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Asymptomatic gallstones seldom require surgical intervention
“Most patients with asymptomatic gallstones never develop symptoms and probably don’t need surgical intervention,” lead study author Gareth Morris-Stiff, MD, PhD, said at the annual Digestive Disease Week.
Dr. Morris-Stiff, of the department of general surgery at Cleveland Clinic, said that, while previous studies have evaluated the time to development of gallstone-related complications following identification of asymptomatic gallstones, factors associated with the need for surgical intervention in this population have not been documented. The aims of the current study were to perform a big data analysis to evaluate risk factors associated with intervention in asymptomatic gallstones and to develop a risk stratification tool to aid in patient consultations by predicting individuals likely to need future intervention for their gallstones.
The researchers included Cleveland Clinic patients with CT/US reports containing “cholelithiasis” or “gallstones” between January 1996 and December 2016. Patients were excluded if they had a concurrent or prior event, had an event within 2 months, or lacked follow-up. Data collection included demographic characteristics, comorbid conditions or surgeries, imaging features, and medication use.
Dr. Morris-Stiff and his colleagues constructed Kaplan-Meier curves to analyze time to intervention and calculated cumulative incidence ratios. They used automated forward stepwise competing risk regression to create their model and receiver operating characteristics curves to analyze it.
Of the 49,414 patients identified with asymptomatic gallstones, 22,257 met criteria for analysis. Slightly more than half (51%) were female, their mean age was 61 years, 80% were white, 16% were black, and the rest were from other racial and ethnic groups. The median follow-up was 4.5 years, and the median follow-up of patients undergoing intervention was 3.9 years. This translated to 112,111 total years of observation.
The researchers found that the cumulative incidence of intervention at 15 years was 25% and it increased linearly from the time of initial diagnosis of asymptomatic gallstones. A total of 1,762 patients (7.9%) underwent a surgical procedure, most often cholecystectomy (5.7%). Three factors were associated with a reduced risk for surgical intervention: increasing age (hazard ratio, 0.94; P less than 0.001), male gender (HR, 0.78; P less than 0.001), and statin use (HR, 0.67; P less than 0.001).
Patient variables associated with an increased need for surgical intervention included obesity (HR, 1.44; P less than 0.001) and having a hemolytic disorder (HR, 2.42; P less than 0.001). Gallstone-specific characteristics that increased the need for surgical intervention included a stone size of greater than 9 mm (HR, 1.56; P less than 0.001), the presence of sludge (HR, 1.46; P less than 0.001), the presence of a polyp (HR, 1.68; P less than 0.001), and having multiple stones (HR, 1.69; P less than 0.001).
The analysis enabled Dr. Morris-Stiff and colleagues to generate a Web-based risk score to reliably identify these patients and provide prognostic information for counseling. An app for smartphones based on the score is being developed. The researchers reported having no financial disclosures.
“Most patients with asymptomatic gallstones never develop symptoms and probably don’t need surgical intervention,” lead study author Gareth Morris-Stiff, MD, PhD, said at the annual Digestive Disease Week.
Dr. Morris-Stiff, of the department of general surgery at Cleveland Clinic, said that, while previous studies have evaluated the time to development of gallstone-related complications following identification of asymptomatic gallstones, factors associated with the need for surgical intervention in this population have not been documented. The aims of the current study were to perform a big data analysis to evaluate risk factors associated with intervention in asymptomatic gallstones and to develop a risk stratification tool to aid in patient consultations by predicting individuals likely to need future intervention for their gallstones.
The researchers included Cleveland Clinic patients with CT/US reports containing “cholelithiasis” or “gallstones” between January 1996 and December 2016. Patients were excluded if they had a concurrent or prior event, had an event within 2 months, or lacked follow-up. Data collection included demographic characteristics, comorbid conditions or surgeries, imaging features, and medication use.
Dr. Morris-Stiff and his colleagues constructed Kaplan-Meier curves to analyze time to intervention and calculated cumulative incidence ratios. They used automated forward stepwise competing risk regression to create their model and receiver operating characteristics curves to analyze it.
Of the 49,414 patients identified with asymptomatic gallstones, 22,257 met criteria for analysis. Slightly more than half (51%) were female, their mean age was 61 years, 80% were white, 16% were black, and the rest were from other racial and ethnic groups. The median follow-up was 4.5 years, and the median follow-up of patients undergoing intervention was 3.9 years. This translated to 112,111 total years of observation.
The researchers found that the cumulative incidence of intervention at 15 years was 25% and it increased linearly from the time of initial diagnosis of asymptomatic gallstones. A total of 1,762 patients (7.9%) underwent a surgical procedure, most often cholecystectomy (5.7%). Three factors were associated with a reduced risk for surgical intervention: increasing age (hazard ratio, 0.94; P less than 0.001), male gender (HR, 0.78; P less than 0.001), and statin use (HR, 0.67; P less than 0.001).
Patient variables associated with an increased need for surgical intervention included obesity (HR, 1.44; P less than 0.001) and having a hemolytic disorder (HR, 2.42; P less than 0.001). Gallstone-specific characteristics that increased the need for surgical intervention included a stone size of greater than 9 mm (HR, 1.56; P less than 0.001), the presence of sludge (HR, 1.46; P less than 0.001), the presence of a polyp (HR, 1.68; P less than 0.001), and having multiple stones (HR, 1.69; P less than 0.001).
The analysis enabled Dr. Morris-Stiff and colleagues to generate a Web-based risk score to reliably identify these patients and provide prognostic information for counseling. An app for smartphones based on the score is being developed. The researchers reported having no financial disclosures.
“Most patients with asymptomatic gallstones never develop symptoms and probably don’t need surgical intervention,” lead study author Gareth Morris-Stiff, MD, PhD, said at the annual Digestive Disease Week.
Dr. Morris-Stiff, of the department of general surgery at Cleveland Clinic, said that, while previous studies have evaluated the time to development of gallstone-related complications following identification of asymptomatic gallstones, factors associated with the need for surgical intervention in this population have not been documented. The aims of the current study were to perform a big data analysis to evaluate risk factors associated with intervention in asymptomatic gallstones and to develop a risk stratification tool to aid in patient consultations by predicting individuals likely to need future intervention for their gallstones.
The researchers included Cleveland Clinic patients with CT/US reports containing “cholelithiasis” or “gallstones” between January 1996 and December 2016. Patients were excluded if they had a concurrent or prior event, had an event within 2 months, or lacked follow-up. Data collection included demographic characteristics, comorbid conditions or surgeries, imaging features, and medication use.
Dr. Morris-Stiff and his colleagues constructed Kaplan-Meier curves to analyze time to intervention and calculated cumulative incidence ratios. They used automated forward stepwise competing risk regression to create their model and receiver operating characteristics curves to analyze it.
Of the 49,414 patients identified with asymptomatic gallstones, 22,257 met criteria for analysis. Slightly more than half (51%) were female, their mean age was 61 years, 80% were white, 16% were black, and the rest were from other racial and ethnic groups. The median follow-up was 4.5 years, and the median follow-up of patients undergoing intervention was 3.9 years. This translated to 112,111 total years of observation.
The researchers found that the cumulative incidence of intervention at 15 years was 25% and it increased linearly from the time of initial diagnosis of asymptomatic gallstones. A total of 1,762 patients (7.9%) underwent a surgical procedure, most often cholecystectomy (5.7%). Three factors were associated with a reduced risk for surgical intervention: increasing age (hazard ratio, 0.94; P less than 0.001), male gender (HR, 0.78; P less than 0.001), and statin use (HR, 0.67; P less than 0.001).
Patient variables associated with an increased need for surgical intervention included obesity (HR, 1.44; P less than 0.001) and having a hemolytic disorder (HR, 2.42; P less than 0.001). Gallstone-specific characteristics that increased the need for surgical intervention included a stone size of greater than 9 mm (HR, 1.56; P less than 0.001), the presence of sludge (HR, 1.46; P less than 0.001), the presence of a polyp (HR, 1.68; P less than 0.001), and having multiple stones (HR, 1.69; P less than 0.001).
The analysis enabled Dr. Morris-Stiff and colleagues to generate a Web-based risk score to reliably identify these patients and provide prognostic information for counseling. An app for smartphones based on the score is being developed. The researchers reported having no financial disclosures.
REPORTING FROM DDW 2019
Gender equity, sexual harassment in health care
SAN FRANCISCO – Women in health care are second only to those in arts and entertainment in contacting* the TIME’S UP Legal Defense Fund, according to two founding members of TIME’S UP Healthcare, which was recently launched to address gender inequity and sexual harassment in medicine.
“As a psychiatrist who has had physicians as patients ... I’d heard this stuff, and I knew it existed,” said Jessica Gold, MD. But to hear it from people who had choked it down ... I understand what it’s like to be a pharma rep and be told that you have to look pretty or wear a thong to get a doctor to look at you.”
In this video, Dr. Gold and Kali D. Cyrus, MD, MPH, sat down at the annual meeting of the American Psychiatric Association and discussed the goals of TIME’S UP Healthcare and the need to bring transgressions – mainly against women – out in the open. The group also wants to advocate for establishing meaningful standards and policies.
“I feel like [psychiatrists are] trained to look for these kinds of dynamics. We should be trained to intervene ... Dr. Cyrus said.
She wants to make sure that all women are equitably represented. We need “a procedure in place where people can voice their concerns.”
All of the group’s founding members are women, and men also need to participate as allies. “There are men who want to mentor women, Dr. Gold said. “We do need men to support us ... We also want to hear about their experiences,” Dr. Cyrus said.
Dr. Gold is assistant professor of psychiatry at Washington University in St. Louis. Dr. Cyrus is an assistant professor at Johns Hopkins University in Baltimore, and offers consultation services for conflict management of issues related to identity differences.
*This story was updated 6/3/2019.
SAN FRANCISCO – Women in health care are second only to those in arts and entertainment in contacting* the TIME’S UP Legal Defense Fund, according to two founding members of TIME’S UP Healthcare, which was recently launched to address gender inequity and sexual harassment in medicine.
“As a psychiatrist who has had physicians as patients ... I’d heard this stuff, and I knew it existed,” said Jessica Gold, MD. But to hear it from people who had choked it down ... I understand what it’s like to be a pharma rep and be told that you have to look pretty or wear a thong to get a doctor to look at you.”
In this video, Dr. Gold and Kali D. Cyrus, MD, MPH, sat down at the annual meeting of the American Psychiatric Association and discussed the goals of TIME’S UP Healthcare and the need to bring transgressions – mainly against women – out in the open. The group also wants to advocate for establishing meaningful standards and policies.
“I feel like [psychiatrists are] trained to look for these kinds of dynamics. We should be trained to intervene ... Dr. Cyrus said.
She wants to make sure that all women are equitably represented. We need “a procedure in place where people can voice their concerns.”
All of the group’s founding members are women, and men also need to participate as allies. “There are men who want to mentor women, Dr. Gold said. “We do need men to support us ... We also want to hear about their experiences,” Dr. Cyrus said.
