (registered at www.clinicaltrials.gov with the identifiers NCT00652990 and NCT00678951, respectively).

Pain, development of a neurologic deficit, or enlargement of a preexisting plexiform neurofibroma may signal a malignant peripheral nerve sheath tumor (MPNST) and require immediate evaluation.¹⁰ Examination by magnetic resonance imaging and positron emission tomography is useful in distinguishing benign and MPNSTs,^8,11,12 but definitive differentiation can only be made by histologic examination of the tumor. Complete surgical excision, when possible, is the only treatment that offers the possibility of cure of MPNSTs. Adjuvant chemotherapy or radiotherapy also is sometimes used, though benefit has not been clearly established.^8,9,13,14

Death certificate and population-based studies have shown that approximately 10% of patients with NFI have a reduced life expectancy due to MPNSTs; indeed, these tumors arising from plexiform neurofibromas are the main cause of death in adults with NFI. In 2003, Mautner et al⁷ studied 50 individuals with NFI. The objective was to establish magnetic resonance imaging criteria for MPNST and to test their usefulness in detecting early malignant change in plexiform neurofibromas. This study found that MPNST in patients with NFI frequently showed inhomogeneous contrast enhancement. This inhomogeneity was due to necrosis and hemorrhage, as shown by macroscopic and histologic analysis of amputated limbs in 2 patients within the study. The investigators found it to be possible to detect malignant transformation at an early stage in patients with no overt clinical signs of progression.⁷ Careful follow-up will determine how frequently early malignancy can be detected and if it is worthwhile carrying out magnetic resonance imaging at defined intervals.^2,7,10,15,16

Annual fecal immunochemical testing (FIT) for colorectal cancer screening demonstrated slightly decreased but steady sensitivity and predictive values over several rounds with a high participation rate.

According to the report, noninvasive fecal blood testing has been shown to decrease colorectal cancer (CRC) incidence and mortality. Further, screening with fecal immunochemical testing (FIT) doesn’t require consideration of medications or dietary factors as guaiac stool testing does.

Dr. Christopher Jensen of the Kaiser Permanente Division of Research in Oakland, Calif., and colleagues conducted a retrospective cohort study of 50- to 70-year-olds to assess the performance of FIT for 4 years of annual screening. Their results were published in Annals of Internal Medicine.

Courtesy Wikimedia Commons/nephron/Creative Commons License

In total, 670,841 participants received FIT kits and 48.2% returned completed kits. Among the participants in round 1, 55.4% were white, 46.4% were men, and the mean age was 58.5 years. In subsequent rounds, eligible participants returned the kits at a rate of 75.3% for round 2, 83.4% for round 3, 86.1% for round 4, and 63.8% overall.

Tests were 5% positive in the first round and ranged from 3.7% to 4.3% positive in subsequent rounds. Further, men compared with women (5.1% versus 3.7%) and older participants compared to younger (5.2% versus 4.1%) had higher rates of FIT positivity. Follow-up colonoscopy was obtained within 1 year (median 45 days) of a positive FIT in 78.4% of participants.

The positive predictive value for adenoma was highest in the first round at 51.5% and ranged from 47.4% to 48.5% in subsequent rounds. Similarly, the positive predictive value for colorectal cancer was 3.4% in the first round and ranged from 2.1% to 2.3% in subsequent rounds.

Finally, the sensitivity of FIT for CRC was 84.5% in the first round and between 73.4% and 78% in subsequent rounds. Across all screening rounds, participants with a diagnosis with CRC had a positive FIT between 79.7% in round 1 to 75.3% in round 4 beforehand. The authors point out that sensitivity was slightly lower for proximal compared with distal cancer. Further, those with a positive FIT the year prior were less likely to have advanced-stage CRC (26.9%) than those with a negative FIT (33.1%) or not screened (37.1%).

Dr. Corley and Dr. Levin reported grants from the National Cancer Institute, which supported the study. Dr. Jensen reported grants from the National Institutes of Health, and Dr. Doubeni reported consulting for Exact Sciences.

Annual fecal immunochemical testing (FIT) for colorectal cancer screening demonstrated slightly decreased but steady sensitivity and predictive values over several rounds with a high participation rate.

According to the report, noninvasive fecal blood testing has been shown to decrease colorectal cancer (CRC) incidence and mortality. Further, screening with fecal immunochemical testing (FIT) doesn’t require consideration of medications or dietary factors as guaiac stool testing does.

Dr. Christopher Jensen of the Kaiser Permanente Division of Research in Oakland, Calif., and colleagues conducted a retrospective cohort study of 50- to 70-year-olds to assess the performance of FIT for 4 years of annual screening. Their results were published in Annals of Internal Medicine.

Courtesy Wikimedia Commons/nephron/Creative Commons License

In total, 670,841 participants received FIT kits and 48.2% returned completed kits. Among the participants in round 1, 55.4% were white, 46.4% were men, and the mean age was 58.5 years. In subsequent rounds, eligible participants returned the kits at a rate of 75.3% for round 2, 83.4% for round 3, 86.1% for round 4, and 63.8% overall.

Tests were 5% positive in the first round and ranged from 3.7% to 4.3% positive in subsequent rounds. Further, men compared with women (5.1% versus 3.7%) and older participants compared to younger (5.2% versus 4.1%) had higher rates of FIT positivity. Follow-up colonoscopy was obtained within 1 year (median 45 days) of a positive FIT in 78.4% of participants.

The positive predictive value for adenoma was highest in the first round at 51.5% and ranged from 47.4% to 48.5% in subsequent rounds. Similarly, the positive predictive value for colorectal cancer was 3.4% in the first round and ranged from 2.1% to 2.3% in subsequent rounds.

Finally, the sensitivity of FIT for CRC was 84.5% in the first round and between 73.4% and 78% in subsequent rounds. Across all screening rounds, participants with a diagnosis with CRC had a positive FIT between 79.7% in round 1 to 75.3% in round 4 beforehand. The authors point out that sensitivity was slightly lower for proximal compared with distal cancer. Further, those with a positive FIT the year prior were less likely to have advanced-stage CRC (26.9%) than those with a negative FIT (33.1%) or not screened (37.1%).

Dr. Corley and Dr. Levin reported grants from the National Cancer Institute, which supported the study. Dr. Jensen reported grants from the National Institutes of Health, and Dr. Doubeni reported consulting for Exact Sciences.

Annual fecal immunochemical testing (FIT) for colorectal cancer screening demonstrated slightly decreased but steady sensitivity and predictive values over several rounds with a high participation rate.

According to the report, noninvasive fecal blood testing has been shown to decrease colorectal cancer (CRC) incidence and mortality. Further, screening with fecal immunochemical testing (FIT) doesn’t require consideration of medications or dietary factors as guaiac stool testing does.

Dr. Christopher Jensen of the Kaiser Permanente Division of Research in Oakland, Calif., and colleagues conducted a retrospective cohort study of 50- to 70-year-olds to assess the performance of FIT for 4 years of annual screening. Their results were published in Annals of Internal Medicine.

Courtesy Wikimedia Commons/nephron/Creative Commons License

In total, 670,841 participants received FIT kits and 48.2% returned completed kits. Among the participants in round 1, 55.4% were white, 46.4% were men, and the mean age was 58.5 years. In subsequent rounds, eligible participants returned the kits at a rate of 75.3% for round 2, 83.4% for round 3, 86.1% for round 4, and 63.8% overall.

Tests were 5% positive in the first round and ranged from 3.7% to 4.3% positive in subsequent rounds. Further, men compared with women (5.1% versus 3.7%) and older participants compared to younger (5.2% versus 4.1%) had higher rates of FIT positivity. Follow-up colonoscopy was obtained within 1 year (median 45 days) of a positive FIT in 78.4% of participants.

The positive predictive value for adenoma was highest in the first round at 51.5% and ranged from 47.4% to 48.5% in subsequent rounds. Similarly, the positive predictive value for colorectal cancer was 3.4% in the first round and ranged from 2.1% to 2.3% in subsequent rounds.

Finally, the sensitivity of FIT for CRC was 84.5% in the first round and between 73.4% and 78% in subsequent rounds. Across all screening rounds, participants with a diagnosis with CRC had a positive FIT between 79.7% in round 1 to 75.3% in round 4 beforehand. The authors point out that sensitivity was slightly lower for proximal compared with distal cancer. Further, those with a positive FIT the year prior were less likely to have advanced-stage CRC (26.9%) than those with a negative FIT (33.1%) or not screened (37.1%).

Dr. Corley and Dr. Levin reported grants from the National Cancer Institute, which supported the study. Dr. Jensen reported grants from the National Institutes of Health, and Dr. Doubeni reported consulting for Exact Sciences.

There were no states in the “high” range of influenza-like illness (ILI) activity during week 14 of the 2015-2016 flu season, but there were more states with elevated levels, compared with the previous week, the Centers for Disease Control and Prevention reported.

Arizona had the highest activity (level 7) for the week ending Jan. 16, with Maryland and South Carolina (level 6) the only other states in the “moderate” range of ILI activity. There were 21 states at level 2 or higher, up from 18 the week before, but still below the peak of 24 that was seen 2 weeks ago. The overall proportion of outpatient visits for ILI was 2.1% for week 14, which was up from 2% for week 13 but was right at the national baseline, according to data from the CDC’s Outpatient Influenza-like Illness Surveillance Network.

There were no influenza-related pediatric deaths reported for week 14, so the number of total deaths remains at seven for the season, which is well below the week-14 totals for each of the previous three seasons. There have been 494 laboratory-confirmed influenza-associated hospitalizations reported in the 13 states of the CDC’s Influenza Hospitalization Surveillance Network through week 14, for an overall hospitalization rate of 1.8/100,000 population, the CDC said.

