The practice of oncology and the science driving it have undergone substantial change in recent years, so it was particularly exciting when this year’s Nobel Prize for Physiology or Medicine was awarded to James Allison and Tasuko Honjo for their discovery that the body’s immune system can be harnessed to fight cancer. The advent of immunotherapy has expanded our therapeutic options, especially for patients whose previous treatments have failed, and in some patients, improvement in overall survival and safety profiles have been encouraging. But we still have a way to go with immunotherapies: not all patients respond to them and they are a costly therapeutic option. In addition, while chemotherapy supresses the immune system, immune-checkpoint inhibitors can hyperactivate it, and patients can experience serious immune-related adverse events that can result in life-threatening toxicities. Among the many things we grapple with in our daily practice is pairing these new and thrilling findings with our patients on a case-by-case basis to ensure the best-possible outcomes at every level – clinical, psychosocial, financial.

In recent years, we have seen an uptick in the number of FDA approvals, and as our therapeutic options have expanded, we have been able to refine and microtarget our treatment approaches, with encouraging clinical and quality-of-life outcomes. Our approach to practice has changed as well – our care is more patient focused, and we work more as part of a team, rather than individually, to ensure that our patients’ clinical and supportive needs are met. We hope our content reflects these shifts. For example, on page e188, Ibrahimi and colleagues looked at the time from admission to treatment initiation (TAT) in patients who were newly diagnosed with acute myeloid leukemia to see if it had an impact on overall survival (OS) and event-free survival. They obtained retrospective data over 5 years, focusing on patients with a TAT of 0-4 days and those with a TAT of >4 days, and found that the median OS in the 0-4 days group was almost double that of the <4 days group (1.3 years and 0.57 years, respectively). Median event-free survival for the groups was 1.21 years and 0.57 years, respectively. Moreover, that association remained significant in a multivariate analysis adjusting for age, white blood cell count, molecular risk group, and undergoing allogeneic stem cell transplant.
 

Marriage and survival

Does marital status have a prognostic bearing on outcomes in patients with cancer? Vyfhuis and colleagues addressed that question in their study of patients with stage III non–small-cell lung cancer (NSCLC) who had been treated uniformly with curative intent (p. e194). Specifically, they looked at OS and freedom from recurrence and they adjusted for patient-, disease-, and treatment-specific factors, as well as the interaction with racial, nutritional, and immunologic status.

In all, 52% of patients in the study were married, and were more likely to self-identify as white; live in areas with a higher household median income; undergo surgery; and have insurance, an ECOG of 0, and higher pretreatment albumin. The authors report that on multivariate analysis, marital status remained an independent predictor of survival and was associated with a 40% decreased risk of death, further stratifying outcomes beyond gender and stage grouping. Freedom from recurrence was comparable between the married and not-married patients. These findings suggest that in a cancer such as NSCLC, for which survival is modest despite therapeutic advances and which is associated with considerable treatment-related toxicities, marital status might be an independent predictor for survival. The authors suggest that marriage is likely a surrogate for better psychosocial support, and that the survival improvements might justify investment in supportive care interventional strategies to help advance overall outcomes.

Cancer in children and AYAs

Two articles in this issue examine cancers in pediatric patients and in adolescents and young adults (AYAs), and by doing so, demonstrate the importance of having evidence-based research findings to help us refine and deliver better-quality, patient-focused care. On page e217, Sharon Worcester documents the growing efforts by researchers and clinicians to understand and address the disparities in survival outcomes between AYAs with cancer and their pediatric and adult counterparts.

It has been known for a while that some cancers are more common among AYAs compared with the other 2 populations, and others are less common. More recent findings suggest that the biology and molecular make-up of AYA cancers might also be different and therefore necessitate different therapeutic protocols, and that the social and psychological needs unique to this population also require specifically tailored supportive care. What about treatment setting for AYAs with cancer – would outcomes be better in a pediatric or adult care center? There is evidence that the pediatric setting might have some advantage, but a recent study from Canada suggests that the cost of care in that setting might be higher. Despite these encouraging findings, there are very few trials designed specifically for the AYA cancer population, and the “pediatric-versus-adult” question also applies to AYA participation in trials. Worcester’s comprehensive article weaves together these issues and offers insights and useful explanations from a number of experts who study or care for AYAs with cancers.

Pediatric cancers are rare, representing just 1% of all new cancers diagnosed annually in the United States, but they are the second leading cause of death in children aged 1 to 14 years and therefore warrant attention, writes Jane de Lartigue in an article on page e210. She echoes Worcester’s point that better understanding of cancers in this younger population has brought to light their unique molecular drivers and challenged the assumption that drugs developed for adults can be used in children and young adults. Dr de Lartigue drills down into the science behind the unique biology and molecular aberrations in pediatric cancers and provides a useful list of ongoing clinical trials of targeted therapies in this population. She notes that because of their rarity, pediatric cancers are difficult to study and adequate enrollment in trials is challenging, although that is changing with researchers’ greater awareness of the uniqueness of these cancers and need for age-specific trials.

Also included in this issue are Community Translation articles on the approval of an immunotherapy combination – nivolumab plus ipilimumab – for the treatment of advanced RCC (p. e182), and for venetoclax as a therapy for patients with chronic lymphocytic leukemia, regardless of genotype (p. e185); and 2 Case Reports, one describing a diagnostic dilemma relating to a patient eventually diagnosed with primary renal synovial sarcoma (p. e202), and another detailing prolonged survival in a patient with adenocarcinoma of unknown primary who was treated with chemoradiotherapy (p. e206).

The practice of oncology and the science driving it have undergone substantial change in recent years, so it was particularly exciting when this year’s Nobel Prize for Physiology or Medicine was awarded to James Allison and Tasuko Honjo for their discovery that the body’s immune system can be harnessed to fight cancer. The advent of immunotherapy has expanded our therapeutic options, especially for patients whose previous treatments have failed, and in some patients, improvement in overall survival and safety profiles have been encouraging. But we still have a way to go with immunotherapies: not all patients respond to them and they are a costly therapeutic option. In addition, while chemotherapy supresses the immune system, immune-checkpoint inhibitors can hyperactivate it, and patients can experience serious immune-related adverse events that can result in life-threatening toxicities. Among the many things we grapple with in our daily practice is pairing these new and thrilling findings with our patients on a case-by-case basis to ensure the best-possible outcomes at every level – clinical, psychosocial, financial.

In recent years, we have seen an uptick in the number of FDA approvals, and as our therapeutic options have expanded, we have been able to refine and microtarget our treatment approaches, with encouraging clinical and quality-of-life outcomes. Our approach to practice has changed as well – our care is more patient focused, and we work more as part of a team, rather than individually, to ensure that our patients’ clinical and supportive needs are met. We hope our content reflects these shifts. For example, on page e188, Ibrahimi and colleagues looked at the time from admission to treatment initiation (TAT) in patients who were newly diagnosed with acute myeloid leukemia to see if it had an impact on overall survival (OS) and event-free survival. They obtained retrospective data over 5 years, focusing on patients with a TAT of 0-4 days and those with a TAT of >4 days, and found that the median OS in the 0-4 days group was almost double that of the <4 days group (1.3 years and 0.57 years, respectively). Median event-free survival for the groups was 1.21 years and 0.57 years, respectively. Moreover, that association remained significant in a multivariate analysis adjusting for age, white blood cell count, molecular risk group, and undergoing allogeneic stem cell transplant.
 

Marriage and survival

Does marital status have a prognostic bearing on outcomes in patients with cancer? Vyfhuis and colleagues addressed that question in their study of patients with stage III non–small-cell lung cancer (NSCLC) who had been treated uniformly with curative intent (p. e194). Specifically, they looked at OS and freedom from recurrence and they adjusted for patient-, disease-, and treatment-specific factors, as well as the interaction with racial, nutritional, and immunologic status.

In all, 52% of patients in the study were married, and were more likely to self-identify as white; live in areas with a higher household median income; undergo surgery; and have insurance, an ECOG of 0, and higher pretreatment albumin. The authors report that on multivariate analysis, marital status remained an independent predictor of survival and was associated with a 40% decreased risk of death, further stratifying outcomes beyond gender and stage grouping. Freedom from recurrence was comparable between the married and not-married patients. These findings suggest that in a cancer such as NSCLC, for which survival is modest despite therapeutic advances and which is associated with considerable treatment-related toxicities, marital status might be an independent predictor for survival. The authors suggest that marriage is likely a surrogate for better psychosocial support, and that the survival improvements might justify investment in supportive care interventional strategies to help advance overall outcomes.

Cancer in children and AYAs

Two articles in this issue examine cancers in pediatric patients and in adolescents and young adults (AYAs), and by doing so, demonstrate the importance of having evidence-based research findings to help us refine and deliver better-quality, patient-focused care. On page e217, Sharon Worcester documents the growing efforts by researchers and clinicians to understand and address the disparities in survival outcomes between AYAs with cancer and their pediatric and adult counterparts.

It has been known for a while that some cancers are more common among AYAs compared with the other 2 populations, and others are less common. More recent findings suggest that the biology and molecular make-up of AYA cancers might also be different and therefore necessitate different therapeutic protocols, and that the social and psychological needs unique to this population also require specifically tailored supportive care. What about treatment setting for AYAs with cancer – would outcomes be better in a pediatric or adult care center? There is evidence that the pediatric setting might have some advantage, but a recent study from Canada suggests that the cost of care in that setting might be higher. Despite these encouraging findings, there are very few trials designed specifically for the AYA cancer population, and the “pediatric-versus-adult” question also applies to AYA participation in trials. Worcester’s comprehensive article weaves together these issues and offers insights and useful explanations from a number of experts who study or care for AYAs with cancers.

Pediatric cancers are rare, representing just 1% of all new cancers diagnosed annually in the United States, but they are the second leading cause of death in children aged 1 to 14 years and therefore warrant attention, writes Jane de Lartigue in an article on page e210. She echoes Worcester’s point that better understanding of cancers in this younger population has brought to light their unique molecular drivers and challenged the assumption that drugs developed for adults can be used in children and young adults. Dr de Lartigue drills down into the science behind the unique biology and molecular aberrations in pediatric cancers and provides a useful list of ongoing clinical trials of targeted therapies in this population. She notes that because of their rarity, pediatric cancers are difficult to study and adequate enrollment in trials is challenging, although that is changing with researchers’ greater awareness of the uniqueness of these cancers and need for age-specific trials.

Also included in this issue are Community Translation articles on the approval of an immunotherapy combination – nivolumab plus ipilimumab – for the treatment of advanced RCC (p. e182), and for venetoclax as a therapy for patients with chronic lymphocytic leukemia, regardless of genotype (p. e185); and 2 Case Reports, one describing a diagnostic dilemma relating to a patient eventually diagnosed with primary renal synovial sarcoma (p. e202), and another detailing prolonged survival in a patient with adenocarcinoma of unknown primary who was treated with chemoradiotherapy (p. e206).

The practice of oncology and the science driving it have undergone substantial change in recent years, so it was particularly exciting when this year’s Nobel Prize for Physiology or Medicine was awarded to James Allison and Tasuko Honjo for their discovery that the body’s immune system can be harnessed to fight cancer. The advent of immunotherapy has expanded our therapeutic options, especially for patients whose previous treatments have failed, and in some patients, improvement in overall survival and safety profiles have been encouraging. But we still have a way to go with immunotherapies: not all patients respond to them and they are a costly therapeutic option. In addition, while chemotherapy supresses the immune system, immune-checkpoint inhibitors can hyperactivate it, and patients can experience serious immune-related adverse events that can result in life-threatening toxicities. Among the many things we grapple with in our daily practice is pairing these new and thrilling findings with our patients on a case-by-case basis to ensure the best-possible outcomes at every level – clinical, psychosocial, financial.