Dr. Gold is assistant professor of psychiatry at Washington University in St. Louis. Dr. Cyrus is an assistant professor at Johns Hopkins University in Baltimore, and offers consultation services for conflict management of issues related to identity differences.
*This story was updated 6/3/2019.
SAN FRANCISCO – Women in health care are second only to those in arts and entertainment in contacting* the TIME’S UP Legal Defense Fund, according to two founding members of TIME’S UP Healthcare, which was recently launched to address gender inequity and sexual harassment in medicine.
“As a psychiatrist who has had physicians as patients ... I’d heard this stuff, and I knew it existed,” said Jessica Gold, MD. But to hear it from people who had choked it down ... I understand what it’s like to be a pharma rep and be told that you have to look pretty or wear a thong to get a doctor to look at you.”
In this video, Dr. Gold and Kali D. Cyrus, MD, MPH, sat down at the annual meeting of the American Psychiatric Association and discussed the goals of TIME’S UP Healthcare and the need to bring transgressions – mainly against women – out in the open. The group also wants to advocate for establishing meaningful standards and policies.
“I feel like [psychiatrists are] trained to look for these kinds of dynamics. We should be trained to intervene ... Dr. Cyrus said.
She wants to make sure that all women are equitably represented. We need “a procedure in place where people can voice their concerns.”
All of the group’s founding members are women, and men also need to participate as allies. “There are men who want to mentor women, Dr. Gold said. “We do need men to support us ... We also want to hear about their experiences,” Dr. Cyrus said.
Dr. Gold is assistant professor of psychiatry at Washington University in St. Louis. Dr. Cyrus is an assistant professor at Johns Hopkins University in Baltimore, and offers consultation services for conflict management of issues related to identity differences.
*This story was updated 6/3/2019.
REPORTING FROM APA 2019
Adjuvant CAPOX: Three months may be as good as 6 in high-risk stage II colon cancer
CHICAGO – In patients with high-risk stage II colon cancer, capecitabine plus oxaliplatin (CAPOX) given for 3 months may have efficacy as good as that of 6 months, with considerably less toxicity, as suggested by results of a new analysis by the IDEA (International Duration Evaluation of Adjuvant Chemotherapy) Collaboration.
By contrast, 6 months of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) had better efficacy than that of 3 months of FOLFOX, albeit with significantly more toxicity than the shorter duration of treatment, according to IDEA investigator Timothy Iveson, MD, FRCP, of University Hospital Southampton (England) NHS Foundation Trust.
“As oncologists, we have patients in front of us, and we have the ability to choose which chemotherapy regimen we would choose,” Dr. Iveson said in a presentation at the annual meeting of the American Society of Clinical Oncology, “and we now have good data on both the efficacy and also toxicity of the regimens according to duration of treatment, and therefore, that should really allow us to recommend both the chemotherapy regimen and duration of treatment to our patients.”
The findings echo those of the previous study by the collaborative group, presented at ASCO in 2017 and subsequently published in the New England Journal of Medicine, focused on patients with stage III colon cancer. The overall analysis was negative, in that they could not confirm the noninferiority of 3 versus 6 months of adjuvant FOLFOX or CAPOX in the overall population; however, further analysis showed that, specifically for CAPOX, 3 months of treatment delivered the same efficacy as 6 months, especially in the lower-risk subgroup.
Treatment of stage III colon cancer got “more complicated” as a result of that study, said David P. Ryan, MD, of Harvard Medical School, Boston.
That’s in part because the National Comprehensive Cancer Network (NCCN) colon cancer guidelines subsequently divided stage III disease into low and high risk, with different recommendations for each, he said in an oral presentation at the ASCO meeting.
Specifically, the NCCN’s preferred regimens for low-risk stage III disease (T1-3, N1) are now 3 months of CAPOX or 3-6 months of FOLFOX, while for high-risk stage III disease (T4, N1-2; T any, N2), the preferred regimens are 3-6 months of CAPOX or 6 months of FOLFOX.
“The reason for this study is the toxicity of oxaliplatin, particularly neuropathy,” Dr. Ryan said in his remarks from the podium. “It can be substantial and life altering.” The incidence of grade 2 or greater neuropathy was cut from about 45% to 15% by going from 6 to 3 months of treatment, though reporting of the rate of chronic neuropathy would be informative to better qualify these results, he said.
The more recent prospective, preplanned, pooled analysis from the IDEA group focused on the four phase 3 IDEA studies (SCOT, TOSCA, ACHIEVE-2, and HORG), out of six total studies, that enrolled high-risk stage II patients. Their primary analysis included 3,273 patients, of whom 2,019 received CAPOX and 1,254 received FOLFOX.
Rates of grade 2 or greater neuropathy were 36% for 6 months of treatment, but just 13% for 3 months of treatment. However, in the overall analysis, IDEA investigators could not demonstrate the noninferiority of 3 versus 6 months of treatment in terms of efficacy—similar to what was reported in the previously reported analysis of stage III patients.
Results for CAPOX, however, did demonstrate noninferiority, according to Dr. Iveson, with a 5-year disease-free survival (DFS) of 81.7% for 3 months of treatment versus 82.0% for 6 months, an absolute difference of 0.3%, he said in his presentation. By contrast, the 5-year DFS for FOLFOX was 79.2% for 3 months of treatment versus 86.5%, an absolute 7.3% difference in favor of longer treatment duration.
“Therefore, the data strongly suggest noninferiority of 3 months’ CAPOX treatment compared to 6 months, but equally, it suggests inferiority of 3 months FOLFOX compared to 6 months,” Dr. Iveson said.
Whether these findings also change practice remains to be seen.
Dr. Ryan, discussant for the study, agreed that 3 months of CAPOX, but not FOLFOX, is likely sufficient for patients with high-risk stage II disease, with one caveat: “Remember, it is not proven as the primary endpoint,” he told attendees at ASCO.
He said a new era of adjuvant studies is needed to address individual subsets of colon cancer in the adjuvant setting, particularly those defined by different biologies, such as BRAF-mutant, MSI-high, or HER2-amplified.
“I have little enthusiasm to return to the fundamental question posed by IDEA in a new prospective study, given that the magnitude of benefit or difference is so small,” he said.
Dr. Iveson reported disclosures related to Lilly, Servier, BMS, Celgene, Roche, and Bayer.
CHICAGO – In patients with high-risk stage II colon cancer, capecitabine plus oxaliplatin (CAPOX) given for 3 months may have efficacy as good as that of 6 months, with considerably less toxicity, as suggested by results of a new analysis by the IDEA (International Duration Evaluation of Adjuvant Chemotherapy) Collaboration.
By contrast, 6 months of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) had better efficacy than that of 3 months of FOLFOX, albeit with significantly more toxicity than the shorter duration of treatment, according to IDEA investigator Timothy Iveson, MD, FRCP, of University Hospital Southampton (England) NHS Foundation Trust.
“As oncologists, we have patients in front of us, and we have the ability to choose which chemotherapy regimen we would choose,” Dr. Iveson said in a presentation at the annual meeting of the American Society of Clinical Oncology, “and we now have good data on both the efficacy and also toxicity of the regimens according to duration of treatment, and therefore, that should really allow us to recommend both the chemotherapy regimen and duration of treatment to our patients.”
The findings echo those of the previous study by the collaborative group, presented at ASCO in 2017 and subsequently published in the New England Journal of Medicine, focused on patients with stage III colon cancer. The overall analysis was negative, in that they could not confirm the noninferiority of 3 versus 6 months of adjuvant FOLFOX or CAPOX in the overall population; however, further analysis showed that, specifically for CAPOX, 3 months of treatment delivered the same efficacy as 6 months, especially in the lower-risk subgroup.
Treatment of stage III colon cancer got “more complicated” as a result of that study, said David P. Ryan, MD, of Harvard Medical School, Boston.
That’s in part because the National Comprehensive Cancer Network (NCCN) colon cancer guidelines subsequently divided stage III disease into low and high risk, with different recommendations for each, he said in an oral presentation at the ASCO meeting.
Specifically, the NCCN’s preferred regimens for low-risk stage III disease (T1-3, N1) are now 3 months of CAPOX or 3-6 months of FOLFOX, while for high-risk stage III disease (T4, N1-2; T any, N2), the preferred regimens are 3-6 months of CAPOX or 6 months of FOLFOX.
“The reason for this study is the toxicity of oxaliplatin, particularly neuropathy,” Dr. Ryan said in his remarks from the podium. “It can be substantial and life altering.” The incidence of grade 2 or greater neuropathy was cut from about 45% to 15% by going from 6 to 3 months of treatment, though reporting of the rate of chronic neuropathy would be informative to better qualify these results, he said.
The more recent prospective, preplanned, pooled analysis from the IDEA group focused on the four phase 3 IDEA studies (SCOT, TOSCA, ACHIEVE-2, and HORG), out of six total studies, that enrolled high-risk stage II patients. Their primary analysis included 3,273 patients, of whom 2,019 received CAPOX and 1,254 received FOLFOX.
Rates of grade 2 or greater neuropathy were 36% for 6 months of treatment, but just 13% for 3 months of treatment. However, in the overall analysis, IDEA investigators could not demonstrate the noninferiority of 3 versus 6 months of treatment in terms of efficacy—similar to what was reported in the previously reported analysis of stage III patients.
Results for CAPOX, however, did demonstrate noninferiority, according to Dr. Iveson, with a 5-year disease-free survival (DFS) of 81.7% for 3 months of treatment versus 82.0% for 6 months, an absolute difference of 0.3%, he said in his presentation. By contrast, the 5-year DFS for FOLFOX was 79.2% for 3 months of treatment versus 86.5%, an absolute 7.3% difference in favor of longer treatment duration.
“Therefore, the data strongly suggest noninferiority of 3 months’ CAPOX treatment compared to 6 months, but equally, it suggests inferiority of 3 months FOLFOX compared to 6 months,” Dr. Iveson said.
Whether these findings also change practice remains to be seen.
Dr. Ryan, discussant for the study, agreed that 3 months of CAPOX, but not FOLFOX, is likely sufficient for patients with high-risk stage II disease, with one caveat: “Remember, it is not proven as the primary endpoint,” he told attendees at ASCO.
He said a new era of adjuvant studies is needed to address individual subsets of colon cancer in the adjuvant setting, particularly those defined by different biologies, such as BRAF-mutant, MSI-high, or HER2-amplified.
“I have little enthusiasm to return to the fundamental question posed by IDEA in a new prospective study, given that the magnitude of benefit or difference is so small,” he said.
Dr. Iveson reported disclosures related to Lilly, Servier, BMS, Celgene, Roche, and Bayer.
CHICAGO – In patients with high-risk stage II colon cancer, capecitabine plus oxaliplatin (CAPOX) given for 3 months may have efficacy as good as that of 6 months, with considerably less toxicity, as suggested by results of a new analysis by the IDEA (International Duration Evaluation of Adjuvant Chemotherapy) Collaboration.
By contrast, 6 months of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) had better efficacy than that of 3 months of FOLFOX, albeit with significantly more toxicity than the shorter duration of treatment, according to IDEA investigator Timothy Iveson, MD, FRCP, of University Hospital Southampton (England) NHS Foundation Trust.
