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Hospitalized COVID-19 patients with cardiometabolic risk do not benefit from dapagliflozin
Key clinical point: Dapagliflozin does not improve COVID-19 hospitalization outcomes for patients with cardiometabolic risk factors.
Major finding: Dapagliflozin vs placebo failed to meet the primary composite outcome of organ dysfunction or all-cause death (hazard ratio, 0.80; 95% confidence interval, 0.58-1.10). There was no difference in the rates of new/worsened organ dysfunction, deaths, or clinical improvement between the groups.
Study details: In the DARE-19 phase 3 trial, patients were randomly assigned to receive either dapagliflozin (n=625) or placebo (n=625).
Disclosures: The study was funded by AstraZeneca. R Esterline, J Oscarsson, SB Gasparyan, J Buenconsejo, AM Langkilde, and P Ambery are employees and stockholders of AstraZeneca. M Aboudara, E Akin, WKS Barroso, ADM Feitosa, CRH Filho, A Fonseca, K Gosch, RA Gordon, CP Jaeger, LN Maia, DDF Moia, JRL Soto, F Tang, SL Windsor, O Mukhtar, V Chopra, RVP Soares, V Garla, PE Leaes, FS Silveira, and M Pursley declared no conflict of interests. The remaining authors disclosed relationships with pharmaceutical companies and/or research institutions.
Source: Kosiborod MN et al. Lancet Diabetes Endocrinol. 2021 Jul 21. doi: 10.1016/S2213-8587(21)00180-7.
Key clinical point: Dapagliflozin does not improve COVID-19 hospitalization outcomes for patients with cardiometabolic risk factors.
Major finding: Dapagliflozin vs placebo failed to meet the primary composite outcome of organ dysfunction or all-cause death (hazard ratio, 0.80; 95% confidence interval, 0.58-1.10). There was no difference in the rates of new/worsened organ dysfunction, deaths, or clinical improvement between the groups.
Study details: In the DARE-19 phase 3 trial, patients were randomly assigned to receive either dapagliflozin (n=625) or placebo (n=625).
Disclosures: The study was funded by AstraZeneca. R Esterline, J Oscarsson, SB Gasparyan, J Buenconsejo, AM Langkilde, and P Ambery are employees and stockholders of AstraZeneca. M Aboudara, E Akin, WKS Barroso, ADM Feitosa, CRH Filho, A Fonseca, K Gosch, RA Gordon, CP Jaeger, LN Maia, DDF Moia, JRL Soto, F Tang, SL Windsor, O Mukhtar, V Chopra, RVP Soares, V Garla, PE Leaes, FS Silveira, and M Pursley declared no conflict of interests. The remaining authors disclosed relationships with pharmaceutical companies and/or research institutions.
Source: Kosiborod MN et al. Lancet Diabetes Endocrinol. 2021 Jul 21. doi: 10.1016/S2213-8587(21)00180-7.
Key clinical point: Dapagliflozin does not improve COVID-19 hospitalization outcomes for patients with cardiometabolic risk factors.
Major finding: Dapagliflozin vs placebo failed to meet the primary composite outcome of organ dysfunction or all-cause death (hazard ratio, 0.80; 95% confidence interval, 0.58-1.10). There was no difference in the rates of new/worsened organ dysfunction, deaths, or clinical improvement between the groups.
Study details: In the DARE-19 phase 3 trial, patients were randomly assigned to receive either dapagliflozin (n=625) or placebo (n=625).
Disclosures: The study was funded by AstraZeneca. R Esterline, J Oscarsson, SB Gasparyan, J Buenconsejo, AM Langkilde, and P Ambery are employees and stockholders of AstraZeneca. M Aboudara, E Akin, WKS Barroso, ADM Feitosa, CRH Filho, A Fonseca, K Gosch, RA Gordon, CP Jaeger, LN Maia, DDF Moia, JRL Soto, F Tang, SL Windsor, O Mukhtar, V Chopra, RVP Soares, V Garla, PE Leaes, FS Silveira, and M Pursley declared no conflict of interests. The remaining authors disclosed relationships with pharmaceutical companies and/or research institutions.
Source: Kosiborod MN et al. Lancet Diabetes Endocrinol. 2021 Jul 21. doi: 10.1016/S2213-8587(21)00180-7.
Canakinumab fails to improve survival in hospitalized patients with severe COVID-19
Key clinical point: Canakinumab does not improve survival in hospitalized patients with severe COVID-19.
Major finding: There was no significant difference in survival without invasive mechanical ventilation between days 3 and 29 with canakinumab vs. placebo (88.8% vs. 85.7%; rate difference, 3.1 percentage points; 95% confidence interval [CI], −3.1 to 9.3). COVID-19 mortality also did not differ with canakinumab vs. placebo (4.9% vs 7.2%; rate difference, −2.3 percentage points; 95% CI, −6.7 to 2.2).
Study details: The data come from the randomized, double-blind, placebo-controlled phase 3 CAN-COVID trial (n=454).
Disclosures: The study was sponsored by Novartis Pharma AG, Basel, Switzerland. All authors received funding from Novartis during the conduct of the study. The authors also reported relationships with other pharmaceutical companies.
Source: Caricchio R et al. JAMA. 2021 Jul 20. doi: 10.1001/jama.2021.9508.
Key clinical point: Canakinumab does not improve survival in hospitalized patients with severe COVID-19.
Major finding: There was no significant difference in survival without invasive mechanical ventilation between days 3 and 29 with canakinumab vs. placebo (88.8% vs. 85.7%; rate difference, 3.1 percentage points; 95% confidence interval [CI], −3.1 to 9.3). COVID-19 mortality also did not differ with canakinumab vs. placebo (4.9% vs 7.2%; rate difference, −2.3 percentage points; 95% CI, −6.7 to 2.2).
Study details: The data come from the randomized, double-blind, placebo-controlled phase 3 CAN-COVID trial (n=454).
Disclosures: The study was sponsored by Novartis Pharma AG, Basel, Switzerland. All authors received funding from Novartis during the conduct of the study. The authors also reported relationships with other pharmaceutical companies.
Source: Caricchio R et al. JAMA. 2021 Jul 20. doi: 10.1001/jama.2021.9508.
Key clinical point: Canakinumab does not improve survival in hospitalized patients with severe COVID-19.
Major finding: There was no significant difference in survival without invasive mechanical ventilation between days 3 and 29 with canakinumab vs. placebo (88.8% vs. 85.7%; rate difference, 3.1 percentage points; 95% confidence interval [CI], −3.1 to 9.3). COVID-19 mortality also did not differ with canakinumab vs. placebo (4.9% vs 7.2%; rate difference, −2.3 percentage points; 95% CI, −6.7 to 2.2).
Study details: The data come from the randomized, double-blind, placebo-controlled phase 3 CAN-COVID trial (n=454).
Disclosures: The study was sponsored by Novartis Pharma AG, Basel, Switzerland. All authors received funding from Novartis during the conduct of the study. The authors also reported relationships with other pharmaceutical companies.
Source: Caricchio R et al. JAMA. 2021 Jul 20. doi: 10.1001/jama.2021.9508.