Among all hospitalizations, 65.4% were associated with influenza A, 28.7% with influenza B, 3.2% with influenza A and B coinfection, and 2.6% had no virus type information, the CDC report noted.

[email protected]

There were no states in the “high” range of influenza-like illness (ILI) activity during week 14 of the 2015-2016 flu season, but there were more states with elevated levels, compared with the previous week, the Centers for Disease Control and Prevention reported.

Arizona had the highest activity (level 7) for the week ending Jan. 16, with Maryland and South Carolina (level 6) the only other states in the “moderate” range of ILI activity. There were 21 states at level 2 or higher, up from 18 the week before, but still below the peak of 24 that was seen 2 weeks ago. The overall proportion of outpatient visits for ILI was 2.1% for week 14, which was up from 2% for week 13 but was right at the national baseline, according to data from the CDC’s Outpatient Influenza-like Illness Surveillance Network.

There were no influenza-related pediatric deaths reported for week 14, so the number of total deaths remains at seven for the season, which is well below the week-14 totals for each of the previous three seasons. There have been 494 laboratory-confirmed influenza-associated hospitalizations reported in the 13 states of the CDC’s Influenza Hospitalization Surveillance Network through week 14, for an overall hospitalization rate of 1.8/100,000 population, the CDC said.

Among all hospitalizations, 65.4% were associated with influenza A, 28.7% with influenza B, 3.2% with influenza A and B coinfection, and 2.6% had no virus type information, the CDC report noted.

[email protected]

There were no states in the “high” range of influenza-like illness (ILI) activity during week 14 of the 2015-2016 flu season, but there were more states with elevated levels, compared with the previous week, the Centers for Disease Control and Prevention reported.

Arizona had the highest activity (level 7) for the week ending Jan. 16, with Maryland and South Carolina (level 6) the only other states in the “moderate” range of ILI activity. There were 21 states at level 2 or higher, up from 18 the week before, but still below the peak of 24 that was seen 2 weeks ago. The overall proportion of outpatient visits for ILI was 2.1% for week 14, which was up from 2% for week 13 but was right at the national baseline, according to data from the CDC’s Outpatient Influenza-like Illness Surveillance Network.

There were no influenza-related pediatric deaths reported for week 14, so the number of total deaths remains at seven for the season, which is well below the week-14 totals for each of the previous three seasons. There have been 494 laboratory-confirmed influenza-associated hospitalizations reported in the 13 states of the CDC’s Influenza Hospitalization Surveillance Network through week 14, for an overall hospitalization rate of 1.8/100,000 population, the CDC said.

Among all hospitalizations, 65.4% were associated with influenza A, 28.7% with influenza B, 3.2% with influenza A and B coinfection, and 2.6% had no virus type information, the CDC report noted.

[email protected]

Peripheral T-cell lymphoma (PTCL) incidence, proportions of subtypes, and survival differed markedly among racial/ethnic subpopulations in the United States, according to analysis of SEER cancer registries.

Compared with non-Hispanic whites, blacks had higher incidence rates overall of PTCL, due to higher rates of PTCL not otherwise specified (PTCL-NOS) (incidence rate ratio [IRR], 1.67; 95% CI, 1.53-1.82) and adult T-cell leukemia/lymphoma (ATLL) (IRR, 4.37; 3.42-5.56). By contrast, blacks had lower incidence rates of angioimmunoblastic T-cell lymphoma (AITL) and extranodal NK/T-cell lymphoma and natural killer–cell leukemia (ENKCL) than non-Hispanic whites. Underlying causes for these differences are not understood.

“Our findings also highlight the need for stronger efforts to increase recruitment of blacks into clinical trials of PTCL therapies,” wrote Dr. Scott Adams of Fred Hutchinson Cancer Research Center, Seattle, and colleagues (J Clin Oncol. 2016 Jan 25. doi: 10.1200/JCO.2015.635540).

Asians/Pacific Islanders and Hispanic whites had higher rates of ENKCL (IRR, 3.61; 2.93-4.42), and ENKCL comprised a larger proportion of PTCL (14%) in these populations than for non-Hispanic whites (3%), findings which reflect global variations. High rates of ENKCL may be influenced by both genetic and environmental factors, as 35% of this subpopulation was born outside the U.S., compared with 16% of all patients with PTCL. Epstein-Barre virus infection is associated with ENKCL.

Similar to global incidence patterns, Asians/Pacific Islanders had lower rates of anaplastic large-cell lymphoma (ALCL).

Higher incidence of ATLL among blacks and Asians/Pacific Islanders corresponded to a higher prevalence of human T-lymphotropic virus type 1 in these populations. Substantial differences in survival were also observed. Compared with non-Hispanic whites, survival with PTCL-NOS was shorter for every minority group, and blacks had worse prognoses for almost every histology. For patients with any PTCL, median survival time varied by race: 49 months for non-Hispanic whites, 24 for blacks, 22 for Asians/Pacific Islanders, 28 for Hispanic whites, and 36 for American Indians/Alaskan natives.

Reasons for survival disparities are not known, but contributing factors may include racial variations in pharmacokinetics or pharmacodynamics of therapeutic agents and genomic variations of the tumors, as well as healthcare disparities and socioeconomic factors.

The analysis used data from SEER cancer registries of 13,107 patients 15 years and older who had PTCL diagnosed in the U.S. between 2000 and 2012.

For non-Hispanic whites, the annual incidence rate of all PTCLs was 1.56 (95% CI; 1.52-1.59) per 100,000. Compared with non-Hispanic whites, incidence rate ratios were 1.32 (1.25-1.39; P less than .001) for blacks, 0.89 (0.83-0.95; P less than .001) for Asians/Pacific Islanders, 0.63 (0.49-0.79; P less than .001) for American Indians/Alaskan natives, and 0.96 (0.90-1.01; P = .13) for Hispanic whites.

Peripheral T-cell lymphoma (PTCL) incidence, proportions of subtypes, and survival differed markedly among racial/ethnic subpopulations in the United States, according to analysis of SEER cancer registries.

Compared with non-Hispanic whites, blacks had higher incidence rates overall of PTCL, due to higher rates of PTCL not otherwise specified (PTCL-NOS) (incidence rate ratio [IRR], 1.67; 95% CI, 1.53-1.82) and adult T-cell leukemia/lymphoma (ATLL) (IRR, 4.37; 3.42-5.56). By contrast, blacks had lower incidence rates of angioimmunoblastic T-cell lymphoma (AITL) and extranodal NK/T-cell lymphoma and natural killer–cell leukemia (ENKCL) than non-Hispanic whites. Underlying causes for these differences are not understood.

“Our findings also highlight the need for stronger efforts to increase recruitment of blacks into clinical trials of PTCL therapies,” wrote Dr. Scott Adams of Fred Hutchinson Cancer Research Center, Seattle, and colleagues (J Clin Oncol. 2016 Jan 25. doi: 10.1200/JCO.2015.635540).

Asians/Pacific Islanders and Hispanic whites had higher rates of ENKCL (IRR, 3.61; 2.93-4.42), and ENKCL comprised a larger proportion of PTCL (14%) in these populations than for non-Hispanic whites (3%), findings which reflect global variations. High rates of ENKCL may be influenced by both genetic and environmental factors, as 35% of this subpopulation was born outside the U.S., compared with 16% of all patients with PTCL. Epstein-Barre virus infection is associated with ENKCL.

Similar to global incidence patterns, Asians/Pacific Islanders had lower rates of anaplastic large-cell lymphoma (ALCL).

Higher incidence of ATLL among blacks and Asians/Pacific Islanders corresponded to a higher prevalence of human T-lymphotropic virus type 1 in these populations. Substantial differences in survival were also observed. Compared with non-Hispanic whites, survival with PTCL-NOS was shorter for every minority group, and blacks had worse prognoses for almost every histology. For patients with any PTCL, median survival time varied by race: 49 months for non-Hispanic whites, 24 for blacks, 22 for Asians/Pacific Islanders, 28 for Hispanic whites, and 36 for American Indians/Alaskan natives.

Reasons for survival disparities are not known, but contributing factors may include racial variations in pharmacokinetics or pharmacodynamics of therapeutic agents and genomic variations of the tumors, as well as healthcare disparities and socioeconomic factors.

The analysis used data from SEER cancer registries of 13,107 patients 15 years and older who had PTCL diagnosed in the U.S. between 2000 and 2012.

For non-Hispanic whites, the annual incidence rate of all PTCLs was 1.56 (95% CI; 1.52-1.59) per 100,000. Compared with non-Hispanic whites, incidence rate ratios were 1.32 (1.25-1.39; P less than .001) for blacks, 0.89 (0.83-0.95; P less than .001) for Asians/Pacific Islanders, 0.63 (0.49-0.79; P less than .001) for American Indians/Alaskan natives, and 0.96 (0.90-1.01; P = .13) for Hispanic whites.

Peripheral T-cell lymphoma (PTCL) incidence, proportions of subtypes, and survival differed markedly among racial/ethnic subpopulations in the United States, according to analysis of SEER cancer registries.

Compared with non-Hispanic whites, blacks had higher incidence rates overall of PTCL, due to higher rates of PTCL not otherwise specified (PTCL-NOS) (incidence rate ratio [IRR], 1.67; 95% CI, 1.53-1.82) and adult T-cell leukemia/lymphoma (ATLL) (IRR, 4.37; 3.42-5.56). By contrast, blacks had lower incidence rates of angioimmunoblastic T-cell lymphoma (AITL) and extranodal NK/T-cell lymphoma and natural killer–cell leukemia (ENKCL) than non-Hispanic whites. Underlying causes for these differences are not understood.