“As oncologists, we have patients in front of us, and we have the ability to choose which chemotherapy regimen we would choose,” Dr. Iveson said in a presentation at the annual meeting of the American Society of Clinical Oncology, “and we now have good data on both the efficacy and also toxicity of the regimens according to duration of treatment, and therefore, that should really allow us to recommend both the chemotherapy regimen and duration of treatment to our patients.”
The findings echo those of the previous study by the collaborative group, presented at ASCO in 2017 and subsequently published in the New England Journal of Medicine, focused on patients with stage III colon cancer. The overall analysis was negative, in that they could not confirm the noninferiority of 3 versus 6 months of adjuvant FOLFOX or CAPOX in the overall population; however, further analysis showed that, specifically for CAPOX, 3 months of treatment delivered the same efficacy as 6 months, especially in the lower-risk subgroup.
Treatment of stage III colon cancer got “more complicated” as a result of that study, said David P. Ryan, MD, of Harvard Medical School, Boston.
That’s in part because the National Comprehensive Cancer Network (NCCN) colon cancer guidelines subsequently divided stage III disease into low and high risk, with different recommendations for each, he said in an oral presentation at the ASCO meeting.
Specifically, the NCCN’s preferred regimens for low-risk stage III disease (T1-3, N1) are now 3 months of CAPOX or 3-6 months of FOLFOX, while for high-risk stage III disease (T4, N1-2; T any, N2), the preferred regimens are 3-6 months of CAPOX or 6 months of FOLFOX.
“The reason for this study is the toxicity of oxaliplatin, particularly neuropathy,” Dr. Ryan said in his remarks from the podium. “It can be substantial and life altering.” The incidence of grade 2 or greater neuropathy was cut from about 45% to 15% by going from 6 to 3 months of treatment, though reporting of the rate of chronic neuropathy would be informative to better qualify these results, he said.
The more recent prospective, preplanned, pooled analysis from the IDEA group focused on the four phase 3 IDEA studies (SCOT, TOSCA, ACHIEVE-2, and HORG), out of six total studies, that enrolled high-risk stage II patients. Their primary analysis included 3,273 patients, of whom 2,019 received CAPOX and 1,254 received FOLFOX.
Rates of grade 2 or greater neuropathy were 36% for 6 months of treatment, but just 13% for 3 months of treatment. However, in the overall analysis, IDEA investigators could not demonstrate the noninferiority of 3 versus 6 months of treatment in terms of efficacy—similar to what was reported in the previously reported analysis of stage III patients.
Results for CAPOX, however, did demonstrate noninferiority, according to Dr. Iveson, with a 5-year disease-free survival (DFS) of 81.7% for 3 months of treatment versus 82.0% for 6 months, an absolute difference of 0.3%, he said in his presentation. By contrast, the 5-year DFS for FOLFOX was 79.2% for 3 months of treatment versus 86.5%, an absolute 7.3% difference in favor of longer treatment duration.
“Therefore, the data strongly suggest noninferiority of 3 months’ CAPOX treatment compared to 6 months, but equally, it suggests inferiority of 3 months FOLFOX compared to 6 months,” Dr. Iveson said.
Whether these findings also change practice remains to be seen.
Dr. Ryan, discussant for the study, agreed that 3 months of CAPOX, but not FOLFOX, is likely sufficient for patients with high-risk stage II disease, with one caveat: “Remember, it is not proven as the primary endpoint,” he told attendees at ASCO.
He said a new era of adjuvant studies is needed to address individual subsets of colon cancer in the adjuvant setting, particularly those defined by different biologies, such as BRAF-mutant, MSI-high, or HER2-amplified.
“I have little enthusiasm to return to the fundamental question posed by IDEA in a new prospective study, given that the magnitude of benefit or difference is so small,” he said.
Dr. Iveson reported disclosures related to Lilly, Servier, BMS, Celgene, Roche, and Bayer.
EXPERT ANALYSIS FROM ASCO 2019
NCCN publishes pediatric ALL guidelines
“The cure rate for pediatric ALL in the U.S. has risen from 0% in the 1960s to nearly 90% today. This is among the most profound medical success stories in history,” Patrick Brown, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, said in a statement announcing the guidelines. Dr. Brown chairs the NCCN Clinical Practice Guidelines for adult and pediatric ALL.
“Pediatric ALL survivors live a long time; we have to consider long-term effects as well,” Hiroto Inaba, MD, PhD, of St. Jude Children’s Research Hospital, Memphis, and vice chair of the guidelines committee, said in the statement.
The new recommendations highlight the importance of supportive care interventions in an effort to reduce the chances of patients experiencing severe adverse effects.
The pediatric ALL guidelines provide evidence-based recommendations about optimal treatment strategies for ALL to prolong survival in children affected, with a focus on treatment outside of clinical trials (Pediatric Acute Lymphoblastic Leukemia. NCCN.org, Version 1.2019, published May 30, 2019).
While treatment for ALL often includes long-term chemotherapy regimens that involve multiple stages, several novel treatment strategies are summarized in the guidelines, including various types of immunotherapy and targeted therapy.
The guidelines are intended to accompany the NCCN Guidelines for Adult ALL and integrate treatment recommendations for patients in overlapping age categories. The recommendations are organized based on risk level, which may also be associated with age.
“The highest risk [is] associated with those diagnosed within the first 12 months of life or between the ages 10 and 21 years old,” the guideline authors wrote.
Another unique aspect of the guidelines is the recognition of vulnerable populations, such as young infants or children with Down syndrome, who face distinct treatment challenges. The authors provide guidance on the best supportive care measures for these patients.
The NCCN is currently expanding the collection of clinical practice guidelines for additional pediatric malignancies. At present, they are planning to undertake a minimum of 90% of all incident pediatric cancers.
Upcoming guidelines include treatment recommendations for pediatric Burkitt lymphoma, and are scheduled for release later in 2019.
Future efforts include modifying the guidelines for use in low- and middle-income countries, with the goal of providing direction in resource-limited environments.
“We know that many, many children can be cured with inexpensive and widely-available therapies,” Dr. Brown said. “With the increasing global reach of the NCCN Guidelines, we can really pave the way for increasing the cure rates throughout the world.”
“The cure rate for pediatric ALL in the U.S. has risen from 0% in the 1960s to nearly 90% today. This is among the most profound medical success stories in history,” Patrick Brown, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, said in a statement announcing the guidelines. Dr. Brown chairs the NCCN Clinical Practice Guidelines for adult and pediatric ALL.
“Pediatric ALL survivors live a long time; we have to consider long-term effects as well,” Hiroto Inaba, MD, PhD, of St. Jude Children’s Research Hospital, Memphis, and vice chair of the guidelines committee, said in the statement.
The new recommendations highlight the importance of supportive care interventions in an effort to reduce the chances of patients experiencing severe adverse effects.
The pediatric ALL guidelines provide evidence-based recommendations about optimal treatment strategies for ALL to prolong survival in children affected, with a focus on treatment outside of clinical trials (Pediatric Acute Lymphoblastic Leukemia. NCCN.org, Version 1.2019, published May 30, 2019).
While treatment for ALL often includes long-term chemotherapy regimens that involve multiple stages, several novel treatment strategies are summarized in the guidelines, including various types of immunotherapy and targeted therapy.
The guidelines are intended to accompany the NCCN Guidelines for Adult ALL and integrate treatment recommendations for patients in overlapping age categories. The recommendations are organized based on risk level, which may also be associated with age.
“The highest risk [is] associated with those diagnosed within the first 12 months of life or between the ages 10 and 21 years old,” the guideline authors wrote.
Another unique aspect of the guidelines is the recognition of vulnerable populations, such as young infants or children with Down syndrome, who face distinct treatment challenges. The authors provide guidance on the best supportive care measures for these patients.
The NCCN is currently expanding the collection of clinical practice guidelines for additional pediatric malignancies. At present, they are planning to undertake a minimum of 90% of all incident pediatric cancers.
Upcoming guidelines include treatment recommendations for pediatric Burkitt lymphoma, and are scheduled for release later in 2019.
Future efforts include modifying the guidelines for use in low- and middle-income countries, with the goal of providing direction in resource-limited environments.
“We know that many, many children can be cured with inexpensive and widely-available therapies,” Dr. Brown said. “With the increasing global reach of the NCCN Guidelines, we can really pave the way for increasing the cure rates throughout the world.”
“The cure rate for pediatric ALL in the U.S. has risen from 0% in the 1960s to nearly 90% today. This is among the most profound medical success stories in history,” Patrick Brown, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, said in a statement announcing the guidelines. Dr. Brown chairs the NCCN Clinical Practice Guidelines for adult and pediatric ALL.
“Pediatric ALL survivors live a long time; we have to consider long-term effects as well,” Hiroto Inaba, MD, PhD, of St. Jude Children’s Research Hospital, Memphis, and vice chair of the guidelines committee, said in the statement.
The new recommendations highlight the importance of supportive care interventions in an effort to reduce the chances of patients experiencing severe adverse effects.
The pediatric ALL guidelines provide evidence-based recommendations about optimal treatment strategies for ALL to prolong survival in children affected, with a focus on treatment outside of clinical trials (Pediatric Acute Lymphoblastic Leukemia. NCCN.org, Version 1.2019, published May 30, 2019).
While treatment for ALL often includes long-term chemotherapy regimens that involve multiple stages, several novel treatment strategies are summarized in the guidelines, including various types of immunotherapy and targeted therapy.
The guidelines are intended to accompany the NCCN Guidelines for Adult ALL and integrate treatment recommendations for patients in overlapping age categories. The recommendations are organized based on risk level, which may also be associated with age.
“The highest risk [is] associated with those diagnosed within the first 12 months of life or between the ages 10 and 21 years old,” the guideline authors wrote.
Another unique aspect of the guidelines is the recognition of vulnerable populations, such as young infants or children with Down syndrome, who face distinct treatment challenges. The authors provide guidance on the best supportive care measures for these patients.
The NCCN is currently expanding the collection of clinical practice guidelines for additional pediatric malignancies. At present, they are planning to undertake a minimum of 90% of all incident pediatric cancers.
Upcoming guidelines include treatment recommendations for pediatric Burkitt lymphoma, and are scheduled for release later in 2019.
Future efforts include modifying the guidelines for use in low- and middle-income countries, with the goal of providing direction in resource-limited environments.
“We know that many, many children can be cured with inexpensive and widely-available therapies,” Dr. Brown said. “With the increasing global reach of the NCCN Guidelines, we can really pave the way for increasing the cure rates throughout the world.”
FROM THE NATIONAL COMPREHENSIVE CANCER NETWORK
Slow breathing: An effective, pragmatic analgesic technique?
MILWAUKEE – Mindfulness-based practices are effective in reducing pain perceptions, but a more easily taught breath control technique also showed efficacy in a recent study. Slow, rhythmic breathing alone, even without the additional attentional components of mindfulness, had significant analgesic effects in a human experimental model of pain.