COVID-19: Inhaled budesonide may shorten recovery time
Key clinical point: Inhaled budesonide is associated with a shorter time to recovery but fails to reduce the risk for hospitalization or death in high-risk primary care patients with COVID-19.
Major finding: Budesonide vs usual care was associated with a shorter time to recovery (11.8 days vs 14.7 days). Budesonide was associated with a nonsignificant 2.0% reduction in hospitalization or death compared with usual care.
Study details: The data come from the PRINCIPLE trial, where 2,530 patients were randomly assigned to either inhaled budesonide (n=787), usual care alone (n=1,069), or usual care plus other interventions (n=674).
Disclosures: The study was funded by the National Institute of Health Research and United Kingdom Research Innovation. M Bafadhel, D Richards, BR Saville, N Berry, MA Detry, M Fitzgerald, S de Lusignan, MI Andersson, PJ Barnes, REK Russell, S Ramakrishnan, FDR Hobbs, and CC Butler reported relationships with pharmaceutical companies and/or research institutions. The remaining authors declared no conflict of interests.
Source: Yu LM et al. Lancet. 2021 Aug 10. doi: 10.1016/S0140-6736(21)01744-X.
Key clinical point: Inhaled budesonide is associated with a shorter time to recovery but fails to reduce the risk for hospitalization or death in high-risk primary care patients with COVID-19.
Major finding: Budesonide vs usual care was associated with a shorter time to recovery (11.8 days vs 14.7 days). Budesonide was associated with a nonsignificant 2.0% reduction in hospitalization or death compared with usual care.
Study details: The data come from the PRINCIPLE trial, where 2,530 patients were randomly assigned to either inhaled budesonide (n=787), usual care alone (n=1,069), or usual care plus other interventions (n=674).
Disclosures: The study was funded by the National Institute of Health Research and United Kingdom Research Innovation. M Bafadhel, D Richards, BR Saville, N Berry, MA Detry, M Fitzgerald, S de Lusignan, MI Andersson, PJ Barnes, REK Russell, S Ramakrishnan, FDR Hobbs, and CC Butler reported relationships with pharmaceutical companies and/or research institutions. The remaining authors declared no conflict of interests.
Source: Yu LM et al. Lancet. 2021 Aug 10. doi: 10.1016/S0140-6736(21)01744-X.
Key clinical point: Inhaled budesonide is associated with a shorter time to recovery but fails to reduce the risk for hospitalization or death in high-risk primary care patients with COVID-19.
Major finding: Budesonide vs usual care was associated with a shorter time to recovery (11.8 days vs 14.7 days). Budesonide was associated with a nonsignificant 2.0% reduction in hospitalization or death compared with usual care.
Study details: The data come from the PRINCIPLE trial, where 2,530 patients were randomly assigned to either inhaled budesonide (n=787), usual care alone (n=1,069), or usual care plus other interventions (n=674).
Disclosures: The study was funded by the National Institute of Health Research and United Kingdom Research Innovation. M Bafadhel, D Richards, BR Saville, N Berry, MA Detry, M Fitzgerald, S de Lusignan, MI Andersson, PJ Barnes, REK Russell, S Ramakrishnan, FDR Hobbs, and CC Butler reported relationships with pharmaceutical companies and/or research institutions. The remaining authors declared no conflict of interests.
Source: Yu LM et al. Lancet. 2021 Aug 10. doi: 10.1016/S0140-6736(21)01744-X.
COVID-19: Pulmonary embolism not tied to increased mortality risk
Key clinical point: Presence of pulmonary embolism (PE) is not associated with increased mortality in patients with COVID-19 risk.
Major finding: Risk factors for PE in patients with COVID-19 included male sex, mechanical ventilation, intensive care unit admission, and circulating D-dimer. Patients with PE did not have an increased risk for mortality compared with those without PE (odds ratio, 1.31; P = .25).
Study details: The data come from a meta-analysis of 16 cohort studies involving 5,826 patients with COVID-19.
Disclosures: No funding information was available. The authors declared no conflict of interests.
Source: Gómez CA et al. Sci Rep. 2021 Aug 6. doi: 10.1038/s41598-021-95512-7.
Key clinical point: Presence of pulmonary embolism (PE) is not associated with increased mortality in patients with COVID-19 risk.
Major finding: Risk factors for PE in patients with COVID-19 included male sex, mechanical ventilation, intensive care unit admission, and circulating D-dimer. Patients with PE did not have an increased risk for mortality compared with those without PE (odds ratio, 1.31; P = .25).
Study details: The data come from a meta-analysis of 16 cohort studies involving 5,826 patients with COVID-19.
Disclosures: No funding information was available. The authors declared no conflict of interests.
Source: Gómez CA et al. Sci Rep. 2021 Aug 6. doi: 10.1038/s41598-021-95512-7.
Key clinical point: Presence of pulmonary embolism (PE) is not associated with increased mortality in patients with COVID-19 risk.
Major finding: Risk factors for PE in patients with COVID-19 included male sex, mechanical ventilation, intensive care unit admission, and circulating D-dimer. Patients with PE did not have an increased risk for mortality compared with those without PE (odds ratio, 1.31; P = .25).
Study details: The data come from a meta-analysis of 16 cohort studies involving 5,826 patients with COVID-19.
Disclosures: No funding information was available. The authors declared no conflict of interests.
Source: Gómez CA et al. Sci Rep. 2021 Aug 6. doi: 10.1038/s41598-021-95512-7.
COVID-19: Early administration of plasma fails to prevent disease progression
Key clinical point: Administration of convalescent plasma within 7 days of symptom onset fails to prevent disease progression in acutely ill, high-risk patients with COVID-19.
Major finding: There was no difference between the convalescent plasma group and the placebo group in disease progression (30.0% vs 31.9%; risk difference, 1.9 percentage points; 95% credible interval, −6.0 to 9.8).
Study details: The multicenter, single-blind SIREN-C3PO trial included patients with COVID-19 (n=511) randomly assigned to receive either plasma or placebo in the emergency department.
Disclosures: The study was supported by the National Institutes of Health, the Biomedical Advanced Research and Development Authority, and the Operation Warp Speed interagency program. D Beiser, A Burnett R Davenport, L Dumont, V Durkalski-Mauldin, N El Kassar, L Foster, C Greineder, N Haas, J Hah, A Kaplan, B Kea, F Korley, E Lowell, J McDyer, J Quinn, J Reynolds, R Silbergleit, C Van Huysen, and K Yadav declared no conflict of interests. The remaining authors disclosed relationships with pharmaceutical companies and/or research institutions.
Source: Korley FK et al. N Engl J Med. 2021 Aug 18. doi: 10.1056/NEJMoa2103784.
Key clinical point: Administration of convalescent plasma within 7 days of symptom onset fails to prevent disease progression in acutely ill, high-risk patients with COVID-19.
Major finding: There was no difference between the convalescent plasma group and the placebo group in disease progression (30.0% vs 31.9%; risk difference, 1.9 percentage points; 95% credible interval, −6.0 to 9.8).