In recent years, we have seen an uptick in the number of FDA approvals, and as our therapeutic options have expanded, we have been able to refine and microtarget our treatment approaches, with encouraging clinical and quality-of-life outcomes. Our approach to practice has changed as well – our care is more patient focused, and we work more as part of a team, rather than individually, to ensure that our patients’ clinical and supportive needs are met. We hope our content reflects these shifts. For example, on page e188, Ibrahimi and colleagues looked at the time from admission to treatment initiation (TAT) in patients who were newly diagnosed with acute myeloid leukemia to see if it had an impact on overall survival (OS) and event-free survival. They obtained retrospective data over 5 years, focusing on patients with a TAT of 0-4 days and those with a TAT of >4 days, and found that the median OS in the 0-4 days group was almost double that of the <4 days group (1.3 years and 0.57 years, respectively). Median event-free survival for the groups was 1.21 years and 0.57 years, respectively. Moreover, that association remained significant in a multivariate analysis adjusting for age, white blood cell count, molecular risk group, and undergoing allogeneic stem cell transplant.
 

Marriage and survival

Does marital status have a prognostic bearing on outcomes in patients with cancer? Vyfhuis and colleagues addressed that question in their study of patients with stage III non–small-cell lung cancer (NSCLC) who had been treated uniformly with curative intent (p. e194). Specifically, they looked at OS and freedom from recurrence and they adjusted for patient-, disease-, and treatment-specific factors, as well as the interaction with racial, nutritional, and immunologic status.

In all, 52% of patients in the study were married, and were more likely to self-identify as white; live in areas with a higher household median income; undergo surgery; and have insurance, an ECOG of 0, and higher pretreatment albumin. The authors report that on multivariate analysis, marital status remained an independent predictor of survival and was associated with a 40% decreased risk of death, further stratifying outcomes beyond gender and stage grouping. Freedom from recurrence was comparable between the married and not-married patients. These findings suggest that in a cancer such as NSCLC, for which survival is modest despite therapeutic advances and which is associated with considerable treatment-related toxicities, marital status might be an independent predictor for survival. The authors suggest that marriage is likely a surrogate for better psychosocial support, and that the survival improvements might justify investment in supportive care interventional strategies to help advance overall outcomes.

Cancer in children and AYAs

Two articles in this issue examine cancers in pediatric patients and in adolescents and young adults (AYAs), and by doing so, demonstrate the importance of having evidence-based research findings to help us refine and deliver better-quality, patient-focused care. On page e217, Sharon Worcester documents the growing efforts by researchers and clinicians to understand and address the disparities in survival outcomes between AYAs with cancer and their pediatric and adult counterparts.

It has been known for a while that some cancers are more common among AYAs compared with the other 2 populations, and others are less common. More recent findings suggest that the biology and molecular make-up of AYA cancers might also be different and therefore necessitate different therapeutic protocols, and that the social and psychological needs unique to this population also require specifically tailored supportive care. What about treatment setting for AYAs with cancer – would outcomes be better in a pediatric or adult care center? There is evidence that the pediatric setting might have some advantage, but a recent study from Canada suggests that the cost of care in that setting might be higher. Despite these encouraging findings, there are very few trials designed specifically for the AYA cancer population, and the “pediatric-versus-adult” question also applies to AYA participation in trials. Worcester’s comprehensive article weaves together these issues and offers insights and useful explanations from a number of experts who study or care for AYAs with cancers.

Pediatric cancers are rare, representing just 1% of all new cancers diagnosed annually in the United States, but they are the second leading cause of death in children aged 1 to 14 years and therefore warrant attention, writes Jane de Lartigue in an article on page e210. She echoes Worcester’s point that better understanding of cancers in this younger population has brought to light their unique molecular drivers and challenged the assumption that drugs developed for adults can be used in children and young adults. Dr de Lartigue drills down into the science behind the unique biology and molecular aberrations in pediatric cancers and provides a useful list of ongoing clinical trials of targeted therapies in this population. She notes that because of their rarity, pediatric cancers are difficult to study and adequate enrollment in trials is challenging, although that is changing with researchers’ greater awareness of the uniqueness of these cancers and need for age-specific trials.

Also included in this issue are Community Translation articles on the approval of an immunotherapy combination – nivolumab plus ipilimumab – for the treatment of advanced RCC (p. e182), and for venetoclax as a therapy for patients with chronic lymphocytic leukemia, regardless of genotype (p. e185); and 2 Case Reports, one describing a diagnostic dilemma relating to a patient eventually diagnosed with primary renal synovial sarcoma (p. e202), and another detailing prolonged survival in a patient with adenocarcinoma of unknown primary who was treated with chemoradiotherapy (p. e206).

Photo by Aaron Logan

Researchers have identified a promising therapeutic target for t(8;21) acute myeloid leukemia (AML), according to preclinical data published in Cancer Cell.

The fusion protein RUNX1/ETO drives t(8;21) AML by promoting cell-cycle progression.

Using an RNAi screen, the team recognized the cell-cycle regulator cyclin D2 (CCND2) as having critical involvement in RUNX1/ETO-driven leukemia propagation.

And when they knocked down CCND2 with palbociclib, a drug already approved for breast cancer, leukemic expansion of human AML cells and engraftment in murine models were significantly impaired.

"Our discovery that this treatment can be effective in AML is an important step towards a more effective and less toxic treatment for patients with this form of leukemia,” said study author Olaf Heidenreich, PhD, from the Wolfson Childhood Cancer Research Centre at Newcastle University in the U.K.

After identifying the fusion protein with the RNAi screen, the investigators determined that RUNX1/ETO regulates CCND2 transcription. They knocked down the fusion protein and found the expression of CCND2 was diminished in primary AML blasts. They therefore concluded that RUNX1/ETO maintains CCND2 expression.

The team then examined the significance of CCND2 in engraftment, proliferation, and clonal expansion of AML cells and its impact on the accumulation of cells in the G1 phase of the cell cycle. They found that depletion of CCND2 inhibited cell proliferation and clonogenic capacity and arrested the cell cycle in G0/G1 without increasing apoptosis.

They also confirmed that knockdown of RUNX1/ETO or CCND2 did not affect the expression of other D cyclins and G1 cyclin-dependent kinase (CDK)-CCND complexes, such as CDK4/6.

Next, they explored whether RUNX1/ETO-expressing cells were sensitive to the CDK4/6 inhibitor palbociclib. AML cells were highly sensitive to palbociclib and did not proliferate during drug exposure.

The researchers cultured cells from t(8;21)-positive and -negative AML patients and found palbociclib to cause a dose-dependent inhibition of proliferation of AML blasts.

They also tested palbociclib on a sample from a relapsed t(8;21) AML patient. The sample was highly sensitive to palbociclib, with a five-fold reduction in cell numbers using 300 nM of drug.

The investigators conducted in vivo experiments with palbociclib in mice transplanted with AML cells. Mice treated with palbociclib at doses of 100–150 mg/kg had a significantly longer survival than control mice.

Finally, the team examined whether interference with G1 CDK activity would create other vulnerabilities, such as activating KIT mutations, which are frequent secondary mutations found in t(8;21) AML.

They found that G1 CDK inhibition sensitized AML cells toward KIT inhibition, suggesting that “concurrent targeting of the two mutations may offer substantial therapeutic benefit.”

The team plans to conduct experiments that will refine the precise palbociclib dose in AML either as a single agent or in combination.

This study was supported by grants from Bloodwise, Children with Cancer, North of England Children’s Cancer Research Fund, Children's Cancer and Leukaemia Group, and a CRUK program grant in addition to an Aga Khan PhD studentship, a University Sains Malaysia PhD studentship, and an NC3R fellowship.

The authors had no competing interests to disclose. 

Photo by Aaron Logan

Researchers have identified a promising therapeutic target for t(8;21) acute myeloid leukemia (AML), according to preclinical data published in Cancer Cell.

The fusion protein RUNX1/ETO drives t(8;21) AML by promoting cell-cycle progression.

Using an RNAi screen, the team recognized the cell-cycle regulator cyclin D2 (CCND2) as having critical involvement in RUNX1/ETO-driven leukemia propagation.

And when they knocked down CCND2 with palbociclib, a drug already approved for breast cancer, leukemic expansion of human AML cells and engraftment in murine models were significantly impaired.

"Our discovery that this treatment can be effective in AML is an important step towards a more effective and less toxic treatment for patients with this form of leukemia,” said study author Olaf Heidenreich, PhD, from the Wolfson Childhood Cancer Research Centre at Newcastle University in the U.K.

After identifying the fusion protein with the RNAi screen, the investigators determined that RUNX1/ETO regulates CCND2 transcription. They knocked down the fusion protein and found the expression of CCND2 was diminished in primary AML blasts. They therefore concluded that RUNX1/ETO maintains CCND2 expression.

The team then examined the significance of CCND2 in engraftment, proliferation, and clonal expansion of AML cells and its impact on the accumulation of cells in the G1 phase of the cell cycle. They found that depletion of CCND2 inhibited cell proliferation and clonogenic capacity and arrested the cell cycle in G0/G1 without increasing apoptosis.

They also confirmed that knockdown of RUNX1/ETO or CCND2 did not affect the expression of other D cyclins and G1 cyclin-dependent kinase (CDK)-CCND complexes, such as CDK4/6.

Next, they explored whether RUNX1/ETO-expressing cells were sensitive to the CDK4/6 inhibitor palbociclib. AML cells were highly sensitive to palbociclib and did not proliferate during drug exposure.

The researchers cultured cells from t(8;21)-positive and -negative AML patients and found palbociclib to cause a dose-dependent inhibition of proliferation of AML blasts.

They also tested palbociclib on a sample from a relapsed t(8;21) AML patient. The sample was highly sensitive to palbociclib, with a five-fold reduction in cell numbers using 300 nM of drug.

The investigators conducted in vivo experiments with palbociclib in mice transplanted with AML cells. Mice treated with palbociclib at doses of 100–150 mg/kg had a significantly longer survival than control mice.

Finally, the team examined whether interference with G1 CDK activity would create other vulnerabilities, such as activating KIT mutations, which are frequent secondary mutations found in t(8;21) AML.

They found that G1 CDK inhibition sensitized AML cells toward KIT inhibition, suggesting that “concurrent targeting of the two mutations may offer substantial therapeutic benefit.”

The team plans to conduct experiments that will refine the precise palbociclib dose in AML either as a single agent or in combination.

This study was supported by grants from Bloodwise, Children with Cancer, North of England Children’s Cancer Research Fund, Children's Cancer and Leukaemia Group, and a CRUK program grant in addition to an Aga Khan PhD studentship, a University Sains Malaysia PhD studentship, and an NC3R fellowship.

The authors had no competing interests to disclose. 

Photo by Aaron Logan

Researchers have identified a promising therapeutic target for t(8;21) acute myeloid leukemia (AML), according to preclinical data published in Cancer Cell.

The fusion protein RUNX1/ETO drives t(8;21) AML by promoting cell-cycle progression.

Using an RNAi screen, the team recognized the cell-cycle regulator cyclin D2 (CCND2) as having critical involvement in RUNX1/ETO-driven leukemia propagation.

And when they knocked down CCND2 with palbociclib, a drug already approved for breast cancer, leukemic expansion of human AML cells and engraftment in murine models were significantly impaired.

"Our discovery that this treatment can be effective in AML is an important step towards a more effective and less toxic treatment for patients with this form of leukemia,” said study author Olaf Heidenreich, PhD, from the Wolfson Childhood Cancer Research Centre at Newcastle University in the U.K.