“Slow breathing is much easier to perform” than mindfulness-based meditation, Fadel Zeidan, PhD, said at the scientific meeting of the American Pain Society. More research into the technique may offer a “clinically pragmatic” nonpharmacologic option for pain control, he said. And there may be some similarities between how the two techniques work: like mindfulness meditation, slow, rhythmic breathing’s analgesic properties are not dependent on the endogenous opioid system, said Dr. Zeidan, assistant professor of anesthesiology at the University of California, San Diego. His interests include mindfulness meditation–based pain relief.
In previous work, Dr. Zeidan and his collaborators had shown that the analgesic effect of mindfulness practices is not mediated by endogenous opioids. Participants in a study were trained in mindfulness meditation, and then exposed to a pain stimulus. Compared with a control group who listened to an audiobook rather than using mindfulness practices when exposed to pain, the meditators experienced a significant reduction in pain unpleasantness (J Neurosci. 16 March 2016;36[11]:3391-7).
In the experiment, both the meditation and the control group received first an intravenous saline solution, and then the opioid antagonist naloxone, which blocks endogenous opioids. When receiving naloxone, the meditators experienced reductions in the perceived unpleasantness of pain that were similar to what they experienced when they had received saline, showing that endogenous opioids weren’t responsible for meditation’s analgesic effects.
After verifying those findings, said Dr. Zeidan, he became interested in conducting a “graded analytical dissection of mindfulness,” to see exactly which components of the practice are nonopioidergic.
With mindfulness meditation, participants engage in slow, rhythmic breathing, and they learn about observation and appraisal practices, which can briefly be described as “the awareness of arising sensory events without reaction,” Dr. Zeidan said.
Mere belief in meditation in combination with the slow rhythmic breathing might have an analgesic effect, he said. In effect, this is sham mindfulness.
To try to tease out the contributions of each component of mindfulness meditation, Dr. Zeidan and his colleagues devised an experiment that trained participants in one of three ways. Over the course of four 20-minute sessions, randomized participants were trained in slow breathing techniques, with a goal respiratory rate of 6 breaths per minute; in mindfulness meditation techniques; or in a sham mindfulness technique that did not teach specific mindfulness principles.
The randomized participants were subject to a painful heat stimulus before the training to establish a baseline.
After training, they returned for two further sessions. At each visit, they experienced the noxious stimulus with no medication. After a rest period, they then received either high-dose intravenous naloxone or saline. The allocation was randomized and administration of the study drug was double-blinded.
With naloxone or saline infusion ongoing, participants were then again subjected to the painful heat stimulus.
“All manipulations effectively reduced the respiration rate,” by 18%-21%, Dr. Zeidan said.
However, with the introduction of naloxone, both the slow-breathing group and the mindfulness group maintained reductions in pain unpleasantness, while those in the sham group had significant increases in pain unpleasantness. Reductions in pain unpleasantness ranged from 11% to 18% for these two groups, while the initial 8% reduction for the sham group climbed to a 13% increase in pain unpleasantness when this group received naloxone.
An unexpected finding was how effective slow breathing alone was as an analgesic. “There’s really something here,” said Dr. Zeidan, in reference to the analgesic effect of breath control. He explained that the slow breathing technique training was done with the aid of a device that emitted a blue glow that dimmed and brightened at the target respiratory rate.
Dr. Zeidan added that few participants were able to slow their breathing to 6 respirations per minute, but that the average rate did slow to about 12 from the normal 16 or so breaths per minute.
Dr. Zeidan reported no conflicts of interest. The National Institutes of Health funded the research.
MILWAUKEE – Mindfulness-based practices are effective in reducing pain perceptions, but a more easily taught breath control technique also showed efficacy in a recent study. Slow, rhythmic breathing alone, even without the additional attentional components of mindfulness, had significant analgesic effects in a human experimental model of pain.
“Slow breathing is much easier to perform” than mindfulness-based meditation, Fadel Zeidan, PhD, said at the scientific meeting of the American Pain Society. More research into the technique may offer a “clinically pragmatic” nonpharmacologic option for pain control, he said. And there may be some similarities between how the two techniques work: like mindfulness meditation, slow, rhythmic breathing’s analgesic properties are not dependent on the endogenous opioid system, said Dr. Zeidan, assistant professor of anesthesiology at the University of California, San Diego. His interests include mindfulness meditation–based pain relief.
In previous work, Dr. Zeidan and his collaborators had shown that the analgesic effect of mindfulness practices is not mediated by endogenous opioids. Participants in a study were trained in mindfulness meditation, and then exposed to a pain stimulus. Compared with a control group who listened to an audiobook rather than using mindfulness practices when exposed to pain, the meditators experienced a significant reduction in pain unpleasantness (J Neurosci. 16 March 2016;36[11]:3391-7).
In the experiment, both the meditation and the control group received first an intravenous saline solution, and then the opioid antagonist naloxone, which blocks endogenous opioids. When receiving naloxone, the meditators experienced reductions in the perceived unpleasantness of pain that were similar to what they experienced when they had received saline, showing that endogenous opioids weren’t responsible for meditation’s analgesic effects.
After verifying those findings, said Dr. Zeidan, he became interested in conducting a “graded analytical dissection of mindfulness,” to see exactly which components of the practice are nonopioidergic.
With mindfulness meditation, participants engage in slow, rhythmic breathing, and they learn about observation and appraisal practices, which can briefly be described as “the awareness of arising sensory events without reaction,” Dr. Zeidan said.
Mere belief in meditation in combination with the slow rhythmic breathing might have an analgesic effect, he said. In effect, this is sham mindfulness.
To try to tease out the contributions of each component of mindfulness meditation, Dr. Zeidan and his colleagues devised an experiment that trained participants in one of three ways. Over the course of four 20-minute sessions, randomized participants were trained in slow breathing techniques, with a goal respiratory rate of 6 breaths per minute; in mindfulness meditation techniques; or in a sham mindfulness technique that did not teach specific mindfulness principles.
The randomized participants were subject to a painful heat stimulus before the training to establish a baseline.
After training, they returned for two further sessions. At each visit, they experienced the noxious stimulus with no medication. After a rest period, they then received either high-dose intravenous naloxone or saline. The allocation was randomized and administration of the study drug was double-blinded.
With naloxone or saline infusion ongoing, participants were then again subjected to the painful heat stimulus.
“All manipulations effectively reduced the respiration rate,” by 18%-21%, Dr. Zeidan said.
However, with the introduction of naloxone, both the slow-breathing group and the mindfulness group maintained reductions in pain unpleasantness, while those in the sham group had significant increases in pain unpleasantness. Reductions in pain unpleasantness ranged from 11% to 18% for these two groups, while the initial 8% reduction for the sham group climbed to a 13% increase in pain unpleasantness when this group received naloxone.
An unexpected finding was how effective slow breathing alone was as an analgesic. “There’s really something here,” said Dr. Zeidan, in reference to the analgesic effect of breath control. He explained that the slow breathing technique training was done with the aid of a device that emitted a blue glow that dimmed and brightened at the target respiratory rate.
Dr. Zeidan added that few participants were able to slow their breathing to 6 respirations per minute, but that the average rate did slow to about 12 from the normal 16 or so breaths per minute.
Dr. Zeidan reported no conflicts of interest. The National Institutes of Health funded the research.
MILWAUKEE – Mindfulness-based practices are effective in reducing pain perceptions, but a more easily taught breath control technique also showed efficacy in a recent study. Slow, rhythmic breathing alone, even without the additional attentional components of mindfulness, had significant analgesic effects in a human experimental model of pain.
“Slow breathing is much easier to perform” than mindfulness-based meditation, Fadel Zeidan, PhD, said at the scientific meeting of the American Pain Society. More research into the technique may offer a “clinically pragmatic” nonpharmacologic option for pain control, he said. And there may be some similarities between how the two techniques work: like mindfulness meditation, slow, rhythmic breathing’s analgesic properties are not dependent on the endogenous opioid system, said Dr. Zeidan, assistant professor of anesthesiology at the University of California, San Diego. His interests include mindfulness meditation–based pain relief.
In previous work, Dr. Zeidan and his collaborators had shown that the analgesic effect of mindfulness practices is not mediated by endogenous opioids. Participants in a study were trained in mindfulness meditation, and then exposed to a pain stimulus. Compared with a control group who listened to an audiobook rather than using mindfulness practices when exposed to pain, the meditators experienced a significant reduction in pain unpleasantness (J Neurosci. 16 March 2016;36[11]:3391-7).
In the experiment, both the meditation and the control group received first an intravenous saline solution, and then the opioid antagonist naloxone, which blocks endogenous opioids. When receiving naloxone, the meditators experienced reductions in the perceived unpleasantness of pain that were similar to what they experienced when they had received saline, showing that endogenous opioids weren’t responsible for meditation’s analgesic effects.
After verifying those findings, said Dr. Zeidan, he became interested in conducting a “graded analytical dissection of mindfulness,” to see exactly which components of the practice are nonopioidergic.
With mindfulness meditation, participants engage in slow, rhythmic breathing, and they learn about observation and appraisal practices, which can briefly be described as “the awareness of arising sensory events without reaction,” Dr. Zeidan said.
Mere belief in meditation in combination with the slow rhythmic breathing might have an analgesic effect, he said. In effect, this is sham mindfulness.
To try to tease out the contributions of each component of mindfulness meditation, Dr. Zeidan and his colleagues devised an experiment that trained participants in one of three ways. Over the course of four 20-minute sessions, randomized participants were trained in slow breathing techniques, with a goal respiratory rate of 6 breaths per minute; in mindfulness meditation techniques; or in a sham mindfulness technique that did not teach specific mindfulness principles.
The randomized participants were subject to a painful heat stimulus before the training to establish a baseline.
After training, they returned for two further sessions. At each visit, they experienced the noxious stimulus with no medication. After a rest period, they then received either high-dose intravenous naloxone or saline. The allocation was randomized and administration of the study drug was double-blinded.
With naloxone or saline infusion ongoing, participants were then again subjected to the painful heat stimulus.
“All manipulations effectively reduced the respiration rate,” by 18%-21%, Dr. Zeidan said.
However, with the introduction of naloxone, both the slow-breathing group and the mindfulness group maintained reductions in pain unpleasantness, while those in the sham group had significant increases in pain unpleasantness. Reductions in pain unpleasantness ranged from 11% to 18% for these two groups, while the initial 8% reduction for the sham group climbed to a 13% increase in pain unpleasantness when this group received naloxone.
An unexpected finding was how effective slow breathing alone was as an analgesic. “There’s really something here,” said Dr. Zeidan, in reference to the analgesic effect of breath control. He explained that the slow breathing technique training was done with the aid of a device that emitted a blue glow that dimmed and brightened at the target respiratory rate.
Dr. Zeidan added that few participants were able to slow their breathing to 6 respirations per minute, but that the average rate did slow to about 12 from the normal 16 or so breaths per minute.
Dr. Zeidan reported no conflicts of interest. The National Institutes of Health funded the research.
REPORTING FROM APS 2019
Five rules for evaluating melanonychia
WAIKOLOA, HAWAII – Many dermatologists find melanonychia to be intimidating. The clinical features are ambiguous, and the prospect of doing a painful nail apparatus biopsy can be daunting for the inexperienced. As a result, the biopsy gets delayed and melanoma of the nail is often initially a missed diagnosis, not uncommonly for years, with devastating consequences.