Study details: The multicenter, single-blind SIREN-C3PO trial included patients with COVID-19 (n=511) randomly assigned to receive either plasma or placebo in the emergency department.
Disclosures: The study was supported by the National Institutes of Health, the Biomedical Advanced Research and Development Authority, and the Operation Warp Speed interagency program. D Beiser, A Burnett R Davenport, L Dumont, V Durkalski-Mauldin, N El Kassar, L Foster, C Greineder, N Haas, J Hah, A Kaplan, B Kea, F Korley, E Lowell, J McDyer, J Quinn, J Reynolds, R Silbergleit, C Van Huysen, and K Yadav declared no conflict of interests. The remaining authors disclosed relationships with pharmaceutical companies and/or research institutions.
Source: Korley FK et al. N Engl J Med. 2021 Aug 18. doi: 10.1056/NEJMoa2103784.
Key clinical point: Administration of convalescent plasma within 7 days of symptom onset fails to prevent disease progression in acutely ill, high-risk patients with COVID-19.
Major finding: There was no difference between the convalescent plasma group and the placebo group in disease progression (30.0% vs 31.9%; risk difference, 1.9 percentage points; 95% credible interval, −6.0 to 9.8).
Study details: The multicenter, single-blind SIREN-C3PO trial included patients with COVID-19 (n=511) randomly assigned to receive either plasma or placebo in the emergency department.
Disclosures: The study was supported by the National Institutes of Health, the Biomedical Advanced Research and Development Authority, and the Operation Warp Speed interagency program. D Beiser, A Burnett R Davenport, L Dumont, V Durkalski-Mauldin, N El Kassar, L Foster, C Greineder, N Haas, J Hah, A Kaplan, B Kea, F Korley, E Lowell, J McDyer, J Quinn, J Reynolds, R Silbergleit, C Van Huysen, and K Yadav declared no conflict of interests. The remaining authors disclosed relationships with pharmaceutical companies and/or research institutions.
Source: Korley FK et al. N Engl J Med. 2021 Aug 18. doi: 10.1056/NEJMoa2103784.
Baricitinib plus standard of care may reduce mortality risk in hospitalized patients with COVID-19
Key clinical point: Addition of baricitinib to standard of care treatment may reduce 28-day mortality risk in patients hospitalized with COVID-19, but does not significantly reduce the frequency of disease progression.
Major finding: There was a 38.2% relative reduction in 28-day all-cause mortality risk with baricitinib vs placebo. There was no significant difference between the baricitinib and placebo groups in the primary composite endpoint of disease progression outcomes (odds ratio, 0.85; P = .18).
Study details: In a phase 3, double-blind trial, hospitalized patients with COVID-19 receiving standard of care were randomly assigned to either baricitinib (n=764) or placebo group (n=761).
Disclosures: The study was funded by Eli Lilly and Company. S de Bono, CE Kartman, V Krishnan, R Liao, MLB Piruzeli, A Cardose, S Chakladar, B Crowe, P Reis, X Zhang, and DH Adams are employees and shareholders of Eli Lilly and Company. RD Pellegrini declared no conflict of interests. Other authors reported relationships with pharmaceutical companies including Eli Lilly and Company.
Source: Marconi VC et al. Lancet Respir Med. 2021 Sep 1. doi: 10.1016/S2213-2600(21)00331-3.
Key clinical point: Addition of baricitinib to standard of care treatment may reduce 28-day mortality risk in patients hospitalized with COVID-19, but does not significantly reduce the frequency of disease progression.
Major finding: There was a 38.2% relative reduction in 28-day all-cause mortality risk with baricitinib vs placebo. There was no significant difference between the baricitinib and placebo groups in the primary composite endpoint of disease progression outcomes (odds ratio, 0.85; P = .18).
Study details: In a phase 3, double-blind trial, hospitalized patients with COVID-19 receiving standard of care were randomly assigned to either baricitinib (n=764) or placebo group (n=761).
Disclosures: The study was funded by Eli Lilly and Company. S de Bono, CE Kartman, V Krishnan, R Liao, MLB Piruzeli, A Cardose, S Chakladar, B Crowe, P Reis, X Zhang, and DH Adams are employees and shareholders of Eli Lilly and Company. RD Pellegrini declared no conflict of interests. Other authors reported relationships with pharmaceutical companies including Eli Lilly and Company.
Source: Marconi VC et al. Lancet Respir Med. 2021 Sep 1. doi: 10.1016/S2213-2600(21)00331-3.
Key clinical point: Addition of baricitinib to standard of care treatment may reduce 28-day mortality risk in patients hospitalized with COVID-19, but does not significantly reduce the frequency of disease progression.
Major finding: There was a 38.2% relative reduction in 28-day all-cause mortality risk with baricitinib vs placebo. There was no significant difference between the baricitinib and placebo groups in the primary composite endpoint of disease progression outcomes (odds ratio, 0.85; P = .18).
Study details: In a phase 3, double-blind trial, hospitalized patients with COVID-19 receiving standard of care were randomly assigned to either baricitinib (n=764) or placebo group (n=761).
Disclosures: The study was funded by Eli Lilly and Company. S de Bono, CE Kartman, V Krishnan, R Liao, MLB Piruzeli, A Cardose, S Chakladar, B Crowe, P Reis, X Zhang, and DH Adams are employees and shareholders of Eli Lilly and Company. RD Pellegrini declared no conflict of interests. Other authors reported relationships with pharmaceutical companies including Eli Lilly and Company.
Source: Marconi VC et al. Lancet Respir Med. 2021 Sep 1. doi: 10.1016/S2213-2600(21)00331-3.
Lower risk for COVID-19 in patients with asthma
Key clinical point: Individuals with asthma have a 17% lower risk for COVID-19 infection than those without asthma.
Major finding: Individuals with asthma had a lower risk for COVID-19 infection (risk ratio [RR], 0.83; P = .01), but not for COVID-19-related hospitalization (RR, 1.18; P = .08), intensive care unit admission (RR, 1.21; P = .09), and ICU admission (RR, 1.06; P = .65).
Study details: The data come from a meta-analysis of 51 studies involving 965,551 individuals with and without asthma who tested positive for COVID-19.
Disclosures: This study was self-funded. The authors declared no conflict of interests.
Source: Sunjaya AP et al. Eur Respir J. 2021 Aug 24. doi: 10.1183/13993003.01209-2021.
Key clinical point: Individuals with asthma have a 17% lower risk for COVID-19 infection than those without asthma.
Major finding: Individuals with asthma had a lower risk for COVID-19 infection (risk ratio [RR], 0.83; P = .01), but not for COVID-19-related hospitalization (RR, 1.18; P = .08), intensive care unit admission (RR, 1.21; P = .09), and ICU admission (RR, 1.06; P = .65).
Study details: The data come from a meta-analysis of 51 studies involving 965,551 individuals with and without asthma who tested positive for COVID-19.
Disclosures: This study was self-funded. The authors declared no conflict of interests.
Source: Sunjaya AP et al. Eur Respir J. 2021 Aug 24. doi: 10.1183/13993003.01209-2021.
