Cancer

In 2020, the US Multi-Society Task Force (USMSTF) on Colorectal Cancer (CRC) increased the recommended colon polyp surveillance interval for 1 to 2 subcentimeter tubular adenomas from 5 to 10 years to 7 to 10 years.¹ This change was prompted by emerging research indicating that rates of CRC and advanced neoplasia among patients with a history of only 1 to 2 subcentimeter tubular adenomas are lower than initially estimated.^2,3 This extension provides an opportunity to increase endoscopy capacity and improve access to colonoscopies by retroactively applying the 2020 guidelines to surveillance interval recommendations made before their introduction. For example, based on the updated guidelines, patients previously recommended to undergo colon polyp surveillance colonoscopy 5 years after an index colonoscopy could extend their surveillance interval by 2 to 5 years. Increasing endoscopic capacity could address the growing demand for colonoscopies from new screening guidelines that reduced the age of initial CRC screening from 50 years to 45 years and the backlog of procedures due to COVID-19 restrictions.⁴

As part of a project to increase endoscopic capacity at the US Department of Veterans Affairs (VA) Pittsburgh Healthcare System (VAPHS), this study assessed the potential impact of retroactively applying the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity. These results may be informative for other VA and private-sector health care systems seeking to identify strategies to improve endoscopy capacity.

Methods

VAPHS is an integrated health care system in the Veterans Health Administration (VHA) serving 85,000 patients across 8 health care institutions in Pennsylvania, Ohio, and West Virginia. VAPHS manages colorectal screening recommendations for patients receiving medical care in the health care system regardless of whether their prior colonoscopy was performed at VAPHS or external facilities. The VA maintains a national CRC screening and surveillance electronic medical record reminder that prompts health care practitioners to order colon polyp surveillance based on interval recommendations from the index colonoscopy. This study reviewed all patients from the VAPHS panel with a reminder to undergo colonoscopy for screening for CRC or surveillance of colon polyps within 12 months from September 1, 2022.

Among patients with a reminder, 3 investigators reviewed index colonoscopy and pathology reports to identify CRC risk category, colonoscopy indication, procedural quality, and recommended repeat colonoscopy interval. Per the USMSTF guidelines, patients with incomplete colonoscopy or pathology records, high-risk indications (ie, personal history of inflammatory bowel disease, personal history of CRC, or family history of CRC), or inadequate bowel preparation (Boston Bowel Preparation Score < 6) were excluded. Additionally, patients who had CRC screening or surveillance discontinued due to age or comorbidities, had completed a subsequent follow-up colonoscopy, or were deceased at the time of review were excluded.

Retroactive Interval Reclassification

Among eligible patients, this study compared the repeat colonoscopy interval recommended by the prior endoscopist with those from the 2020 USMSTF guidelines. In cases where the interval was documented as a range of years, the lower end was considered the recommendation. Similarly, the lower end of the range from the 2020 USMSTF guidelines was used for the reclassified surveillance interval. Years extended per patient were quantified relative to September 1, 2023 (ie, 1 year after the review date). For example, if the index colonoscopy was completed on September 1, 2016, the initial surveillance recommendation was 5 years, and the reclassified recommendation was 7 years, the interval extension beyond September 1, 2023, was 0 years.

Furthermore, because index surveillance recommendations are not always guideline concordant, the years extended per patient were calculated by harmonizing the index endoscopist’s recommendations with the guidelines at the time of the index colonoscopy.⁵ For example, if the index colonoscopy was completed on September 1, 2018, and the endoscopist recommended a 5-year follow-up for a patient with average risk for CRC, adequate bowel preparation, and no colorectal polyps, that patient is eligible to extend their colonoscopy to September 1, 2028, based on guideline recommendations at the time of index endoscopy recommending that the next colonoscopy occur in 10 years. In this analysis the 2012 USMSTF guidelines were applied to all index colonoscopies completed in 2021 or earlier to allow time for adoption of the 2020 guidelines. 

This project fulfilled a facility mandate to increase capacity to conduct endoscopic procedures. Institutional review board approval was not required by VAPHS policy relating to clinical operations projects. Approval for publication of clinical operations activity was obtained from the VAPHS facility director.

Results

Within 1 year of the September 1, 2022, review date, 637 patients receiving care at VAPHS had clinical reminders for an upcoming colonoscopy. Of these, 54 (8.4%) were already up to date or were deceased at the time of review. Of the 583 eligible patients, 96% were male, the median age was 74 years, the median index colonoscopy year was 2016, and 178 (30.5%) had an average-risk CRC screening indication at the index colonoscopy (Table).

Of the 583 patients due for colonoscopy, 331 (56.7%) had both colonoscopy and pathology reports available. The majority of those with incomplete records had the index colonoscopy completed outside VAPHS. Among these patients, 222 (67.0%) had adequate bowel preparation. Of those with adequate bowel preparation, 43 were not eligible for interval extension because of high-risk conditions and 13 were not eligible because there was no index surveillance interval recommendation from the index endoscopist. Of the patients due for colonoscopy, 166 (28.4%) were potentially eligible for surveillance interval extension (Figure).  

Sixty-five (39.2%) of the 166 patients had 1 to 2 subcentimeter tubular adenomas on their index colonoscopy. Sixty-two patients were eligible for interval extension to 7 years, but this only resulted in ≥ 1 year of extension beyond the review date for 36 (6% of all 583 patients due for colonoscopy). The 36 patients were extended 63 years. By harmonizing the index endoscopists’ surveillance interval recommendation with the guideline at the time of the index colonoscopy, 29 additional patients could have their colonoscopy extended by ≥ 1 year. Harmonization extended colonoscopy intervals by 93 years. Retroactively applying the 2020 USMSTF polyp surveillance guidelines and harmonizing recommendations to guidelines extended the time of index colonoscopy by 153 years.

Discussion

With retroactive application of the 2020 USMSTF polyp surveillance guidelines, 6% of patients due for an upcoming colonoscopy could extend their follow-up by ≥ 1 year by extending the surveillance interval for 1 to 2 subcentimeter tubular adenomas to 7 years. An additional 5% of patients could extend their interval by harmonizing the index endoscopist’s interval recommendation with polyp surveillance guidelines at the time of the index colonoscopy. These findings are consistent with the results of 2 studies that demonstrated that about 14% of patients due for colonoscopy could have their interval extended.^6,7 The current study enhances those insights by separating the contribution of 2020 USMSTF polyp surveillance guidelines from the contribution of harmonizing surveillance intervals with guidelines for other polyp histologies. This study found that there is an opportunity to improve endoscopic capacity by harmonizing recommendations with guidelines. This complements a 2023 study showing that even when knowledgeable about guidelines, clinicians do not necessarily follow recommendations.⁸ While this and previous research have identified that 11% to 14% of patients are eligible for extension, these individuals would also have to be willing to have their polyp surveillance intervals extended for there to be a real-world impact on endoscopic capacity. A 2024 study found that only 19% to 37% of patients with 1 to 2 small tubular adenomas were willing to have polyps surveillance interval extension.⁹ This suggests the actual effect on capacity may be even lower than reported.

Limitations

The overall impact of the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity was blunted by the high prevalence of incomplete index colonoscopy records among the study population. Without data on bowel preparation quality or procedure indications, this study could not assess whether 43% of patients were eligible for surveillance interval extension. Most index colonoscopies with incomplete documentation were completed at community-care gastroenterology facilities. This high rate of incomplete documentation is likely generalizable to other VA health care systems—especially in the era of the Veterans Access, Choice, and Accountability Act of 2014, which increased veteran access to non-VA community care.¹⁰ Veterans due for colon polyp surveillance colonoscopies are more likely to have had their prior colonoscopy in community care compared with prior eras.¹¹ Furthermore, because the VHA is among the most established integrated health care systems offering primary and subspecialty care in the US, private sector health care systems may have even greater rates of care fragmentation for longitudinal CRC screening and colon polyp surveillance, as these systems have only begun to regionally integrate recently.^12,13

Another limitation is that nearly one-third of the individuals with documentation had inadequate bowel preparation for surveillance recommendations. This results in shorter surveillance follow-up colonoscopies and increases downstream demand for future colonoscopies. The low yield of extending colon polyp surveillance interval in this study emphasizes that improved efforts to obtain colonoscopy and pathology reports from community care, right-sizing the colon polyp surveillance intervals recommended by endoscopists, and improving quality of bowel preparation could have downstream health care system benefits in the future. These efforts could increase colonoscopy capacity at VA health care systems, thereby shortening colonoscopy wait times, decreasing fragmentation of care, and increasing the number of veterans who receive high-quality colonoscopies at VA health care systems.¹⁴

Conclusions

Eleven percent of patients in this study due for a colonoscopy could extend their follow-up by ≥ 1 year. About half of these extensions were directly due to the 2020 USMSTF polyp surveillance interval extension for 1 to 2 subcentimeter tubular adenomas. The rest resulted from harmonizing recommendations with guidelines at the time of the procedure. To determine whether retroactively applying polyp surveillance guidelines to follow-up interval recommendations will result in improved endoscopic capacity, health care system administrators should consider the degree of CRC screening care fragmentation in their patient population. Greater long-term gains in endoscopic capacity may be achieved by proactively supporting endoscopists in making guideline-concordant screening recommendations at the time of colonoscopy.