“Our findings also highlight the need for stronger efforts to increase recruitment of blacks into clinical trials of PTCL therapies,” wrote Dr. Scott Adams of Fred Hutchinson Cancer Research Center, Seattle, and colleagues (J Clin Oncol. 2016 Jan 25. doi: 10.1200/JCO.2015.635540).

Asians/Pacific Islanders and Hispanic whites had higher rates of ENKCL (IRR, 3.61; 2.93-4.42), and ENKCL comprised a larger proportion of PTCL (14%) in these populations than for non-Hispanic whites (3%), findings which reflect global variations. High rates of ENKCL may be influenced by both genetic and environmental factors, as 35% of this subpopulation was born outside the U.S., compared with 16% of all patients with PTCL. Epstein-Barre virus infection is associated with ENKCL.

Similar to global incidence patterns, Asians/Pacific Islanders had lower rates of anaplastic large-cell lymphoma (ALCL).

Higher incidence of ATLL among blacks and Asians/Pacific Islanders corresponded to a higher prevalence of human T-lymphotropic virus type 1 in these populations. Substantial differences in survival were also observed. Compared with non-Hispanic whites, survival with PTCL-NOS was shorter for every minority group, and blacks had worse prognoses for almost every histology. For patients with any PTCL, median survival time varied by race: 49 months for non-Hispanic whites, 24 for blacks, 22 for Asians/Pacific Islanders, 28 for Hispanic whites, and 36 for American Indians/Alaskan natives.

Reasons for survival disparities are not known, but contributing factors may include racial variations in pharmacokinetics or pharmacodynamics of therapeutic agents and genomic variations of the tumors, as well as healthcare disparities and socioeconomic factors.

The analysis used data from SEER cancer registries of 13,107 patients 15 years and older who had PTCL diagnosed in the U.S. between 2000 and 2012.

For non-Hispanic whites, the annual incidence rate of all PTCLs was 1.56 (95% CI; 1.52-1.59) per 100,000. Compared with non-Hispanic whites, incidence rate ratios were 1.32 (1.25-1.39; P less than .001) for blacks, 0.89 (0.83-0.95; P less than .001) for Asians/Pacific Islanders, 0.63 (0.49-0.79; P less than .001) for American Indians/Alaskan natives, and 0.96 (0.90-1.01; P = .13) for Hispanic whites.

In patients with B-cell malignancies who did not obtain remissions after allogeneic hematopoietic stem-cell transplantation (alloHSCT), infusion of anti-CD19 chimeric antigen receptor (CAR19) T-cells induced remissions without causing graft-versus-host disease (GVHD).

Of 20 patients treated, 6 obtained complete remission and 2 obtained partial remissions, while none of the patients experienced new-onset acute GVHD.

“The increased antimalignancy potency of CAR19 T-cells allowed small doses of T-cells to eradicate malignancy without causing GVHD; therefore, this work demonstrates a solution to the central problem of alloHSCT, the separation of [graft-versus-malignancy] from GVHD,” wrote Dr. Jennifer Brudno of the National Cancer Institute, Bethesda, Md., and colleagues (J Clin Onc. 2016 Jan. 25. doi: 10.1200/JCO.2015.64.5929).

In general, CAR19 T-cells did not persist longer than 4 weeks, the median time it takes for GVHD to develop after donor lymphocyte infusion, which may be a factor in avoiding GVHD. Smaller doses may be another contributing factor: CAR19 T-cell doses administered in the trial ranged from 106/kg to 107/kg, which is 10-fold smaller than typical donor lymphocyte infusions.

In contrast to previous CAR T-cell studies, patients did not receive chemotherapy before CAR19 T-cell infusion, so endogenous T-cells and natural killer cells were not depleted. Evidence indicates that lymphocyte depletion enhances antitumor activity of adoptively transferred T-cells, but the current results indicate that prior lymphocyte depletion is not an absolute requirement.

The CAR19 T-cell infusion was especially effective in acute lymphoblastic leukemia (ALL), with four of the five ALL patients obtaining complete remission. Patients with chronic lymphocyte leukemia and lymphoma also obtained remissions.

Toxicities observed were consistent with previous CAR T-cell studies and included fever, tachycardia, and hypotension, indicative of cytokine release syndrome.

Peak levels of CAR19 T-cells were significantly higher in patients with complete or partial responses, and patients who did not obtain a complete or partial response were more likely to have undetectable or very low levels. Increasing peak blood levels of CAR19 T-cells in vivo is an important goal for future research, according to investigators. Since endogenous CD19+ cells may promote proliferation of CAR19 T- cells, CD19+ cellular vaccines might enhance CAR19 T-cell proliferation in patients with low levels, they suggested.

Administration of programmed cell death protein-1 (PD-1) antagonists may also offer improvements. High levels of PD-1 expression on CAR19 T-cells were observed at the time of peak blood CAR19 T-cell levels.

Dr. Brudno reported having no disclosures. Dr. Goy and Dr. Rosenberg reported ties to industry, and Dr. Kochenderfer reported patents pending on CAR T-cell therapy.

In patients with B-cell malignancies who did not obtain remissions after allogeneic hematopoietic stem-cell transplantation (alloHSCT), infusion of anti-CD19 chimeric antigen receptor (CAR19) T-cells induced remissions without causing graft-versus-host disease (GVHD).

Of 20 patients treated, 6 obtained complete remission and 2 obtained partial remissions, while none of the patients experienced new-onset acute GVHD.

“The increased antimalignancy potency of CAR19 T-cells allowed small doses of T-cells to eradicate malignancy without causing GVHD; therefore, this work demonstrates a solution to the central problem of alloHSCT, the separation of [graft-versus-malignancy] from GVHD,” wrote Dr. Jennifer Brudno of the National Cancer Institute, Bethesda, Md., and colleagues (J Clin Onc. 2016 Jan. 25. doi: 10.1200/JCO.2015.64.5929).

In general, CAR19 T-cells did not persist longer than 4 weeks, the median time it takes for GVHD to develop after donor lymphocyte infusion, which may be a factor in avoiding GVHD. Smaller doses may be another contributing factor: CAR19 T-cell doses administered in the trial ranged from 106/kg to 107/kg, which is 10-fold smaller than typical donor lymphocyte infusions.

In contrast to previous CAR T-cell studies, patients did not receive chemotherapy before CAR19 T-cell infusion, so endogenous T-cells and natural killer cells were not depleted. Evidence indicates that lymphocyte depletion enhances antitumor activity of adoptively transferred T-cells, but the current results indicate that prior lymphocyte depletion is not an absolute requirement.

The CAR19 T-cell infusion was especially effective in acute lymphoblastic leukemia (ALL), with four of the five ALL patients obtaining complete remission. Patients with chronic lymphocyte leukemia and lymphoma also obtained remissions.

Toxicities observed were consistent with previous CAR T-cell studies and included fever, tachycardia, and hypotension, indicative of cytokine release syndrome.

Peak levels of CAR19 T-cells were significantly higher in patients with complete or partial responses, and patients who did not obtain a complete or partial response were more likely to have undetectable or very low levels. Increasing peak blood levels of CAR19 T-cells in vivo is an important goal for future research, according to investigators. Since endogenous CD19+ cells may promote proliferation of CAR19 T- cells, CD19+ cellular vaccines might enhance CAR19 T-cell proliferation in patients with low levels, they suggested.

Administration of programmed cell death protein-1 (PD-1) antagonists may also offer improvements. High levels of PD-1 expression on CAR19 T-cells were observed at the time of peak blood CAR19 T-cell levels.

Dr. Brudno reported having no disclosures. Dr. Goy and Dr. Rosenberg reported ties to industry, and Dr. Kochenderfer reported patents pending on CAR T-cell therapy.

In patients with B-cell malignancies who did not obtain remissions after allogeneic hematopoietic stem-cell transplantation (alloHSCT), infusion of anti-CD19 chimeric antigen receptor (CAR19) T-cells induced remissions without causing graft-versus-host disease (GVHD).

Of 20 patients treated, 6 obtained complete remission and 2 obtained partial remissions, while none of the patients experienced new-onset acute GVHD.

“The increased antimalignancy potency of CAR19 T-cells allowed small doses of T-cells to eradicate malignancy without causing GVHD; therefore, this work demonstrates a solution to the central problem of alloHSCT, the separation of [graft-versus-malignancy] from GVHD,” wrote Dr. Jennifer Brudno of the National Cancer Institute, Bethesda, Md., and colleagues (J Clin Onc. 2016 Jan. 25. doi: 10.1200/JCO.2015.64.5929).

In general, CAR19 T-cells did not persist longer than 4 weeks, the median time it takes for GVHD to develop after donor lymphocyte infusion, which may be a factor in avoiding GVHD. Smaller doses may be another contributing factor: CAR19 T-cell doses administered in the trial ranged from 106/kg to 107/kg, which is 10-fold smaller than typical donor lymphocyte infusions.

In contrast to previous CAR T-cell studies, patients did not receive chemotherapy before CAR19 T-cell infusion, so endogenous T-cells and natural killer cells were not depleted. Evidence indicates that lymphocyte depletion enhances antitumor activity of adoptively transferred T-cells, but the current results indicate that prior lymphocyte depletion is not an absolute requirement.

The CAR19 T-cell infusion was especially effective in acute lymphoblastic leukemia (ALL), with four of the five ALL patients obtaining complete remission. Patients with chronic lymphocyte leukemia and lymphoma also obtained remissions.

Toxicities observed were consistent with previous CAR T-cell studies and included fever, tachycardia, and hypotension, indicative of cytokine release syndrome.