After identifying the fusion protein with the RNAi screen, the investigators determined that RUNX1/ETO regulates CCND2 transcription. They knocked down the fusion protein and found the expression of CCND2 was diminished in primary AML blasts. They therefore concluded that RUNX1/ETO maintains CCND2 expression.

The team then examined the significance of CCND2 in engraftment, proliferation, and clonal expansion of AML cells and its impact on the accumulation of cells in the G1 phase of the cell cycle. They found that depletion of CCND2 inhibited cell proliferation and clonogenic capacity and arrested the cell cycle in G0/G1 without increasing apoptosis.

They also confirmed that knockdown of RUNX1/ETO or CCND2 did not affect the expression of other D cyclins and G1 cyclin-dependent kinase (CDK)-CCND complexes, such as CDK4/6.

Next, they explored whether RUNX1/ETO-expressing cells were sensitive to the CDK4/6 inhibitor palbociclib. AML cells were highly sensitive to palbociclib and did not proliferate during drug exposure.

The researchers cultured cells from t(8;21)-positive and -negative AML patients and found palbociclib to cause a dose-dependent inhibition of proliferation of AML blasts.

They also tested palbociclib on a sample from a relapsed t(8;21) AML patient. The sample was highly sensitive to palbociclib, with a five-fold reduction in cell numbers using 300 nM of drug.

The investigators conducted in vivo experiments with palbociclib in mice transplanted with AML cells. Mice treated with palbociclib at doses of 100–150 mg/kg had a significantly longer survival than control mice.

Finally, the team examined whether interference with G1 CDK activity would create other vulnerabilities, such as activating KIT mutations, which are frequent secondary mutations found in t(8;21) AML.

They found that G1 CDK inhibition sensitized AML cells toward KIT inhibition, suggesting that “concurrent targeting of the two mutations may offer substantial therapeutic benefit.”

The team plans to conduct experiments that will refine the precise palbociclib dose in AML either as a single agent or in combination.

This study was supported by grants from Bloodwise, Children with Cancer, North of England Children’s Cancer Research Fund, Children's Cancer and Leukaemia Group, and a CRUK program grant in addition to an Aga Khan PhD studentship, a University Sains Malaysia PhD studentship, and an NC3R fellowship.

The authors had no competing interests to disclose. 

ATLANTA – The risk of infection from flexible endoscopes is far greater than generally believed, despite the excessive use of prophylactic antimicrobials in patients undergoing endoscopy, recent studies show.

romaset/Getty Images

Many gastroenterologists and guidelines from professional organizations use a reference point of “less than one per million” regarding the risk of infection from scopes, but a Johns Hopkins University study of more than 2.3 million patients in 6 states showed that the infection risk with colonoscopy is about 1 per 1,000, the risk for upper gastrointestinal endoscopy is about 3 per 1,000, and the risk with cystoscopy is about 4 per 1,000, Cori Ofstead said at the International Conference on Emerging Infectious Diseases.

“For bronchoscopy [the infection risk] was 15.6 in 1,000, which is 1.6% – not anywhere in the 1 in a million range,” said Ms. Ofstead, president and chief executive officer of Ofstead & Associates, a St. Paul, Minn. health care research firm.

It also turns out that prophylactic antibiotics are frequently given to patients undergoing routine endoscopy procedures, she said, noting that four major associations – two gastroenterology associations and two urology associations in the United States and Europe – recommend that prophylactic antimicrobials be given with routine endoscopies for certain patients undergoing certain types of procedures.

One U.S. organization is recommending prophylactic antimicrobials for every patient undergoing ureteroscopy, she added.

A Cleveland Clinic study looking at the impact of those American Urological Association guidelines for prophylactic antimicrobials showed that in a subset of patients with negative urine cultures before ureteroscopy, 100% received the prophylaxis, and 68% were also given other antimicrobials to take home.

“So the question, of course, is how well does this work...,” Ms. Ofstead said. “They found 3%-4% infection, with the rates exactly the same – no statistically significant differences – between patients who got prophylaxis just in the hospital or who went home with prophylactic meds, and they concluded that there was no benefit to the extra take-home antimicrobials.”

Others studies in multiple countries show either no impact or only minor impact of this prophylaxis on infection rates, and yet all show infection rates after endoscopy that are not one in a million, but in “the percentage point range,” she said.

“As we move toward more of these minimally invasive procedures, we need to be aware that we’re using extremely complex instruments that are very difficult to clean and disinfect or sterilize,” she said, adding that “in the field we’re seeing that improper reprocessing is actually business as usual.”

Infections have been seen with all kinds of scopes, Ms. Ofstead noted.

“The potential for this becoming a bit of a monster is enhanced by the widespread use of prophylactic antimicrobials during endoscopy, and I’m also troubled by the quick reaction of giving people antimicrobials when they have a positive culture from a scope rather than making sure the scope is clean,” she said, explaining that while most scopes have microbes and patients could be getting infections, they also may be reacting to soil and endotoxins in the scope rather than microbes.

“In any case, to reduce risks there are a number of things people can do,” she said. When using reusable scopes, proper cleaning is essential. “I think we should be moving toward scopes that can be disassembled so we can see inside and get those channels clean,” adding that efforts should also be made to move toward single-use scopes.

“Particularly in these outbreak situations where we’re using bronchoscopy on multiple patients, there’s just no excuse for reusing bronchoscopes and not sterilizing them between uses and making darn sure that they’re not full of whatever our outbreak pathogen is,” Ms. Ofstead said. “And lastly, I’m hoping that some folks here can talk some sense into people at the professional associations who are recommending prophylactic antimicrobial use, because if we don’t get some stewardship going, we’re going to be in big trouble.”

The guidelines create a conundrum for doctors who are torn between that stewardship and a failure to follow the recommendations.

“Their professional organization is telling them to give prophylactic antimicrobials. If they don’t do it and a patients gets an infection, that’s a malpractice issue. So we’ve got to go through those associations and get them to stop recommending prophylactic antimicrobials when there is no evidence of their effectiveness,” she said.

Ms. Ofstead has been a consultant for 3M Company, Ambu, Auris, Boston Scientific, Cogentix, Convergascent, Healthmark, Invendo Medical, Nanosonics, and Advanced Sterilization Products, and has received grant/research support from 3M Company, Advanced Sterilization Products, Ambu, Boston Scientific, Cogentix, Healthmark, Invendo Medical, Medivators, and Steris.

[email protected]

SOURCE: Ofstead C., ICEID 2018 Presentation.

ATLANTA – The risk of infection from flexible endoscopes is far greater than generally believed, despite the excessive use of prophylactic antimicrobials in patients undergoing endoscopy, recent studies show.

romaset/Getty Images

Many gastroenterologists and guidelines from professional organizations use a reference point of “less than one per million” regarding the risk of infection from scopes, but a Johns Hopkins University study of more than 2.3 million patients in 6 states showed that the infection risk with colonoscopy is about 1 per 1,000, the risk for upper gastrointestinal endoscopy is about 3 per 1,000, and the risk with cystoscopy is about 4 per 1,000, Cori Ofstead said at the International Conference on Emerging Infectious Diseases.

“For bronchoscopy [the infection risk] was 15.6 in 1,000, which is 1.6% – not anywhere in the 1 in a million range,” said Ms. Ofstead, president and chief executive officer of Ofstead & Associates, a St. Paul, Minn. health care research firm.

It also turns out that prophylactic antibiotics are frequently given to patients undergoing routine endoscopy procedures, she said, noting that four major associations – two gastroenterology associations and two urology associations in the United States and Europe – recommend that prophylactic antimicrobials be given with routine endoscopies for certain patients undergoing certain types of procedures.

One U.S. organization is recommending prophylactic antimicrobials for every patient undergoing ureteroscopy, she added.

A Cleveland Clinic study looking at the impact of those American Urological Association guidelines for prophylactic antimicrobials showed that in a subset of patients with negative urine cultures before ureteroscopy, 100% received the prophylaxis, and 68% were also given other antimicrobials to take home.

“So the question, of course, is how well does this work...,” Ms. Ofstead said. “They found 3%-4% infection, with the rates exactly the same – no statistically significant differences – between patients who got prophylaxis just in the hospital or who went home with prophylactic meds, and they concluded that there was no benefit to the extra take-home antimicrobials.”

Others studies in multiple countries show either no impact or only minor impact of this prophylaxis on infection rates, and yet all show infection rates after endoscopy that are not one in a million, but in “the percentage point range,” she said.

“As we move toward more of these minimally invasive procedures, we need to be aware that we’re using extremely complex instruments that are very difficult to clean and disinfect or sterilize,” she said, adding that “in the field we’re seeing that improper reprocessing is actually business as usual.”

Infections have been seen with all kinds of scopes, Ms. Ofstead noted.

“The potential for this becoming a bit of a monster is enhanced by the widespread use of prophylactic antimicrobials during endoscopy, and I’m also troubled by the quick reaction of giving people antimicrobials when they have a positive culture from a scope rather than making sure the scope is clean,” she said, explaining that while most scopes have microbes and patients could be getting infections, they also may be reacting to soil and endotoxins in the scope rather than microbes.

“In any case, to reduce risks there are a number of things people can do,” she said. When using reusable scopes, proper cleaning is essential. “I think we should be moving toward scopes that can be disassembled so we can see inside and get those channels clean,” adding that efforts should also be made to move toward single-use scopes.

“Particularly in these outbreak situations where we’re using bronchoscopy on multiple patients, there’s just no excuse for reusing bronchoscopes and not sterilizing them between uses and making darn sure that they’re not full of whatever our outbreak pathogen is,” Ms. Ofstead said. “And lastly, I’m hoping that some folks here can talk some sense into people at the professional associations who are recommending prophylactic antimicrobial use, because if we don’t get some stewardship going, we’re going to be in big trouble.”

The guidelines create a conundrum for doctors who are torn between that stewardship and a failure to follow the recommendations.

“Their professional organization is telling them to give prophylactic antimicrobials. If they don’t do it and a patients gets an infection, that’s a malpractice issue. So we’ve got to go through those associations and get them to stop recommending prophylactic antimicrobials when there is no evidence of their effectiveness,” she said.

Ms. Ofstead has been a consultant for 3M Company, Ambu, Auris, Boston Scientific, Cogentix, Convergascent, Healthmark, Invendo Medical, Nanosonics, and Advanced Sterilization Products, and has received grant/research support from 3M Company, Advanced Sterilization Products, Ambu, Boston Scientific, Cogentix, Healthmark, Invendo Medical, Medivators, and Steris.

[email protected]

SOURCE: Ofstead C., ICEID 2018 Presentation.

ATLANTA – The risk of infection from flexible endoscopes is far greater than generally believed, despite the excessive use of prophylactic antimicrobials in patients undergoing endoscopy, recent studies show.

romaset/Getty Images

Many gastroenterologists and guidelines from professional organizations use a reference point of “less than one per million” regarding the risk of infection from scopes, but a Johns Hopkins University study of more than 2.3 million patients in 6 states showed that the infection risk with colonoscopy is about 1 per 1,000, the risk for upper gastrointestinal endoscopy is about 3 per 1,000, and the risk with cystoscopy is about 4 per 1,000, Cori Ofstead said at the International Conference on Emerging Infectious Diseases.

“For bronchoscopy [the infection risk] was 15.6 in 1,000, which is 1.6% – not anywhere in the 1 in a million range,” said Ms. Ofstead, president and chief executive officer of Ofstead & Associates, a St. Paul, Minn. health care research firm.

It also turns out that prophylactic antibiotics are frequently given to patients undergoing routine endoscopy procedures, she said, noting that four major associations – two gastroenterology associations and two urology associations in the United States and Europe – recommend that prophylactic antimicrobials be given with routine endoscopies for certain patients undergoing certain types of procedures.

One U.S. organization is recommending prophylactic antimicrobials for every patient undergoing ureteroscopy, she added.