In 2020, the US Multi-Society Task Force (USMSTF) on Colorectal Cancer (CRC) increased the recommended colon polyp surveillance interval for 1 to 2 subcentimeter tubular adenomas from 5 to 10 years to 7 to 10 years.¹ This change was prompted by emerging research indicating that rates of CRC and advanced neoplasia among patients with a history of only 1 to 2 subcentimeter tubular adenomas are lower than initially estimated.^2,3 This extension provides an opportunity to increase endoscopy capacity and improve access to colonoscopies by retroactively applying the 2020 guidelines to surveillance interval recommendations made before their introduction. For example, based on the updated guidelines, patients previously recommended to undergo colon polyp surveillance colonoscopy 5 years after an index colonoscopy could extend their surveillance interval by 2 to 5 years. Increasing endoscopic capacity could address the growing demand for colonoscopies from new screening guidelines that reduced the age of initial CRC screening from 50 years to 45 years and the backlog of procedures due to COVID-19 restrictions.⁴

As part of a project to increase endoscopic capacity at the US Department of Veterans Affairs (VA) Pittsburgh Healthcare System (VAPHS), this study assessed the potential impact of retroactively applying the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity. These results may be informative for other VA and private-sector health care systems seeking to identify strategies to improve endoscopy capacity.

Methods

VAPHS is an integrated health care system in the Veterans Health Administration (VHA) serving 85,000 patients across 8 health care institutions in Pennsylvania, Ohio, and West Virginia. VAPHS manages colorectal screening recommendations for patients receiving medical care in the health care system regardless of whether their prior colonoscopy was performed at VAPHS or external facilities. The VA maintains a national CRC screening and surveillance electronic medical record reminder that prompts health care practitioners to order colon polyp surveillance based on interval recommendations from the index colonoscopy. This study reviewed all patients from the VAPHS panel with a reminder to undergo colonoscopy for screening for CRC or surveillance of colon polyps within 12 months from September 1, 2022.

Among patients with a reminder, 3 investigators reviewed index colonoscopy and pathology reports to identify CRC risk category, colonoscopy indication, procedural quality, and recommended repeat colonoscopy interval. Per the USMSTF guidelines, patients with incomplete colonoscopy or pathology records, high-risk indications (ie, personal history of inflammatory bowel disease, personal history of CRC, or family history of CRC), or inadequate bowel preparation (Boston Bowel Preparation Score < 6) were excluded. Additionally, patients who had CRC screening or surveillance discontinued due to age or comorbidities, had completed a subsequent follow-up colonoscopy, or were deceased at the time of review were excluded.

Retroactive Interval Reclassification

Among eligible patients, this study compared the repeat colonoscopy interval recommended by the prior endoscopist with those from the 2020 USMSTF guidelines. In cases where the interval was documented as a range of years, the lower end was considered the recommendation. Similarly, the lower end of the range from the 2020 USMSTF guidelines was used for the reclassified surveillance interval. Years extended per patient were quantified relative to September 1, 2023 (ie, 1 year after the review date). For example, if the index colonoscopy was completed on September 1, 2016, the initial surveillance recommendation was 5 years, and the reclassified recommendation was 7 years, the interval extension beyond September 1, 2023, was 0 years.

Furthermore, because index surveillance recommendations are not always guideline concordant, the years extended per patient were calculated by harmonizing the index endoscopist’s recommendations with the guidelines at the time of the index colonoscopy.⁵ For example, if the index colonoscopy was completed on September 1, 2018, and the endoscopist recommended a 5-year follow-up for a patient with average risk for CRC, adequate bowel preparation, and no colorectal polyps, that patient is eligible to extend their colonoscopy to September 1, 2028, based on guideline recommendations at the time of index endoscopy recommending that the next colonoscopy occur in 10 years. In this analysis the 2012 USMSTF guidelines were applied to all index colonoscopies completed in 2021 or earlier to allow time for adoption of the 2020 guidelines. 

This project fulfilled a facility mandate to increase capacity to conduct endoscopic procedures. Institutional review board approval was not required by VAPHS policy relating to clinical operations projects. Approval for publication of clinical operations activity was obtained from the VAPHS facility director.

Results

Within 1 year of the September 1, 2022, review date, 637 patients receiving care at VAPHS had clinical reminders for an upcoming colonoscopy. Of these, 54 (8.4%) were already up to date or were deceased at the time of review. Of the 583 eligible patients, 96% were male, the median age was 74 years, the median index colonoscopy year was 2016, and 178 (30.5%) had an average-risk CRC screening indication at the index colonoscopy (Table).

Of the 583 patients due for colonoscopy, 331 (56.7%) had both colonoscopy and pathology reports available. The majority of those with incomplete records had the index colonoscopy completed outside VAPHS. Among these patients, 222 (67.0%) had adequate bowel preparation. Of those with adequate bowel preparation, 43 were not eligible for interval extension because of high-risk conditions and 13 were not eligible because there was no index surveillance interval recommendation from the index endoscopist. Of the patients due for colonoscopy, 166 (28.4%) were potentially eligible for surveillance interval extension (Figure).  

Sixty-five (39.2%) of the 166 patients had 1 to 2 subcentimeter tubular adenomas on their index colonoscopy. Sixty-two patients were eligible for interval extension to 7 years, but this only resulted in ≥ 1 year of extension beyond the review date for 36 (6% of all 583 patients due for colonoscopy). The 36 patients were extended 63 years. By harmonizing the index endoscopists’ surveillance interval recommendation with the guideline at the time of the index colonoscopy, 29 additional patients could have their colonoscopy extended by ≥ 1 year. Harmonization extended colonoscopy intervals by 93 years. Retroactively applying the 2020 USMSTF polyp surveillance guidelines and harmonizing recommendations to guidelines extended the time of index colonoscopy by 153 years.

Discussion

With retroactive application of the 2020 USMSTF polyp surveillance guidelines, 6% of patients due for an upcoming colonoscopy could extend their follow-up by ≥ 1 year by extending the surveillance interval for 1 to 2 subcentimeter tubular adenomas to 7 years. An additional 5% of patients could extend their interval by harmonizing the index endoscopist’s interval recommendation with polyp surveillance guidelines at the time of the index colonoscopy. These findings are consistent with the results of 2 studies that demonstrated that about 14% of patients due for colonoscopy could have their interval extended.^6,7 The current study enhances those insights by separating the contribution of 2020 USMSTF polyp surveillance guidelines from the contribution of harmonizing surveillance intervals with guidelines for other polyp histologies. This study found that there is an opportunity to improve endoscopic capacity by harmonizing recommendations with guidelines. This complements a 2023 study showing that even when knowledgeable about guidelines, clinicians do not necessarily follow recommendations.⁸ While this and previous research have identified that 11% to 14% of patients are eligible for extension, these individuals would also have to be willing to have their polyp surveillance intervals extended for there to be a real-world impact on endoscopic capacity. A 2024 study found that only 19% to 37% of patients with 1 to 2 small tubular adenomas were willing to have polyps surveillance interval extension.⁹ This suggests the actual effect on capacity may be even lower than reported.

Limitations

The overall impact of the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity was blunted by the high prevalence of incomplete index colonoscopy records among the study population. Without data on bowel preparation quality or procedure indications, this study could not assess whether 43% of patients were eligible for surveillance interval extension. Most index colonoscopies with incomplete documentation were completed at community-care gastroenterology facilities. This high rate of incomplete documentation is likely generalizable to other VA health care systems—especially in the era of the Veterans Access, Choice, and Accountability Act of 2014, which increased veteran access to non-VA community care.¹⁰ Veterans due for colon polyp surveillance colonoscopies are more likely to have had their prior colonoscopy in community care compared with prior eras.¹¹ Furthermore, because the VHA is among the most established integrated health care systems offering primary and subspecialty care in the US, private sector health care systems may have even greater rates of care fragmentation for longitudinal CRC screening and colon polyp surveillance, as these systems have only begun to regionally integrate recently.^12,13

Another limitation is that nearly one-third of the individuals with documentation had inadequate bowel preparation for surveillance recommendations. This results in shorter surveillance follow-up colonoscopies and increases downstream demand for future colonoscopies. The low yield of extending colon polyp surveillance interval in this study emphasizes that improved efforts to obtain colonoscopy and pathology reports from community care, right-sizing the colon polyp surveillance intervals recommended by endoscopists, and improving quality of bowel preparation could have downstream health care system benefits in the future. These efforts could increase colonoscopy capacity at VA health care systems, thereby shortening colonoscopy wait times, decreasing fragmentation of care, and increasing the number of veterans who receive high-quality colonoscopies at VA health care systems.¹⁴

Conclusions

Eleven percent of patients in this study due for a colonoscopy could extend their follow-up by ≥ 1 year. About half of these extensions were directly due to the 2020 USMSTF polyp surveillance interval extension for 1 to 2 subcentimeter tubular adenomas. The rest resulted from harmonizing recommendations with guidelines at the time of the procedure. To determine whether retroactively applying polyp surveillance guidelines to follow-up interval recommendations will result in improved endoscopic capacity, health care system administrators should consider the degree of CRC screening care fragmentation in their patient population. Greater long-term gains in endoscopic capacity may be achieved by proactively supporting endoscopists in making guideline-concordant screening recommendations at the time of colonoscopy.