Peak levels of CAR19 T-cells were significantly higher in patients with complete or partial responses, and patients who did not obtain a complete or partial response were more likely to have undetectable or very low levels. Increasing peak blood levels of CAR19 T-cells in vivo is an important goal for future research, according to investigators. Since endogenous CD19+ cells may promote proliferation of CAR19 T- cells, CD19+ cellular vaccines might enhance CAR19 T-cell proliferation in patients with low levels, they suggested.

Administration of programmed cell death protein-1 (PD-1) antagonists may also offer improvements. High levels of PD-1 expression on CAR19 T-cells were observed at the time of peak blood CAR19 T-cell levels.

Dr. Brudno reported having no disclosures. Dr. Goy and Dr. Rosenberg reported ties to industry, and Dr. Kochenderfer reported patents pending on CAR T-cell therapy.

Older patients with newly diagnosed acute myeloid leukemia who were unsuitable for intensive chemotherapy had significantly longer overall survival with gemtuzumab ozogamicin, compared with best supportive care, according to phase III trial results published Jan. 25.

The phase III EORTC-GIMEMA AML-19 trial randomly assigned 118 patients to receive gemtuzumab ozogamicin and 119 to receive best supportive care, including hydroxyurea. The median age was 77 years. In total, 104 of 118 patients in the gemtuzumab ozogamicin arm received the full induction course, and the median number of gemtuzumab ozogamicin infusions was three (range: 1 to 10).

Median overall survival (OS) for patients who received gemtuzumab ozogamicin was 4.9 months, compared with 3.6 months for those who received best supportive care, including hydroxyurea (hazard ratio, 0.69; 95% confidence interval, 0.53-0.90; P = .005).

One-year survival rates were 24.3% (95% CI, 16.9 to 32.4) for gemtuzumab ozogamicin and 9.7% (5.1 to 15.9) for best supportive care (J Clin Onc. 2016 Jan 25. doi: 10.1200/JCO.2015.64.0060).

The low intensity gemtuzumab ozogamicin regimen was generally well tolerated, with comparable toxicity between arms. Pancytopenia was observed in nearly all patients during gemtuzumab ozogamicin induction, however.

“Of importance, liver toxicity, a hallmark of [gemtuzumab ozogamicin] safety profile, was not increased in [gemtuzumab ozogamicin] recipients. Furthermore, it appeared to be less frequent and severe than previously reported by our group in a first-line trial, in which a more intensive [gemtuzumab ozogamicin] regimen was used in elderly patients with AML unfit for intensive chemotherapy,” wrote Dr. Sergio Amadori of the Tor Vergata University, Rome, and his colleagues.

Gemtuzumab ozogamicin therapy resulted in an overall complete response (CR) rate of 27% (15.3% CR and 11.7% CRi [incomplete recovery of peripheral blood counts]). The overall clinical benefit rate (CR + CRi+ partial response + stable disease for 30 days) was 56.7%.

Gemtuzumab ozogamicin combines a human monoclonal antibody specific for CD33 on myeloid cells with the DNA intercalator calicheamicin.

Patient characteristics that influenced gemtuzumab ozogamicin treatment effect were CD33 expression status, sex, and cytogenic profile. In patients with more than 80% CD33-positive blasts, gemtuzumab ozogamicin resulted in greater improvements over best supportive care (HR, 0.49; 95% CI, 0.32 to 0.76).

In women, OS was significantly improved (HR, 0.53; 95% CI, 0.35 to 0.79), whereas in men the hazard ratio was near 1. Patients with favorable/intermediate cytogenetic risk profiles had significant gemtuzumab ozogamicin benefit (HR, 0.52; 95% CI, 0.34 to 0.77), and those with adverse risk profiles had no treatment difference between arms.

The research was supported by Wyeth (Pfizer) and by the European Organisation for Research and Treatment of Cancer . Dr. Amadori reported having no disclosures. Several of his coauthors reported ties to industry.

Older patients with newly diagnosed acute myeloid leukemia who were unsuitable for intensive chemotherapy had significantly longer overall survival with gemtuzumab ozogamicin, compared with best supportive care, according to phase III trial results published Jan. 25.

The phase III EORTC-GIMEMA AML-19 trial randomly assigned 118 patients to receive gemtuzumab ozogamicin and 119 to receive best supportive care, including hydroxyurea. The median age was 77 years. In total, 104 of 118 patients in the gemtuzumab ozogamicin arm received the full induction course, and the median number of gemtuzumab ozogamicin infusions was three (range: 1 to 10).

Median overall survival (OS) for patients who received gemtuzumab ozogamicin was 4.9 months, compared with 3.6 months for those who received best supportive care, including hydroxyurea (hazard ratio, 0.69; 95% confidence interval, 0.53-0.90; P = .005).

One-year survival rates were 24.3% (95% CI, 16.9 to 32.4) for gemtuzumab ozogamicin and 9.7% (5.1 to 15.9) for best supportive care (J Clin Onc. 2016 Jan 25. doi: 10.1200/JCO.2015.64.0060).

The low intensity gemtuzumab ozogamicin regimen was generally well tolerated, with comparable toxicity between arms. Pancytopenia was observed in nearly all patients during gemtuzumab ozogamicin induction, however.

“Of importance, liver toxicity, a hallmark of [gemtuzumab ozogamicin] safety profile, was not increased in [gemtuzumab ozogamicin] recipients. Furthermore, it appeared to be less frequent and severe than previously reported by our group in a first-line trial, in which a more intensive [gemtuzumab ozogamicin] regimen was used in elderly patients with AML unfit for intensive chemotherapy,” wrote Dr. Sergio Amadori of the Tor Vergata University, Rome, and his colleagues.

Gemtuzumab ozogamicin therapy resulted in an overall complete response (CR) rate of 27% (15.3% CR and 11.7% CRi [incomplete recovery of peripheral blood counts]). The overall clinical benefit rate (CR + CRi+ partial response + stable disease for 30 days) was 56.7%.

Gemtuzumab ozogamicin combines a human monoclonal antibody specific for CD33 on myeloid cells with the DNA intercalator calicheamicin.

Patient characteristics that influenced gemtuzumab ozogamicin treatment effect were CD33 expression status, sex, and cytogenic profile. In patients with more than 80% CD33-positive blasts, gemtuzumab ozogamicin resulted in greater improvements over best supportive care (HR, 0.49; 95% CI, 0.32 to 0.76).

In women, OS was significantly improved (HR, 0.53; 95% CI, 0.35 to 0.79), whereas in men the hazard ratio was near 1. Patients with favorable/intermediate cytogenetic risk profiles had significant gemtuzumab ozogamicin benefit (HR, 0.52; 95% CI, 0.34 to 0.77), and those with adverse risk profiles had no treatment difference between arms.

The research was supported by Wyeth (Pfizer) and by the European Organisation for Research and Treatment of Cancer . Dr. Amadori reported having no disclosures. Several of his coauthors reported ties to industry.

Older patients with newly diagnosed acute myeloid leukemia who were unsuitable for intensive chemotherapy had significantly longer overall survival with gemtuzumab ozogamicin, compared with best supportive care, according to phase III trial results published Jan. 25.

The phase III EORTC-GIMEMA AML-19 trial randomly assigned 118 patients to receive gemtuzumab ozogamicin and 119 to receive best supportive care, including hydroxyurea. The median age was 77 years. In total, 104 of 118 patients in the gemtuzumab ozogamicin arm received the full induction course, and the median number of gemtuzumab ozogamicin infusions was three (range: 1 to 10).

Median overall survival (OS) for patients who received gemtuzumab ozogamicin was 4.9 months, compared with 3.6 months for those who received best supportive care, including hydroxyurea (hazard ratio, 0.69; 95% confidence interval, 0.53-0.90; P = .005).

One-year survival rates were 24.3% (95% CI, 16.9 to 32.4) for gemtuzumab ozogamicin and 9.7% (5.1 to 15.9) for best supportive care (J Clin Onc. 2016 Jan 25. doi: 10.1200/JCO.2015.64.0060).

The low intensity gemtuzumab ozogamicin regimen was generally well tolerated, with comparable toxicity between arms. Pancytopenia was observed in nearly all patients during gemtuzumab ozogamicin induction, however.

“Of importance, liver toxicity, a hallmark of [gemtuzumab ozogamicin] safety profile, was not increased in [gemtuzumab ozogamicin] recipients. Furthermore, it appeared to be less frequent and severe than previously reported by our group in a first-line trial, in which a more intensive [gemtuzumab ozogamicin] regimen was used in elderly patients with AML unfit for intensive chemotherapy,” wrote Dr. Sergio Amadori of the Tor Vergata University, Rome, and his colleagues.

Gemtuzumab ozogamicin therapy resulted in an overall complete response (CR) rate of 27% (15.3% CR and 11.7% CRi [incomplete recovery of peripheral blood counts]). The overall clinical benefit rate (CR + CRi+ partial response + stable disease for 30 days) was 56.7%.

Gemtuzumab ozogamicin combines a human monoclonal antibody specific for CD33 on myeloid cells with the DNA intercalator calicheamicin.

Patient characteristics that influenced gemtuzumab ozogamicin treatment effect were CD33 expression status, sex, and cytogenic profile. In patients with more than 80% CD33-positive blasts, gemtuzumab ozogamicin resulted in greater improvements over best supportive care (HR, 0.49; 95% CI, 0.32 to 0.76).

In women, OS was significantly improved (HR, 0.53; 95% CI, 0.35 to 0.79), whereas in men the hazard ratio was near 1. Patients with favorable/intermediate cytogenetic risk profiles had significant gemtuzumab ozogamicin benefit (HR, 0.52; 95% CI, 0.34 to 0.77), and those with adverse risk profiles had no treatment difference between arms.