A Cleveland Clinic study looking at the impact of those American Urological Association guidelines for prophylactic antimicrobials showed that in a subset of patients with negative urine cultures before ureteroscopy, 100% received the prophylaxis, and 68% were also given other antimicrobials to take home.

“So the question, of course, is how well does this work...,” Ms. Ofstead said. “They found 3%-4% infection, with the rates exactly the same – no statistically significant differences – between patients who got prophylaxis just in the hospital or who went home with prophylactic meds, and they concluded that there was no benefit to the extra take-home antimicrobials.”

Others studies in multiple countries show either no impact or only minor impact of this prophylaxis on infection rates, and yet all show infection rates after endoscopy that are not one in a million, but in “the percentage point range,” she said.

“As we move toward more of these minimally invasive procedures, we need to be aware that we’re using extremely complex instruments that are very difficult to clean and disinfect or sterilize,” she said, adding that “in the field we’re seeing that improper reprocessing is actually business as usual.”

Infections have been seen with all kinds of scopes, Ms. Ofstead noted.

“The potential for this becoming a bit of a monster is enhanced by the widespread use of prophylactic antimicrobials during endoscopy, and I’m also troubled by the quick reaction of giving people antimicrobials when they have a positive culture from a scope rather than making sure the scope is clean,” she said, explaining that while most scopes have microbes and patients could be getting infections, they also may be reacting to soil and endotoxins in the scope rather than microbes.

“In any case, to reduce risks there are a number of things people can do,” she said. When using reusable scopes, proper cleaning is essential. “I think we should be moving toward scopes that can be disassembled so we can see inside and get those channels clean,” adding that efforts should also be made to move toward single-use scopes.

“Particularly in these outbreak situations where we’re using bronchoscopy on multiple patients, there’s just no excuse for reusing bronchoscopes and not sterilizing them between uses and making darn sure that they’re not full of whatever our outbreak pathogen is,” Ms. Ofstead said. “And lastly, I’m hoping that some folks here can talk some sense into people at the professional associations who are recommending prophylactic antimicrobial use, because if we don’t get some stewardship going, we’re going to be in big trouble.”

The guidelines create a conundrum for doctors who are torn between that stewardship and a failure to follow the recommendations.

“Their professional organization is telling them to give prophylactic antimicrobials. If they don’t do it and a patients gets an infection, that’s a malpractice issue. So we’ve got to go through those associations and get them to stop recommending prophylactic antimicrobials when there is no evidence of their effectiveness,” she said.

Ms. Ofstead has been a consultant for 3M Company, Ambu, Auris, Boston Scientific, Cogentix, Convergascent, Healthmark, Invendo Medical, Nanosonics, and Advanced Sterilization Products, and has received grant/research support from 3M Company, Advanced Sterilization Products, Ambu, Boston Scientific, Cogentix, Healthmark, Invendo Medical, Medivators, and Steris.

[email protected]

SOURCE: Ofstead C., ICEID 2018 Presentation.

SAN DIEGO – After implementation of a new chest pain protocol in the emergency department, a greater proportion of patients with low-risk chest pain were discharged, yet a higher rate of ED recidivism was observed, results from a single-center study in Detroit showed.

While the precise cause of this finding is unclear, it may stem from factors affecting socioeconomically disadvantaged populations, Eric M. Blake, one of the study authors, said at the annual meeting of the American College of Emergency Physicians. “Recurrent ED visits are associated with social determinants of health, including race and economic status,” said Mr. Blake, a second-year student at Wayne State University School of Medicine, Detroit. “Socioeconomically disadvantaged patients often lack the transportation and monetary resources to follow up at an outpatient clinic. Detroit is an example of this type of a community; 83% of our population is African American, 36% of people live below the poverty line, and Detroit has an illiteracy rate of 47% in its adult population.”

He and his colleagues hypothesized that implementation of a standardized chest pain protocol in Detroit Receiving Hospital would safely reduce the number of hospital inpatient admissions and ED recidivism rates. Implemented on Nov. 1, 2012, the protocol uses the thrombolysis in myocardial infarction (TIMI) risk score, electrocardiography, and contemporary sensitivity troponin I to triage patients into low-, intermediate-, and high-risk categories. Low-risk patients were discharged and asked to follow up with a cardiologist within 48 hours. For the current study, the researchers retrospectively analyzed patients older than age 18 who presented with low-risk chest pain in the six months before the protocol was implemented and six months after.

A total of 3,613 patients were studied: 1,837 in the pre-protocol group and 1,776 in the post-protocol group. Their mean age was 47 years, 82% were African American, and 53% were male. No differences were observed between the pre- and post-protocol groups in terms of race (P = .280) or sex (P = .497). There was no statistical difference in the proportion of patients deemed at low risk in the pre- vs. post-protocol periods (P = .167). Significantly more low-risk patients were discharged in the post-protocol group, , compared with the pre-protocol group (55% vs. 44%; P less than .001), however. ED recidivism was also significantly greater in the post-protocol vs. pre-protocol group (3% vs. 1.6%; P = .0035).

“These findings may reflect an embedded racial mistrust of the medical system by certain minority groups,” Mr. Blake said. “Due to an extensive history of racism and segregation, a community like Detroit may have reservations when it comes to medical follow-up at outpatient clinics. Difficulty assessing outpatient follow-up for a variety of logistical and monetary reasons common among underprivileged communities may also be reflected in the increased recidivism rates.”

He concluded that administrators and clinicians in EDs nationwide “need to better understand the needs of underprivileged patients. A reduction in resource expenditures when a patient is discharged must be balanced with the cost of a recidivism in vulnerable populations like Detroit.”

To address poor cardiac outpatient follow-up rates, he and his colleagues are conducting a prospective randomized controlled trial investigating the use of motivational interviewing techniques with these patients.

The study’s senior author was Vijaya “Arun” Kumar, MD of Wayne State University School of Medicine. Mr. Blake reported having no financial disclosures.

SOURCE: Kumar VA et al. Ann Emerg Med. 2018 Oct;72;4:S117-18. doi. 10.1016/j.annemergmed.2018.08.304.

[email protected]

SAN DIEGO – After implementation of a new chest pain protocol in the emergency department, a greater proportion of patients with low-risk chest pain were discharged, yet a higher rate of ED recidivism was observed, results from a single-center study in Detroit showed.

While the precise cause of this finding is unclear, it may stem from factors affecting socioeconomically disadvantaged populations, Eric M. Blake, one of the study authors, said at the annual meeting of the American College of Emergency Physicians. “Recurrent ED visits are associated with social determinants of health, including race and economic status,” said Mr. Blake, a second-year student at Wayne State University School of Medicine, Detroit. “Socioeconomically disadvantaged patients often lack the transportation and monetary resources to follow up at an outpatient clinic. Detroit is an example of this type of a community; 83% of our population is African American, 36% of people live below the poverty line, and Detroit has an illiteracy rate of 47% in its adult population.”

He and his colleagues hypothesized that implementation of a standardized chest pain protocol in Detroit Receiving Hospital would safely reduce the number of hospital inpatient admissions and ED recidivism rates. Implemented on Nov. 1, 2012, the protocol uses the thrombolysis in myocardial infarction (TIMI) risk score, electrocardiography, and contemporary sensitivity troponin I to triage patients into low-, intermediate-, and high-risk categories. Low-risk patients were discharged and asked to follow up with a cardiologist within 48 hours. For the current study, the researchers retrospectively analyzed patients older than age 18 who presented with low-risk chest pain in the six months before the protocol was implemented and six months after.

A total of 3,613 patients were studied: 1,837 in the pre-protocol group and 1,776 in the post-protocol group. Their mean age was 47 years, 82% were African American, and 53% were male. No differences were observed between the pre- and post-protocol groups in terms of race (P = .280) or sex (P = .497). There was no statistical difference in the proportion of patients deemed at low risk in the pre- vs. post-protocol periods (P = .167). Significantly more low-risk patients were discharged in the post-protocol group, , compared with the pre-protocol group (55% vs. 44%; P less than .001), however. ED recidivism was also significantly greater in the post-protocol vs. pre-protocol group (3% vs. 1.6%; P = .0035).

“These findings may reflect an embedded racial mistrust of the medical system by certain minority groups,” Mr. Blake said. “Due to an extensive history of racism and segregation, a community like Detroit may have reservations when it comes to medical follow-up at outpatient clinics. Difficulty assessing outpatient follow-up for a variety of logistical and monetary reasons common among underprivileged communities may also be reflected in the increased recidivism rates.”

He concluded that administrators and clinicians in EDs nationwide “need to better understand the needs of underprivileged patients. A reduction in resource expenditures when a patient is discharged must be balanced with the cost of a recidivism in vulnerable populations like Detroit.”

To address poor cardiac outpatient follow-up rates, he and his colleagues are conducting a prospective randomized controlled trial investigating the use of motivational interviewing techniques with these patients.

The study’s senior author was Vijaya “Arun” Kumar, MD of Wayne State University School of Medicine. Mr. Blake reported having no financial disclosures.

SOURCE: Kumar VA et al. Ann Emerg Med. 2018 Oct;72;4:S117-18. doi. 10.1016/j.annemergmed.2018.08.304.

[email protected]

SAN DIEGO – After implementation of a new chest pain protocol in the emergency department, a greater proportion of patients with low-risk chest pain were discharged, yet a higher rate of ED recidivism was observed, results from a single-center study in Detroit showed.

While the precise cause of this finding is unclear, it may stem from factors affecting socioeconomically disadvantaged populations, Eric M. Blake, one of the study authors, said at the annual meeting of the American College of Emergency Physicians. “Recurrent ED visits are associated with social determinants of health, including race and economic status,” said Mr. Blake, a second-year student at Wayne State University School of Medicine, Detroit. “Socioeconomically disadvantaged patients often lack the transportation and monetary resources to follow up at an outpatient clinic. Detroit is an example of this type of a community; 83% of our population is African American, 36% of people live below the poverty line, and Detroit has an illiteracy rate of 47% in its adult population.”

He and his colleagues hypothesized that implementation of a standardized chest pain protocol in Detroit Receiving Hospital would safely reduce the number of hospital inpatient admissions and ED recidivism rates. Implemented on Nov. 1, 2012, the protocol uses the thrombolysis in myocardial infarction (TIMI) risk score, electrocardiography, and contemporary sensitivity troponin I to triage patients into low-, intermediate-, and high-risk categories. Low-risk patients were discharged and asked to follow up with a cardiologist within 48 hours. For the current study, the researchers retrospectively analyzed patients older than age 18 who presented with low-risk chest pain in the six months before the protocol was implemented and six months after.

A total of 3,613 patients were studied: 1,837 in the pre-protocol group and 1,776 in the post-protocol group. Their mean age was 47 years, 82% were African American, and 53% were male. No differences were observed between the pre- and post-protocol groups in terms of race (P = .280) or sex (P = .497). There was no statistical difference in the proportion of patients deemed at low risk in the pre- vs. post-protocol periods (P = .167). Significantly more low-risk patients were discharged in the post-protocol group, , compared with the pre-protocol group (55% vs. 44%; P less than .001), however. ED recidivism was also significantly greater in the post-protocol vs. pre-protocol group (3% vs. 1.6%; P = .0035).

“These findings may reflect an embedded racial mistrust of the medical system by certain minority groups,” Mr. Blake said. “Due to an extensive history of racism and segregation, a community like Detroit may have reservations when it comes to medical follow-up at outpatient clinics. Difficulty assessing outpatient follow-up for a variety of logistical and monetary reasons common among underprivileged communities may also be reflected in the increased recidivism rates.”