In 2020, the US Multi-Society Task Force (USMSTF) on Colorectal Cancer (CRC) increased the recommended colon polyp surveillance interval for 1 to 2 subcentimeter tubular adenomas from 5 to 10 years to 7 to 10 years.¹ This change was prompted by emerging research indicating that rates of CRC and advanced neoplasia among patients with a history of only 1 to 2 subcentimeter tubular adenomas are lower than initially estimated.^2,3 This extension provides an opportunity to increase endoscopy capacity and improve access to colonoscopies by retroactively applying the 2020 guidelines to surveillance interval recommendations made before their introduction. For example, based on the updated guidelines, patients previously recommended to undergo colon polyp surveillance colonoscopy 5 years after an index colonoscopy could extend their surveillance interval by 2 to 5 years. Increasing endoscopic capacity could address the growing demand for colonoscopies from new screening guidelines that reduced the age of initial CRC screening from 50 years to 45 years and the backlog of procedures due to COVID-19 restrictions.⁴

As part of a project to increase endoscopic capacity at the US Department of Veterans Affairs (VA) Pittsburgh Healthcare System (VAPHS), this study assessed the potential impact of retroactively applying the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity. These results may be informative for other VA and private-sector health care systems seeking to identify strategies to improve endoscopy capacity.

Methods

VAPHS is an integrated health care system in the Veterans Health Administration (VHA) serving 85,000 patients across 8 health care institutions in Pennsylvania, Ohio, and West Virginia. VAPHS manages colorectal screening recommendations for patients receiving medical care in the health care system regardless of whether their prior colonoscopy was performed at VAPHS or external facilities. The VA maintains a national CRC screening and surveillance electronic medical record reminder that prompts health care practitioners to order colon polyp surveillance based on interval recommendations from the index colonoscopy. This study reviewed all patients from the VAPHS panel with a reminder to undergo colonoscopy for screening for CRC or surveillance of colon polyps within 12 months from September 1, 2022.

Among patients with a reminder, 3 investigators reviewed index colonoscopy and pathology reports to identify CRC risk category, colonoscopy indication, procedural quality, and recommended repeat colonoscopy interval. Per the USMSTF guidelines, patients with incomplete colonoscopy or pathology records, high-risk indications (ie, personal history of inflammatory bowel disease, personal history of CRC, or family history of CRC), or inadequate bowel preparation (Boston Bowel Preparation Score < 6) were excluded. Additionally, patients who had CRC screening or surveillance discontinued due to age or comorbidities, had completed a subsequent follow-up colonoscopy, or were deceased at the time of review were excluded.

Retroactive Interval Reclassification

Among eligible patients, this study compared the repeat colonoscopy interval recommended by the prior endoscopist with those from the 2020 USMSTF guidelines. In cases where the interval was documented as a range of years, the lower end was considered the recommendation. Similarly, the lower end of the range from the 2020 USMSTF guidelines was used for the reclassified surveillance interval. Years extended per patient were quantified relative to September 1, 2023 (ie, 1 year after the review date). For example, if the index colonoscopy was completed on September 1, 2016, the initial surveillance recommendation was 5 years, and the reclassified recommendation was 7 years, the interval extension beyond September 1, 2023, was 0 years.

Furthermore, because index surveillance recommendations are not always guideline concordant, the years extended per patient were calculated by harmonizing the index endoscopist’s recommendations with the guidelines at the time of the index colonoscopy.⁵ For example, if the index colonoscopy was completed on September 1, 2018, and the endoscopist recommended a 5-year follow-up for a patient with average risk for CRC, adequate bowel preparation, and no colorectal polyps, that patient is eligible to extend their colonoscopy to September 1, 2028, based on guideline recommendations at the time of index endoscopy recommending that the next colonoscopy occur in 10 years. In this analysis the 2012 USMSTF guidelines were applied to all index colonoscopies completed in 2021 or earlier to allow time for adoption of the 2020 guidelines. 

This project fulfilled a facility mandate to increase capacity to conduct endoscopic procedures. Institutional review board approval was not required by VAPHS policy relating to clinical operations projects. Approval for publication of clinical operations activity was obtained from the VAPHS facility director.

Results

Within 1 year of the September 1, 2022, review date, 637 patients receiving care at VAPHS had clinical reminders for an upcoming colonoscopy. Of these, 54 (8.4%) were already up to date or were deceased at the time of review. Of the 583 eligible patients, 96% were male, the median age was 74 years, the median index colonoscopy year was 2016, and 178 (30.5%) had an average-risk CRC screening indication at the index colonoscopy (Table).

Of the 583 patients due for colonoscopy, 331 (56.7%) had both colonoscopy and pathology reports available. The majority of those with incomplete records had the index colonoscopy completed outside VAPHS. Among these patients, 222 (67.0%) had adequate bowel preparation. Of those with adequate bowel preparation, 43 were not eligible for interval extension because of high-risk conditions and 13 were not eligible because there was no index surveillance interval recommendation from the index endoscopist. Of the patients due for colonoscopy, 166 (28.4%) were potentially eligible for surveillance interval extension (Figure).  

Sixty-five (39.2%) of the 166 patients had 1 to 2 subcentimeter tubular adenomas on their index colonoscopy. Sixty-two patients were eligible for interval extension to 7 years, but this only resulted in ≥ 1 year of extension beyond the review date for 36 (6% of all 583 patients due for colonoscopy). The 36 patients were extended 63 years. By harmonizing the index endoscopists’ surveillance interval recommendation with the guideline at the time of the index colonoscopy, 29 additional patients could have their colonoscopy extended by ≥ 1 year. Harmonization extended colonoscopy intervals by 93 years. Retroactively applying the 2020 USMSTF polyp surveillance guidelines and harmonizing recommendations to guidelines extended the time of index colonoscopy by 153 years.

Discussion

With retroactive application of the 2020 USMSTF polyp surveillance guidelines, 6% of patients due for an upcoming colonoscopy could extend their follow-up by ≥ 1 year by extending the surveillance interval for 1 to 2 subcentimeter tubular adenomas to 7 years. An additional 5% of patients could extend their interval by harmonizing the index endoscopist’s interval recommendation with polyp surveillance guidelines at the time of the index colonoscopy. These findings are consistent with the results of 2 studies that demonstrated that about 14% of patients due for colonoscopy could have their interval extended.^6,7 The current study enhances those insights by separating the contribution of 2020 USMSTF polyp surveillance guidelines from the contribution of harmonizing surveillance intervals with guidelines for other polyp histologies. This study found that there is an opportunity to improve endoscopic capacity by harmonizing recommendations with guidelines. This complements a 2023 study showing that even when knowledgeable about guidelines, clinicians do not necessarily follow recommendations.⁸ While this and previous research have identified that 11% to 14% of patients are eligible for extension, these individuals would also have to be willing to have their polyp surveillance intervals extended for there to be a real-world impact on endoscopic capacity. A 2024 study found that only 19% to 37% of patients with 1 to 2 small tubular adenomas were willing to have polyps surveillance interval extension.⁹ This suggests the actual effect on capacity may be even lower than reported.

Limitations

The overall impact of the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity was blunted by the high prevalence of incomplete index colonoscopy records among the study population. Without data on bowel preparation quality or procedure indications, this study could not assess whether 43% of patients were eligible for surveillance interval extension. Most index colonoscopies with incomplete documentation were completed at community-care gastroenterology facilities. This high rate of incomplete documentation is likely generalizable to other VA health care systems—especially in the era of the Veterans Access, Choice, and Accountability Act of 2014, which increased veteran access to non-VA community care.¹⁰ Veterans due for colon polyp surveillance colonoscopies are more likely to have had their prior colonoscopy in community care compared with prior eras.¹¹ Furthermore, because the VHA is among the most established integrated health care systems offering primary and subspecialty care in the US, private sector health care systems may have even greater rates of care fragmentation for longitudinal CRC screening and colon polyp surveillance, as these systems have only begun to regionally integrate recently.^12,13

Another limitation is that nearly one-third of the individuals with documentation had inadequate bowel preparation for surveillance recommendations. This results in shorter surveillance follow-up colonoscopies and increases downstream demand for future colonoscopies. The low yield of extending colon polyp surveillance interval in this study emphasizes that improved efforts to obtain colonoscopy and pathology reports from community care, right-sizing the colon polyp surveillance intervals recommended by endoscopists, and improving quality of bowel preparation could have downstream health care system benefits in the future. These efforts could increase colonoscopy capacity at VA health care systems, thereby shortening colonoscopy wait times, decreasing fragmentation of care, and increasing the number of veterans who receive high-quality colonoscopies at VA health care systems.¹⁴

Conclusions

Eleven percent of patients in this study due for a colonoscopy could extend their follow-up by ≥ 1 year. About half of these extensions were directly due to the 2020 USMSTF polyp surveillance interval extension for 1 to 2 subcentimeter tubular adenomas. The rest resulted from harmonizing recommendations with guidelines at the time of the procedure. To determine whether retroactively applying polyp surveillance guidelines to follow-up interval recommendations will result in improved endoscopic capacity, health care system administrators should consider the degree of CRC screening care fragmentation in their patient population. Greater long-term gains in endoscopic capacity may be achieved by proactively supporting endoscopists in making guideline-concordant screening recommendations at the time of colonoscopy.

Since 1965, messenger RNA (mRNA) vaccines have been studied for cancer treatment, but it was the technological advances in vaccines during the COVID pandemic that helped accelerate research. Currently, no vaccine has been approved for tumor treatment, although many clinical studies are ongoing worldwide. According to experts consulted by Medscape’s Portuguese edition, the outlook is very promising, and these studies are expected to open doors for personalized therapies.

In cancer treatment, the vaccine would function as an immunotherapy, in which the immune system can be “trained” to act against an invader. Just as with pathogens, the platform would use parts of the tumor — which have altered proteins or are expressed at abnormal levels — to teach the body to defend itself against cancer.