Key clinical point: Individuals with asthma have a 17% lower risk for COVID-19 infection than those without asthma.
Major finding: Individuals with asthma had a lower risk for COVID-19 infection (risk ratio [RR], 0.83; P = .01), but not for COVID-19-related hospitalization (RR, 1.18; P = .08), intensive care unit admission (RR, 1.21; P = .09), and ICU admission (RR, 1.06; P = .65).
Study details: The data come from a meta-analysis of 51 studies involving 965,551 individuals with and without asthma who tested positive for COVID-19.
Disclosures: This study was self-funded. The authors declared no conflict of interests.
Source: Sunjaya AP et al. Eur Respir J. 2021 Aug 24. doi: 10.1183/13993003.01209-2021.
What’s the best approach for dysplasia surveillance in IBD?
Chromoendoscopy
Chromoendoscopy is superior in both the detection and long-term management of dysplasia in IBD when compared to high-definition white-light examination. Chromoendoscopy not only enhances dysplasia detection but further improves the definition of these lesions which then facilitates endoscopic management.
Human beings have an innate visual perception limitation due to our inability to perceive depth in the red/green wavelength of light compared to the blue wavelength. All of the improvements in scope magnification and resolution bump up against this fact of our biology. Blue dye enhances our ability to perceive depth in this milieu and therefore detect and define flat lesions.
The superiority of chromoendoscopy when using standard definition colonoscopes has been demonstrated repeatedly and set the stage for the 2015 SCENIC international consensus statement and a seismic shift in our endoscopic management of dysplasia in patients with colitis. This evidence base remains relevant because only 77% of colonoscopies performed in the United States are performed using high-definition equipment. Nearly one-quarter of our patients lack access to the newer equipment and therefore without chromoendoscopy are being surveyed outside of current guidelines.
Since the SCENIC statement multiple studies comparing chromoendoscopy with newer higher resolution colonoscopes have been performed. The vast preponderance of evidence has shown either a trend toward superiority or the outright superiority of chromoendoscopy when compared with high-definition white-light examination in detection and long-term management of dysplasia.
Chromoendoscopy has allowed us to increase our visual vocabulary in describing dysplasia in the setting of colitis and, thus, open the door to further innovation and perhaps adoption of artificial intelligence going forward. Our ability to classify lesions encountered in colitis mucosa has become more precise with the expanded terminology the dye-enhanced high-definition view affords, with the Frankfurt Advanced Chromoendoscopic IBD Lesion Classification being the best and most detailed example.
It is no accident that advanced endoscopists have universally adopted chromoendoscopy for the management of dysplastic lesions whether by mucosal resection or submucosal dissection techniques. Chromoendoscopy is recommended by all society guidelines because of these inherent advantages.
Is high-definition white-light “good enough” for surveilling our patients with colitis? The overall incidence of CRC in IBD has been declining which makes each colonoscopy count more. We are performing up to 88 colonoscopies in patients with colitis to find a single cancer (compared to 8 in non-IBD surveillance patients). We need to be performing fewer and more precise chromoendoscopic examinations. We are otherwise failing to serve our IBD patients by performing too many negative procedures at too high a cost. Our patients deserve more than merely “good enough.”
James F. Marion, MD, is professor of medicine at the Icahn School of Medicine at Mount Sinai and director of education and outreach at The Susan and Leonard Feinstein Inflammatory Bowel Disease Center of The Mount Sinai Hospital, both in New York. He is on the advisory board for Janssen.
High-definition white light endoscopy
Longstanding ulcerative colitis and Crohn’s colitis increase the risk for developing colorectal cancer. The majority of neoplastic lesions are visible endoscopically, and therefore, dye spraying chromoendoscopy (DCE) may not be necessary for all inflammatory bowel disease (IBD) patients undergoing a routine dysplasia surveillance colonoscopy.
High-definition white light (HDWL) endoscopes have higher magnification capacities and pixel density than the standard definition (SD) systems and provide sharper images with fewer artifacts. Although DCE has been proven to be superior to SD, there have been no differences in detection of dysplasia for routine surveillance with use of HDWL compared to DCE.
The SCENIC guidelines key recommendation for optimizing detection and management of dysplasia in IBD is to use a HD colonoscope. Further, based on the recent ACG Practice Guidelines for Dysplasia Screening and Surveillance in 2019, HD colonoscopes are also recommended.
In a network meta-analysis of eight parallel-group randomized controlled trials (RCT), there was very low quality of evidence to support the use of DCE over HDWL. This was contrary to prior, non-RCT studies which suggested that both SD and HDWL were inferior to DCE. More recently, Iacucci and colleagues conducted a randomized noninferiority trial to determine detection rates of neoplastic lesions in IBD patients with longstanding colitis who had inactive disease and enrolled in HDWL, DCE, or virtual chromoendoscopy (VCE) groups. The conclusion was that VCE and HDWL was not inferior to DCE, and HDWL was sufficient in detection of all neoplastic lesions including dysplasia and adenocarcinoma. In another large multicenter, prospective RCT of nine tertiary hospitals in South Korea, the detection rates of colitis-associated dysplasia or all colorectal neoplasia were comparable in HDWL versus high-definition chromoendoscopy. Lastly, a meta-analysis of six RCTs concluded that, although DCE is superior to SD in identification of dysplasia, there was no benefit of DCE compared to HDWL.
In summary, HDWL colonoscopy should be the standard of care for routine dysplasia surveillance in IBD. DCE should be considered in patients who are found to have a dysplastic lesion by HDWL in order to better delineate the lesion margins, endoscopically resect or remove, and for future dysplasia surveillance colonoscopies in the higher-risk IBD patient. Overall, a close and careful examination of the entire colon with use of HDWL is sufficient in detection of dysplasia and for routine surveillance in IBD patients.
Anita Afzali, MD, MPH, AGAF, is medical director of the Inflammatory Bowel Disease Center and program director of the Advanced Inflammatory Bowel Disease Fellowship at Ohio State University in Hilliard, Ohio. She has no relevant conflicts of interest.
These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.
Chromoendoscopy
Chromoendoscopy is superior in both the detection and long-term management of dysplasia in IBD when compared to high-definition white-light examination. Chromoendoscopy not only enhances dysplasia detection but further improves the definition of these lesions which then facilitates endoscopic management.
Human beings have an innate visual perception limitation due to our inability to perceive depth in the red/green wavelength of light compared to the blue wavelength. All of the improvements in scope magnification and resolution bump up against this fact of our biology. Blue dye enhances our ability to perceive depth in this milieu and therefore detect and define flat lesions.
The superiority of chromoendoscopy when using standard definition colonoscopes has been demonstrated repeatedly and set the stage for the 2015 SCENIC international consensus statement and a seismic shift in our endoscopic management of dysplasia in patients with colitis. This evidence base remains relevant because only 77% of colonoscopies performed in the United States are performed using high-definition equipment. Nearly one-quarter of our patients lack access to the newer equipment and therefore without chromoendoscopy are being surveyed outside of current guidelines.