He concluded that administrators and clinicians in EDs nationwide “need to better understand the needs of underprivileged patients. A reduction in resource expenditures when a patient is discharged must be balanced with the cost of a recidivism in vulnerable populations like Detroit.”

To address poor cardiac outpatient follow-up rates, he and his colleagues are conducting a prospective randomized controlled trial investigating the use of motivational interviewing techniques with these patients.

The study’s senior author was Vijaya “Arun” Kumar, MD of Wayne State University School of Medicine. Mr. Blake reported having no financial disclosures.

SOURCE: Kumar VA et al. Ann Emerg Med. 2018 Oct;72;4:S117-18. doi. 10.1016/j.annemergmed.2018.08.304.

[email protected]

BOSTON – Choosing an operative approach for ventral hernia can be a matter of weighing the trade-offs between infection risk, postop quality of life, and patient and defect characteristics. A predictive algorithm has been developed to help with this decision, according to a study presented at the annual clinical congress of the American College of Surgeons.

jacoblund/Thinkstock

SOURCE: Schlosser KA, et al. abstract SF215 presented at the American College of Surgeons Clinical Congress 2018.

BOSTON – Choosing an operative approach for ventral hernia can be a matter of weighing the trade-offs between infection risk, postop quality of life, and patient and defect characteristics. A predictive algorithm has been developed to help with this decision, according to a study presented at the annual clinical congress of the American College of Surgeons.

jacoblund/Thinkstock

SOURCE: Schlosser KA, et al. abstract SF215 presented at the American College of Surgeons Clinical Congress 2018.

BOSTON – Choosing an operative approach for ventral hernia can be a matter of weighing the trade-offs between infection risk, postop quality of life, and patient and defect characteristics. A predictive algorithm has been developed to help with this decision, according to a study presented at the annual clinical congress of the American College of Surgeons.

jacoblund/Thinkstock

SOURCE: Schlosser KA, et al. abstract SF215 presented at the American College of Surgeons Clinical Congress 2018.

ESTES PARK, CO – Primary care providers are arguably the health care professionals best positioned to put a major dent in the ongoing – and perplexing – increase in early-onset colorectal cancer, said gastroenterologist Swati G. Patel, MD, at a conference on internal medicine sponsored by the University of Colorado.

Bruce Jancin/MDedge News

The startling rise in the incidence of colorectal cancer (CRC) in younger individuals in recent decades has generated much media coverage and considerable public concern. Reliable national data document a steady decline in CRC incidence over the past several decades in every age group 50 years and older – but a steady rise in incidence in those under age 50.

“The overall decline in CRC incidence and mortality beginning in the mid-1980s is an extremely amazing success story in cancer prevention. But there is still substantial work to be done,” observed Dr. Patel, who directs the Gastrointestinal Cancer Risk and Prevention Center at the university and is a staff physician at the Denver Veterans Affairs Medical Center.

Toward that end, in May 2018 the American Cancer Society issued updated guidelines recommending that people at average risk for CRC should now start undergoing regular screening for the disease at age 45. Models show that starting at age 45 rather than 50 would result in a 6.2% boost in life-years gained and a 17% increase in colonoscopies (CA Cancer J Clin. 2018 Jul;68(4):250-281).

“A different clinical and pathological entity”

Compared to CRC with onset at age 50 or later, early-onset disease is more often symptomatic at presentation. It is also significantly more likely to be located in the left colon or rectum, have a mucinous or signet ring histology, and be Stage III or IV.

“The disease seems to be a different clinical and pathological entity in younger patients,” Dr. Patel said.

The incidence of CRC before age 50 increased by 51% from 1994 to 2014. Mortality due to early-onset CRC rose by 11% during 2005-2015. Up to 90% of cases of early-onset CRC are diagnosed in individuals in their 40s. At the current rate of increase, early-onset CRC is projected to account for 20% of all cases of CRC by the year 2030.

The steadily rising incidence of early-onset CRC can’t be explained away as being due to earlier detection through greater availability of colonoscopy, in Dr. Patel’s view.

Numerous hypotheses have been put forth regarding the etiology of the rise in early-onset CRC. Correlations have variously been noted with the obesity epidemic, red meat consumption, diabetes, metabolic syndrome, increased early childhood exposure to antibiotics with resultant changes in gut microbiota in recent decades, and atopy.

“These are all fascinating hypotheses that will take decades to answer,” she said. “But in the meantime, what can we do about it now?”

Vital role for primary care

It’s going to take time to unravel the etiologies of early-onset CRC, both genetic and non-genetic. In the interim, opportunities abound for prevention and earlier detection. These opportunities are most available to primary care clinicians, since they provide continuity of care and are best positioned to detect red flags for patients at high risk for hereditary cancers.

“This is a time when we should concentrate our efforts on picking the low-hanging fruit,” Dr. Patel advised. She explained that this will entail a three-pronged approach: doing a better job of promptly evaluating potential symptoms of CRC, casting a wider net in search of patients with a hereditary cancer syndrome, and initiating earlier screening, especially in high-risk patients – a category that she said should include all African-Americans.

Prompt evaluation of symptoms

In one major study, the average time from symptom onset – bleeding, unexplained abdominal pain, changes in bowel habits, and/or iron deficiency – to diagnosis of CRC was 217 days in those with early-onset CRC, compared with 29.5 days in patients age 50 or older.

This huge disparity in time to diagnosis occurs largely because physicians typically assume that scant blood present in the stool of younger patients is due to hemorrhoids. Also frequently overlooked is the fact that the presence of hemorrhoids on physical examination can obscure an upstream malignant lesion.

“The initial plan is often to treat assumed benign pathology and only if symptoms persist to consider other causes,” Dr. Patel noted. That practice, she said, has to change: “The tools that we rely on in the clinic for this particular complaint – history and physical examination – are just not as reliable as we need them to be.”

Assessing for increased genetic/familial risk

The best estimate is that 16%-25% of early-onset CRC may be due to a high- or moderate-penetrance genetic mutation. Another 35% or so of cases are associated with a positive family history for CRC without a defined genetic condition.

In a 2011 study a mere 1.2% of Americans carrying a Lynch mutation were aware of it. “I suspect today it’s still less than 10%. We’re still not doing a very good job of identifying high-risk patients,” Dr. Patel said.

The National Comprehensive Cancer Network has published a guideline for assessment of genetic/familial high risk for CRC, but it’s far too complex and detailed for practical use in a busy primary care practice, in her view.

“You don’t have to remember all the detailed branching algorithms and criteria in the NCCN guideline. I propose a gut check. Increased risk boils down to three key points: any patient with onset of advanced neoplasia before age 50, or a personal history of multiple cancers, whether synchronous or metachronous, or with a strong family history of cancer on one side of the family should be sent on for a detailed risk assessment,” she said.

Similarly, don’t sweat trying to remember all the types of cancer associated with Lynch syndrome.

“We’re learning that the true answer is that it could be any kind of cancer,” Dr. Patel said.

It’s worth bearing in mind, however, that just because a patient doesn’t have a positive family history doesn’t mean that a hereditary cancer syndrome can be ruled out. Incomplete penetrance is characteristic of all of these hereditary syndromes. Indeed, 2 out of 10 patients with Lynch syndrome will never develop CRC.

Multiple gastroenterology societies now recommend routine PCR screening of all colon cancers for microsatellite instability markers – the hallmark of Lynch syndrome tumors – even if the cancer occurs in an 88-year-old. And if the screen is positive, genetic testing is appropriate. The University of Colorado is among a growing number of medical centers that have implemented this policy.

Dr. Patel noted that the American Cancer Society characterized its start-screening-at-45 guideline for average-risk patients as “conditional” rather than a “strong” recommendation. She advised applying it without reservation – and in some instances even starting at age 40 – for three groups clearly at high risk for early-onset CRC: African Americans, patients with a family history of CRC, and those with a family history of advanced adenoma, such as a tubular adenoma, which if not removed has an 80% chance of progressing to cancer.

She reported having no financial conflicts regarding her presentation.

[email protected]

ESTES PARK, CO – Primary care providers are arguably the health care professionals best positioned to put a major dent in the ongoing – and perplexing – increase in early-onset colorectal cancer, said gastroenterologist Swati G. Patel, MD, at a conference on internal medicine sponsored by the University of Colorado.

Bruce Jancin/MDedge News

The startling rise in the incidence of colorectal cancer (CRC) in younger individuals in recent decades has generated much media coverage and considerable public concern. Reliable national data document a steady decline in CRC incidence over the past several decades in every age group 50 years and older – but a steady rise in incidence in those under age 50.

“The overall decline in CRC incidence and mortality beginning in the mid-1980s is an extremely amazing success story in cancer prevention. But there is still substantial work to be done,” observed Dr. Patel, who directs the Gastrointestinal Cancer Risk and Prevention Center at the university and is a staff physician at the Denver Veterans Affairs Medical Center.

Toward that end, in May 2018 the American Cancer Society issued updated guidelines recommending that people at average risk for CRC should now start undergoing regular screening for the disease at age 45. Models show that starting at age 45 rather than 50 would result in a 6.2% boost in life-years gained and a 17% increase in colonoscopies (CA Cancer J Clin. 2018 Jul;68(4):250-281).

“A different clinical and pathological entity”

Compared to CRC with onset at age 50 or later, early-onset disease is more often symptomatic at presentation. It is also significantly more likely to be located in the left colon or rectum, have a mucinous or signet ring histology, and be Stage III or IV.

“The disease seems to be a different clinical and pathological entity in younger patients,” Dr. Patel said.

The incidence of CRC before age 50 increased by 51% from 1994 to 2014. Mortality due to early-onset CRC rose by 11% during 2005-2015. Up to 90% of cases of early-onset CRC are diagnosed in individuals in their 40s. At the current rate of increase, early-onset CRC is projected to account for 20% of all cases of CRC by the year 2030.

The steadily rising incidence of early-onset CRC can’t be explained away as being due to earlier detection through greater availability of colonoscopy, in Dr. Patel’s view.

Numerous hypotheses have been put forth regarding the etiology of the rise in early-onset CRC. Correlations have variously been noted with the obesity epidemic, red meat consumption, diabetes, metabolic syndrome, increased early childhood exposure to antibiotics with resultant changes in gut microbiota in recent decades, and atopy.

“These are all fascinating hypotheses that will take decades to answer,” she said. “But in the meantime, what can we do about it now?”

Vital role for primary care

It’s going to take time to unravel the etiologies of early-onset CRC, both genetic and non-genetic. In the interim, opportunities abound for prevention and earlier detection. These opportunities are most available to primary care clinicians, since they provide continuity of care and are best positioned to detect red flags for patients at high risk for hereditary cancers.

“This is a time when we should concentrate our efforts on picking the low-hanging fruit,” Dr. Patel advised. She explained that this will entail a three-pronged approach: doing a better job of promptly evaluating potential symptoms of CRC, casting a wider net in search of patients with a hereditary cancer syndrome, and initiating earlier screening, especially in high-risk patients – a category that she said should include all African-Americans.

Prompt evaluation of symptoms

In one major study, the average time from symptom onset – bleeding, unexplained abdominal pain, changes in bowel habits, and/or iron deficiency – to diagnosis of CRC was 217 days in those with early-onset CRC, compared with 29.5 days in patients age 50 or older.

This huge disparity in time to diagnosis occurs largely because physicians typically assume that scant blood present in the stool of younger patients is due to hemorrhoids. Also frequently overlooked is the fact that the presence of hemorrhoids on physical examination can obscure an upstream malignant lesion.

“The initial plan is often to treat assumed benign pathology and only if symptoms persist to consider other causes,” Dr. Patel noted. That practice, she said, has to change: “The tools that we rely on in the clinic for this particular complaint – history and physical examination – are just not as reliable as we need them to be.”