Vladmir Lima, MD, PhD, clinical oncologist at A.C. Camargo Cancer Center, São Paulo, Brazil, explained that with this technology it will be possible to produce personalized vaccines, which prevents, for example, large-scale manufacturing. “In theory, these vaccines can be developed for any tumor type, but this does not mean that efficacy will be the same for all,” he said. Because cancer has specific characteristics in each individual, it is difficult to envision a single vaccine that works for all cancers.

Current evidence suggests the vaccine could be administered after chemotherapy or radiotherapy, with the goal of reducing tumor mass and increasing the effectiveness of mRNA-based treatment, according to Ana Paula Lepique, professor and researcher in tumor immunology at the Institute of Biomedical Sciences, University of São Paulo, São Paulo.

“There is also a study with pancreatic cancer patients, in which the vaccine was administered after surgery,” she explained. “It would not work, for example, to give chemotherapy or radiotherapy while the immune response is being triggered by the vaccine. This would make the vaccine ineffective, since chemotherapy and radiotherapy are toxic to lymphocytes.”

Lepique also clarified that it is possible to combine the vaccine with immunotherapy targeting immune regulatory molecules. “In this case, in addition to administering the mRNA with the antigen, a strategy is used to improve the patient’s immune response.”

 

Challenges With mRNA Vaccines

Despite being a promising technology, there are challenges, warned Lepique. mRNA molecules degrade quickly when injected into the body, which can compromise vaccine efficacy. To overcome this, researchers have developed nanoencapsulation technologies that protect the molecules and allow safe use in vaccines. “Another alternative is transferring the mRNA into dendritic cells, known as antigen-presenting cells, and then administering these cells to the patient,” she explained.

Global Research Status

According to a study published this year in Med, over 120 clinical trials are exploring mRNA vaccines to treat lung, breast, prostate, and pancreatic tumors, as well as melanoma.

Lepique noted that the countries leading this research are the US, UK, Germany, China, and Japan. “Unfortunately, the US government recently cut funding for mRNA vaccine development and testing, which will likely have significant consequences,” she said.

Lepique reported that Brazilian researchers are collaborating with international institutions to develop these vaccines. “The Brazilian government, through the Ministry of Health and the Ministry of Science, Technology, and Innovation, recently announced investments in mRNA technologies for vaccines. While not specifically targeting cancer, these investments could also benefit this field,” she clarified.

 

Leading Studies

Lepique highlighted the most advanced studies to date:

• Pancreatic cancer: A study published in Nature in February demonstrated that a personalized mRNA vaccine reduced the risk for recurrence after surgery in 16 patients, with 3 years of follow-up.
• Melanoma: A study published in The Lancet reported improved survival in melanoma patients after mRNA vaccine administration combined with the checkpoint inhibitor pembrolizumab applied after surgical tumor resection.
• Universal vaccine: A study in Nature Biomedical Engineering described the creation of a “generic” vaccine capable of activating the patient’s immune system and inducing tumor regression. Lepique explained that this vaccine acts more as an immune response modulator than a classical neoantigen-specific vaccine. “Because it is not limited to a single neoantigen, it could potentially be universal, though further testing is needed to determine efficacy across all cancer types,” she added.

Lima highlighted a 2024 study being conducted by MSD and Moderna against lung cancer, with results yet to be published. “Patients first receive immunotherapy after surgery. Once the vaccine is ready, it is added to the ongoing immunotherapy,” he explained. The global phase 3 study involves 868 patients with resected lung cancer who previously underwent chemotherapy. Participants receive the vaccine (1 mg every 3 weeks, up to nine doses) alongside pembrolizumab (400 mg every 6 weeks, up to nine cycles) over approximately 1 year.

Other mRNA vaccines remain in early-stage development. For example, in May 2024, the UK National Health Service recruited participants for a personalized colorectal cancer mRNA vaccine trial.

 

Advantages of mRNA Technology

Experts noted that mRNA-based cancer vaccines are considered safer for patients because the tumor mRNA is synthesized in the laboratory. According to Lepique, these vaccines are more specific than many other cancer therapies, and therefore carry a lower risk for serious side effects.

“Clinical studies have shown that these vaccines can generate immunological memory, meaning lymphocytes that recognize tumor antigens remain in the body and can respond to recurrence,” she explained.

It is also possible to combine multiple mRNA molecules in a single vaccine, creating a platform that targets several tumor antigens simultaneously. “Formulations can additionally include adjuvants to further enhance immune responses against tumors,” she said. However, as a personalized therapy, costs are high, and vaccine formulation requires considerable time.

Lima emphasized the customization advantage: “We can take a portion of the patient’s tumor, sequence it to identify alterations, and develop a vaccine specifically for that tumor.” He also highlighted safety data, noting that the platform has been widely used in SARS-CoV-2 vaccine development, providing confidence in large-scale application. “The potential exists to achieve more personalized, tumor-directed immunotherapy with greater scalability,” he explained.

 

Outlook and Limitations

Lima noted that although the projected efficacy is promising, definitive results are still pending.

“We have very positive expectations, but we must wait for study outcomes. Efficacy may vary across scenarios and among patients. The immune system may also respond against the vaccine itself, potentially reducing effectiveness at times,” he explained.

According to Lima, mRNA vaccines are expected to complement current treatments, enhancing outcomes without replacing conventional approaches entirely.

“It will not be a panacea. These vaccines are likely to add to and improve strategies we already use, but they will not work for all patients in every scenario,” he concluded.

Lepique highlighted the promise of combination strategies. “The outlook is positive, particularly because multiple mRNA types can be combined in a single formulation and used alongside drugs that enhance immune responses,” she explained.

Although mRNA vaccine research has been ongoing for many years, prior results have brought both progress and setbacks. “This new protocol appears more effective [and] capable of generating immunological memory and is also safe,” she noted. Still, she cautioned that cancer presents unique challenges: “The disease has multiple mechanisms to evade immune responses. Additionally, some tumors are naturally unrecognized by the immune system, the so-called ‘cold tumors.’”

This story was translated from Medscape’s Portuguese edition. A version of this article appeared on Medscape.com.

Since 1965, messenger RNA (mRNA) vaccines have been studied for cancer treatment, but it was the technological advances in vaccines during the COVID pandemic that helped accelerate research. Currently, no vaccine has been approved for tumor treatment, although many clinical studies are ongoing worldwide. According to experts consulted by Medscape’s Portuguese edition, the outlook is very promising, and these studies are expected to open doors for personalized therapies.

In cancer treatment, the vaccine would function as an immunotherapy, in which the immune system can be “trained” to act against an invader. Just as with pathogens, the platform would use parts of the tumor — which have altered proteins or are expressed at abnormal levels — to teach the body to defend itself against cancer.

Vladmir Lima, MD, PhD, clinical oncologist at A.C. Camargo Cancer Center, São Paulo, Brazil, explained that with this technology it will be possible to produce personalized vaccines, which prevents, for example, large-scale manufacturing. “In theory, these vaccines can be developed for any tumor type, but this does not mean that efficacy will be the same for all,” he said. Because cancer has specific characteristics in each individual, it is difficult to envision a single vaccine that works for all cancers.

Current evidence suggests the vaccine could be administered after chemotherapy or radiotherapy, with the goal of reducing tumor mass and increasing the effectiveness of mRNA-based treatment, according to Ana Paula Lepique, professor and researcher in tumor immunology at the Institute of Biomedical Sciences, University of São Paulo, São Paulo.

“There is also a study with pancreatic cancer patients, in which the vaccine was administered after surgery,” she explained. “It would not work, for example, to give chemotherapy or radiotherapy while the immune response is being triggered by the vaccine. This would make the vaccine ineffective, since chemotherapy and radiotherapy are toxic to lymphocytes.”

Lepique also clarified that it is possible to combine the vaccine with immunotherapy targeting immune regulatory molecules. “In this case, in addition to administering the mRNA with the antigen, a strategy is used to improve the patient’s immune response.”

 

Challenges With mRNA Vaccines

Despite being a promising technology, there are challenges, warned Lepique. mRNA molecules degrade quickly when injected into the body, which can compromise vaccine efficacy. To overcome this, researchers have developed nanoencapsulation technologies that protect the molecules and allow safe use in vaccines. “Another alternative is transferring the mRNA into dendritic cells, known as antigen-presenting cells, and then administering these cells to the patient,” she explained.

Global Research Status

According to a study published this year in Med, over 120 clinical trials are exploring mRNA vaccines to treat lung, breast, prostate, and pancreatic tumors, as well as melanoma.

Lepique noted that the countries leading this research are the US, UK, Germany, China, and Japan. “Unfortunately, the US government recently cut funding for mRNA vaccine development and testing, which will likely have significant consequences,” she said.

Lepique reported that Brazilian researchers are collaborating with international institutions to develop these vaccines. “The Brazilian government, through the Ministry of Health and the Ministry of Science, Technology, and Innovation, recently announced investments in mRNA technologies for vaccines. While not specifically targeting cancer, these investments could also benefit this field,” she clarified.