Here are five at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Rule #1: Always look beyond the nail
When a light-skinned person presents with more than one nail with pigmentation, the likelihood that one of them is melanoma is much less than if there is only one nail with melanonychia, according to Dr. Jellinek, a dermatologist in private practice in East Greenwich, R.I.
Also, be sure to look at the skin and mucosa. Consider the medications the patients may be taking: For example, cyclophosphamide (Cytoxan) is notorious for causing nail changes as a side effect. A past medical history of lichen planus, carpal tunnel syndrome, Addison disease, or other conditions may explain the melanonychia.
Laugier-Hunziker syndrome is a condition worth getting to know. It’s an acquired disorder characterized longitudinal melanonychia and other pigmentary changes, which may include diffuse hyperpigmentation of the orolabial mucosa, ocular pigment, and/or pigmented palmoplantar lesions. It’s said to be rare, but Dr. Jellinek disagrees.
“Learn this one if you don’t know it. I see a case about every 2 weeks. It’s not heritable and not associated with any other medical condition,” he said.
Rule #2: Your dermatoscope is great for nails
What Dr. Jellinek considers to be among the all-time best papers on the value of dermoscopy for nail pigmentation was authored by French investigators. They analyzed 148 consecutive cases of longitudinal melanonychia and concluded that the dermoscopic combination of a brown background coupled with irregular longitudinal lines in terms of color, spacing, diameter, and/or lack of parallelism strongly suggests melanoma. A micro-Hutchinson’s sign, while a rare finding, occurred only in melanoma, where it represented periungual spread of a radial growth phase malignancy (Arch Dermatol. 2002 Oct;138[10]:1327-33).
“I think nail dermoscopy is most helpful for subungual hemorrhage. I average one referral per week for hemorrhage under the nail. On dermoscopy it’s as if someone took paint and threw it at the nail. Purple to brown blood spots, with no background color. This should be a doorway diagnosis of hemorrhage,” Dr. Jellinek said.
Rule #3: Know when you don’t know
“This is really the key for me,” the dermatologist commented. “There are automatic cases for biopsy, and more commonly routine cases for reassurance. But the gray zone, when you know you don’t know, is the key decision making moment.”
When something just doesn’t feel right, there’s absolutely nothing wrong with getting a second opinion, he stressed.
“It’s worthwhile getting to know people whose opinions you trust. There’s a saying I like to teach our fellows: ‘Never worry alone.’ So if you’re worried about someone, listen to that inner voice. There’s no shame in getting a second opinion. It’s great! Patients are never upset, either. They feel really well taken care of,” he said.
Rule #4: Don’t wimp out when a biopsy is warranted
Many dermatologists hem and haw about doing a biopsy for a concerning lesion on the nail, when they wouldn’t hesitate to biopsy a similarly suspicious lesion on the face.
But it’s essential to biopsy the right area, he added. For longitudinal melanonychia, that’s the matrix. The nail plate is the wrong place; a biopsy obtained there will result in an inappropriate benign diagnosis.
“The starter set is to do a punch biopsy. This is your gateway drug to the world of nail surgery. Lots of dermatologists are intimidated by nail surgery, but if you can do any minor surgery, you can do a punch of the matrix. All it takes is a little practice. And if all you can do is punch biopsies, you’re good for your career. If you can do that, you’re golden. There are people who’ve just done punch biopsies for their whole career and they don’t miss melanomas,” he said.
Step one is to undermine the proximal nail fold using a pediatric elevator, which costs only about $30. “If you’re going to do a lot of nail surgery, they’re really helpful,” he said.
There’s no need at all to evulse the nail. Just make oblique incisions in the proximal nail fold in order to reflect it and look at the matrix. A 3-mm punch is standard, directed right over the origin of the pigment. Resist the temptation to force or squeeze the specimen in order to extract it. Instead, use really fine-tipped scissors to nibble at the base of the specimen, then gently pull it out, making an effort to keep the nail plate attached to the digit and avoid getting it stuck up in the punch.
Rule #5: Have dermatopathologists extensively experienced with nail pathology on your Rolodex
The histopathologic findings present in early subungual melanoma in situ are often too subtle for general dermatopathologists to appreciate, in Dr. Jellinek’s experience. He cited other investigators’ study of 18 cases of subungual melanoma in situ, all marked by longitudinal melanonychia. Only half showed the classic giveaway on the original nail matrix biopsy, consisting of a significantly increased number of atypical melanocytes with marked nuclear atypia. Blatant pagetoid spread was infrequent. However, all 18 cases displayed a novel, more subtle, and previously undescribed finding: haphazard and uneven distribution of atypical solitary melanocytes with variably sized and shaped hyperchromatic nuclei (J Cutan Pathol. 2016 Jan;43[1]:41-52).
Dr. Jellinek reported having no financial conflicts regarding his presentation. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – Many dermatologists find melanonychia to be intimidating. The clinical features are ambiguous, and the prospect of doing a painful nail apparatus biopsy can be daunting for the inexperienced. As a result, the biopsy gets delayed and melanoma of the nail is often initially a missed diagnosis, not uncommonly for years, with devastating consequences.
Here are five at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Rule #1: Always look beyond the nail
When a light-skinned person presents with more than one nail with pigmentation, the likelihood that one of them is melanoma is much less than if there is only one nail with melanonychia, according to Dr. Jellinek, a dermatologist in private practice in East Greenwich, R.I.
Also, be sure to look at the skin and mucosa. Consider the medications the patients may be taking: For example, cyclophosphamide (Cytoxan) is notorious for causing nail changes as a side effect. A past medical history of lichen planus, carpal tunnel syndrome, Addison disease, or other conditions may explain the melanonychia.
Laugier-Hunziker syndrome is a condition worth getting to know. It’s an acquired disorder characterized longitudinal melanonychia and other pigmentary changes, which may include diffuse hyperpigmentation of the orolabial mucosa, ocular pigment, and/or pigmented palmoplantar lesions. It’s said to be rare, but Dr. Jellinek disagrees.
“Learn this one if you don’t know it. I see a case about every 2 weeks. It’s not heritable and not associated with any other medical condition,” he said.
Rule #2: Your dermatoscope is great for nails
What Dr. Jellinek considers to be among the all-time best papers on the value of dermoscopy for nail pigmentation was authored by French investigators. They analyzed 148 consecutive cases of longitudinal melanonychia and concluded that the dermoscopic combination of a brown background coupled with irregular longitudinal lines in terms of color, spacing, diameter, and/or lack of parallelism strongly suggests melanoma. A micro-Hutchinson’s sign, while a rare finding, occurred only in melanoma, where it represented periungual spread of a radial growth phase malignancy (Arch Dermatol. 2002 Oct;138[10]:1327-33).
“I think nail dermoscopy is most helpful for subungual hemorrhage. I average one referral per week for hemorrhage under the nail. On dermoscopy it’s as if someone took paint and threw it at the nail. Purple to brown blood spots, with no background color. This should be a doorway diagnosis of hemorrhage,” Dr. Jellinek said.
Rule #3: Know when you don’t know
“This is really the key for me,” the dermatologist commented. “There are automatic cases for biopsy, and more commonly routine cases for reassurance. But the gray zone, when you know you don’t know, is the key decision making moment.”
When something just doesn’t feel right, there’s absolutely nothing wrong with getting a second opinion, he stressed.
“It’s worthwhile getting to know people whose opinions you trust. There’s a saying I like to teach our fellows: ‘Never worry alone.’ So if you’re worried about someone, listen to that inner voice. There’s no shame in getting a second opinion. It’s great! Patients are never upset, either. They feel really well taken care of,” he said.
Rule #4: Don’t wimp out when a biopsy is warranted
Many dermatologists hem and haw about doing a biopsy for a concerning lesion on the nail, when they wouldn’t hesitate to biopsy a similarly suspicious lesion on the face.
But it’s essential to biopsy the right area, he added. For longitudinal melanonychia, that’s the matrix. The nail plate is the wrong place; a biopsy obtained there will result in an inappropriate benign diagnosis.
“The starter set is to do a punch biopsy. This is your gateway drug to the world of nail surgery. Lots of dermatologists are intimidated by nail surgery, but if you can do any minor surgery, you can do a punch of the matrix. All it takes is a little practice. And if all you can do is punch biopsies, you’re good for your career. If you can do that, you’re golden. There are people who’ve just done punch biopsies for their whole career and they don’t miss melanomas,” he said.
Step one is to undermine the proximal nail fold using a pediatric elevator, which costs only about $30. “If you’re going to do a lot of nail surgery, they’re really helpful,” he said.
There’s no need at all to evulse the nail. Just make oblique incisions in the proximal nail fold in order to reflect it and look at the matrix. A 3-mm punch is standard, directed right over the origin of the pigment. Resist the temptation to force or squeeze the specimen in order to extract it. Instead, use really fine-tipped scissors to nibble at the base of the specimen, then gently pull it out, making an effort to keep the nail plate attached to the digit and avoid getting it stuck up in the punch.
Rule #5: Have dermatopathologists extensively experienced with nail pathology on your Rolodex
The histopathologic findings present in early subungual melanoma in situ are often too subtle for general dermatopathologists to appreciate, in Dr. Jellinek’s experience. He cited other investigators’ study of 18 cases of subungual melanoma in situ, all marked by longitudinal melanonychia. Only half showed the classic giveaway on the original nail matrix biopsy, consisting of a significantly increased number of atypical melanocytes with marked nuclear atypia. Blatant pagetoid spread was infrequent. However, all 18 cases displayed a novel, more subtle, and previously undescribed finding: haphazard and uneven distribution of atypical solitary melanocytes with variably sized and shaped hyperchromatic nuclei (J Cutan Pathol. 2016 Jan;43[1]:41-52).
Dr. Jellinek reported having no financial conflicts regarding his presentation. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – Many dermatologists find melanonychia to be intimidating. The clinical features are ambiguous, and the prospect of doing a painful nail apparatus biopsy can be daunting for the inexperienced. As a result, the biopsy gets delayed and melanoma of the nail is often initially a missed diagnosis, not uncommonly for years, with devastating consequences.
Here are five at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Rule #1: Always look beyond the nail
When a light-skinned person presents with more than one nail with pigmentation, the likelihood that one of them is melanoma is much less than if there is only one nail with melanonychia, according to Dr. Jellinek, a dermatologist in private practice in East Greenwich, R.I.
Also, be sure to look at the skin and mucosa. Consider the medications the patients may be taking: For example, cyclophosphamide (Cytoxan) is notorious for causing nail changes as a side effect. A past medical history of lichen planus, carpal tunnel syndrome, Addison disease, or other conditions may explain the melanonychia.
Laugier-Hunziker syndrome is a condition worth getting to know. It’s an acquired disorder characterized longitudinal melanonychia and other pigmentary changes, which may include diffuse hyperpigmentation of the orolabial mucosa, ocular pigment, and/or pigmented palmoplantar lesions. It’s said to be rare, but Dr. Jellinek disagrees.