The research was supported by Wyeth (Pfizer) and by the European Organisation for Research and Treatment of Cancer . Dr. Amadori reported having no disclosures. Several of his coauthors reported ties to industry.

Postinflammatory hyperpigmentation (PIH) develops as darkly pigmented macules that occur after an inflammatory process of the skin such as acne, folliculitis, eczema, or shaving irritation. Patients with Fitzpatrick skin types III to VI usually are most commonly affected, and for many, the remnant pigmentation can be an even greater concern than the original inflammatory process.^1,2 Reported treatments of PIH include tretinoin, hydroquinone, azelaic acid, and chemical peels. The ideal combination of therapy has yet to be delineated.

Tretinoin (Vitamin A Derivative)

Bulengo-Ransby et al³ performed one of the first clinical trials testing tretinoin cream 0.1% for PIH in patients with Fitzpatrick skin types IV to VI . The study included 54 patients (24 applied tretinoin and 30 applied a vehicle) with moderate to severe PIH on the face and arms. The patients were divided into therapy and placebo groups and were evaluated for 40 weeks. Changes were evaluated through colorimetry, light microscopy, histology, and photography, with significant clinical improvement in the tretinoin-treated group (P<.001).³ A double-blind, randomized study of 45 photoaged Chinese and Japanese patients using tretinoin cream 0.1% also was conducted for treatment of photoaging-associated hyperpigmented lesions of the face and hands. Assessment was done with clinical, colorimetric, and histological evaluation, with an overall statistical improvement noted in hyperpigmentation.⁴ Both of the above studies showed mild irritation (ie, retinoid dermatitis) with application of tretinoin, which creates a compliance issue in patients who are recommended to continue therapy with higher-strength tretinoin. This side-effect profile can be circumvented through gradual elevation in the strength of tretinoin.⁵

Combination Therapies

Combination therapies with tretinoin also have been used to improve PIH. Callender et al⁶ conducted a study evaluating the efficacy of clindamycin phosphate 1.2%–tretinoin 0.025% gel for the treatment of PIH secondary to mild to moderate acne in patients with Fitzpatrick skin types IV to VI. Thirty patients participated in the randomized, double-blinded, placebo-controlled study, with 15 patients in the clindamycin-tretinoin gel group and 15 in the placebo control group. Based on objective assessment using a chromameter and evaluator global acne severity scale score, clinical efficacy was demonstrated for treating acne and PIH as well as preventing further PIH.⁶

Hydroquinone Formulation (Tyrosine Inhibitor)

Hydroquinone bleaching cream has been the standard therapy for hyperpigmentation. It works by blocking the conversion of dihydroxyphenylalanine to melanin by inhibiting tyrosinase.⁷ Topical steroids directly inhibit the synthesis of melanin, and when combined with hydroquinone and tretinoin, they can be effective for short periods of time and may decrease the irritation of application.^7,8 The most widely accepted formula consists of a topical steroid (triamcinolone cream 0.1%) in combination with hydroquinone 4% and tretinoin cream 0.05%.⁸ In a similar 12-week open-label study of 25 patients with darker skin types, Grimes⁹ used an alternative combination formula of hydroquinone 4% and retinol 0.15%. Overall improvement and tolerance was demonstrated through the use of colorimetry measurement. A combination of hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01% also has been used effectively for the treatment of melasma.¹⁰ This formulation has been used more anecdotally for the treatment of PIH and has yet to have a randomized-controlled trial. The concern with repeated long-term use of hydroquinone remains. Permanent leukoderma, exogenous ochronosis, and hyperpigmentation of the surrounding normal skin (halo effect) can occur.

Azelaic Acid (Tyrosinase Inhibitor)

Azelaic acid is a dicarboxylic acid isolated from pityriasis versicolor that acts similar to a tyrosine inhibitor and has an antiproliferative effect toward abnormal melanocytes. Lowe et al¹¹ conducted a randomized, double-blind, vehicle-controlled trial in patients with Fitzpatrick skin types IV through VI with facial hyperpigmentation using azelaic acid cream 20%. Over the course of 24 weeks, patients noted a decrease in overall pigment using both an investigator subjective scale and chromometer analysis.¹¹

Kojic Acid (Tyrosinase Inhibitor)

Kojic acid is a tyrosinase inhibitor found in fungal metabolite species such as Acetobacter, Aspergillus, and Penicillium. It is commonly combined with other skin lightening agents such as hydroquinone or vitamin C to further enhance its efficacy. A randomized, 12-week, split-face study of Chinese women with melasma compared treatment with a glycolic acid 10%–hydroquinone 2% gel versus the combination plus kojic acid 2%. The results showed that 60% (24/40) of patients improved with the use of kojic acid as compared to those using the medication without kojic acid.¹² Anecdotal data suggest kojic acid may be effective for PIH¹³; however, no studies specifically for PIH have been conducted.

Chemical Peels

Chemical peels have been used for a number of years, though their benefits in patients with skin of color is still being elucidated. The ideal chemical peels for Fitzpatrick skin types IV through VI are superficial to medium-depth peeling agents and techniques.¹⁴ Glycolic acid is a naturally occurring α-hydroxy acid that causes an increase in collagen synthesis, stimulates epidermolysis, and disperses basal layer melanin. Neutralization of glycolic acid peels can be done with the use of water, sodium bicarbonate, or sodium hydroxide to avoid unnecessary epidermal damage. Multiple clinical trials have been conducted to determine the response of glycolic acid peels in clearing PIH in patients with skin of color. Kessler et al¹⁵ compared glycolic acid 30% to salicylic acid 30% in 20 patients with mild to moderate acne and associated PIH. Chemical peels were performed every 2 weeks for 12 weeks. The study showed that salicylic acid was better tolerated than glycolic acid and both were equally effective after the second application (P<.05) for PIH.¹⁵ Finally, another study conducted for PIH in patients with Fitzpatrick skin types III and IV utilized glycolic acid peels with 20%, 35%, and 70% concentrations. The results showed overall improvement of PIH and acne from the use of all concentrations of glycolic peels, though faster efficacy was noted at higher concentrations.¹⁶

Other self-neutralizing peeling agents include salicylic acid and Jessner solution. Salicylic acid is a β-hydroxy acid that works through keratolysis and disrupting intercellular linkages. Jessner solution is a combination of resorcinol 14%, lactic acid 14%, and salicylic acid 14% in an alcohol base. Salicylic acid is well-tolerated in patients with Fitzpatrick skin types I through VI and has been helpful in treating acne, rosacea, melasma, hyperpigmentation, texturally rough skin, and mild photoaging. Jessner peeling solution has been used for a number of years and works as a keratolytic agent causing intercellular and intracellular edema, and due to its self-neutralizing agent, it is fairly superficial.¹⁷ Overall, superficial peeling agents should be used on patients with darker skin types to avoid the risk for worsening dyspigmentation, keloid formation, or deep scarring.¹⁸

Conclusion

These treatments are only some of the topical and chemical modalities for PIH in patients with skin of color. The patient history, evaluation, skin type, and underlying medical problems should be considered prior to using any topical or peeling agent. Lastly, photoprotection should be heavily emphasized with both sun protective gear and use of broad-spectrum sunscreens with a high sun protection factor, as UV radiation can cause darkening of PIH areas regardless of skin type and can reverse the progress made by a given therapy.¹⁸

Postinflammatory hyperpigmentation (PIH) develops as darkly pigmented macules that occur after an inflammatory process of the skin such as acne, folliculitis, eczema, or shaving irritation. Patients with Fitzpatrick skin types III to VI usually are most commonly affected, and for many, the remnant pigmentation can be an even greater concern than the original inflammatory process.^1,2 Reported treatments of PIH include tretinoin, hydroquinone, azelaic acid, and chemical peels. The ideal combination of therapy has yet to be delineated.

Tretinoin (Vitamin A Derivative)

Bulengo-Ransby et al³ performed one of the first clinical trials testing tretinoin cream 0.1% for PIH in patients with Fitzpatrick skin types IV to VI . The study included 54 patients (24 applied tretinoin and 30 applied a vehicle) with moderate to severe PIH on the face and arms. The patients were divided into therapy and placebo groups and were evaluated for 40 weeks. Changes were evaluated through colorimetry, light microscopy, histology, and photography, with significant clinical improvement in the tretinoin-treated group (P<.001).³ A double-blind, randomized study of 45 photoaged Chinese and Japanese patients using tretinoin cream 0.1% also was conducted for treatment of photoaging-associated hyperpigmented lesions of the face and hands. Assessment was done with clinical, colorimetric, and histological evaluation, with an overall statistical improvement noted in hyperpigmentation.⁴ Both of the above studies showed mild irritation (ie, retinoid dermatitis) with application of tretinoin, which creates a compliance issue in patients who are recommended to continue therapy with higher-strength tretinoin. This side-effect profile can be circumvented through gradual elevation in the strength of tretinoin.⁵

Combination Therapies

Combination therapies with tretinoin also have been used to improve PIH. Callender et al⁶ conducted a study evaluating the efficacy of clindamycin phosphate 1.2%–tretinoin 0.025% gel for the treatment of PIH secondary to mild to moderate acne in patients with Fitzpatrick skin types IV to VI. Thirty patients participated in the randomized, double-blinded, placebo-controlled study, with 15 patients in the clindamycin-tretinoin gel group and 15 in the placebo control group. Based on objective assessment using a chromameter and evaluator global acne severity scale score, clinical efficacy was demonstrated for treating acne and PIH as well as preventing further PIH.⁶

Hydroquinone Formulation (Tyrosine Inhibitor)

Hydroquinone bleaching cream has been the standard therapy for hyperpigmentation. It works by blocking the conversion of dihydroxyphenylalanine to melanin by inhibiting tyrosinase.⁷ Topical steroids directly inhibit the synthesis of melanin, and when combined with hydroquinone and tretinoin, they can be effective for short periods of time and may decrease the irritation of application.^7,8 The most widely accepted formula consists of a topical steroid (triamcinolone cream 0.1%) in combination with hydroquinone 4% and tretinoin cream 0.05%.⁸ In a similar 12-week open-label study of 25 patients with darker skin types, Grimes⁹ used an alternative combination formula of hydroquinone 4% and retinol 0.15%. Overall improvement and tolerance was demonstrated through the use of colorimetry measurement. A combination of hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01% also has been used effectively for the treatment of melasma.¹⁰ This formulation has been used more anecdotally for the treatment of PIH and has yet to have a randomized-controlled trial. The concern with repeated long-term use of hydroquinone remains. Permanent leukoderma, exogenous ochronosis, and hyperpigmentation of the surrounding normal skin (halo effect) can occur.