 

Leading Studies

Lepique highlighted the most advanced studies to date:

• Pancreatic cancer: A study published in Nature in February demonstrated that a personalized mRNA vaccine reduced the risk for recurrence after surgery in 16 patients, with 3 years of follow-up.
• Melanoma: A study published in The Lancet reported improved survival in melanoma patients after mRNA vaccine administration combined with the checkpoint inhibitor pembrolizumab applied after surgical tumor resection.
• Universal vaccine: A study in Nature Biomedical Engineering described the creation of a “generic” vaccine capable of activating the patient’s immune system and inducing tumor regression. Lepique explained that this vaccine acts more as an immune response modulator than a classical neoantigen-specific vaccine. “Because it is not limited to a single neoantigen, it could potentially be universal, though further testing is needed to determine efficacy across all cancer types,” she added.

Lima highlighted a 2024 study being conducted by MSD and Moderna against lung cancer, with results yet to be published. “Patients first receive immunotherapy after surgery. Once the vaccine is ready, it is added to the ongoing immunotherapy,” he explained. The global phase 3 study involves 868 patients with resected lung cancer who previously underwent chemotherapy. Participants receive the vaccine (1 mg every 3 weeks, up to nine doses) alongside pembrolizumab (400 mg every 6 weeks, up to nine cycles) over approximately 1 year.

Other mRNA vaccines remain in early-stage development. For example, in May 2024, the UK National Health Service recruited participants for a personalized colorectal cancer mRNA vaccine trial.

 

Advantages of mRNA Technology

Experts noted that mRNA-based cancer vaccines are considered safer for patients because the tumor mRNA is synthesized in the laboratory. According to Lepique, these vaccines are more specific than many other cancer therapies, and therefore carry a lower risk for serious side effects.

“Clinical studies have shown that these vaccines can generate immunological memory, meaning lymphocytes that recognize tumor antigens remain in the body and can respond to recurrence,” she explained.

It is also possible to combine multiple mRNA molecules in a single vaccine, creating a platform that targets several tumor antigens simultaneously. “Formulations can additionally include adjuvants to further enhance immune responses against tumors,” she said. However, as a personalized therapy, costs are high, and vaccine formulation requires considerable time.

Lima emphasized the customization advantage: “We can take a portion of the patient’s tumor, sequence it to identify alterations, and develop a vaccine specifically for that tumor.” He also highlighted safety data, noting that the platform has been widely used in SARS-CoV-2 vaccine development, providing confidence in large-scale application. “The potential exists to achieve more personalized, tumor-directed immunotherapy with greater scalability,” he explained.

 

Outlook and Limitations

Lima noted that although the projected efficacy is promising, definitive results are still pending.

“We have very positive expectations, but we must wait for study outcomes. Efficacy may vary across scenarios and among patients. The immune system may also respond against the vaccine itself, potentially reducing effectiveness at times,” he explained.

According to Lima, mRNA vaccines are expected to complement current treatments, enhancing outcomes without replacing conventional approaches entirely.

“It will not be a panacea. These vaccines are likely to add to and improve strategies we already use, but they will not work for all patients in every scenario,” he concluded.

Lepique highlighted the promise of combination strategies. “The outlook is positive, particularly because multiple mRNA types can be combined in a single formulation and used alongside drugs that enhance immune responses,” she explained.

Although mRNA vaccine research has been ongoing for many years, prior results have brought both progress and setbacks. “This new protocol appears more effective [and] capable of generating immunological memory and is also safe,” she noted. Still, she cautioned that cancer presents unique challenges: “The disease has multiple mechanisms to evade immune responses. Additionally, some tumors are naturally unrecognized by the immune system, the so-called ‘cold tumors.’”

This story was translated from Medscape’s Portuguese edition. A version of this article appeared on Medscape.com.

Since 1965, messenger RNA (mRNA) vaccines have been studied for cancer treatment, but it was the technological advances in vaccines during the COVID pandemic that helped accelerate research. Currently, no vaccine has been approved for tumor treatment, although many clinical studies are ongoing worldwide. According to experts consulted by Medscape’s Portuguese edition, the outlook is very promising, and these studies are expected to open doors for personalized therapies.

In cancer treatment, the vaccine would function as an immunotherapy, in which the immune system can be “trained” to act against an invader. Just as with pathogens, the platform would use parts of the tumor — which have altered proteins or are expressed at abnormal levels — to teach the body to defend itself against cancer.

Vladmir Lima, MD, PhD, clinical oncologist at A.C. Camargo Cancer Center, São Paulo, Brazil, explained that with this technology it will be possible to produce personalized vaccines, which prevents, for example, large-scale manufacturing. “In theory, these vaccines can be developed for any tumor type, but this does not mean that efficacy will be the same for all,” he said. Because cancer has specific characteristics in each individual, it is difficult to envision a single vaccine that works for all cancers.

Current evidence suggests the vaccine could be administered after chemotherapy or radiotherapy, with the goal of reducing tumor mass and increasing the effectiveness of mRNA-based treatment, according to Ana Paula Lepique, professor and researcher in tumor immunology at the Institute of Biomedical Sciences, University of São Paulo, São Paulo.

“There is also a study with pancreatic cancer patients, in which the vaccine was administered after surgery,” she explained. “It would not work, for example, to give chemotherapy or radiotherapy while the immune response is being triggered by the vaccine. This would make the vaccine ineffective, since chemotherapy and radiotherapy are toxic to lymphocytes.”

Lepique also clarified that it is possible to combine the vaccine with immunotherapy targeting immune regulatory molecules. “In this case, in addition to administering the mRNA with the antigen, a strategy is used to improve the patient’s immune response.”

 

Challenges With mRNA Vaccines

Despite being a promising technology, there are challenges, warned Lepique. mRNA molecules degrade quickly when injected into the body, which can compromise vaccine efficacy. To overcome this, researchers have developed nanoencapsulation technologies that protect the molecules and allow safe use in vaccines. “Another alternative is transferring the mRNA into dendritic cells, known as antigen-presenting cells, and then administering these cells to the patient,” she explained.

Global Research Status

According to a study published this year in Med, over 120 clinical trials are exploring mRNA vaccines to treat lung, breast, prostate, and pancreatic tumors, as well as melanoma.

Lepique noted that the countries leading this research are the US, UK, Germany, China, and Japan. “Unfortunately, the US government recently cut funding for mRNA vaccine development and testing, which will likely have significant consequences,” she said.

Lepique reported that Brazilian researchers are collaborating with international institutions to develop these vaccines. “The Brazilian government, through the Ministry of Health and the Ministry of Science, Technology, and Innovation, recently announced investments in mRNA technologies for vaccines. While not specifically targeting cancer, these investments could also benefit this field,” she clarified.

 

Leading Studies

Lepique highlighted the most advanced studies to date:

• Pancreatic cancer: A study published in Nature in February demonstrated that a personalized mRNA vaccine reduced the risk for recurrence after surgery in 16 patients, with 3 years of follow-up.
• Melanoma: A study published in The Lancet reported improved survival in melanoma patients after mRNA vaccine administration combined with the checkpoint inhibitor pembrolizumab applied after surgical tumor resection.
• Universal vaccine: A study in Nature Biomedical Engineering described the creation of a “generic” vaccine capable of activating the patient’s immune system and inducing tumor regression. Lepique explained that this vaccine acts more as an immune response modulator than a classical neoantigen-specific vaccine. “Because it is not limited to a single neoantigen, it could potentially be universal, though further testing is needed to determine efficacy across all cancer types,” she added.

Lima highlighted a 2024 study being conducted by MSD and Moderna against lung cancer, with results yet to be published. “Patients first receive immunotherapy after surgery. Once the vaccine is ready, it is added to the ongoing immunotherapy,” he explained. The global phase 3 study involves 868 patients with resected lung cancer who previously underwent chemotherapy. Participants receive the vaccine (1 mg every 3 weeks, up to nine doses) alongside pembrolizumab (400 mg every 6 weeks, up to nine cycles) over approximately 1 year.

Other mRNA vaccines remain in early-stage development. For example, in May 2024, the UK National Health Service recruited participants for a personalized colorectal cancer mRNA vaccine trial.

 

Advantages of mRNA Technology

Experts noted that mRNA-based cancer vaccines are considered safer for patients because the tumor mRNA is synthesized in the laboratory. According to Lepique, these vaccines are more specific than many other cancer therapies, and therefore carry a lower risk for serious side effects.

“Clinical studies have shown that these vaccines can generate immunological memory, meaning lymphocytes that recognize tumor antigens remain in the body and can respond to recurrence,” she explained.

It is also possible to combine multiple mRNA molecules in a single vaccine, creating a platform that targets several tumor antigens simultaneously. “Formulations can additionally include adjuvants to further enhance immune responses against tumors,” she said. However, as a personalized therapy, costs are high, and vaccine formulation requires considerable time.

Lima emphasized the customization advantage: “We can take a portion of the patient’s tumor, sequence it to identify alterations, and develop a vaccine specifically for that tumor.” He also highlighted safety data, noting that the platform has been widely used in SARS-CoV-2 vaccine development, providing confidence in large-scale application. “The potential exists to achieve more personalized, tumor-directed immunotherapy with greater scalability,” he explained.

 

Outlook and Limitations

Lima noted that although the projected efficacy is promising, definitive results are still pending.

“We have very positive expectations, but we must wait for study outcomes. Efficacy may vary across scenarios and among patients. The immune system may also respond against the vaccine itself, potentially reducing effectiveness at times,” he explained.

According to Lima, mRNA vaccines are expected to complement current treatments, enhancing outcomes without replacing conventional approaches entirely.

“It will not be a panacea. These vaccines are likely to add to and improve strategies we already use, but they will not work for all patients in every scenario,” he concluded.