Since the SCENIC statement multiple studies comparing chromoendoscopy with newer higher resolution colonoscopes have been performed. The vast preponderance of evidence has shown either a trend toward superiority or the outright superiority of chromoendoscopy when compared with high-definition white-light examination in detection and long-term management of dysplasia.
Chromoendoscopy has allowed us to increase our visual vocabulary in describing dysplasia in the setting of colitis and, thus, open the door to further innovation and perhaps adoption of artificial intelligence going forward. Our ability to classify lesions encountered in colitis mucosa has become more precise with the expanded terminology the dye-enhanced high-definition view affords, with the Frankfurt Advanced Chromoendoscopic IBD Lesion Classification being the best and most detailed example.
It is no accident that advanced endoscopists have universally adopted chromoendoscopy for the management of dysplastic lesions whether by mucosal resection or submucosal dissection techniques. Chromoendoscopy is recommended by all society guidelines because of these inherent advantages.
Is high-definition white-light “good enough” for surveilling our patients with colitis? The overall incidence of CRC in IBD has been declining which makes each colonoscopy count more. We are performing up to 88 colonoscopies in patients with colitis to find a single cancer (compared to 8 in non-IBD surveillance patients). We need to be performing fewer and more precise chromoendoscopic examinations. We are otherwise failing to serve our IBD patients by performing too many negative procedures at too high a cost. Our patients deserve more than merely “good enough.”
James F. Marion, MD, is professor of medicine at the Icahn School of Medicine at Mount Sinai and director of education and outreach at The Susan and Leonard Feinstein Inflammatory Bowel Disease Center of The Mount Sinai Hospital, both in New York. He is on the advisory board for Janssen.
High-definition white light endoscopy
Longstanding ulcerative colitis and Crohn’s colitis increase the risk for developing colorectal cancer. The majority of neoplastic lesions are visible endoscopically, and therefore, dye spraying chromoendoscopy (DCE) may not be necessary for all inflammatory bowel disease (IBD) patients undergoing a routine dysplasia surveillance colonoscopy.
High-definition white light (HDWL) endoscopes have higher magnification capacities and pixel density than the standard definition (SD) systems and provide sharper images with fewer artifacts. Although DCE has been proven to be superior to SD, there have been no differences in detection of dysplasia for routine surveillance with use of HDWL compared to DCE.
The SCENIC guidelines key recommendation for optimizing detection and management of dysplasia in IBD is to use a HD colonoscope. Further, based on the recent ACG Practice Guidelines for Dysplasia Screening and Surveillance in 2019, HD colonoscopes are also recommended.
In a network meta-analysis of eight parallel-group randomized controlled trials (RCT), there was very low quality of evidence to support the use of DCE over HDWL. This was contrary to prior, non-RCT studies which suggested that both SD and HDWL were inferior to DCE. More recently, Iacucci and colleagues conducted a randomized noninferiority trial to determine detection rates of neoplastic lesions in IBD patients with longstanding colitis who had inactive disease and enrolled in HDWL, DCE, or virtual chromoendoscopy (VCE) groups. The conclusion was that VCE and HDWL was not inferior to DCE, and HDWL was sufficient in detection of all neoplastic lesions including dysplasia and adenocarcinoma. In another large multicenter, prospective RCT of nine tertiary hospitals in South Korea, the detection rates of colitis-associated dysplasia or all colorectal neoplasia were comparable in HDWL versus high-definition chromoendoscopy. Lastly, a meta-analysis of six RCTs concluded that, although DCE is superior to SD in identification of dysplasia, there was no benefit of DCE compared to HDWL.
In summary, HDWL colonoscopy should be the standard of care for routine dysplasia surveillance in IBD. DCE should be considered in patients who are found to have a dysplastic lesion by HDWL in order to better delineate the lesion margins, endoscopically resect or remove, and for future dysplasia surveillance colonoscopies in the higher-risk IBD patient. Overall, a close and careful examination of the entire colon with use of HDWL is sufficient in detection of dysplasia and for routine surveillance in IBD patients.
Anita Afzali, MD, MPH, AGAF, is medical director of the Inflammatory Bowel Disease Center and program director of the Advanced Inflammatory Bowel Disease Fellowship at Ohio State University in Hilliard, Ohio. She has no relevant conflicts of interest.
These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.
Chromoendoscopy
Chromoendoscopy is superior in both the detection and long-term management of dysplasia in IBD when compared to high-definition white-light examination. Chromoendoscopy not only enhances dysplasia detection but further improves the definition of these lesions which then facilitates endoscopic management.
Human beings have an innate visual perception limitation due to our inability to perceive depth in the red/green wavelength of light compared to the blue wavelength. All of the improvements in scope magnification and resolution bump up against this fact of our biology. Blue dye enhances our ability to perceive depth in this milieu and therefore detect and define flat lesions.
The superiority of chromoendoscopy when using standard definition colonoscopes has been demonstrated repeatedly and set the stage for the 2015 SCENIC international consensus statement and a seismic shift in our endoscopic management of dysplasia in patients with colitis. This evidence base remains relevant because only 77% of colonoscopies performed in the United States are performed using high-definition equipment. Nearly one-quarter of our patients lack access to the newer equipment and therefore without chromoendoscopy are being surveyed outside of current guidelines.
Since the SCENIC statement multiple studies comparing chromoendoscopy with newer higher resolution colonoscopes have been performed. The vast preponderance of evidence has shown either a trend toward superiority or the outright superiority of chromoendoscopy when compared with high-definition white-light examination in detection and long-term management of dysplasia.
Chromoendoscopy has allowed us to increase our visual vocabulary in describing dysplasia in the setting of colitis and, thus, open the door to further innovation and perhaps adoption of artificial intelligence going forward. Our ability to classify lesions encountered in colitis mucosa has become more precise with the expanded terminology the dye-enhanced high-definition view affords, with the Frankfurt Advanced Chromoendoscopic IBD Lesion Classification being the best and most detailed example.
It is no accident that advanced endoscopists have universally adopted chromoendoscopy for the management of dysplastic lesions whether by mucosal resection or submucosal dissection techniques. Chromoendoscopy is recommended by all society guidelines because of these inherent advantages.
Is high-definition white-light “good enough” for surveilling our patients with colitis? The overall incidence of CRC in IBD has been declining which makes each colonoscopy count more. We are performing up to 88 colonoscopies in patients with colitis to find a single cancer (compared to 8 in non-IBD surveillance patients). We need to be performing fewer and more precise chromoendoscopic examinations. We are otherwise failing to serve our IBD patients by performing too many negative procedures at too high a cost. Our patients deserve more than merely “good enough.”
James F. Marion, MD, is professor of medicine at the Icahn School of Medicine at Mount Sinai and director of education and outreach at The Susan and Leonard Feinstein Inflammatory Bowel Disease Center of The Mount Sinai Hospital, both in New York. He is on the advisory board for Janssen.
High-definition white light endoscopy
Longstanding ulcerative colitis and Crohn’s colitis increase the risk for developing colorectal cancer. The majority of neoplastic lesions are visible endoscopically, and therefore, dye spraying chromoendoscopy (DCE) may not be necessary for all inflammatory bowel disease (IBD) patients undergoing a routine dysplasia surveillance colonoscopy.