Azelaic Acid (Tyrosinase Inhibitor)

Azelaic acid is a dicarboxylic acid isolated from pityriasis versicolor that acts similar to a tyrosine inhibitor and has an antiproliferative effect toward abnormal melanocytes. Lowe et al¹¹ conducted a randomized, double-blind, vehicle-controlled trial in patients with Fitzpatrick skin types IV through VI with facial hyperpigmentation using azelaic acid cream 20%. Over the course of 24 weeks, patients noted a decrease in overall pigment using both an investigator subjective scale and chromometer analysis.¹¹

Kojic Acid (Tyrosinase Inhibitor)

Kojic acid is a tyrosinase inhibitor found in fungal metabolite species such as Acetobacter, Aspergillus, and Penicillium. It is commonly combined with other skin lightening agents such as hydroquinone or vitamin C to further enhance its efficacy. A randomized, 12-week, split-face study of Chinese women with melasma compared treatment with a glycolic acid 10%–hydroquinone 2% gel versus the combination plus kojic acid 2%. The results showed that 60% (24/40) of patients improved with the use of kojic acid as compared to those using the medication without kojic acid.¹² Anecdotal data suggest kojic acid may be effective for PIH¹³; however, no studies specifically for PIH have been conducted.

Chemical Peels

Chemical peels have been used for a number of years, though their benefits in patients with skin of color is still being elucidated. The ideal chemical peels for Fitzpatrick skin types IV through VI are superficial to medium-depth peeling agents and techniques.¹⁴ Glycolic acid is a naturally occurring α-hydroxy acid that causes an increase in collagen synthesis, stimulates epidermolysis, and disperses basal layer melanin. Neutralization of glycolic acid peels can be done with the use of water, sodium bicarbonate, or sodium hydroxide to avoid unnecessary epidermal damage. Multiple clinical trials have been conducted to determine the response of glycolic acid peels in clearing PIH in patients with skin of color. Kessler et al¹⁵ compared glycolic acid 30% to salicylic acid 30% in 20 patients with mild to moderate acne and associated PIH. Chemical peels were performed every 2 weeks for 12 weeks. The study showed that salicylic acid was better tolerated than glycolic acid and both were equally effective after the second application (P<.05) for PIH.¹⁵ Finally, another study conducted for PIH in patients with Fitzpatrick skin types III and IV utilized glycolic acid peels with 20%, 35%, and 70% concentrations. The results showed overall improvement of PIH and acne from the use of all concentrations of glycolic peels, though faster efficacy was noted at higher concentrations.¹⁶

Other self-neutralizing peeling agents include salicylic acid and Jessner solution. Salicylic acid is a β-hydroxy acid that works through keratolysis and disrupting intercellular linkages. Jessner solution is a combination of resorcinol 14%, lactic acid 14%, and salicylic acid 14% in an alcohol base. Salicylic acid is well-tolerated in patients with Fitzpatrick skin types I through VI and has been helpful in treating acne, rosacea, melasma, hyperpigmentation, texturally rough skin, and mild photoaging. Jessner peeling solution has been used for a number of years and works as a keratolytic agent causing intercellular and intracellular edema, and due to its self-neutralizing agent, it is fairly superficial.¹⁷ Overall, superficial peeling agents should be used on patients with darker skin types to avoid the risk for worsening dyspigmentation, keloid formation, or deep scarring.¹⁸

Conclusion

These treatments are only some of the topical and chemical modalities for PIH in patients with skin of color. The patient history, evaluation, skin type, and underlying medical problems should be considered prior to using any topical or peeling agent. Lastly, photoprotection should be heavily emphasized with both sun protective gear and use of broad-spectrum sunscreens with a high sun protection factor, as UV radiation can cause darkening of PIH areas regardless of skin type and can reverse the progress made by a given therapy.¹⁸

Postinflammatory hyperpigmentation (PIH) develops as darkly pigmented macules that occur after an inflammatory process of the skin such as acne, folliculitis, eczema, or shaving irritation. Patients with Fitzpatrick skin types III to VI usually are most commonly affected, and for many, the remnant pigmentation can be an even greater concern than the original inflammatory process.^1,2 Reported treatments of PIH include tretinoin, hydroquinone, azelaic acid, and chemical peels. The ideal combination of therapy has yet to be delineated.

Tretinoin (Vitamin A Derivative)

Bulengo-Ransby et al³ performed one of the first clinical trials testing tretinoin cream 0.1% for PIH in patients with Fitzpatrick skin types IV to VI . The study included 54 patients (24 applied tretinoin and 30 applied a vehicle) with moderate to severe PIH on the face and arms. The patients were divided into therapy and placebo groups and were evaluated for 40 weeks. Changes were evaluated through colorimetry, light microscopy, histology, and photography, with significant clinical improvement in the tretinoin-treated group (P<.001).³ A double-blind, randomized study of 45 photoaged Chinese and Japanese patients using tretinoin cream 0.1% also was conducted for treatment of photoaging-associated hyperpigmented lesions of the face and hands. Assessment was done with clinical, colorimetric, and histological evaluation, with an overall statistical improvement noted in hyperpigmentation.⁴ Both of the above studies showed mild irritation (ie, retinoid dermatitis) with application of tretinoin, which creates a compliance issue in patients who are recommended to continue therapy with higher-strength tretinoin. This side-effect profile can be circumvented through gradual elevation in the strength of tretinoin.⁵

Combination Therapies

Combination therapies with tretinoin also have been used to improve PIH. Callender et al⁶ conducted a study evaluating the efficacy of clindamycin phosphate 1.2%–tretinoin 0.025% gel for the treatment of PIH secondary to mild to moderate acne in patients with Fitzpatrick skin types IV to VI. Thirty patients participated in the randomized, double-blinded, placebo-controlled study, with 15 patients in the clindamycin-tretinoin gel group and 15 in the placebo control group. Based on objective assessment using a chromameter and evaluator global acne severity scale score, clinical efficacy was demonstrated for treating acne and PIH as well as preventing further PIH.⁶

Hydroquinone Formulation (Tyrosine Inhibitor)

Hydroquinone bleaching cream has been the standard therapy for hyperpigmentation. It works by blocking the conversion of dihydroxyphenylalanine to melanin by inhibiting tyrosinase.⁷ Topical steroids directly inhibit the synthesis of melanin, and when combined with hydroquinone and tretinoin, they can be effective for short periods of time and may decrease the irritation of application.^7,8 The most widely accepted formula consists of a topical steroid (triamcinolone cream 0.1%) in combination with hydroquinone 4% and tretinoin cream 0.05%.⁸ In a similar 12-week open-label study of 25 patients with darker skin types, Grimes⁹ used an alternative combination formula of hydroquinone 4% and retinol 0.15%. Overall improvement and tolerance was demonstrated through the use of colorimetry measurement. A combination of hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01% also has been used effectively for the treatment of melasma.¹⁰ This formulation has been used more anecdotally for the treatment of PIH and has yet to have a randomized-controlled trial. The concern with repeated long-term use of hydroquinone remains. Permanent leukoderma, exogenous ochronosis, and hyperpigmentation of the surrounding normal skin (halo effect) can occur.

Azelaic Acid (Tyrosinase Inhibitor)

Azelaic acid is a dicarboxylic acid isolated from pityriasis versicolor that acts similar to a tyrosine inhibitor and has an antiproliferative effect toward abnormal melanocytes. Lowe et al¹¹ conducted a randomized, double-blind, vehicle-controlled trial in patients with Fitzpatrick skin types IV through VI with facial hyperpigmentation using azelaic acid cream 20%. Over the course of 24 weeks, patients noted a decrease in overall pigment using both an investigator subjective scale and chromometer analysis.¹¹

Kojic Acid (Tyrosinase Inhibitor)

Kojic acid is a tyrosinase inhibitor found in fungal metabolite species such as Acetobacter, Aspergillus, and Penicillium. It is commonly combined with other skin lightening agents such as hydroquinone or vitamin C to further enhance its efficacy. A randomized, 12-week, split-face study of Chinese women with melasma compared treatment with a glycolic acid 10%–hydroquinone 2% gel versus the combination plus kojic acid 2%. The results showed that 60% (24/40) of patients improved with the use of kojic acid as compared to those using the medication without kojic acid.¹² Anecdotal data suggest kojic acid may be effective for PIH¹³; however, no studies specifically for PIH have been conducted.