Lepique highlighted the promise of combination strategies. “The outlook is positive, particularly because multiple mRNA types can be combined in a single formulation and used alongside drugs that enhance immune responses,” she explained.

Although mRNA vaccine research has been ongoing for many years, prior results have brought both progress and setbacks. “This new protocol appears more effective [and] capable of generating immunological memory and is also safe,” she noted. Still, she cautioned that cancer presents unique challenges: “The disease has multiple mechanisms to evade immune responses. Additionally, some tumors are naturally unrecognized by the immune system, the so-called ‘cold tumors.’”

This story was translated from Medscape’s Portuguese edition. A version of this article appeared on Medscape.com.

The International Agency for Research on Cancer (IARC) of the World Health Organization has classified hepatitis D virus (HDV) as carcinogenic, citing sufficient evidence and placing it alongside hepatitis B virus (HBV) and hepatitis C virus (HCV) as a cause of hepatocellular carcinoma (HCC).

Individuals with HBV-HDV coinfection face an elevated risk for liver cancer, highlighting the need for HBV vaccination, systematic screening, and early antiviral treatment to reduce the progression to cirrhosis and HCC.

About 12 million people globally have HBV-HDV coinfection, representing 5% of all chronic HBV cases. The prevalence of this condition varies regionally, with a likely underdiagnosis. True coinfection rates may reach 13%-14%, the highest in Europe’s Mediterranean region.

 

Virus Biology

HDV is an incomplete virus that infects hepatocytes and requires the envelope protein of hepatitis B surface antigen (HBsAg) for cell exit. Infection occurs only with chronic HBV infection, either as a superinfection or simultaneous acquisition. Humans are the only known natural host.

HDV coinfection worsens HBV-induced hepatic inflammation and prognosis, and up to 80% of patients develop cirrhosis. Triple infection with the HBV virus, HDV, and HIV further increases this risk, and the global prevalence is likely underestimated.

 

Cancer Risk

HDV infection significantly increases the risk for HCC compared with HBV infection alone. Many patients die from decompensated cirrhosis or HCC, reflecting the aggressive nature of coinfection.

The molecular mechanisms underlying HDV oncogenesis remain unclear. Research conducted over the past 15 years has provided insights that could inform the development of more effective treatments.

Early vaccination prophylaxis is critical for reducing the risk for HCC, despite limited options.

 

Treatment Options

Randomized controlled trials have demonstrated antiviral efficacy for:

• Pegylated interferon alpha (Peg-IFN) is approved for HBV and is active against HDV.
• Bulevirtide, a synthetic myristoylated lipopeptide entry inhibitor, is used alone or in combination with Peg-IFN.

Suppression of HBV remains central. Nucleoside and nucleotide analogs, such as entecavir, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate, significantly reduce HCC progression in treated patients compared with untreated patients at risk.

Promising therapeutics include lonafarnib, a farnesyltransferase inhibitor that blocks HDV particle formation, and nucleic acid polymers targeting the host chaperone DNAJB12 to inhibit HBV and HDV replication.

 

Guideline Updates

The 2023 addendum to the S3 guidelines covers the prophylaxis, diagnosis, and treatment of HBV, including HDV management.

IARC experts also re-evaluated the human cytomegalovirus and Merkel cell polyomavirus. Complete assessments are expected in the next edition of IARC Monographs.

 

HBV Vaccination

HBV vaccination is the only effective prophylaxis against HBV and HDV. Introduced in 1982 for high-risk groups, it reduced chronic infections, with the WHO expanding its recommendations from 1992 onward.

Infants and young children are at the highest risk of developing this disease. Acute HBV infection often resolves in adults, but infants face up to a 90% risk of developing chronic infection. Newborns of mothers with chronic or undiagnosed HBV infections are particularly vulnerable.

Routine infant immunization includes three doses, with the first dose administered within 12 hours of birth. In Germany, the Standing Committee on Vaccination (STIKO) recommends the administration of combination vaccines, with the hexavalent vaccine administered at 2, 4, and 11 months in a 2 + 1 schedule.

Timely vaccination is crucial because undetected chronic infections often lead to late-stage HCC diagnosis. Adults in high-risk groups should receive HBV vaccination counseling.

STIKO recommends vaccination for close contacts of individuals who are HBsAg-positive, individuals with high-risk sexual contacts, immunocompromised persons, and those with preexisting conditions that increase the risk for severe HBV infection.

Since 2021, insured adults aged 35 years or older in Germany have undergone one-time HBV and HCV screening. HDV testing is recommended for all HBsAg-positive patients. Current frameworks may miss cases, and additional or personalized screening could improve the detection of previously unrecognized infections.

This story was translated from Univadis Germany.

A version of this article appeared on Medscape.com.

The International Agency for Research on Cancer (IARC) of the World Health Organization has classified hepatitis D virus (HDV) as carcinogenic, citing sufficient evidence and placing it alongside hepatitis B virus (HBV) and hepatitis C virus (HCV) as a cause of hepatocellular carcinoma (HCC).

Individuals with HBV-HDV coinfection face an elevated risk for liver cancer, highlighting the need for HBV vaccination, systematic screening, and early antiviral treatment to reduce the progression to cirrhosis and HCC.

About 12 million people globally have HBV-HDV coinfection, representing 5% of all chronic HBV cases. The prevalence of this condition varies regionally, with a likely underdiagnosis. True coinfection rates may reach 13%-14%, the highest in Europe’s Mediterranean region.

 

Virus Biology

HDV is an incomplete virus that infects hepatocytes and requires the envelope protein of hepatitis B surface antigen (HBsAg) for cell exit. Infection occurs only with chronic HBV infection, either as a superinfection or simultaneous acquisition. Humans are the only known natural host.

HDV coinfection worsens HBV-induced hepatic inflammation and prognosis, and up to 80% of patients develop cirrhosis. Triple infection with the HBV virus, HDV, and HIV further increases this risk, and the global prevalence is likely underestimated.

 

Cancer Risk

HDV infection significantly increases the risk for HCC compared with HBV infection alone. Many patients die from decompensated cirrhosis or HCC, reflecting the aggressive nature of coinfection.

The molecular mechanisms underlying HDV oncogenesis remain unclear. Research conducted over the past 15 years has provided insights that could inform the development of more effective treatments.

Early vaccination prophylaxis is critical for reducing the risk for HCC, despite limited options.

 

Treatment Options

Randomized controlled trials have demonstrated antiviral efficacy for:

• Pegylated interferon alpha (Peg-IFN) is approved for HBV and is active against HDV.
• Bulevirtide, a synthetic myristoylated lipopeptide entry inhibitor, is used alone or in combination with Peg-IFN.

Suppression of HBV remains central. Nucleoside and nucleotide analogs, such as entecavir, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate, significantly reduce HCC progression in treated patients compared with untreated patients at risk.

Promising therapeutics include lonafarnib, a farnesyltransferase inhibitor that blocks HDV particle formation, and nucleic acid polymers targeting the host chaperone DNAJB12 to inhibit HBV and HDV replication.

 

Guideline Updates

The 2023 addendum to the S3 guidelines covers the prophylaxis, diagnosis, and treatment of HBV, including HDV management.

IARC experts also re-evaluated the human cytomegalovirus and Merkel cell polyomavirus. Complete assessments are expected in the next edition of IARC Monographs.

 

HBV Vaccination

HBV vaccination is the only effective prophylaxis against HBV and HDV. Introduced in 1982 for high-risk groups, it reduced chronic infections, with the WHO expanding its recommendations from 1992 onward.

Infants and young children are at the highest risk of developing this disease. Acute HBV infection often resolves in adults, but infants face up to a 90% risk of developing chronic infection. Newborns of mothers with chronic or undiagnosed HBV infections are particularly vulnerable.

Routine infant immunization includes three doses, with the first dose administered within 12 hours of birth. In Germany, the Standing Committee on Vaccination (STIKO) recommends the administration of combination vaccines, with the hexavalent vaccine administered at 2, 4, and 11 months in a 2 + 1 schedule.

Timely vaccination is crucial because undetected chronic infections often lead to late-stage HCC diagnosis. Adults in high-risk groups should receive HBV vaccination counseling.

STIKO recommends vaccination for close contacts of individuals who are HBsAg-positive, individuals with high-risk sexual contacts, immunocompromised persons, and those with preexisting conditions that increase the risk for severe HBV infection.

Since 2021, insured adults aged 35 years or older in Germany have undergone one-time HBV and HCV screening. HDV testing is recommended for all HBsAg-positive patients. Current frameworks may miss cases, and additional or personalized screening could improve the detection of previously unrecognized infections.

This story was translated from Univadis Germany.

A version of this article appeared on Medscape.com.

The International Agency for Research on Cancer (IARC) of the World Health Organization has classified hepatitis D virus (HDV) as carcinogenic, citing sufficient evidence and placing it alongside hepatitis B virus (HBV) and hepatitis C virus (HCV) as a cause of hepatocellular carcinoma (HCC).

Individuals with HBV-HDV coinfection face an elevated risk for liver cancer, highlighting the need for HBV vaccination, systematic screening, and early antiviral treatment to reduce the progression to cirrhosis and HCC.

About 12 million people globally have HBV-HDV coinfection, representing 5% of all chronic HBV cases. The prevalence of this condition varies regionally, with a likely underdiagnosis. True coinfection rates may reach 13%-14%, the highest in Europe’s Mediterranean region.

 

Virus Biology

HDV is an incomplete virus that infects hepatocytes and requires the envelope protein of hepatitis B surface antigen (HBsAg) for cell exit. Infection occurs only with chronic HBV infection, either as a superinfection or simultaneous acquisition. Humans are the only known natural host.