“Learn this one if you don’t know it. I see a case about every 2 weeks. It’s not heritable and not associated with any other medical condition,” he said.
Rule #2: Your dermatoscope is great for nails
What Dr. Jellinek considers to be among the all-time best papers on the value of dermoscopy for nail pigmentation was authored by French investigators. They analyzed 148 consecutive cases of longitudinal melanonychia and concluded that the dermoscopic combination of a brown background coupled with irregular longitudinal lines in terms of color, spacing, diameter, and/or lack of parallelism strongly suggests melanoma. A micro-Hutchinson’s sign, while a rare finding, occurred only in melanoma, where it represented periungual spread of a radial growth phase malignancy (Arch Dermatol. 2002 Oct;138[10]:1327-33).
“I think nail dermoscopy is most helpful for subungual hemorrhage. I average one referral per week for hemorrhage under the nail. On dermoscopy it’s as if someone took paint and threw it at the nail. Purple to brown blood spots, with no background color. This should be a doorway diagnosis of hemorrhage,” Dr. Jellinek said.
Rule #3: Know when you don’t know
“This is really the key for me,” the dermatologist commented. “There are automatic cases for biopsy, and more commonly routine cases for reassurance. But the gray zone, when you know you don’t know, is the key decision making moment.”
When something just doesn’t feel right, there’s absolutely nothing wrong with getting a second opinion, he stressed.
“It’s worthwhile getting to know people whose opinions you trust. There’s a saying I like to teach our fellows: ‘Never worry alone.’ So if you’re worried about someone, listen to that inner voice. There’s no shame in getting a second opinion. It’s great! Patients are never upset, either. They feel really well taken care of,” he said.
Rule #4: Don’t wimp out when a biopsy is warranted
Many dermatologists hem and haw about doing a biopsy for a concerning lesion on the nail, when they wouldn’t hesitate to biopsy a similarly suspicious lesion on the face.
But it’s essential to biopsy the right area, he added. For longitudinal melanonychia, that’s the matrix. The nail plate is the wrong place; a biopsy obtained there will result in an inappropriate benign diagnosis.
“The starter set is to do a punch biopsy. This is your gateway drug to the world of nail surgery. Lots of dermatologists are intimidated by nail surgery, but if you can do any minor surgery, you can do a punch of the matrix. All it takes is a little practice. And if all you can do is punch biopsies, you’re good for your career. If you can do that, you’re golden. There are people who’ve just done punch biopsies for their whole career and they don’t miss melanomas,” he said.
Step one is to undermine the proximal nail fold using a pediatric elevator, which costs only about $30. “If you’re going to do a lot of nail surgery, they’re really helpful,” he said.
There’s no need at all to evulse the nail. Just make oblique incisions in the proximal nail fold in order to reflect it and look at the matrix. A 3-mm punch is standard, directed right over the origin of the pigment. Resist the temptation to force or squeeze the specimen in order to extract it. Instead, use really fine-tipped scissors to nibble at the base of the specimen, then gently pull it out, making an effort to keep the nail plate attached to the digit and avoid getting it stuck up in the punch.
Rule #5: Have dermatopathologists extensively experienced with nail pathology on your Rolodex
The histopathologic findings present in early subungual melanoma in situ are often too subtle for general dermatopathologists to appreciate, in Dr. Jellinek’s experience. He cited other investigators’ study of 18 cases of subungual melanoma in situ, all marked by longitudinal melanonychia. Only half showed the classic giveaway on the original nail matrix biopsy, consisting of a significantly increased number of atypical melanocytes with marked nuclear atypia. Blatant pagetoid spread was infrequent. However, all 18 cases displayed a novel, more subtle, and previously undescribed finding: haphazard and uneven distribution of atypical solitary melanocytes with variably sized and shaped hyperchromatic nuclei (J Cutan Pathol. 2016 Jan;43[1]:41-52).
Dr. Jellinek reported having no financial conflicts regarding his presentation. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
GI practice consolidation continues
Digestive Disease Week® (DDW) 2019 is now history. This was the 50th anniversary of DDW and again, it lived up to its reputation as the world’s foremost meeting dedicated to digestive diseases. GI & Hepatology News will publish multiple articles highlighting the best of DDW in the coming months.
The AGA Presidential Plenary session is an annual DDW highlight. This year’s session did not disappoint and was attended by a large crowd. David Lieberman, MD, AGAF (outgoing AGA president) and Hashem B. El-Serag MD, MPH, AGAF (incoming AGA president) moderated the session. Outstanding presentations about management of obesity, new findings in IBD, the use of virtual reality in the treatment of functional abdominal pain, and findings from a long-term colorectal cancer screening trial were some of the key presentations.
Recent behind-the-scenes work by the AGA is paying off for its members and the larger GI community. The AGA was again awarded an NIH-funded grant to advance its education and training of under-represented minorities. This is the second NIH grant given to the AGA, who now has become a leader in diversity and inclusive education. The AGA has strengthened its close bond with the Crohn's and Colitis Foundation, adding to its portfolio of scientific and clinical offerings focused on IBD. The AGA Center for Gut Microbiome Research and Education has emerged as one of the best sources of education and research about the microbiome’s impact on digestive health.
On the business front, there are tectonic changes occurring. In 2018, three large GI practices were sold to private equity companies and each has completed multiple arbitrage plays (acquisition of smaller practices), growing to over 200 physicians. This year we will see 6-10 additional private equity acquisitions and will likely see one or more GI practices of 500-1000 providers. This consolidation will have profound implications for the practice of gastroenterology and will provide some interesting opportunities to conduct population-based research for physicians who can capture that potential through academic-community partnerships.
John I. Allen, MD, MBA, AGAF
Editor in Chief
Digestive Disease Week® (DDW) 2019 is now history. This was the 50th anniversary of DDW and again, it lived up to its reputation as the world’s foremost meeting dedicated to digestive diseases. GI & Hepatology News will publish multiple articles highlighting the best of DDW in the coming months.
The AGA Presidential Plenary session is an annual DDW highlight. This year’s session did not disappoint and was attended by a large crowd. David Lieberman, MD, AGAF (outgoing AGA president) and Hashem B. El-Serag MD, MPH, AGAF (incoming AGA president) moderated the session. Outstanding presentations about management of obesity, new findings in IBD, the use of virtual reality in the treatment of functional abdominal pain, and findings from a long-term colorectal cancer screening trial were some of the key presentations.
Recent behind-the-scenes work by the AGA is paying off for its members and the larger GI community. The AGA was again awarded an NIH-funded grant to advance its education and training of under-represented minorities. This is the second NIH grant given to the AGA, who now has become a leader in diversity and inclusive education. The AGA has strengthened its close bond with the Crohn's and Colitis Foundation, adding to its portfolio of scientific and clinical offerings focused on IBD. The AGA Center for Gut Microbiome Research and Education has emerged as one of the best sources of education and research about the microbiome’s impact on digestive health.
On the business front, there are tectonic changes occurring. In 2018, three large GI practices were sold to private equity companies and each has completed multiple arbitrage plays (acquisition of smaller practices), growing to over 200 physicians. This year we will see 6-10 additional private equity acquisitions and will likely see one or more GI practices of 500-1000 providers. This consolidation will have profound implications for the practice of gastroenterology and will provide some interesting opportunities to conduct population-based research for physicians who can capture that potential through academic-community partnerships.
John I. Allen, MD, MBA, AGAF
Editor in Chief
Digestive Disease Week® (DDW) 2019 is now history. This was the 50th anniversary of DDW and again, it lived up to its reputation as the world’s foremost meeting dedicated to digestive diseases. GI & Hepatology News will publish multiple articles highlighting the best of DDW in the coming months.
The AGA Presidential Plenary session is an annual DDW highlight. This year’s session did not disappoint and was attended by a large crowd. David Lieberman, MD, AGAF (outgoing AGA president) and Hashem B. El-Serag MD, MPH, AGAF (incoming AGA president) moderated the session. Outstanding presentations about management of obesity, new findings in IBD, the use of virtual reality in the treatment of functional abdominal pain, and findings from a long-term colorectal cancer screening trial were some of the key presentations.
Recent behind-the-scenes work by the AGA is paying off for its members and the larger GI community. The AGA was again awarded an NIH-funded grant to advance its education and training of under-represented minorities. This is the second NIH grant given to the AGA, who now has become a leader in diversity and inclusive education. The AGA has strengthened its close bond with the Crohn's and Colitis Foundation, adding to its portfolio of scientific and clinical offerings focused on IBD. The AGA Center for Gut Microbiome Research and Education has emerged as one of the best sources of education and research about the microbiome’s impact on digestive health.
On the business front, there are tectonic changes occurring. In 2018, three large GI practices were sold to private equity companies and each has completed multiple arbitrage plays (acquisition of smaller practices), growing to over 200 physicians. This year we will see 6-10 additional private equity acquisitions and will likely see one or more GI practices of 500-1000 providers. This consolidation will have profound implications for the practice of gastroenterology and will provide some interesting opportunities to conduct population-based research for physicians who can capture that potential through academic-community partnerships.
John I. Allen, MD, MBA, AGAF
Editor in Chief
Consider patients’ perceptions of tardive dyskinesia
SAN FRANCISCO – Stanley N. Caroff, MD, said at the annual meeting of the American Psychiatric Association.
“You really need to ask the patient a lot of questions – and the family and the caregivers – about how much tardive dyskinesia affects their lives,” he said.
Those were some of the early results of RE-KINECT, an ongoing study of patients with schizophrenia and schizoaffective disorder who were being treated with antipsychotic agents.
TD occurs in more than 25% of patients in outpatient practices who are exposed to dopamine receptor blockers. Symptoms can include involuntary movements of the tongue, hands, and feet; facial distortions; rapid eye blinking; and difficulty speaking. In some cases, the side effects resolve after patients stop taking the medications.
In this video, Dr. Caroff discussed the studies’ findings and their implications for everyday clinical practice. He also presented some of the early RE-KINECT findings in a poster at the meeting.
Dr. Caroff is professor of psychiatry at the University of Pennsylvania, Philadelphia. He also is affiliated with the Michael J. Crescenz VA Medical Center in Philadelphia. He disclosed working as a consultant for and receiving research funding from Neurocrine Biosciences. He also is a consultant for DisperSol Technologies, Osmotica Pharmaceuticals, Teva Pharmaceutical.
SAN FRANCISCO – Stanley N. Caroff, MD, said at the annual meeting of the American Psychiatric Association.
“You really need to ask the patient a lot of questions – and the family and the caregivers – about how much tardive dyskinesia affects their lives,” he said.
Those were some of the early results of RE-KINECT, an ongoing study of patients with schizophrenia and schizoaffective disorder who were being treated with antipsychotic agents.
TD occurs in more than 25% of patients in outpatient practices who are exposed to dopamine receptor blockers. Symptoms can include involuntary movements of the tongue, hands, and feet; facial distortions; rapid eye blinking; and difficulty speaking. In some cases, the side effects resolve after patients stop taking the medications.