Chemical Peels

Chemical peels have been used for a number of years, though their benefits in patients with skin of color is still being elucidated. The ideal chemical peels for Fitzpatrick skin types IV through VI are superficial to medium-depth peeling agents and techniques.¹⁴ Glycolic acid is a naturally occurring α-hydroxy acid that causes an increase in collagen synthesis, stimulates epidermolysis, and disperses basal layer melanin. Neutralization of glycolic acid peels can be done with the use of water, sodium bicarbonate, or sodium hydroxide to avoid unnecessary epidermal damage. Multiple clinical trials have been conducted to determine the response of glycolic acid peels in clearing PIH in patients with skin of color. Kessler et al¹⁵ compared glycolic acid 30% to salicylic acid 30% in 20 patients with mild to moderate acne and associated PIH. Chemical peels were performed every 2 weeks for 12 weeks. The study showed that salicylic acid was better tolerated than glycolic acid and both were equally effective after the second application (P<.05) for PIH.¹⁵ Finally, another study conducted for PIH in patients with Fitzpatrick skin types III and IV utilized glycolic acid peels with 20%, 35%, and 70% concentrations. The results showed overall improvement of PIH and acne from the use of all concentrations of glycolic peels, though faster efficacy was noted at higher concentrations.¹⁶

Other self-neutralizing peeling agents include salicylic acid and Jessner solution. Salicylic acid is a β-hydroxy acid that works through keratolysis and disrupting intercellular linkages. Jessner solution is a combination of resorcinol 14%, lactic acid 14%, and salicylic acid 14% in an alcohol base. Salicylic acid is well-tolerated in patients with Fitzpatrick skin types I through VI and has been helpful in treating acne, rosacea, melasma, hyperpigmentation, texturally rough skin, and mild photoaging. Jessner peeling solution has been used for a number of years and works as a keratolytic agent causing intercellular and intracellular edema, and due to its self-neutralizing agent, it is fairly superficial.¹⁷ Overall, superficial peeling agents should be used on patients with darker skin types to avoid the risk for worsening dyspigmentation, keloid formation, or deep scarring.¹⁸

Conclusion

These treatments are only some of the topical and chemical modalities for PIH in patients with skin of color. The patient history, evaluation, skin type, and underlying medical problems should be considered prior to using any topical or peeling agent. Lastly, photoprotection should be heavily emphasized with both sun protective gear and use of broad-spectrum sunscreens with a high sun protection factor, as UV radiation can cause darkening of PIH areas regardless of skin type and can reverse the progress made by a given therapy.¹⁸

PHOENIX – Being underweight is associated with a substantially increased risk of complications following lung resection for cancer, results from a large database study found.

“This is not generally known among surgeons or their patients,” Dr. Trevor Williams said in an interview before the annual meeting of the Society of Thoracic Surgeons. “Studies are conflicting about the relationship of BMI [body mass index] to surgical outcomes. Most of the previous studies simply categorize BMI as overweight or not. We’ve stratified based on World Health Organization categories to get a more precise look at BMI.”

Dr. Williams, a surgeon at the University of Chicago Medical Center, and his associates evaluated 41,446 patients in the STS General Thoracic Surgery Database who underwent elective anatomic lung resection for cancer between 2009 and 2014. Their mean age was 68 years, and 53% were female. The researchers performed multivariable analysis after adjusting for validated STS risk model covariates, including gender and spirometry.

According to WHO criteria for BMI, 3% were underweight (less than 18.5 kg/m²); 33.5% were normal weight (18.5-24.9 kg/m²); 35.4% were overweight (25-29.9 kg/m²); 18.1% were obese I (30-34.9 kg/m²); 6.4% were obese II (35-39.9 kg/m²), and 3.6% were obese III (40 kg/m² or greater). Dr. Williams and his associates observed that women were more often underweight, compared with men (4.1% vs. 1.8%, respectively; P less than .001), and underweight patients more often had chronic obstructive pulmonary disease (51.7% vs. 35.2%; P less than .001). Pulmonary complication rates were higher among underweight and obese III patients (P less than .001), while being underweight was also associated with higher rates of infections and any surgical complications.

Multivariable analysis revealed that pulmonary and any postoperative complications were more common among underweight patients (odds ratio, 1.44 and OR, 1.41, respectively), while any major complication was more common among obese III patients (OR, 1.18). Overweight and obese I-II patients were less likely to have any postoperative and pulmonary complications, compared with patients who had a normal BMI. “The finding of underweight patients being such a high-risk patient population is suggested in the literature but not demonstrated as clearly as in this study,” Dr. Williams said. “A truly surprising finding was that obese patients actually have a lower risk of pulmonary and overall complications than ‘normal’-BMI patients.”

He concluded that according to the current analysis, “careful risk assessment is appropriate when considering operating on underweight patients. Whether there are interventions that could be instituted to improve an individual’s risk profile has not been determined. Any preconceived notions about not operating on obese patients due to elevated risk appear to be unfounded.”

Dr. Williams reported having no financial disclosures.

[email protected]

PHOENIX – Being underweight is associated with a substantially increased risk of complications following lung resection for cancer, results from a large database study found.

“This is not generally known among surgeons or their patients,” Dr. Trevor Williams said in an interview before the annual meeting of the Society of Thoracic Surgeons. “Studies are conflicting about the relationship of BMI [body mass index] to surgical outcomes. Most of the previous studies simply categorize BMI as overweight or not. We’ve stratified based on World Health Organization categories to get a more precise look at BMI.”

Dr. Williams, a surgeon at the University of Chicago Medical Center, and his associates evaluated 41,446 patients in the STS General Thoracic Surgery Database who underwent elective anatomic lung resection for cancer between 2009 and 2014. Their mean age was 68 years, and 53% were female. The researchers performed multivariable analysis after adjusting for validated STS risk model covariates, including gender and spirometry.

According to WHO criteria for BMI, 3% were underweight (less than 18.5 kg/m²); 33.5% were normal weight (18.5-24.9 kg/m²); 35.4% were overweight (25-29.9 kg/m²); 18.1% were obese I (30-34.9 kg/m²); 6.4% were obese II (35-39.9 kg/m²), and 3.6% were obese III (40 kg/m² or greater). Dr. Williams and his associates observed that women were more often underweight, compared with men (4.1% vs. 1.8%, respectively; P less than .001), and underweight patients more often had chronic obstructive pulmonary disease (51.7% vs. 35.2%; P less than .001). Pulmonary complication rates were higher among underweight and obese III patients (P less than .001), while being underweight was also associated with higher rates of infections and any surgical complications.

Multivariable analysis revealed that pulmonary and any postoperative complications were more common among underweight patients (odds ratio, 1.44 and OR, 1.41, respectively), while any major complication was more common among obese III patients (OR, 1.18). Overweight and obese I-II patients were less likely to have any postoperative and pulmonary complications, compared with patients who had a normal BMI. “The finding of underweight patients being such a high-risk patient population is suggested in the literature but not demonstrated as clearly as in this study,” Dr. Williams said. “A truly surprising finding was that obese patients actually have a lower risk of pulmonary and overall complications than ‘normal’-BMI patients.”

He concluded that according to the current analysis, “careful risk assessment is appropriate when considering operating on underweight patients. Whether there are interventions that could be instituted to improve an individual’s risk profile has not been determined. Any preconceived notions about not operating on obese patients due to elevated risk appear to be unfounded.”

Dr. Williams reported having no financial disclosures.

[email protected]

PHOENIX – Being underweight is associated with a substantially increased risk of complications following lung resection for cancer, results from a large database study found.

“This is not generally known among surgeons or their patients,” Dr. Trevor Williams said in an interview before the annual meeting of the Society of Thoracic Surgeons. “Studies are conflicting about the relationship of BMI [body mass index] to surgical outcomes. Most of the previous studies simply categorize BMI as overweight or not. We’ve stratified based on World Health Organization categories to get a more precise look at BMI.”

Dr. Williams, a surgeon at the University of Chicago Medical Center, and his associates evaluated 41,446 patients in the STS General Thoracic Surgery Database who underwent elective anatomic lung resection for cancer between 2009 and 2014. Their mean age was 68 years, and 53% were female. The researchers performed multivariable analysis after adjusting for validated STS risk model covariates, including gender and spirometry.

According to WHO criteria for BMI, 3% were underweight (less than 18.5 kg/m²); 33.5% were normal weight (18.5-24.9 kg/m²); 35.4% were overweight (25-29.9 kg/m²); 18.1% were obese I (30-34.9 kg/m²); 6.4% were obese II (35-39.9 kg/m²), and 3.6% were obese III (40 kg/m² or greater). Dr. Williams and his associates observed that women were more often underweight, compared with men (4.1% vs. 1.8%, respectively; P less than .001), and underweight patients more often had chronic obstructive pulmonary disease (51.7% vs. 35.2%; P less than .001). Pulmonary complication rates were higher among underweight and obese III patients (P less than .001), while being underweight was also associated with higher rates of infections and any surgical complications.

Multivariable analysis revealed that pulmonary and any postoperative complications were more common among underweight patients (odds ratio, 1.44 and OR, 1.41, respectively), while any major complication was more common among obese III patients (OR, 1.18). Overweight and obese I-II patients were less likely to have any postoperative and pulmonary complications, compared with patients who had a normal BMI. “The finding of underweight patients being such a high-risk patient population is suggested in the literature but not demonstrated as clearly as in this study,” Dr. Williams said. “A truly surprising finding was that obese patients actually have a lower risk of pulmonary and overall complications than ‘normal’-BMI patients.”

He concluded that according to the current analysis, “careful risk assessment is appropriate when considering operating on underweight patients. Whether there are interventions that could be instituted to improve an individual’s risk profile has not been determined. Any preconceived notions about not operating on obese patients due to elevated risk appear to be unfounded.”

Dr. Williams reported having no financial disclosures.

[email protected]

PHOENIX – Each year more than 250,000 patients present with ground-glass opacities and other solitary pulmonary nodules, and they are difficult to locate.