HDV coinfection worsens HBV-induced hepatic inflammation and prognosis, and up to 80% of patients develop cirrhosis. Triple infection with the HBV virus, HDV, and HIV further increases this risk, and the global prevalence is likely underestimated.

 

Cancer Risk

HDV infection significantly increases the risk for HCC compared with HBV infection alone. Many patients die from decompensated cirrhosis or HCC, reflecting the aggressive nature of coinfection.

The molecular mechanisms underlying HDV oncogenesis remain unclear. Research conducted over the past 15 years has provided insights that could inform the development of more effective treatments.

Early vaccination prophylaxis is critical for reducing the risk for HCC, despite limited options.

 

Treatment Options

Randomized controlled trials have demonstrated antiviral efficacy for:

• Pegylated interferon alpha (Peg-IFN) is approved for HBV and is active against HDV.
• Bulevirtide, a synthetic myristoylated lipopeptide entry inhibitor, is used alone or in combination with Peg-IFN.

Suppression of HBV remains central. Nucleoside and nucleotide analogs, such as entecavir, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate, significantly reduce HCC progression in treated patients compared with untreated patients at risk.

Promising therapeutics include lonafarnib, a farnesyltransferase inhibitor that blocks HDV particle formation, and nucleic acid polymers targeting the host chaperone DNAJB12 to inhibit HBV and HDV replication.

 

Guideline Updates

The 2023 addendum to the S3 guidelines covers the prophylaxis, diagnosis, and treatment of HBV, including HDV management.

IARC experts also re-evaluated the human cytomegalovirus and Merkel cell polyomavirus. Complete assessments are expected in the next edition of IARC Monographs.

 

HBV Vaccination

HBV vaccination is the only effective prophylaxis against HBV and HDV. Introduced in 1982 for high-risk groups, it reduced chronic infections, with the WHO expanding its recommendations from 1992 onward.

Infants and young children are at the highest risk of developing this disease. Acute HBV infection often resolves in adults, but infants face up to a 90% risk of developing chronic infection. Newborns of mothers with chronic or undiagnosed HBV infections are particularly vulnerable.

Routine infant immunization includes three doses, with the first dose administered within 12 hours of birth. In Germany, the Standing Committee on Vaccination (STIKO) recommends the administration of combination vaccines, with the hexavalent vaccine administered at 2, 4, and 11 months in a 2 + 1 schedule.

Timely vaccination is crucial because undetected chronic infections often lead to late-stage HCC diagnosis. Adults in high-risk groups should receive HBV vaccination counseling.

STIKO recommends vaccination for close contacts of individuals who are HBsAg-positive, individuals with high-risk sexual contacts, immunocompromised persons, and those with preexisting conditions that increase the risk for severe HBV infection.

Since 2021, insured adults aged 35 years or older in Germany have undergone one-time HBV and HCV screening. HDV testing is recommended for all HBsAg-positive patients. Current frameworks may miss cases, and additional or personalized screening could improve the detection of previously unrecognized infections.

This story was translated from Univadis Germany.

A version of this article appeared on Medscape.com.

PHOENIX – Three decades after he initiated the transformation of the Veterans Health Administration (VHA) into a model research and clinical health care system, former US Department of Veterans Affairs (VA) Under Secretary of Health Kenneth W. Kizer, MD, MPH, urged cancer specialists to embrace this challenging moment as an opportunity for bold innovation.

At the annual meeting of the Association of VA Hematology/Oncology (AVAHO), Kizer acknowledged that the VA faces an “uncertain and turbulent time” in areas such as funding, staffing, community care implementation, and the rollout of a new electronic health record system. 

He also noted the grim rise of global instability, economic turmoil, climate change, infectious diseases, political violence, and mass shootings.

“This can be stressful. It can create negative energy. But this uncertainty can also be liberating, and it can prompt positive energy and innovation, depending on choices that we make,” said Kizer, who also has served as California’s top health official prior to leading the VHA from 1994 to 1999.

From “Bloated Bureaucracy’ to High-Quality Health Care System

Kizer has been credited with revitalizing VHA care through a greater commitment to quality, and harkened to his work with the VA as an example of how bold goals can lead to bold innovation. 

“What were the perceptions of VA health care in 1994? Well, they weren’t very good, frankly,” Kizer recalled. He described the VA as having a reputation at that time as “highly dysfunctional” with “a very bloated and entrenched bureaucracy.” As for quality of care, it “wasn’t viewed as very good.”

The system’s problems were so severe that patients would park motorhomes in VA medical center parking lots as they waited for care. “While they might have an appointment for one day, they may not be seen for 3 or 4 or 5 days. So they would stay in their motorhome until they finally got into their clinic appointment,” Kizer said.

Overall, “the public viewed the VA as this bleak backwater of incompetence and difference and inefficiency, and there were very strong calls to privatize the VA,” Kizer said. 

Kizer asked colleagues about what he should do after he was asked to take the under secretary job. “With one exception, they all said, don’t go near it. Don’t touch it. Walk away. That it’s impossible to change the organization.

“I looked at the VA and I saw an opportunity. When I told [members of the President Bill] Clinton [Administration] yes, my bold aim was that I would like to pursue this was to make VHA a model of excellent health care, an exemplary health care system. Most everyone else thought that I was totally delusional, but sometimes it’s good to be delusional.”

Revolutionary Changes Despite Opposition

Kizer sought reforms in 5 major strategic objectives, all without explicit congressional approval: creating an accountable management structure, decentralizing decision-making, integrating care, implementing universal primary care, and pursuing eligibility reform to create the current 8-tier VA system.

One major innovation was the implementation of community-based outpatient clinics (CBOCs): “Those were strongly opposed initially,” Kizer said. “Everyone, the veteran community in particular, had been led to believe that the only good care was in the hospital.”

The resistance was substantial. “There was a lot of opposition when we said we’re going to move out into the community where you live to make [care] easier to access,” Kizer said.

To make things more difficult, Congress wouldn’t fund the project: “For the first 3 years, every CBOC had to be funded by redirected savings from other things that we could do within the system,” he said. “All of this was through redirected savings and finding ways to save and reinvest.”

Innovation From the Ground Up

Kizer emphasized that many breakthrough innovations came from frontline staff rather than executive mandates. He cited the example of Barcode Medication Administration, which originated from a nurse in Topeka, Kan.

The nurse saw a barcode scanner put to work at a rental car company where it was used to check cars in and out. She wondered, “Why can’t we do this with medications when they’re given on the floor? We followed up on it, pursued those things, tested it out, it worked.”

The results were dramatic. “I was told at a meeting that they had achieved close to 80% reduction in medication errors,” Kizer said. After verifying the results personally, he “authorized $20 million, and we moved forward with it systemwide.”

This experience reinforced his belief in harvesting ideas from staff at all levels. 

Innovation remains part of the VA’s culture “despite what some people would have you believe,” Kizer said. Recently, the VA has made major advances in areas such as patient transportation and the climate crisis, he said. 

Inside the Recipe for Innovation

Boldness, persistence, adaptability, and tolerance for risk are necessary ingredients for high-risk goals, Kizer said. Ambition is also part of the picture. 

He highlighted examples such as the Apollo moon landing, the first sub-4-minute mile, and the first swim across the English Channel by a woman.

In medicine, Kizer pointed to a national patient safety campaign that saved an estimated 122,000 lives. He also mentioned recent progress in organ transplantation such as recommendations from the National Academies of Sciences, Engineering, and Medicine to establish national performance goals and the Organ Procurement and Transplantation Network’s target of 60,000 deceased donor transplants by 2026.

Bold doesn’t mean being reckless or careless, Kizer said. “But it does require innovation. And it does require that you try some new things, some of which aren’t going to work out.”

The key mindset, he explained, is to “embrace the unknown” because “you often really don’t know how you will accomplish the aim when you start. But you’ll figure it out as you go.”

Kizer highlighted 2 opposing strategies to handling challenging times. 

According to him, the “negative energy” approach focuses on frustrations, limitations, and asking “Why is this happening to me?” 

In contrast, a “positive energy” approach expects problems, focuses on available resources and capabilities, and asks, “What are the opportunities that these changes are creating for me?”

Kizer made it crystal clear which option he prefers.

Dr. Kizer disclosed that his comments represent his opinions only, and he noted his ongoing connections to the VA.

PHOENIX – Three decades after he initiated the transformation of the Veterans Health Administration (VHA) into a model research and clinical health care system, former US Department of Veterans Affairs (VA) Under Secretary of Health Kenneth W. Kizer, MD, MPH, urged cancer specialists to embrace this challenging moment as an opportunity for bold innovation.

At the annual meeting of the Association of VA Hematology/Oncology (AVAHO), Kizer acknowledged that the VA faces an “uncertain and turbulent time” in areas such as funding, staffing, community care implementation, and the rollout of a new electronic health record system. 

He also noted the grim rise of global instability, economic turmoil, climate change, infectious diseases, political violence, and mass shootings.

“This can be stressful. It can create negative energy. But this uncertainty can also be liberating, and it can prompt positive energy and innovation, depending on choices that we make,” said Kizer, who also has served as California’s top health official prior to leading the VHA from 1994 to 1999.

From “Bloated Bureaucracy’ to High-Quality Health Care System

Kizer has been credited with revitalizing VHA care through a greater commitment to quality, and harkened to his work with the VA as an example of how bold goals can lead to bold innovation. 