In this video, Dr. Caroff discussed the studies’ findings and their implications for everyday clinical practice. He also presented some of the early RE-KINECT findings in a poster at the meeting.
Dr. Caroff is professor of psychiatry at the University of Pennsylvania, Philadelphia. He also is affiliated with the Michael J. Crescenz VA Medical Center in Philadelphia. He disclosed working as a consultant for and receiving research funding from Neurocrine Biosciences. He also is a consultant for DisperSol Technologies, Osmotica Pharmaceuticals, Teva Pharmaceutical.
SAN FRANCISCO – Stanley N. Caroff, MD, said at the annual meeting of the American Psychiatric Association.
“You really need to ask the patient a lot of questions – and the family and the caregivers – about how much tardive dyskinesia affects their lives,” he said.
Those were some of the early results of RE-KINECT, an ongoing study of patients with schizophrenia and schizoaffective disorder who were being treated with antipsychotic agents.
TD occurs in more than 25% of patients in outpatient practices who are exposed to dopamine receptor blockers. Symptoms can include involuntary movements of the tongue, hands, and feet; facial distortions; rapid eye blinking; and difficulty speaking. In some cases, the side effects resolve after patients stop taking the medications.
In this video, Dr. Caroff discussed the studies’ findings and their implications for everyday clinical practice. He also presented some of the early RE-KINECT findings in a poster at the meeting.
Dr. Caroff is professor of psychiatry at the University of Pennsylvania, Philadelphia. He also is affiliated with the Michael J. Crescenz VA Medical Center in Philadelphia. He disclosed working as a consultant for and receiving research funding from Neurocrine Biosciences. He also is a consultant for DisperSol Technologies, Osmotica Pharmaceuticals, Teva Pharmaceutical.
REPORTING FROM APA 2019
What is your diagnosis? - June 2019
Multiple myeloma
An abdominal CT scan (Figure D) showed gastric and whole intestinal wall thickening of up to 2 cm. Pathology (Figure E) demonstrated that diffuse plasmacytoid cells, eosinophilic granulocytes, and lymphocytes infiltrated into the lamina propria. Immunohistochemically, the plasmacytoid cells were positive for the common plasma cell marker CD38, and in situ hybridization indicated that they were kappa-Ig light-chain restricted (Figure F).
Results of the subsequent bone marrow aspirate revealed 27.5% atypical plasma cells. Serum electrophoresis and immunofixation showed an M spike of IgA-kappa. Together, these findings confirmed a final diagnosis of a multiple myeloma (MM) involving the whole gastrointestinal (GI) duct, which was the cause of his melena.
MM is a malignant hematologic neoplasm, primarily involving the bone marrow, and has a potent tendency to involve other organs and to present with various clinical manifestations.1
The clinical features of MM with GI involvement are uncommon. Patients may present with nausea, vomiting, diarrhea, protein loss, malabsorption, intestinal obstruction, and hemorrhage. Endoscopic findings can manifest as four types: a discrete ulcer, ulcerating mass, thickening of the mucosal fold, and mucosal polyp.2
However, GI bleeding in MM has only been reported in a few patients. A biopsy reaching the submucosal layer and bone marrow biopsy is essential. Diagnosis of MM as a cause of the GI duct wall edema and multiple small intestinal polypoid ulcers is challenging. An interdisciplinary approach is mandatory to establish such a diagnosis.
References
1. Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;3518:1860-73.
2. Karam AR, Semaan RJ, Buch K, et al. Extramedullary duodenal plasmacytoma presenting with gastric outlet obstruction and painless jaundice. Radiol Cases. 2010;4:22-8.
Multiple myeloma
An abdominal CT scan (Figure D) showed gastric and whole intestinal wall thickening of up to 2 cm. Pathology (Figure E) demonstrated that diffuse plasmacytoid cells, eosinophilic granulocytes, and lymphocytes infiltrated into the lamina propria. Immunohistochemically, the plasmacytoid cells were positive for the common plasma cell marker CD38, and in situ hybridization indicated that they were kappa-Ig light-chain restricted (Figure F).
Results of the subsequent bone marrow aspirate revealed 27.5% atypical plasma cells. Serum electrophoresis and immunofixation showed an M spike of IgA-kappa. Together, these findings confirmed a final diagnosis of a multiple myeloma (MM) involving the whole gastrointestinal (GI) duct, which was the cause of his melena.
MM is a malignant hematologic neoplasm, primarily involving the bone marrow, and has a potent tendency to involve other organs and to present with various clinical manifestations.1
The clinical features of MM with GI involvement are uncommon. Patients may present with nausea, vomiting, diarrhea, protein loss, malabsorption, intestinal obstruction, and hemorrhage. Endoscopic findings can manifest as four types: a discrete ulcer, ulcerating mass, thickening of the mucosal fold, and mucosal polyp.2
However, GI bleeding in MM has only been reported in a few patients. A biopsy reaching the submucosal layer and bone marrow biopsy is essential. Diagnosis of MM as a cause of the GI duct wall edema and multiple small intestinal polypoid ulcers is challenging. An interdisciplinary approach is mandatory to establish such a diagnosis.
References
1. Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;3518:1860-73.
2. Karam AR, Semaan RJ, Buch K, et al. Extramedullary duodenal plasmacytoma presenting with gastric outlet obstruction and painless jaundice. Radiol Cases. 2010;4:22-8.
Multiple myeloma
An abdominal CT scan (Figure D) showed gastric and whole intestinal wall thickening of up to 2 cm. Pathology (Figure E) demonstrated that diffuse plasmacytoid cells, eosinophilic granulocytes, and lymphocytes infiltrated into the lamina propria. Immunohistochemically, the plasmacytoid cells were positive for the common plasma cell marker CD38, and in situ hybridization indicated that they were kappa-Ig light-chain restricted (Figure F).
Results of the subsequent bone marrow aspirate revealed 27.5% atypical plasma cells. Serum electrophoresis and immunofixation showed an M spike of IgA-kappa. Together, these findings confirmed a final diagnosis of a multiple myeloma (MM) involving the whole gastrointestinal (GI) duct, which was the cause of his melena.
MM is a malignant hematologic neoplasm, primarily involving the bone marrow, and has a potent tendency to involve other organs and to present with various clinical manifestations.1
The clinical features of MM with GI involvement are uncommon. Patients may present with nausea, vomiting, diarrhea, protein loss, malabsorption, intestinal obstruction, and hemorrhage. Endoscopic findings can manifest as four types: a discrete ulcer, ulcerating mass, thickening of the mucosal fold, and mucosal polyp.2
However, GI bleeding in MM has only been reported in a few patients. A biopsy reaching the submucosal layer and bone marrow biopsy is essential. Diagnosis of MM as a cause of the GI duct wall edema and multiple small intestinal polypoid ulcers is challenging. An interdisciplinary approach is mandatory to establish such a diagnosis.
References
1. Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;3518:1860-73.
2. Karam AR, Semaan RJ, Buch K, et al. Extramedullary duodenal plasmacytoma presenting with gastric outlet obstruction and painless jaundice. Radiol Cases. 2010;4:22-8.
He denied experiencing hematemesis, abdominal pain, fever, osteodynia, or arthralgia. His medical history included a 6-year history of alcoholic hepatocirrhosis and type 2 diabetes mellitus. Colonoscopy found no evidence of hemorrhage.
What is the underlying condition leading to the endoscopic and CT findings?
Transcatheter pulmonary valve shows 5-year durability in postapproval study
LAS VEGAS – that followed 65 patients, a majority of whom were children or teenagers.
After 5 years, 69% of the replacement valve recipients had no valvular hemodynamic dysfunction, compared with a 67% rate among patients enrolled in the original Investigational Device Exemption (IDE) study that led to Food and Drug Administration marketing approval for the Melody valve in 2010 under a humanitarian device exemption. (Full approval followed in 2017.)
The 5-year rate of any reintervention, including explants, was 78% in the postapproval study, again similar to the 76% rate reported in the IDE study after a median 4.5 year follow-up (Circulation. 2015 Jun 2;131[22]:1960-70), Aimee K. Armstrong, MD, said at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.
The new 5-year postapproval study findings “confirm that the hemodynamic effectiveness achieved by real-world providers is equivalent to the historical control established in the IDE study,” concluded Dr. Armstrong, professor of pediatrics at the Ohio State University and director of cardiac catheterization and interventional therapies at Nationwide Children’s Hospital, both in Columbus.
The postapproval study ran at 10 U.S. centers, none of which were among the five U.S. centers that ran the IDE study. Today, the Melody transcatheter pulmonary valve “is very commonly used” at many additional U.S. sites, Dr. Armstrong said in an interview. And the outcomes achieved using the valve likely surpass those seen in the IDE and postapproval studies because of innovations in technique, such as more routine use of “prestenting,” placing a stent in the vascular site where the pulmonary valve conduit will sit to address stenosis at this location and prevent subsequent conduit fracture (JACC Cardiovasc Interv. 2017 Sep;10[17]:1760-2).
“In 2010 [when the postapproval study began], we didn’t understand the importance of prestenting the way we do now. In 2010, I did not prestent every patient; now I do,” she said. The results reported by Dr. Armstrong included a 5% cumulative rate of major stent fractures in the Melody devices.
The postapproval study results also documented a concerning 4.5% annualized incidence of endocarditis among pulmonary valve recipients, with a nearly 300% increased rate of endocarditis among patients aged 12 years or younger, compared with older patients. Dr. Armstrong cautioned that this age association may be confounded by other factors, such as a residual pressure gradient in the right ventricular outflow tract of 15 mm Hg or greater. “We are discovering that we need to reduce the pressure gradient as much as we can, to perhaps less than 15 mm Hg, to reduce endocarditis, and that is something we did not know even a year ago. Practice is still evolving.”
The Melody Transcatheter Pulmonary Valve Postapproval Study performed cardiac catheterization for valve placement in 121 patients, and successfully implanted the valve for at least 24 hours in 99 of these patients. Patient age ranged from 5 to 45 years, with a median of 17 years; two-thirds were boys or men. The median age of the patients in the postapproval study was about 2 years younger than in the IDE study. Dr. Armstrong and her associates had previously published the 1-year outcomes from the postapproval study (JACC Cardiovasc Interv. 2014 Nov;7[11]:1254-62).
The enrolled patients usually needed a new right ventricular outflow tract because of a congenital heart defect, such as tetralogy of Fallot with pulmonary atresia and truncus arteriosus. Patients also included those who underwent a Ross operation. These patients often receive surgical placement of a right ventricular-to-pulmonary artery conduit, which can over time develop stenosis, insufficiency, or both because of calcification, intimal proliferation, and graft degeneration.
Multiple conduit reoperations to restore right ventricular outflow tract function are usually needed over a patient’s lifetime because of conduit degeneration. This makes a transcatheter procedure in a child or adolescent an attractive option because the prosthetic conduit will need replacement relatively quickly, and the transcatheter approach avoids an episode of open-heart surgery.
The Melody system is not the only transcatheter option for treating a leak or stenosis in a right ventricular outflow tract. The Sapien XT Transcatheter Heart Valve, marketed by Edwards, has FDA labeling for replacement of a dysfunctional right ventricular outflow tract.