Assessing for increased genetic/familial risk

The best estimate is that 16%-25% of early-onset CRC may be due to a high- or moderate-penetrance genetic mutation. Another 35% or so of cases are associated with a positive family history for CRC without a defined genetic condition.

In a 2011 study a mere 1.2% of Americans carrying a Lynch mutation were aware of it. “I suspect today it’s still less than 10%. We’re still not doing a very good job of identifying high-risk patients,” Dr. Patel said.

The National Comprehensive Cancer Network has published a guideline for assessment of genetic/familial high risk for CRC, but it’s far too complex and detailed for practical use in a busy primary care practice, in her view.

“You don’t have to remember all the detailed branching algorithms and criteria in the NCCN guideline. I propose a gut check. Increased risk boils down to three key points: any patient with onset of advanced neoplasia before age 50, or a personal history of multiple cancers, whether synchronous or metachronous, or with a strong family history of cancer on one side of the family should be sent on for a detailed risk assessment,” she said.

Similarly, don’t sweat trying to remember all the types of cancer associated with Lynch syndrome.

“We’re learning that the true answer is that it could be any kind of cancer,” Dr. Patel said.

It’s worth bearing in mind, however, that just because a patient doesn’t have a positive family history doesn’t mean that a hereditary cancer syndrome can be ruled out. Incomplete penetrance is characteristic of all of these hereditary syndromes. Indeed, 2 out of 10 patients with Lynch syndrome will never develop CRC.

Multiple gastroenterology societies now recommend routine PCR screening of all colon cancers for microsatellite instability markers – the hallmark of Lynch syndrome tumors – even if the cancer occurs in an 88-year-old. And if the screen is positive, genetic testing is appropriate. The University of Colorado is among a growing number of medical centers that have implemented this policy.

Dr. Patel noted that the American Cancer Society characterized its start-screening-at-45 guideline for average-risk patients as “conditional” rather than a “strong” recommendation. She advised applying it without reservation – and in some instances even starting at age 40 – for three groups clearly at high risk for early-onset CRC: African Americans, patients with a family history of CRC, and those with a family history of advanced adenoma, such as a tubular adenoma, which if not removed has an 80% chance of progressing to cancer.

She reported having no financial conflicts regarding her presentation.

[email protected]

ESTES PARK, CO – Primary care providers are arguably the health care professionals best positioned to put a major dent in the ongoing – and perplexing – increase in early-onset colorectal cancer, said gastroenterologist Swati G. Patel, MD, at a conference on internal medicine sponsored by the University of Colorado.

Bruce Jancin/MDedge News

The startling rise in the incidence of colorectal cancer (CRC) in younger individuals in recent decades has generated much media coverage and considerable public concern. Reliable national data document a steady decline in CRC incidence over the past several decades in every age group 50 years and older – but a steady rise in incidence in those under age 50.

“The overall decline in CRC incidence and mortality beginning in the mid-1980s is an extremely amazing success story in cancer prevention. But there is still substantial work to be done,” observed Dr. Patel, who directs the Gastrointestinal Cancer Risk and Prevention Center at the university and is a staff physician at the Denver Veterans Affairs Medical Center.

Toward that end, in May 2018 the American Cancer Society issued updated guidelines recommending that people at average risk for CRC should now start undergoing regular screening for the disease at age 45. Models show that starting at age 45 rather than 50 would result in a 6.2% boost in life-years gained and a 17% increase in colonoscopies (CA Cancer J Clin. 2018 Jul;68(4):250-281).

“A different clinical and pathological entity”

Compared to CRC with onset at age 50 or later, early-onset disease is more often symptomatic at presentation. It is also significantly more likely to be located in the left colon or rectum, have a mucinous or signet ring histology, and be Stage III or IV.

“The disease seems to be a different clinical and pathological entity in younger patients,” Dr. Patel said.

The incidence of CRC before age 50 increased by 51% from 1994 to 2014. Mortality due to early-onset CRC rose by 11% during 2005-2015. Up to 90% of cases of early-onset CRC are diagnosed in individuals in their 40s. At the current rate of increase, early-onset CRC is projected to account for 20% of all cases of CRC by the year 2030.

The steadily rising incidence of early-onset CRC can’t be explained away as being due to earlier detection through greater availability of colonoscopy, in Dr. Patel’s view.

Numerous hypotheses have been put forth regarding the etiology of the rise in early-onset CRC. Correlations have variously been noted with the obesity epidemic, red meat consumption, diabetes, metabolic syndrome, increased early childhood exposure to antibiotics with resultant changes in gut microbiota in recent decades, and atopy.

“These are all fascinating hypotheses that will take decades to answer,” she said. “But in the meantime, what can we do about it now?”

Vital role for primary care

It’s going to take time to unravel the etiologies of early-onset CRC, both genetic and non-genetic. In the interim, opportunities abound for prevention and earlier detection. These opportunities are most available to primary care clinicians, since they provide continuity of care and are best positioned to detect red flags for patients at high risk for hereditary cancers.

“This is a time when we should concentrate our efforts on picking the low-hanging fruit,” Dr. Patel advised. She explained that this will entail a three-pronged approach: doing a better job of promptly evaluating potential symptoms of CRC, casting a wider net in search of patients with a hereditary cancer syndrome, and initiating earlier screening, especially in high-risk patients – a category that she said should include all African-Americans.

Prompt evaluation of symptoms

In one major study, the average time from symptom onset – bleeding, unexplained abdominal pain, changes in bowel habits, and/or iron deficiency – to diagnosis of CRC was 217 days in those with early-onset CRC, compared with 29.5 days in patients age 50 or older.

This huge disparity in time to diagnosis occurs largely because physicians typically assume that scant blood present in the stool of younger patients is due to hemorrhoids. Also frequently overlooked is the fact that the presence of hemorrhoids on physical examination can obscure an upstream malignant lesion.

“The initial plan is often to treat assumed benign pathology and only if symptoms persist to consider other causes,” Dr. Patel noted. That practice, she said, has to change: “The tools that we rely on in the clinic for this particular complaint – history and physical examination – are just not as reliable as we need them to be.”

Assessing for increased genetic/familial risk

The best estimate is that 16%-25% of early-onset CRC may be due to a high- or moderate-penetrance genetic mutation. Another 35% or so of cases are associated with a positive family history for CRC without a defined genetic condition.

In a 2011 study a mere 1.2% of Americans carrying a Lynch mutation were aware of it. “I suspect today it’s still less than 10%. We’re still not doing a very good job of identifying high-risk patients,” Dr. Patel said.

The National Comprehensive Cancer Network has published a guideline for assessment of genetic/familial high risk for CRC, but it’s far too complex and detailed for practical use in a busy primary care practice, in her view.

“You don’t have to remember all the detailed branching algorithms and criteria in the NCCN guideline. I propose a gut check. Increased risk boils down to three key points: any patient with onset of advanced neoplasia before age 50, or a personal history of multiple cancers, whether synchronous or metachronous, or with a strong family history of cancer on one side of the family should be sent on for a detailed risk assessment,” she said.

Similarly, don’t sweat trying to remember all the types of cancer associated with Lynch syndrome.

“We’re learning that the true answer is that it could be any kind of cancer,” Dr. Patel said.

It’s worth bearing in mind, however, that just because a patient doesn’t have a positive family history doesn’t mean that a hereditary cancer syndrome can be ruled out. Incomplete penetrance is characteristic of all of these hereditary syndromes. Indeed, 2 out of 10 patients with Lynch syndrome will never develop CRC.

Multiple gastroenterology societies now recommend routine PCR screening of all colon cancers for microsatellite instability markers – the hallmark of Lynch syndrome tumors – even if the cancer occurs in an 88-year-old. And if the screen is positive, genetic testing is appropriate. The University of Colorado is among a growing number of medical centers that have implemented this policy.

Dr. Patel noted that the American Cancer Society characterized its start-screening-at-45 guideline for average-risk patients as “conditional” rather than a “strong” recommendation. She advised applying it without reservation – and in some instances even starting at age 40 – for three groups clearly at high risk for early-onset CRC: African Americans, patients with a family history of CRC, and those with a family history of advanced adenoma, such as a tubular adenoma, which if not removed has an 80% chance of progressing to cancer.

She reported having no financial conflicts regarding her presentation.

[email protected]

BOSTON – Avoiding missed doses of venous thromboembolism (VTE) prophylaxis could result in a reduction in VTE rates, a speaker said at the annual clinical congress of the American College of Surgeons.

Andrew Bowser/MDedge News

The VTE rate dropped by about one-quarter in the trauma care pathway at the University of Pittsburgh Medical Center (UPMC) after implementation of algorithms to risk-stratify patients and guide nursing staff, said Matthew D. Neal, MD, FACS, the Roberta G. Simmons Assistant Professor of Surgery at the University of Pittsburgh.

By incorporating algorithms into the electronic health record (EHR), UPMC was able to realize a “dramatic” 72% reduction in missed doses, from 4,331 missed doses in 2014 to 1,193 in 2015, Dr. Neal told attendees in a session focused on hot topics in surgical patient safety.

That decrease in missed doses has translated into a decreased rate of VTE, from an already relatively low rate of 1.5% in 2015, to 1.1% in 2017, representing a 26.7% reduction, according to data Dr. Neal shared in his podium presentation.

“This has been a sustainable event for us, largely linked to the implementation of an EHR-guided risk assessment pathway to guide the implementation of VTE prophylaxis,” he said.

The change was safe, he added, noting that, since utilization of this pathway, there have been no significant increases in the rate of bleeding events among patients who have mandatory orders.

These results corroborate those of some previous investigations, including one key study from the Johns Hopkins Hospital that described the adoption of a mandatory computerized clinical decision support tool to improve adherence to best practices for VTE prophylaxis.

After incorporation of the tool in the computerized order entry system, there was a significant increase in VTE prophylaxis, translating into a significant drop in preventable harm from VTE, from 1.0% to 0.17% (P = .04), investigators reported in JAMA Surgery.

Reducing missed doses is one of the major contributing factors to decreased VTE rates, according to Dr. Neal.



Missed doses of enoxaparin correlate with increased incidence of deep vein thrombosis (DVT) in trauma and general surgery patients, according to results of one prospective study Dr. Neal described. In that study of 202 patients, reported in JAMA Surgery, DVTs were seen in 23.5% of patients with missed doses, compared with 4.8 for patients with no missed doses (P < .01).

“We need to understand how to risk assess and how to utilize our EHR as a tool,” Dr. Neal told attendees.

Dr. Neal reported disclosures related to Janssen Pharmaceuticals, CSL Behring, Accriva Diagnostics, and Haemonetics, as well as a U.S. patent for a treatment of infectious and inflammatory disorders, and laboratory funding from the National Institutes of Health, Department of Defense, and the Biomedical Advanced Research and Development Authority.
 

SOURCE: Neal MD. Presentation at the American College of Surgeons Clinical Congress. 2018 Oct 25.

BOSTON – Avoiding missed doses of venous thromboembolism (VTE) prophylaxis could result in a reduction in VTE rates, a speaker said at the annual clinical congress of the American College of Surgeons.

Andrew Bowser/MDedge News

The VTE rate dropped by about one-quarter in the trauma care pathway at the University of Pittsburgh Medical Center (UPMC) after implementation of algorithms to risk-stratify patients and guide nursing staff, said Matthew D. Neal, MD, FACS, the Roberta G. Simmons Assistant Professor of Surgery at the University of Pittsburgh.

By incorporating algorithms into the electronic health record (EHR), UPMC was able to realize a “dramatic” 72% reduction in missed doses, from 4,331 missed doses in 2014 to 1,193 in 2015, Dr. Neal told attendees in a session focused on hot topics in surgical patient safety.