“What were the perceptions of VA health care in 1994? Well, they weren’t very good, frankly,” Kizer recalled. He described the VA as having a reputation at that time as “highly dysfunctional” with “a very bloated and entrenched bureaucracy.” As for quality of care, it “wasn’t viewed as very good.”

The system’s problems were so severe that patients would park motorhomes in VA medical center parking lots as they waited for care. “While they might have an appointment for one day, they may not be seen for 3 or 4 or 5 days. So they would stay in their motorhome until they finally got into their clinic appointment,” Kizer said.

Overall, “the public viewed the VA as this bleak backwater of incompetence and difference and inefficiency, and there were very strong calls to privatize the VA,” Kizer said. 

Kizer asked colleagues about what he should do after he was asked to take the under secretary job. “With one exception, they all said, don’t go near it. Don’t touch it. Walk away. That it’s impossible to change the organization.

“I looked at the VA and I saw an opportunity. When I told [members of the President Bill] Clinton [Administration] yes, my bold aim was that I would like to pursue this was to make VHA a model of excellent health care, an exemplary health care system. Most everyone else thought that I was totally delusional, but sometimes it’s good to be delusional.”

Revolutionary Changes Despite Opposition

Kizer sought reforms in 5 major strategic objectives, all without explicit congressional approval: creating an accountable management structure, decentralizing decision-making, integrating care, implementing universal primary care, and pursuing eligibility reform to create the current 8-tier VA system.

One major innovation was the implementation of community-based outpatient clinics (CBOCs): “Those were strongly opposed initially,” Kizer said. “Everyone, the veteran community in particular, had been led to believe that the only good care was in the hospital.”

The resistance was substantial. “There was a lot of opposition when we said we’re going to move out into the community where you live to make [care] easier to access,” Kizer said.

To make things more difficult, Congress wouldn’t fund the project: “For the first 3 years, every CBOC had to be funded by redirected savings from other things that we could do within the system,” he said. “All of this was through redirected savings and finding ways to save and reinvest.”

Innovation From the Ground Up

Kizer emphasized that many breakthrough innovations came from frontline staff rather than executive mandates. He cited the example of Barcode Medication Administration, which originated from a nurse in Topeka, Kan.

The nurse saw a barcode scanner put to work at a rental car company where it was used to check cars in and out. She wondered, “Why can’t we do this with medications when they’re given on the floor? We followed up on it, pursued those things, tested it out, it worked.”

The results were dramatic. “I was told at a meeting that they had achieved close to 80% reduction in medication errors,” Kizer said. After verifying the results personally, he “authorized $20 million, and we moved forward with it systemwide.”

This experience reinforced his belief in harvesting ideas from staff at all levels. 

Innovation remains part of the VA’s culture “despite what some people would have you believe,” Kizer said. Recently, the VA has made major advances in areas such as patient transportation and the climate crisis, he said. 

Inside the Recipe for Innovation

Boldness, persistence, adaptability, and tolerance for risk are necessary ingredients for high-risk goals, Kizer said. Ambition is also part of the picture. 

He highlighted examples such as the Apollo moon landing, the first sub-4-minute mile, and the first swim across the English Channel by a woman.

In medicine, Kizer pointed to a national patient safety campaign that saved an estimated 122,000 lives. He also mentioned recent progress in organ transplantation such as recommendations from the National Academies of Sciences, Engineering, and Medicine to establish national performance goals and the Organ Procurement and Transplantation Network’s target of 60,000 deceased donor transplants by 2026.

Bold doesn’t mean being reckless or careless, Kizer said. “But it does require innovation. And it does require that you try some new things, some of which aren’t going to work out.”

The key mindset, he explained, is to “embrace the unknown” because “you often really don’t know how you will accomplish the aim when you start. But you’ll figure it out as you go.”

Kizer highlighted 2 opposing strategies to handling challenging times. 

According to him, the “negative energy” approach focuses on frustrations, limitations, and asking “Why is this happening to me?” 

In contrast, a “positive energy” approach expects problems, focuses on available resources and capabilities, and asks, “What are the opportunities that these changes are creating for me?”

Kizer made it crystal clear which option he prefers.

Dr. Kizer disclosed that his comments represent his opinions only, and he noted his ongoing connections to the VA.

PHOENIX – Three decades after he initiated the transformation of the Veterans Health Administration (VHA) into a model research and clinical health care system, former US Department of Veterans Affairs (VA) Under Secretary of Health Kenneth W. Kizer, MD, MPH, urged cancer specialists to embrace this challenging moment as an opportunity for bold innovation.

At the annual meeting of the Association of VA Hematology/Oncology (AVAHO), Kizer acknowledged that the VA faces an “uncertain and turbulent time” in areas such as funding, staffing, community care implementation, and the rollout of a new electronic health record system. 

He also noted the grim rise of global instability, economic turmoil, climate change, infectious diseases, political violence, and mass shootings.

“This can be stressful. It can create negative energy. But this uncertainty can also be liberating, and it can prompt positive energy and innovation, depending on choices that we make,” said Kizer, who also has served as California’s top health official prior to leading the VHA from 1994 to 1999.

From “Bloated Bureaucracy’ to High-Quality Health Care System

Kizer has been credited with revitalizing VHA care through a greater commitment to quality, and harkened to his work with the VA as an example of how bold goals can lead to bold innovation. 

“What were the perceptions of VA health care in 1994? Well, they weren’t very good, frankly,” Kizer recalled. He described the VA as having a reputation at that time as “highly dysfunctional” with “a very bloated and entrenched bureaucracy.” As for quality of care, it “wasn’t viewed as very good.”

The system’s problems were so severe that patients would park motorhomes in VA medical center parking lots as they waited for care. “While they might have an appointment for one day, they may not be seen for 3 or 4 or 5 days. So they would stay in their motorhome until they finally got into their clinic appointment,” Kizer said.

Overall, “the public viewed the VA as this bleak backwater of incompetence and difference and inefficiency, and there were very strong calls to privatize the VA,” Kizer said. 

Kizer asked colleagues about what he should do after he was asked to take the under secretary job. “With one exception, they all said, don’t go near it. Don’t touch it. Walk away. That it’s impossible to change the organization.

“I looked at the VA and I saw an opportunity. When I told [members of the President Bill] Clinton [Administration] yes, my bold aim was that I would like to pursue this was to make VHA a model of excellent health care, an exemplary health care system. Most everyone else thought that I was totally delusional, but sometimes it’s good to be delusional.”

Revolutionary Changes Despite Opposition

Kizer sought reforms in 5 major strategic objectives, all without explicit congressional approval: creating an accountable management structure, decentralizing decision-making, integrating care, implementing universal primary care, and pursuing eligibility reform to create the current 8-tier VA system.

One major innovation was the implementation of community-based outpatient clinics (CBOCs): “Those were strongly opposed initially,” Kizer said. “Everyone, the veteran community in particular, had been led to believe that the only good care was in the hospital.”

The resistance was substantial. “There was a lot of opposition when we said we’re going to move out into the community where you live to make [care] easier to access,” Kizer said.

To make things more difficult, Congress wouldn’t fund the project: “For the first 3 years, every CBOC had to be funded by redirected savings from other things that we could do within the system,” he said. “All of this was through redirected savings and finding ways to save and reinvest.”

Innovation From the Ground Up

Kizer emphasized that many breakthrough innovations came from frontline staff rather than executive mandates. He cited the example of Barcode Medication Administration, which originated from a nurse in Topeka, Kan.

The nurse saw a barcode scanner put to work at a rental car company where it was used to check cars in and out. She wondered, “Why can’t we do this with medications when they’re given on the floor? We followed up on it, pursued those things, tested it out, it worked.”

The results were dramatic. “I was told at a meeting that they had achieved close to 80% reduction in medication errors,” Kizer said. After verifying the results personally, he “authorized $20 million, and we moved forward with it systemwide.”

This experience reinforced his belief in harvesting ideas from staff at all levels. 

Innovation remains part of the VA’s culture “despite what some people would have you believe,” Kizer said. Recently, the VA has made major advances in areas such as patient transportation and the climate crisis, he said. 

Inside the Recipe for Innovation

Boldness, persistence, adaptability, and tolerance for risk are necessary ingredients for high-risk goals, Kizer said. Ambition is also part of the picture. 

He highlighted examples such as the Apollo moon landing, the first sub-4-minute mile, and the first swim across the English Channel by a woman.

In medicine, Kizer pointed to a national patient safety campaign that saved an estimated 122,000 lives. He also mentioned recent progress in organ transplantation such as recommendations from the National Academies of Sciences, Engineering, and Medicine to establish national performance goals and the Organ Procurement and Transplantation Network’s target of 60,000 deceased donor transplants by 2026.

Bold doesn’t mean being reckless or careless, Kizer said. “But it does require innovation. And it does require that you try some new things, some of which aren’t going to work out.”

The key mindset, he explained, is to “embrace the unknown” because “you often really don’t know how you will accomplish the aim when you start. But you’ll figure it out as you go.”

Kizer highlighted 2 opposing strategies to handling challenging times. 

According to him, the “negative energy” approach focuses on frustrations, limitations, and asking “Why is this happening to me?” 

In contrast, a “positive energy” approach expects problems, focuses on available resources and capabilities, and asks, “What are the opportunities that these changes are creating for me?”

Kizer made it crystal clear which option he prefers.

Dr. Kizer disclosed that his comments represent his opinions only, and he noted his ongoing connections to the VA.