“There’s been a need for our field to develop new technologies to find these nodules in the OR,” Dr. Sunil Singhal said in a video interview at the annual meeting of the Society of Thoracic Surgeons. “The fallback plan has always been that we can make a thoracotomy. Some studies have shown that in about one out of every two cases you end up opening a patient just to find a tiny little nodule.”

Dr. Singhal of the division of cardiothoracic surgery at the University of Pennsylvania School of Medicine, Philadelphia, discussed preoperative and intraoperative localization methods, including an investigational technology in which patients receive an intravascular dye that localizes the pulmonary tumor. “When we put our video-assisted thoracoscopic surgery camera in, the tumors are glowing,” he said. “We can then do a localized wedge excision and confirm margins of the staple line. We’ve done this [in] about 80 patients, and it’s been non-toxic, very safe, and very effective. Our biggest limitation has been our depth of penetration.”

Dr. Singhal reported having no financial disclosures.

[email protected]

PHOENIX – Each year more than 250,000 patients present with ground-glass opacities and other solitary pulmonary nodules, and they are difficult to locate.

“There’s been a need for our field to develop new technologies to find these nodules in the OR,” Dr. Sunil Singhal said in a video interview at the annual meeting of the Society of Thoracic Surgeons. “The fallback plan has always been that we can make a thoracotomy. Some studies have shown that in about one out of every two cases you end up opening a patient just to find a tiny little nodule.”

Dr. Singhal of the division of cardiothoracic surgery at the University of Pennsylvania School of Medicine, Philadelphia, discussed preoperative and intraoperative localization methods, including an investigational technology in which patients receive an intravascular dye that localizes the pulmonary tumor. “When we put our video-assisted thoracoscopic surgery camera in, the tumors are glowing,” he said. “We can then do a localized wedge excision and confirm margins of the staple line. We’ve done this [in] about 80 patients, and it’s been non-toxic, very safe, and very effective. Our biggest limitation has been our depth of penetration.”

Dr. Singhal reported having no financial disclosures.

[email protected]

PHOENIX – Each year more than 250,000 patients present with ground-glass opacities and other solitary pulmonary nodules, and they are difficult to locate.

“There’s been a need for our field to develop new technologies to find these nodules in the OR,” Dr. Sunil Singhal said in a video interview at the annual meeting of the Society of Thoracic Surgeons. “The fallback plan has always been that we can make a thoracotomy. Some studies have shown that in about one out of every two cases you end up opening a patient just to find a tiny little nodule.”

Dr. Singhal of the division of cardiothoracic surgery at the University of Pennsylvania School of Medicine, Philadelphia, discussed preoperative and intraoperative localization methods, including an investigational technology in which patients receive an intravascular dye that localizes the pulmonary tumor. “When we put our video-assisted thoracoscopic surgery camera in, the tumors are glowing,” he said. “We can then do a localized wedge excision and confirm margins of the staple line. We’ve done this [in] about 80 patients, and it’s been non-toxic, very safe, and very effective. Our biggest limitation has been our depth of penetration.”

Dr. Singhal reported having no financial disclosures.

[email protected]

Review the PDF of the fact sheet on RNA viruses with board-relevant, easy-to-review material. This fact sheet will review the spectrum of RNA viruses that cause or are associated with cutaneous manifestations. RNA virus classification, clinical findings, potential treatments, and other board-relevant facts will be discussed.

Practice Questions

1. Which virus is transmitted by Culex mosquitos?

a. chikungunya virus

b. coxsackievirus A16

c. dengue virus

d. human T-lymphotropic virus

e. West Nile virus

2. Which virus causes an illness associated with an enanthem of grey papules on the buccal mucosa?

a. Paramyxoviridae

b. Parvoviridae

c. Picornaviridae

d. Retroviridae

e. Togaviridae

3. Illness associated with which viral infection may be prevented via vaccination?

a. coxsackievirus

b. dengue virus

c. enterovirus

d. hepatitis C virus

e. togavirus

4. Which virus is classically associated with retro-orbital pain and a morbilliform eruption with areas of sparing?

a. chikungunya virus

b. dengue virus

c. human immunodeficiency virus

d. West Nile virus

e. yellow fever virus

5. Which of the following may be included in the treatment of hepatitis C virus (HCV) infection?

a. doxorubicin

b. HCV vaccine

c. ribavirin

d. tenofovir

e. vitamin A

1. Which virus is transmitted by Culex mosquitos?

a. chikungunya virus

b. coxsackievirus A16

c. dengue virus

d. human T-lymphotropic virus

e. West Nile virus

2. Which virus causes an illness associated with an enanthem of grey papules on the buccal mucosa?

a. Paramyxoviridae

b. Parvoviridae

c. Picornaviridae

d. Retroviridae

e. Togaviridae

3. Illness associated with which viral infection may be prevented via vaccination?

a. coxsackievirus

b. dengue virus c. enterovirus

d. hepatitis C virus

e. togavirus

4. Which virus is classically associated with retro-orbital pain and a morbilliform eruption with areas of sparing?

a. chikungunya virus

b. dengue virus

c. human immunodeficiency virus

d. West Nile virus

e. yellow fever virus

5. Which of the following may be included in the treatment of hepatitis C virus (HCV) infection?

a. doxorubicin

b. HCV vaccine

c. ribavirin

d. tenofovir

e. vitamin A

Review the PDF of the fact sheet on RNA viruses with board-relevant, easy-to-review material. This fact sheet will review the spectrum of RNA viruses that cause or are associated with cutaneous manifestations. RNA virus classification, clinical findings, potential treatments, and other board-relevant facts will be discussed.

Practice Questions

1. Which virus is transmitted by Culex mosquitos?

a. chikungunya virus

b. coxsackievirus A16

c. dengue virus

d. human T-lymphotropic virus

e. West Nile virus

2. Which virus causes an illness associated with an enanthem of grey papules on the buccal mucosa?

a. Paramyxoviridae

b. Parvoviridae

c. Picornaviridae

d. Retroviridae

e. Togaviridae

3. Illness associated with which viral infection may be prevented via vaccination?

a. coxsackievirus

b. dengue virus

c. enterovirus

d. hepatitis C virus

e. togavirus

4. Which virus is classically associated with retro-orbital pain and a morbilliform eruption with areas of sparing?

a. chikungunya virus

b. dengue virus

c. human immunodeficiency virus

d. West Nile virus

e. yellow fever virus

5. Which of the following may be included in the treatment of hepatitis C virus (HCV) infection?

a. doxorubicin

b. HCV vaccine

c. ribavirin

d. tenofovir

e. vitamin A

1. Which virus is transmitted by Culex mosquitos?

a. chikungunya virus

b. coxsackievirus A16

c. dengue virus

d. human T-lymphotropic virus

e. West Nile virus

2. Which virus causes an illness associated with an enanthem of grey papules on the buccal mucosa?

a. Paramyxoviridae

b. Parvoviridae

c. Picornaviridae

d. Retroviridae

e. Togaviridae

3. Illness associated with which viral infection may be prevented via vaccination?

a. coxsackievirus

b. dengue virus c. enterovirus

d. hepatitis C virus

e. togavirus

4. Which virus is classically associated with retro-orbital pain and a morbilliform eruption with areas of sparing?

a. chikungunya virus

b. dengue virus

c. human immunodeficiency virus

d. West Nile virus

e. yellow fever virus

5. Which of the following may be included in the treatment of hepatitis C virus (HCV) infection?

a. doxorubicin

b. HCV vaccine

c. ribavirin

d. tenofovir

e. vitamin A

Review the PDF of the fact sheet on RNA viruses with board-relevant, easy-to-review material. This fact sheet will review the spectrum of RNA viruses that cause or are associated with cutaneous manifestations. RNA virus classification, clinical findings, potential treatments, and other board-relevant facts will be discussed.

Practice Questions

1. Which virus is transmitted by Culex mosquitos?

a. chikungunya virus

b. coxsackievirus A16

c. dengue virus

d. human T-lymphotropic virus

e. West Nile virus

2. Which virus causes an illness associated with an enanthem of grey papules on the buccal mucosa?

a. Paramyxoviridae

b. Parvoviridae

c. Picornaviridae

d. Retroviridae

e. Togaviridae

3. Illness associated with which viral infection may be prevented via vaccination?

a. coxsackievirus

b. dengue virus

c. enterovirus

d. hepatitis C virus

e. togavirus

4. Which virus is classically associated with retro-orbital pain and a morbilliform eruption with areas of sparing?

a. chikungunya virus

b. dengue virus

c. human immunodeficiency virus

d. West Nile virus

e. yellow fever virus

5. Which of the following may be included in the treatment of hepatitis C virus (HCV) infection?

a. doxorubicin

b. HCV vaccine

c. ribavirin

d. tenofovir

e. vitamin A

1. Which virus is transmitted by Culex mosquitos?

a. chikungunya virus

b. coxsackievirus A16

c. dengue virus

d. human T-lymphotropic virus

e. West Nile virus

2. Which virus causes an illness associated with an enanthem of grey papules on the buccal mucosa?

a. Paramyxoviridae

b. Parvoviridae

c. Picornaviridae

d. Retroviridae

e. Togaviridae

3. Illness associated with which viral infection may be prevented via vaccination?

a. coxsackievirus

b. dengue virus c. enterovirus

d. hepatitis C virus

e. togavirus

4. Which virus is classically associated with retro-orbital pain and a morbilliform eruption with areas of sparing?

a. chikungunya virus

b. dengue virus

c. human immunodeficiency virus

d. West Nile virus

e. yellow fever virus

5. Which of the following may be included in the treatment of hepatitis C virus (HCV) infection?

a. doxorubicin

b. HCV vaccine

c. ribavirin

d. tenofovir

e. vitamin A