That decrease in missed doses has translated into a decreased rate of VTE, from an already relatively low rate of 1.5% in 2015, to 1.1% in 2017, representing a 26.7% reduction, according to data Dr. Neal shared in his podium presentation.

“This has been a sustainable event for us, largely linked to the implementation of an EHR-guided risk assessment pathway to guide the implementation of VTE prophylaxis,” he said.

The change was safe, he added, noting that, since utilization of this pathway, there have been no significant increases in the rate of bleeding events among patients who have mandatory orders.

These results corroborate those of some previous investigations, including one key study from the Johns Hopkins Hospital that described the adoption of a mandatory computerized clinical decision support tool to improve adherence to best practices for VTE prophylaxis.

After incorporation of the tool in the computerized order entry system, there was a significant increase in VTE prophylaxis, translating into a significant drop in preventable harm from VTE, from 1.0% to 0.17% (P = .04), investigators reported in JAMA Surgery.

Reducing missed doses is one of the major contributing factors to decreased VTE rates, according to Dr. Neal.



Missed doses of enoxaparin correlate with increased incidence of deep vein thrombosis (DVT) in trauma and general surgery patients, according to results of one prospective study Dr. Neal described. In that study of 202 patients, reported in JAMA Surgery, DVTs were seen in 23.5% of patients with missed doses, compared with 4.8 for patients with no missed doses (P < .01).

“We need to understand how to risk assess and how to utilize our EHR as a tool,” Dr. Neal told attendees.

Dr. Neal reported disclosures related to Janssen Pharmaceuticals, CSL Behring, Accriva Diagnostics, and Haemonetics, as well as a U.S. patent for a treatment of infectious and inflammatory disorders, and laboratory funding from the National Institutes of Health, Department of Defense, and the Biomedical Advanced Research and Development Authority.
 

SOURCE: Neal MD. Presentation at the American College of Surgeons Clinical Congress. 2018 Oct 25.

BOSTON – Avoiding missed doses of venous thromboembolism (VTE) prophylaxis could result in a reduction in VTE rates, a speaker said at the annual clinical congress of the American College of Surgeons.

Andrew Bowser/MDedge News

The VTE rate dropped by about one-quarter in the trauma care pathway at the University of Pittsburgh Medical Center (UPMC) after implementation of algorithms to risk-stratify patients and guide nursing staff, said Matthew D. Neal, MD, FACS, the Roberta G. Simmons Assistant Professor of Surgery at the University of Pittsburgh.

By incorporating algorithms into the electronic health record (EHR), UPMC was able to realize a “dramatic” 72% reduction in missed doses, from 4,331 missed doses in 2014 to 1,193 in 2015, Dr. Neal told attendees in a session focused on hot topics in surgical patient safety.

That decrease in missed doses has translated into a decreased rate of VTE, from an already relatively low rate of 1.5% in 2015, to 1.1% in 2017, representing a 26.7% reduction, according to data Dr. Neal shared in his podium presentation.

“This has been a sustainable event for us, largely linked to the implementation of an EHR-guided risk assessment pathway to guide the implementation of VTE prophylaxis,” he said.

The change was safe, he added, noting that, since utilization of this pathway, there have been no significant increases in the rate of bleeding events among patients who have mandatory orders.

These results corroborate those of some previous investigations, including one key study from the Johns Hopkins Hospital that described the adoption of a mandatory computerized clinical decision support tool to improve adherence to best practices for VTE prophylaxis.

After incorporation of the tool in the computerized order entry system, there was a significant increase in VTE prophylaxis, translating into a significant drop in preventable harm from VTE, from 1.0% to 0.17% (P = .04), investigators reported in JAMA Surgery.

Reducing missed doses is one of the major contributing factors to decreased VTE rates, according to Dr. Neal.



Missed doses of enoxaparin correlate with increased incidence of deep vein thrombosis (DVT) in trauma and general surgery patients, according to results of one prospective study Dr. Neal described. In that study of 202 patients, reported in JAMA Surgery, DVTs were seen in 23.5% of patients with missed doses, compared with 4.8 for patients with no missed doses (P < .01).

“We need to understand how to risk assess and how to utilize our EHR as a tool,” Dr. Neal told attendees.

Dr. Neal reported disclosures related to Janssen Pharmaceuticals, CSL Behring, Accriva Diagnostics, and Haemonetics, as well as a U.S. patent for a treatment of infectious and inflammatory disorders, and laboratory funding from the National Institutes of Health, Department of Defense, and the Biomedical Advanced Research and Development Authority.
 

SOURCE: Neal MD. Presentation at the American College of Surgeons Clinical Congress. 2018 Oct 25.

Frailty defined as functional dependence is a predictor of mortality risk in elderly patients having major vascular surgery, a meta-analysis of studies has found

“Functional dependency may be recommended for use in rapid screening for frailty in major vascular surgery because of the high quality of associated evidence. Additionally, information on central muscle mass also adds incremental predictive value to long-term survival of elderly patients after major vascular surgery,” the study investigaters stated. However, they pointed out that “other newly developed frailty tools require further validation in more studies” before they should be adopted.

The report, published in the European Journal of Vascular and Endovascular Surgery, evaluated the effect of frailty in major vascular surgery from a search of MEDLINE, Embase, Cochrane Database, and Scopus through May 2018. Data were extracted from the articles related to surgery for abdominal aortic aneurysms (AAA) and lower extremity artery disease (LEAD), and a modified Newcastle-Ottawa scale was used to assess the quality of the included studies, according to Jiarong Wang, MD, of the department of vascular surgery, Sichuan University, Sichuan Province, China, and colleagues. A total of 22 cohort studies and one randomized controlled trial was used in the final analysis. The reviewers expressed the impact of frailty on outcomes as odds ratios (OR) or hazard ratios (HR) using a random effects model.

The researchers found that frailty, in terms of functional dependence, was associated with a significantly increased 30-day mortality risk in patients with AAA without heterogeneity (OR 5.15) and also in LEAD patients (OR 3.29). Functionally dependent patients also had a significantly increased 30-day mortality risk, compared with independent patients (OR 4.49), and similar results were observed after stratifying those who underwent AAA repair (OR 5.14) or lower extremity revascularization (OR 4.18). Even for patients who underwent endovascular procedures rather than open surgery, functional dependency was also associated with a significantly increased 30-day mortality risk (OR 4.90). In addition, with regard to 30-day morbidity, frailty was associated with a significantly increased risk in both AAA (OR 2.79) and LEAD (OR 1.40) patients.

As far as long-term outcomes were concerned, frailty was associated with a significantly increased risk of long-term all-cause mortality in the overall studied population (HR 2.22), as well as in patients with AAA repair (HR 2.10) and LEAD revascularization (HR 2.46). Dr. Wang and colleagues found that central muscle mass was the only tool with moderate quality of evidence predicting long-term survival after major vascular surgery (HR .48), with other single-domain tools such as nutrition or cognition scoring being of low quality. The modified Frailty Index was the only multi-domain tool with moderate quality in predicting mortality for AAA, while others were scored as low or very low, the authors added.

“Future research is warranted to establish consensus on how to select the optimal frailty tool for certain clinical settings,” they concluded.

The authors reported that they had no conflicts of interest and no funding sources for the study.
 

SOURCE: Wang, J et al. Eur J Vasc Endovasc Surg. 2018;56:591-602.

Frailty defined as functional dependence is a predictor of mortality risk in elderly patients having major vascular surgery, a meta-analysis of studies has found

“Functional dependency may be recommended for use in rapid screening for frailty in major vascular surgery because of the high quality of associated evidence. Additionally, information on central muscle mass also adds incremental predictive value to long-term survival of elderly patients after major vascular surgery,” the study investigaters stated. However, they pointed out that “other newly developed frailty tools require further validation in more studies” before they should be adopted.

The report, published in the European Journal of Vascular and Endovascular Surgery, evaluated the effect of frailty in major vascular surgery from a search of MEDLINE, Embase, Cochrane Database, and Scopus through May 2018. Data were extracted from the articles related to surgery for abdominal aortic aneurysms (AAA) and lower extremity artery disease (LEAD), and a modified Newcastle-Ottawa scale was used to assess the quality of the included studies, according to Jiarong Wang, MD, of the department of vascular surgery, Sichuan University, Sichuan Province, China, and colleagues. A total of 22 cohort studies and one randomized controlled trial was used in the final analysis. The reviewers expressed the impact of frailty on outcomes as odds ratios (OR) or hazard ratios (HR) using a random effects model.

The researchers found that frailty, in terms of functional dependence, was associated with a significantly increased 30-day mortality risk in patients with AAA without heterogeneity (OR 5.15) and also in LEAD patients (OR 3.29). Functionally dependent patients also had a significantly increased 30-day mortality risk, compared with independent patients (OR 4.49), and similar results were observed after stratifying those who underwent AAA repair (OR 5.14) or lower extremity revascularization (OR 4.18). Even for patients who underwent endovascular procedures rather than open surgery, functional dependency was also associated with a significantly increased 30-day mortality risk (OR 4.90). In addition, with regard to 30-day morbidity, frailty was associated with a significantly increased risk in both AAA (OR 2.79) and LEAD (OR 1.40) patients.

As far as long-term outcomes were concerned, frailty was associated with a significantly increased risk of long-term all-cause mortality in the overall studied population (HR 2.22), as well as in patients with AAA repair (HR 2.10) and LEAD revascularization (HR 2.46). Dr. Wang and colleagues found that central muscle mass was the only tool with moderate quality of evidence predicting long-term survival after major vascular surgery (HR .48), with other single-domain tools such as nutrition or cognition scoring being of low quality. The modified Frailty Index was the only multi-domain tool with moderate quality in predicting mortality for AAA, while others were scored as low or very low, the authors added.

“Future research is warranted to establish consensus on how to select the optimal frailty tool for certain clinical settings,” they concluded.

The authors reported that they had no conflicts of interest and no funding sources for the study.
 

SOURCE: Wang, J et al. Eur J Vasc Endovasc Surg. 2018;56:591-602.

Frailty defined as functional dependence is a predictor of mortality risk in elderly patients having major vascular surgery, a meta-analysis of studies has found

“Functional dependency may be recommended for use in rapid screening for frailty in major vascular surgery because of the high quality of associated evidence. Additionally, information on central muscle mass also adds incremental predictive value to long-term survival of elderly patients after major vascular surgery,” the study investigaters stated. However, they pointed out that “other newly developed frailty tools require further validation in more studies” before they should be adopted.

The report, published in the European Journal of Vascular and Endovascular Surgery, evaluated the effect of frailty in major vascular surgery from a search of MEDLINE, Embase, Cochrane Database, and Scopus through May 2018. Data were extracted from the articles related to surgery for abdominal aortic aneurysms (AAA) and lower extremity artery disease (LEAD), and a modified Newcastle-Ottawa scale was used to assess the quality of the included studies, according to Jiarong Wang, MD, of the department of vascular surgery, Sichuan University, Sichuan Province, China, and colleagues. A total of 22 cohort studies and one randomized controlled trial was used in the final analysis. The reviewers expressed the impact of frailty on outcomes as odds ratios (OR) or hazard ratios (HR) using a random effects model.

The researchers found that frailty, in terms of functional dependence, was associated with a significantly increased 30-day mortality risk in patients with AAA without heterogeneity (OR 5.15) and also in LEAD patients (OR 3.29). Functionally dependent patients also had a significantly increased 30-day mortality risk, compared with independent patients (OR 4.49), and similar results were observed after stratifying those who underwent AAA repair (OR 5.14) or lower extremity revascularization (OR 4.18). Even for patients who underwent endovascular procedures rather than open surgery, functional dependency was also associated with a significantly increased 30-day mortality risk (OR 4.90). In addition, with regard to 30-day morbidity, frailty was associated with a significantly increased risk in both AAA (OR 2.79) and LEAD (OR 1.40) patients.