High-definition white light (HDWL) endoscopes have higher magnification capacities and pixel density than the standard definition (SD) systems and provide sharper images with fewer artifacts. Although DCE has been proven to be superior to SD, there have been no differences in detection of dysplasia for routine surveillance with use of HDWL compared to DCE.
The SCENIC guidelines key recommendation for optimizing detection and management of dysplasia in IBD is to use a HD colonoscope. Further, based on the recent ACG Practice Guidelines for Dysplasia Screening and Surveillance in 2019, HD colonoscopes are also recommended.
In a network meta-analysis of eight parallel-group randomized controlled trials (RCT), there was very low quality of evidence to support the use of DCE over HDWL. This was contrary to prior, non-RCT studies which suggested that both SD and HDWL were inferior to DCE. More recently, Iacucci and colleagues conducted a randomized noninferiority trial to determine detection rates of neoplastic lesions in IBD patients with longstanding colitis who had inactive disease and enrolled in HDWL, DCE, or virtual chromoendoscopy (VCE) groups. The conclusion was that VCE and HDWL was not inferior to DCE, and HDWL was sufficient in detection of all neoplastic lesions including dysplasia and adenocarcinoma. In another large multicenter, prospective RCT of nine tertiary hospitals in South Korea, the detection rates of colitis-associated dysplasia or all colorectal neoplasia were comparable in HDWL versus high-definition chromoendoscopy. Lastly, a meta-analysis of six RCTs concluded that, although DCE is superior to SD in identification of dysplasia, there was no benefit of DCE compared to HDWL.
In summary, HDWL colonoscopy should be the standard of care for routine dysplasia surveillance in IBD. DCE should be considered in patients who are found to have a dysplastic lesion by HDWL in order to better delineate the lesion margins, endoscopically resect or remove, and for future dysplasia surveillance colonoscopies in the higher-risk IBD patient. Overall, a close and careful examination of the entire colon with use of HDWL is sufficient in detection of dysplasia and for routine surveillance in IBD patients.
Anita Afzali, MD, MPH, AGAF, is medical director of the Inflammatory Bowel Disease Center and program director of the Advanced Inflammatory Bowel Disease Fellowship at Ohio State University in Hilliard, Ohio. She has no relevant conflicts of interest.
These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.
Retinopathy risk higher in young-onset T2D, more so in men
Men diagnosed with type 2 diabetes (T2D) by the age of 40 years appear significantly more likely to develop retinopathy than men who are diagnosed at an older age, Norwegian researchers report.
In a cross-sectional study of about 10,000 people, men with young-onset T2D were 72% more likely than men aged 50 years or older to have retinopathy.
While an increased retinopathy risk was also seen in women with young-onset T2D versus older women at first, this difference was not significant after adjusting for various confounding factors.
The effect of young-onset diabetes on retinopathy seems to be gender specific, Katrina Tibballs, MD, of the department of general practice at the University of Oslo, reported at the annual meeting of the European Association for the Study of Diabetes.
“In the unadjusted analysis, the odds ratio for retinopathy was substantially higher in both [young-onset] men [odds ratio, 3.0] and women [OR, 2.46], compared with those 50 or older at diabetes diagnosis,” Dr. Tibballs said.
That relationship was not substantially altered after adjustment for variables such as level of education, country background, gender, and body mass index, with adjusted ORs of 2.56 and 2.55 for men and women, respectively.
However, further adjustment to include current age, duration of diabetes, and blood lipids and glycated hemoglobin levels, led to the difference no longer holding for women (OR, 1.34; 95% confidence interval, 0.95-1.89) as it did for men (OR 1.72; 95% CI, 1.29-2.29).
First data in Norwegian population
Cross-sectional data on more than 10,000 people with T2D were used for the analysis. These came from the ROSA4 study, a general practice study conducted across Norway in 2014.
Just over 10% of the study population used in the analysis was under the age of 40 years at diagnosis of T2D; 21% were aged between 40 and 49 years, and 69% were at least 50 years old.
The mean age of those with young-onset T2D, defined as a diagnosis before the age of 40 years, was 33 years. These individuals had a longer disease duration than those in the other age groups (11.4 vs. 10.0 vs. 7.8 years).
“Looking at clinical characteristics, we say that individuals [with young-onset T2D] have a higher level of hemoglobin A1c than those with diabetes onset later in life,” Dr. Tibballs said.
“This is despite a substantially higher proportion [being] treated with insulin and fewer on lifestyle interventions alone.”
Gender differences were seen in A1c levels, with men with young-onset T2D having consistently higher levels than women, with levels increasing with diabetes duration.
Rise in retinopathy faster in men than in women
Dr. Tibballs reported that, not only did the prevalence of retinopathy rise faster in those of a younger age, but it also rose more quickly in men with young-onset T2D than it in their female counterparts.
“Comparing that [young-onset diabetes] and later-onset diabetes in men and women separately, we see a clearly higher prevalence of retinopathy with increasing diabetes duration for [young-onset] men,” she said.
In women, on the other hand, there was “no clear indication of a higher retinopathy prevalence in [young-onset diabetes], except in those with the longest diabetes duration.”
So, what do the results mean for practice? First, they confirm prior work showing that there is a strong association between retinopathy and age at diagnosis of T2D. Second, they suggest that this is despite intensive glucose-lowering treatment.
She speculated that men with young-onset T2D may have had a delayed diagnosis when compared with women and individuals with later onset diabetes, Dr. Tibballs said.
“This may in turn lead to delayed onset of glucose-lowering treatment, allowing for more time with high glycemic exposure and increased risk of acquiring complications, such as retinopathy at the time of diagnosis, or in the first years after,” said Dr. Tibballs.
These are cross-sectional data, “so we can’t say anything about whether this treatment is sufficient, but it is obviously not reducing HbA1c levels as much as we would like” added Dr. Tibballs, who is a primary care physician and PhD student.
The study was supported by The Norwegian Research Fund for General Practice. Dr. Tibballs had no conflicts of interest to disclose.
Men diagnosed with type 2 diabetes (T2D) by the age of 40 years appear significantly more likely to develop retinopathy than men who are diagnosed at an older age, Norwegian researchers report.
In a cross-sectional study of about 10,000 people, men with young-onset T2D were 72% more likely than men aged 50 years or older to have retinopathy.
While an increased retinopathy risk was also seen in women with young-onset T2D versus older women at first, this difference was not significant after adjusting for various confounding factors.
The effect of young-onset diabetes on retinopathy seems to be gender specific, Katrina Tibballs, MD, of the department of general practice at the University of Oslo, reported at the annual meeting of the European Association for the Study of Diabetes.
“In the unadjusted analysis, the odds ratio for retinopathy was substantially higher in both [young-onset] men [odds ratio, 3.0] and women [OR, 2.46], compared with those 50 or older at diabetes diagnosis,” Dr. Tibballs said.
That relationship was not substantially altered after adjustment for variables such as level of education, country background, gender, and body mass index, with adjusted ORs of 2.56 and 2.55 for men and women, respectively.