Because the Sapien XT system was designed for replacing an aortic valve it’s challenging to place the conduit in the pulmonary valve position, Dr. Armstrong said. Operators find the Sapien 3 valve, a more modern design of the XT model that’s also primarily intended for aortic valve replacement, easier to position than the XT for pulmonary valve replacement, but Sapien 3 does not have FDA labeling for the right ventricular outflow tract indication. The Sapien valves are attractive because they don’t fracture, but Melody is easier to place and operators can reduce the fracture risk by prestenting, she noted.
Overall, the 5-year results from the postapproval study represented success, because 78% of patients who received the Melody device avoided any further interventions during follow-up. “That’s a big deal to a 12, 15, or 18 year old,” said Dr. Armstrong. “A surgically placed valve won’t last long in a teen, so it’s nice to do something noninvasively. It’s great if you can delay surgery for a few years” and avoid having the patient grow out of a surgically placed conduit or developing lots of calcification in the conduit during a growth spurt.
The postapproval study was funded by Medtronic, the company that sells the Melody valve. Dr. Armstrong has received research funding from Medtronic as well as Abbott, Edwards, and Siemens, and she has been a consultant to Abbott.
LAS VEGAS – that followed 65 patients, a majority of whom were children or teenagers.
After 5 years, 69% of the replacement valve recipients had no valvular hemodynamic dysfunction, compared with a 67% rate among patients enrolled in the original Investigational Device Exemption (IDE) study that led to Food and Drug Administration marketing approval for the Melody valve in 2010 under a humanitarian device exemption. (Full approval followed in 2017.)
The 5-year rate of any reintervention, including explants, was 78% in the postapproval study, again similar to the 76% rate reported in the IDE study after a median 4.5 year follow-up (Circulation. 2015 Jun 2;131[22]:1960-70), Aimee K. Armstrong, MD, said at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.
The new 5-year postapproval study findings “confirm that the hemodynamic effectiveness achieved by real-world providers is equivalent to the historical control established in the IDE study,” concluded Dr. Armstrong, professor of pediatrics at the Ohio State University and director of cardiac catheterization and interventional therapies at Nationwide Children’s Hospital, both in Columbus.
The postapproval study ran at 10 U.S. centers, none of which were among the five U.S. centers that ran the IDE study. Today, the Melody transcatheter pulmonary valve “is very commonly used” at many additional U.S. sites, Dr. Armstrong said in an interview. And the outcomes achieved using the valve likely surpass those seen in the IDE and postapproval studies because of innovations in technique, such as more routine use of “prestenting,” placing a stent in the vascular site where the pulmonary valve conduit will sit to address stenosis at this location and prevent subsequent conduit fracture (JACC Cardiovasc Interv. 2017 Sep;10[17]:1760-2).
“In 2010 [when the postapproval study began], we didn’t understand the importance of prestenting the way we do now. In 2010, I did not prestent every patient; now I do,” she said. The results reported by Dr. Armstrong included a 5% cumulative rate of major stent fractures in the Melody devices.
The postapproval study results also documented a concerning 4.5% annualized incidence of endocarditis among pulmonary valve recipients, with a nearly 300% increased rate of endocarditis among patients aged 12 years or younger, compared with older patients. Dr. Armstrong cautioned that this age association may be confounded by other factors, such as a residual pressure gradient in the right ventricular outflow tract of 15 mm Hg or greater. “We are discovering that we need to reduce the pressure gradient as much as we can, to perhaps less than 15 mm Hg, to reduce endocarditis, and that is something we did not know even a year ago. Practice is still evolving.”
The Melody Transcatheter Pulmonary Valve Postapproval Study performed cardiac catheterization for valve placement in 121 patients, and successfully implanted the valve for at least 24 hours in 99 of these patients. Patient age ranged from 5 to 45 years, with a median of 17 years; two-thirds were boys or men. The median age of the patients in the postapproval study was about 2 years younger than in the IDE study. Dr. Armstrong and her associates had previously published the 1-year outcomes from the postapproval study (JACC Cardiovasc Interv. 2014 Nov;7[11]:1254-62).
The enrolled patients usually needed a new right ventricular outflow tract because of a congenital heart defect, such as tetralogy of Fallot with pulmonary atresia and truncus arteriosus. Patients also included those who underwent a Ross operation. These patients often receive surgical placement of a right ventricular-to-pulmonary artery conduit, which can over time develop stenosis, insufficiency, or both because of calcification, intimal proliferation, and graft degeneration.
Multiple conduit reoperations to restore right ventricular outflow tract function are usually needed over a patient’s lifetime because of conduit degeneration. This makes a transcatheter procedure in a child or adolescent an attractive option because the prosthetic conduit will need replacement relatively quickly, and the transcatheter approach avoids an episode of open-heart surgery.
The Melody system is not the only transcatheter option for treating a leak or stenosis in a right ventricular outflow tract. The Sapien XT Transcatheter Heart Valve, marketed by Edwards, has FDA labeling for replacement of a dysfunctional right ventricular outflow tract.
Because the Sapien XT system was designed for replacing an aortic valve it’s challenging to place the conduit in the pulmonary valve position, Dr. Armstrong said. Operators find the Sapien 3 valve, a more modern design of the XT model that’s also primarily intended for aortic valve replacement, easier to position than the XT for pulmonary valve replacement, but Sapien 3 does not have FDA labeling for the right ventricular outflow tract indication. The Sapien valves are attractive because they don’t fracture, but Melody is easier to place and operators can reduce the fracture risk by prestenting, she noted.
Overall, the 5-year results from the postapproval study represented success, because 78% of patients who received the Melody device avoided any further interventions during follow-up. “That’s a big deal to a 12, 15, or 18 year old,” said Dr. Armstrong. “A surgically placed valve won’t last long in a teen, so it’s nice to do something noninvasively. It’s great if you can delay surgery for a few years” and avoid having the patient grow out of a surgically placed conduit or developing lots of calcification in the conduit during a growth spurt.
The postapproval study was funded by Medtronic, the company that sells the Melody valve. Dr. Armstrong has received research funding from Medtronic as well as Abbott, Edwards, and Siemens, and she has been a consultant to Abbott.
LAS VEGAS – that followed 65 patients, a majority of whom were children or teenagers.
After 5 years, 69% of the replacement valve recipients had no valvular hemodynamic dysfunction, compared with a 67% rate among patients enrolled in the original Investigational Device Exemption (IDE) study that led to Food and Drug Administration marketing approval for the Melody valve in 2010 under a humanitarian device exemption. (Full approval followed in 2017.)
The 5-year rate of any reintervention, including explants, was 78% in the postapproval study, again similar to the 76% rate reported in the IDE study after a median 4.5 year follow-up (Circulation. 2015 Jun 2;131[22]:1960-70), Aimee K. Armstrong, MD, said at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.
The new 5-year postapproval study findings “confirm that the hemodynamic effectiveness achieved by real-world providers is equivalent to the historical control established in the IDE study,” concluded Dr. Armstrong, professor of pediatrics at the Ohio State University and director of cardiac catheterization and interventional therapies at Nationwide Children’s Hospital, both in Columbus.
The postapproval study ran at 10 U.S. centers, none of which were among the five U.S. centers that ran the IDE study. Today, the Melody transcatheter pulmonary valve “is very commonly used” at many additional U.S. sites, Dr. Armstrong said in an interview. And the outcomes achieved using the valve likely surpass those seen in the IDE and postapproval studies because of innovations in technique, such as more routine use of “prestenting,” placing a stent in the vascular site where the pulmonary valve conduit will sit to address stenosis at this location and prevent subsequent conduit fracture (JACC Cardiovasc Interv. 2017 Sep;10[17]:1760-2).
“In 2010 [when the postapproval study began], we didn’t understand the importance of prestenting the way we do now. In 2010, I did not prestent every patient; now I do,” she said. The results reported by Dr. Armstrong included a 5% cumulative rate of major stent fractures in the Melody devices.
The postapproval study results also documented a concerning 4.5% annualized incidence of endocarditis among pulmonary valve recipients, with a nearly 300% increased rate of endocarditis among patients aged 12 years or younger, compared with older patients. Dr. Armstrong cautioned that this age association may be confounded by other factors, such as a residual pressure gradient in the right ventricular outflow tract of 15 mm Hg or greater. “We are discovering that we need to reduce the pressure gradient as much as we can, to perhaps less than 15 mm Hg, to reduce endocarditis, and that is something we did not know even a year ago. Practice is still evolving.”
The Melody Transcatheter Pulmonary Valve Postapproval Study performed cardiac catheterization for valve placement in 121 patients, and successfully implanted the valve for at least 24 hours in 99 of these patients. Patient age ranged from 5 to 45 years, with a median of 17 years; two-thirds were boys or men. The median age of the patients in the postapproval study was about 2 years younger than in the IDE study. Dr. Armstrong and her associates had previously published the 1-year outcomes from the postapproval study (JACC Cardiovasc Interv. 2014 Nov;7[11]:1254-62).
The enrolled patients usually needed a new right ventricular outflow tract because of a congenital heart defect, such as tetralogy of Fallot with pulmonary atresia and truncus arteriosus. Patients also included those who underwent a Ross operation. These patients often receive surgical placement of a right ventricular-to-pulmonary artery conduit, which can over time develop stenosis, insufficiency, or both because of calcification, intimal proliferation, and graft degeneration.
Multiple conduit reoperations to restore right ventricular outflow tract function are usually needed over a patient’s lifetime because of conduit degeneration. This makes a transcatheter procedure in a child or adolescent an attractive option because the prosthetic conduit will need replacement relatively quickly, and the transcatheter approach avoids an episode of open-heart surgery.
The Melody system is not the only transcatheter option for treating a leak or stenosis in a right ventricular outflow tract. The Sapien XT Transcatheter Heart Valve, marketed by Edwards, has FDA labeling for replacement of a dysfunctional right ventricular outflow tract.
Because the Sapien XT system was designed for replacing an aortic valve it’s challenging to place the conduit in the pulmonary valve position, Dr. Armstrong said. Operators find the Sapien 3 valve, a more modern design of the XT model that’s also primarily intended for aortic valve replacement, easier to position than the XT for pulmonary valve replacement, but Sapien 3 does not have FDA labeling for the right ventricular outflow tract indication. The Sapien valves are attractive because they don’t fracture, but Melody is easier to place and operators can reduce the fracture risk by prestenting, she noted.
Overall, the 5-year results from the postapproval study represented success, because 78% of patients who received the Melody device avoided any further interventions during follow-up. “That’s a big deal to a 12, 15, or 18 year old,” said Dr. Armstrong. “A surgically placed valve won’t last long in a teen, so it’s nice to do something noninvasively. It’s great if you can delay surgery for a few years” and avoid having the patient grow out of a surgically placed conduit or developing lots of calcification in the conduit during a growth spurt.
The postapproval study was funded by Medtronic, the company that sells the Melody valve. Dr. Armstrong has received research funding from Medtronic as well as Abbott, Edwards, and Siemens, and she has been a consultant to Abbott.
REPORTING FROM SCAI 2019