As far as long-term outcomes were concerned, frailty was associated with a significantly increased risk of long-term all-cause mortality in the overall studied population (HR 2.22), as well as in patients with AAA repair (HR 2.10) and LEAD revascularization (HR 2.46). Dr. Wang and colleagues found that central muscle mass was the only tool with moderate quality of evidence predicting long-term survival after major vascular surgery (HR .48), with other single-domain tools such as nutrition or cognition scoring being of low quality. The modified Frailty Index was the only multi-domain tool with moderate quality in predicting mortality for AAA, while others were scored as low or very low, the authors added.

“Future research is warranted to establish consensus on how to select the optimal frailty tool for certain clinical settings,” they concluded.

The authors reported that they had no conflicts of interest and no funding sources for the study.
 

SOURCE: Wang, J et al. Eur J Vasc Endovasc Surg. 2018;56:591-602.

BOSTON – A multimodal pain regimen allowed for safe and effective same-day discharge of women undergoing mastectomy procedures, a recent study showed.

Women had little need for stronger oral narcotic use in the single center, retrospective study presented at the annual clinical congress of the American College of Surgeons.

The analysis included 72 consecutive mastectomies performed at a single center from November 2015 to July 2017. Most mastectomies were bilateral (61, or 84.7%) while 11 (15.3%) were unilateral.

Patients received a standardized pain regimen including 1 gram of IV acetaminophen interoperatively, combined with 30 mg of IV ketorolac and a 4-level intercostal nerve block with liposomal bupivacaine.

Liposomal bupivacaine has a longer half-life than other anesthetics, according to lead study author Radbeh Torabi, MD, a fifth-year plastic surgery resident at Louisiana State University (LSU) Health Science Center in New Orleans.

“That allows for prolonged pain control, especially during the time when the patient’s going to have the most amount of pain, which is the first day to two days postoperatively,” Dr. Torabi said in an interview.

All 72 patients were discharged home on the same day with just a 1-week prescription for acetaminophen with codeine.

Only 5 patients presented to the emergency room in the 30-day postoperative period, and of those, only 2 (2.8%) required readmission for reasons other than mastectomy-related pain, investigators said. The remaining 3 patients did present with pain, but did not require hospital admission.

Taken together, these findings suggest that this multimodal strategy offers excellent pain control and has the potential to minimize inpatient admissions while decreasing oral narcotic use, investigators said in an interview following their presentation.

“The main takeaway is reducing the amount of prescriptions we give,” Dr. Torabi said.

Study co-author Cameron T. Ward Coker, MD, a fourth-year general surgery resident at LSU, said the multimodal pain strategy used in this study could represent a step toward eliminating the risks associated with opioid prescribing.

“From the feedback we got from our lecture and the other surgeons in the room, it seems like that’s already becoming a widespread phenomenon,” Dr. Coker said.

Patients in the study had an average age of about 57 years and an average BMI of 30, according to the investigators.

Dr. Coker and Dr. Torabi had no disclosures related to the presentation.

SOURCE: Torabi R, et al. Scientific forum abstract at American College of Surgeons Clinical Congress. 2018 Oct 23.

BOSTON – A multimodal pain regimen allowed for safe and effective same-day discharge of women undergoing mastectomy procedures, a recent study showed.

Women had little need for stronger oral narcotic use in the single center, retrospective study presented at the annual clinical congress of the American College of Surgeons.

The analysis included 72 consecutive mastectomies performed at a single center from November 2015 to July 2017. Most mastectomies were bilateral (61, or 84.7%) while 11 (15.3%) were unilateral.

Patients received a standardized pain regimen including 1 gram of IV acetaminophen interoperatively, combined with 30 mg of IV ketorolac and a 4-level intercostal nerve block with liposomal bupivacaine.

Liposomal bupivacaine has a longer half-life than other anesthetics, according to lead study author Radbeh Torabi, MD, a fifth-year plastic surgery resident at Louisiana State University (LSU) Health Science Center in New Orleans.

“That allows for prolonged pain control, especially during the time when the patient’s going to have the most amount of pain, which is the first day to two days postoperatively,” Dr. Torabi said in an interview.

All 72 patients were discharged home on the same day with just a 1-week prescription for acetaminophen with codeine.

Only 5 patients presented to the emergency room in the 30-day postoperative period, and of those, only 2 (2.8%) required readmission for reasons other than mastectomy-related pain, investigators said. The remaining 3 patients did present with pain, but did not require hospital admission.

Taken together, these findings suggest that this multimodal strategy offers excellent pain control and has the potential to minimize inpatient admissions while decreasing oral narcotic use, investigators said in an interview following their presentation.

“The main takeaway is reducing the amount of prescriptions we give,” Dr. Torabi said.

Study co-author Cameron T. Ward Coker, MD, a fourth-year general surgery resident at LSU, said the multimodal pain strategy used in this study could represent a step toward eliminating the risks associated with opioid prescribing.

“From the feedback we got from our lecture and the other surgeons in the room, it seems like that’s already becoming a widespread phenomenon,” Dr. Coker said.

Patients in the study had an average age of about 57 years and an average BMI of 30, according to the investigators.

Dr. Coker and Dr. Torabi had no disclosures related to the presentation.

SOURCE: Torabi R, et al. Scientific forum abstract at American College of Surgeons Clinical Congress. 2018 Oct 23.

BOSTON – A multimodal pain regimen allowed for safe and effective same-day discharge of women undergoing mastectomy procedures, a recent study showed.

Women had little need for stronger oral narcotic use in the single center, retrospective study presented at the annual clinical congress of the American College of Surgeons.

The analysis included 72 consecutive mastectomies performed at a single center from November 2015 to July 2017. Most mastectomies were bilateral (61, or 84.7%) while 11 (15.3%) were unilateral.

Patients received a standardized pain regimen including 1 gram of IV acetaminophen interoperatively, combined with 30 mg of IV ketorolac and a 4-level intercostal nerve block with liposomal bupivacaine.

Liposomal bupivacaine has a longer half-life than other anesthetics, according to lead study author Radbeh Torabi, MD, a fifth-year plastic surgery resident at Louisiana State University (LSU) Health Science Center in New Orleans.

“That allows for prolonged pain control, especially during the time when the patient’s going to have the most amount of pain, which is the first day to two days postoperatively,” Dr. Torabi said in an interview.

All 72 patients were discharged home on the same day with just a 1-week prescription for acetaminophen with codeine.

Only 5 patients presented to the emergency room in the 30-day postoperative period, and of those, only 2 (2.8%) required readmission for reasons other than mastectomy-related pain, investigators said. The remaining 3 patients did present with pain, but did not require hospital admission.

Taken together, these findings suggest that this multimodal strategy offers excellent pain control and has the potential to minimize inpatient admissions while decreasing oral narcotic use, investigators said in an interview following their presentation.

“The main takeaway is reducing the amount of prescriptions we give,” Dr. Torabi said.

Study co-author Cameron T. Ward Coker, MD, a fourth-year general surgery resident at LSU, said the multimodal pain strategy used in this study could represent a step toward eliminating the risks associated with opioid prescribing.

“From the feedback we got from our lecture and the other surgeons in the room, it seems like that’s already becoming a widespread phenomenon,” Dr. Coker said.

Patients in the study had an average age of about 57 years and an average BMI of 30, according to the investigators.

Dr. Coker and Dr. Torabi had no disclosures related to the presentation.

SOURCE: Torabi R, et al. Scientific forum abstract at American College of Surgeons Clinical Congress. 2018 Oct 23.

Photo from Business Wire

The U.S. Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for the JAK1/JAK2 inhibitor ruxolitinib (Jakafi®).

With this sNDA, Incyte Corporation is seeking approval for ruxolitinib as a treatment for patients with acute graft-versus-host-disease (GVHD) who have had an inadequate response to corticosteroids.

“If approved, ruxolitinib will be the first and only treatment available in the U.S. for patients with acute GVHD who have not responded adequately to corticosteroid therapy,” said Steven Stein, MD, chief medical officer at Incyte.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The agency intends to take action on a priority review application within 6 months of receiving it rather than the standard 10 months.

In addition to priority review, ruxolitinib has received breakthrough therapy and orphan drug designations from the FDA as a treatment for acute GVHD.

The sNDA submission for ruxolitinib in acute GVHD is based on data from the phase 2 REACH1 trial (NCT02953678).

In this ongoing trial, researchers are evaluating ruxolitinib in combination with corticosteroids in patients who have steroid-refractory acute GVHD.

Incyte announced topline results from REACH1 in June, reporting on outcomes in 71 patients.

The study’s primary endpoint—overall response rate at day 28—was met. Ruxolitinib produced an overall response rate of 55% (39/71) at that time.

However, 73% of patients (52/71) responded to ruxolitinib at some point during the trial.

Incyte said the most common treatment-emergent adverse events were anemia (61%), thrombocytopenia (61%), and neutropenia (56%).

Photo from Business Wire

The U.S. Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for the JAK1/JAK2 inhibitor ruxolitinib (Jakafi®).

With this sNDA, Incyte Corporation is seeking approval for ruxolitinib as a treatment for patients with acute graft-versus-host-disease (GVHD) who have had an inadequate response to corticosteroids.

“If approved, ruxolitinib will be the first and only treatment available in the U.S. for patients with acute GVHD who have not responded adequately to corticosteroid therapy,” said Steven Stein, MD, chief medical officer at Incyte.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The agency intends to take action on a priority review application within 6 months of receiving it rather than the standard 10 months.

In addition to priority review, ruxolitinib has received breakthrough therapy and orphan drug designations from the FDA as a treatment for acute GVHD.

The sNDA submission for ruxolitinib in acute GVHD is based on data from the phase 2 REACH1 trial (NCT02953678).

In this ongoing trial, researchers are evaluating ruxolitinib in combination with corticosteroids in patients who have steroid-refractory acute GVHD.

Incyte announced topline results from REACH1 in June, reporting on outcomes in 71 patients.

The study’s primary endpoint—overall response rate at day 28—was met. Ruxolitinib produced an overall response rate of 55% (39/71) at that time.

However, 73% of patients (52/71) responded to ruxolitinib at some point during the trial.

Incyte said the most common treatment-emergent adverse events were anemia (61%), thrombocytopenia (61%), and neutropenia (56%).

Photo from Business Wire

The U.S. Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for the JAK1/JAK2 inhibitor ruxolitinib (Jakafi®).

With this sNDA, Incyte Corporation is seeking approval for ruxolitinib as a treatment for patients with acute graft-versus-host-disease (GVHD) who have had an inadequate response to corticosteroids.

“If approved, ruxolitinib will be the first and only treatment available in the U.S. for patients with acute GVHD who have not responded adequately to corticosteroid therapy,” said Steven Stein, MD, chief medical officer at Incyte.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The agency intends to take action on a priority review application within 6 months of receiving it rather than the standard 10 months.

In addition to priority review, ruxolitinib has received breakthrough therapy and orphan drug designations from the FDA as a treatment for acute GVHD.

The sNDA submission for ruxolitinib in acute GVHD is based on data from the phase 2 REACH1 trial (NCT02953678).

In this ongoing trial, researchers are evaluating ruxolitinib in combination with corticosteroids in patients who have steroid-refractory acute GVHD.

Incyte announced topline results from REACH1 in June, reporting on outcomes in 71 patients.

The study’s primary endpoint—overall response rate at day 28—was met. Ruxolitinib produced an overall response rate of 55% (39/71) at that time.

However, 73% of patients (52/71) responded to ruxolitinib at some point during the trial.

Incyte said the most common treatment-emergent adverse events were anemia (61%), thrombocytopenia (61%), and neutropenia (56%).