However, further adjustment to include current age, duration of diabetes, and blood lipids and glycated hemoglobin levels, led to the difference no longer holding for women (OR, 1.34; 95% confidence interval, 0.95-1.89) as it did for men (OR 1.72; 95% CI, 1.29-2.29).
First data in Norwegian population
Cross-sectional data on more than 10,000 people with T2D were used for the analysis. These came from the ROSA4 study, a general practice study conducted across Norway in 2014.
Just over 10% of the study population used in the analysis was under the age of 40 years at diagnosis of T2D; 21% were aged between 40 and 49 years, and 69% were at least 50 years old.
The mean age of those with young-onset T2D, defined as a diagnosis before the age of 40 years, was 33 years. These individuals had a longer disease duration than those in the other age groups (11.4 vs. 10.0 vs. 7.8 years).
“Looking at clinical characteristics, we say that individuals [with young-onset T2D] have a higher level of hemoglobin A1c than those with diabetes onset later in life,” Dr. Tibballs said.
“This is despite a substantially higher proportion [being] treated with insulin and fewer on lifestyle interventions alone.”
Gender differences were seen in A1c levels, with men with young-onset T2D having consistently higher levels than women, with levels increasing with diabetes duration.
Rise in retinopathy faster in men than in women
Dr. Tibballs reported that, not only did the prevalence of retinopathy rise faster in those of a younger age, but it also rose more quickly in men with young-onset T2D than it in their female counterparts.
“Comparing that [young-onset diabetes] and later-onset diabetes in men and women separately, we see a clearly higher prevalence of retinopathy with increasing diabetes duration for [young-onset] men,” she said.
In women, on the other hand, there was “no clear indication of a higher retinopathy prevalence in [young-onset diabetes], except in those with the longest diabetes duration.”
So, what do the results mean for practice? First, they confirm prior work showing that there is a strong association between retinopathy and age at diagnosis of T2D. Second, they suggest that this is despite intensive glucose-lowering treatment.
She speculated that men with young-onset T2D may have had a delayed diagnosis when compared with women and individuals with later onset diabetes, Dr. Tibballs said.
“This may in turn lead to delayed onset of glucose-lowering treatment, allowing for more time with high glycemic exposure and increased risk of acquiring complications, such as retinopathy at the time of diagnosis, or in the first years after,” said Dr. Tibballs.
These are cross-sectional data, “so we can’t say anything about whether this treatment is sufficient, but it is obviously not reducing HbA1c levels as much as we would like” added Dr. Tibballs, who is a primary care physician and PhD student.
The study was supported by The Norwegian Research Fund for General Practice. Dr. Tibballs had no conflicts of interest to disclose.
Men diagnosed with type 2 diabetes (T2D) by the age of 40 years appear significantly more likely to develop retinopathy than men who are diagnosed at an older age, Norwegian researchers report.
In a cross-sectional study of about 10,000 people, men with young-onset T2D were 72% more likely than men aged 50 years or older to have retinopathy.
While an increased retinopathy risk was also seen in women with young-onset T2D versus older women at first, this difference was not significant after adjusting for various confounding factors.
The effect of young-onset diabetes on retinopathy seems to be gender specific, Katrina Tibballs, MD, of the department of general practice at the University of Oslo, reported at the annual meeting of the European Association for the Study of Diabetes.
“In the unadjusted analysis, the odds ratio for retinopathy was substantially higher in both [young-onset] men [odds ratio, 3.0] and women [OR, 2.46], compared with those 50 or older at diabetes diagnosis,” Dr. Tibballs said.
That relationship was not substantially altered after adjustment for variables such as level of education, country background, gender, and body mass index, with adjusted ORs of 2.56 and 2.55 for men and women, respectively.
However, further adjustment to include current age, duration of diabetes, and blood lipids and glycated hemoglobin levels, led to the difference no longer holding for women (OR, 1.34; 95% confidence interval, 0.95-1.89) as it did for men (OR 1.72; 95% CI, 1.29-2.29).
First data in Norwegian population
Cross-sectional data on more than 10,000 people with T2D were used for the analysis. These came from the ROSA4 study, a general practice study conducted across Norway in 2014.
Just over 10% of the study population used in the analysis was under the age of 40 years at diagnosis of T2D; 21% were aged between 40 and 49 years, and 69% were at least 50 years old.
The mean age of those with young-onset T2D, defined as a diagnosis before the age of 40 years, was 33 years. These individuals had a longer disease duration than those in the other age groups (11.4 vs. 10.0 vs. 7.8 years).
“Looking at clinical characteristics, we say that individuals [with young-onset T2D] have a higher level of hemoglobin A1c than those with diabetes onset later in life,” Dr. Tibballs said.
“This is despite a substantially higher proportion [being] treated with insulin and fewer on lifestyle interventions alone.”
Gender differences were seen in A1c levels, with men with young-onset T2D having consistently higher levels than women, with levels increasing with diabetes duration.
Rise in retinopathy faster in men than in women
Dr. Tibballs reported that, not only did the prevalence of retinopathy rise faster in those of a younger age, but it also rose more quickly in men with young-onset T2D than it in their female counterparts.
“Comparing that [young-onset diabetes] and later-onset diabetes in men and women separately, we see a clearly higher prevalence of retinopathy with increasing diabetes duration for [young-onset] men,” she said.
In women, on the other hand, there was “no clear indication of a higher retinopathy prevalence in [young-onset diabetes], except in those with the longest diabetes duration.”
So, what do the results mean for practice? First, they confirm prior work showing that there is a strong association between retinopathy and age at diagnosis of T2D. Second, they suggest that this is despite intensive glucose-lowering treatment.
She speculated that men with young-onset T2D may have had a delayed diagnosis when compared with women and individuals with later onset diabetes, Dr. Tibballs said.
“This may in turn lead to delayed onset of glucose-lowering treatment, allowing for more time with high glycemic exposure and increased risk of acquiring complications, such as retinopathy at the time of diagnosis, or in the first years after,” said Dr. Tibballs.
These are cross-sectional data, “so we can’t say anything about whether this treatment is sufficient, but it is obviously not reducing HbA1c levels as much as we would like” added Dr. Tibballs, who is a primary care physician and PhD student.
The study was supported by The Norwegian Research Fund for General Practice. Dr. Tibballs had no conflicts of interest to disclose.
FROM EASD 2021
Genetic testing for colon cancer: Who, when, and how
Gastroenterologists should be skilled in recognition of patients with inherited risk of colorectal neoplasia.
Fay Kastrinos, MD, presented a 49-year-old female who had more than 10 cumulative adenomas and a cecal adenocarcinoma on two colonoscopies, the first of which was performed for evaluation of rectal bleeding. Carol Burke, MD, reviewed the differential diagnosis of adenomatous polyposis (defined as >10 cumulative adenomas).Germline syndromes include familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), and a number of rare germline syndromes. Lynch syndrome should be considered especially for carriers of pathogenic variants in MSH6 who can present with a polyposis phenotype, as well as in children with constitutional mismatch repair deficiency syndrome. Finally, polyposis can be due to smoking, familial clustering, or previous abdominal radiation called therapy-associated polyposis. Polyposis without a known cause is referred to as colonic polyposis of unknown etiology (CPUE).
Dr. Kastrinos reviewed the patient’s three-generation family history of a brother and mother with “polyps” and second-degree relatives with endometrial and colon cancer. Niloy Jewel Samadder, MD, presented on the role of taking a comprehensive family history, tumor tests for Lynch syndrome, selection of genetic test type, and risks, benefits, and alternatives of genetic testing. Dr. Samadder reviewed indications for germline genetic testing for colorectal neoplasia of which the patient met two criteria, namely colorectal cancer under age 50 and 10 or more cumulative adenomas.
The final section was presented by this author on multigene panel testing, in which multiple genes are sequenced simultaneously. This patient’s panel showed two pathogenic variants in the MUTYH gene consistent with MAP, a recessive polyposis syndrome typically with 10s-100 cumulative adenomas. The test also showed a variant of uncertain significance (VUS) which is not clinically actionable. Providers counseling patients on multigene panel testing should discuss the possibility of VUS results (especially in individuals of non-European descent), moderate penetrant genes for which management recommendations are uncertain, or unexpected findings in genes not associated with colonic neoplasia. Studies have shown that the prevalence of finding an inherited syndrome is increased at younger ages of disease onset.
Dr. Kastrinos summarized key points from the session, including hereditary colorectal cancer syndromes are not rare, red flags for inherited syndromes, include early onset colorectal neoplasia and/or numerous relatives with colorectal and other extra-colonic cancer, extended family history assessment is recommended, and genetic risk assessment and genetic testing with multigene panels is a process and should be personalized. The question and answer session was lively with discussion of cost as well as direct-to-consumer genetic testing.
Sonia Kupfer, MD, AGAF, is an associate professor in the section of gastroenterology, hepatology, and nutrition at the University of Chicago. She has no financial conflicts of interest. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.
Gastroenterologists should be skilled in recognition of patients with inherited risk of colorectal neoplasia.
Fay Kastrinos, MD, presented a 49-year-old female who had more than 10 cumulative adenomas and a cecal adenocarcinoma on two colonoscopies, the first of which was performed for evaluation of rectal bleeding. Carol Burke, MD, reviewed the differential diagnosis of adenomatous polyposis (defined as >10 cumulative adenomas).Germline syndromes include familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), and a number of rare germline syndromes. Lynch syndrome should be considered especially for carriers of pathogenic variants in MSH6 who can present with a polyposis phenotype, as well as in children with constitutional mismatch repair deficiency syndrome. Finally, polyposis can be due to smoking, familial clustering, or previous abdominal radiation called therapy-associated polyposis. Polyposis without a known cause is referred to as colonic polyposis of unknown etiology (CPUE).
Dr. Kastrinos reviewed the patient’s three-generation family history of a brother and mother with “polyps” and second-degree relatives with endometrial and colon cancer. Niloy Jewel Samadder, MD, presented on the role of taking a comprehensive family history, tumor tests for Lynch syndrome, selection of genetic test type, and risks, benefits, and alternatives of genetic testing. Dr. Samadder reviewed indications for germline genetic testing for colorectal neoplasia of which the patient met two criteria, namely colorectal cancer under age 50 and 10 or more cumulative adenomas.
The final section was presented by this author on multigene panel testing, in which multiple genes are sequenced simultaneously. This patient’s panel showed two pathogenic variants in the MUTYH gene consistent with MAP, a recessive polyposis syndrome typically with 10s-100 cumulative adenomas. The test also showed a variant of uncertain significance (VUS) which is not clinically actionable. Providers counseling patients on multigene panel testing should discuss the possibility of VUS results (especially in individuals of non-European descent), moderate penetrant genes for which management recommendations are uncertain, or unexpected findings in genes not associated with colonic neoplasia. Studies have shown that the prevalence of finding an inherited syndrome is increased at younger ages of disease onset.
Dr. Kastrinos summarized key points from the session, including hereditary colorectal cancer syndromes are not rare, red flags for inherited syndromes, include early onset colorectal neoplasia and/or numerous relatives with colorectal and other extra-colonic cancer, extended family history assessment is recommended, and genetic risk assessment and genetic testing with multigene panels is a process and should be personalized. The question and answer session was lively with discussion of cost as well as direct-to-consumer genetic testing.
Sonia Kupfer, MD, AGAF, is an associate professor in the section of gastroenterology, hepatology, and nutrition at the University of Chicago. She has no financial conflicts of interest. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.
Gastroenterologists should be skilled in recognition of patients with inherited risk of colorectal neoplasia.
Fay Kastrinos, MD, presented a 49-year-old female who had more than 10 cumulative adenomas and a cecal adenocarcinoma on two colonoscopies, the first of which was performed for evaluation of rectal bleeding. Carol Burke, MD, reviewed the differential diagnosis of adenomatous polyposis (defined as >10 cumulative adenomas).Germline syndromes include familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), and a number of rare germline syndromes. Lynch syndrome should be considered especially for carriers of pathogenic variants in MSH6 who can present with a polyposis phenotype, as well as in children with constitutional mismatch repair deficiency syndrome. Finally, polyposis can be due to smoking, familial clustering, or previous abdominal radiation called therapy-associated polyposis. Polyposis without a known cause is referred to as colonic polyposis of unknown etiology (CPUE).
Dr. Kastrinos reviewed the patient’s three-generation family history of a brother and mother with “polyps” and second-degree relatives with endometrial and colon cancer. Niloy Jewel Samadder, MD, presented on the role of taking a comprehensive family history, tumor tests for Lynch syndrome, selection of genetic test type, and risks, benefits, and alternatives of genetic testing. Dr. Samadder reviewed indications for germline genetic testing for colorectal neoplasia of which the patient met two criteria, namely colorectal cancer under age 50 and 10 or more cumulative adenomas.
The final section was presented by this author on multigene panel testing, in which multiple genes are sequenced simultaneously. This patient’s panel showed two pathogenic variants in the MUTYH gene consistent with MAP, a recessive polyposis syndrome typically with 10s-100 cumulative adenomas. The test also showed a variant of uncertain significance (VUS) which is not clinically actionable. Providers counseling patients on multigene panel testing should discuss the possibility of VUS results (especially in individuals of non-European descent), moderate penetrant genes for which management recommendations are uncertain, or unexpected findings in genes not associated with colonic neoplasia. Studies have shown that the prevalence of finding an inherited syndrome is increased at younger ages of disease onset.
Dr. Kastrinos summarized key points from the session, including hereditary colorectal cancer syndromes are not rare, red flags for inherited syndromes, include early onset colorectal neoplasia and/or numerous relatives with colorectal and other extra-colonic cancer, extended family history assessment is recommended, and genetic risk assessment and genetic testing with multigene panels is a process and should be personalized. The question and answer session was lively with discussion of cost as well as direct-to-consumer genetic testing.
Sonia Kupfer, MD, AGAF, is an associate professor in the section of gastroenterology, hepatology, and nutrition at the University of Chicago. She has no financial conflicts of interest. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.