Neil Osterweil

SCOTTSDALE, ARIZ. – When it comes to holding or continuing with ACE inhibitors before surgery, all bets are off, a perioperative medicine consultant suggested.

Patients on angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) have about a 50% risk of developing hypotension during surgery, and a significant proportion of those episodes could be severe, said Dr. Paul Grant, of the University of Michigan Health System in Ann Arbor.

"I recommend having some sort of standard approach [to perioperative ACE inhibitor use] at your institution if that’s at all possible, either for a certain surgery type or across the board," he said at a meeting on perioperative medicine sponsored by the University of Miami.

Evidence from a small number of randomized trials and observational studies suggests that continuing ACE inhibitors during cardiac surgery may result in less cardiac enzyme release, less kidney injury, and a lower incidence of atrial fibrillation. In vascular surgery, evidence suggests that patients on ACE inhibitors who are undergoing surgery have less of a drop in cardiac output and may have improved creatinine clearance.

On the other hand, patients who remain on ACE inhibitors during surgery can experience a "profound" drop in blood pressure requiring immediate intervention, he said.

Data to support the continue vs. hold debate are sparse, but include a trial of 51 patients randomized to continue ACE inhibitors on the day of surgery or to have the drugs held for 12-24 hours before surgery. In all, 33 of the patients were on captopril (Capoten), and 18 were on enalapril (Vasotec).

The investigators found that among patients randomized to continue ACE inhibitor therapy, 7 of 7 on captopril and 9 of 14 on enalapril developed hypotension, defined as a systolic blood pressure (SBP) less than 90 mm Hg. In contrast, among patients assigned to the ACE-inhibitor hold protocol, only 2 of 11 on captopril and 4 of 19 on enalapril developed hypotension during surgery.

In a second randomized trial, investigators looked at 37 patients on an ARB who were randomly assigned to either discontinue ARB on the day before surgery (18 patients), or to receive their ARB 1 hour before anesthesia induction (19 patients).

The authors defined hypotension for their study as an SBP less than 80 mm Hg for more than 1 minute. They found that all 19 patients who continued on ARB had hypotension during surgery, compared with 12 of 18 who discontinued their ARB the day before. Patients who received their ARB on the day of surgery used significantly more vasoactive drugs. Despite the discontinuation of the ARB, there were no differences in hypertension between the groups in the recovery period. Postoperative cardiac complications occurred in 1 patient in each group.

In the final randomized study that Dr. Grant cited, 40 patients on an ACE inhibitor with good left-ventricular function were scheduled to undergo coronary artery bypass graft (CABG). They were randomly assigned to hold or continue on ACE inhibitors on the day of surgery.

Patients in whom the ACE inhibitors were held before CABG had higher mean blood pressures than patients who continued on the drugs, and they used less vasopressor during the surgery. In contrast, patients who continued on ACE inhibitors needed more vasodilators after CABG and in the recovery period. The authors of this trial did not study other clinical endpoints, Dr. Grant noted.

Evidence from two observational studies was more equivocal, however.

In a retrospective observational study, investigators studied the relationship between the timing of discontinuing ACE inhibitors and angiotensin II receptor subtype 1 antagonists (ARA) and the onset of hypotension in 267 patients scheduled for general surgery.

They found that patients exposed to an ACE inhibitor or ARA within 10 hours of anesthesia had an adjusted odds ratio of 1.74 for moderate hypotension (SBP 85 mm Hg or less; P = .04), but there was no difference in severe hypotension between these patients and those who discontinued the drugs more than 10 hours before surgery. There were no differences in either vasopressor use or postoperative complications, including unplanned intensive care unit stay, myocardial infarction, stroke, renal impairment, or death.

A second, smaller study compared 12 vascular surgery patients on ARB the day of surgery with matched cohorts of patients taking beta-blockers and/or calcium channel blockers the day of surgery, or ACE inhibitors held on the day of surgery.

Hypotension (SBP less than 90 mm Hg in this study) occurred in all of the patients on ARB but in only 60% (27 of 45) patients on the beta-blocker/calcium channel blockers, and in 67% (18 of 27) in the ACE-inhibitor hold cohort. The ARB patients were also less responsive to ephedrine and phenylephrine than other patients, and in some cases responded only to a vasopressin system agonist, Dr. Grant noted.

Finally, the authors of a random-effects meta-analysis of five studies with a total of 434 patients reported that patients receiving an immediate preoperative ACE inhibitor or ARA dose had a relative risk of 1.50 for developing hypotension requiring vasopressors at or shortly after induction of anesthesia, compared with patients who did not receive the drugs.

Dr. Grant noted that the American College of Physicians’ Smart Medicine guidelines on perioperative management of hypertensive patients recommend continuing ACE inhibitors "with caution," and they advise clinicians to avoid hypovolemia in patients maintained on ACE inhibitors during surgery. He said that in certain cases, it may be appropriate to continue surgical patients on ACE inhibitors or ARB, as in patients with hypertension that is difficult to control with multiple medications, or in those with severe heart disease who have adequate blood pressure.

Dr. Grant reported having no financial disclosures.

SCOTTSDALE, ARIZ. – When it comes to holding or continuing with ACE inhibitors before surgery, all bets are off, a perioperative medicine consultant suggested.

Patients on angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) have about a 50% risk of developing hypotension during surgery, and a significant proportion of those episodes could be severe, said Dr. Paul Grant, of the University of Michigan Health System in Ann Arbor.

"I recommend having some sort of standard approach [to perioperative ACE inhibitor use] at your institution if that’s at all possible, either for a certain surgery type or across the board," he said at a meeting on perioperative medicine sponsored by the University of Miami.

Evidence from a small number of randomized trials and observational studies suggests that continuing ACE inhibitors during cardiac surgery may result in less cardiac enzyme release, less kidney injury, and a lower incidence of atrial fibrillation. In vascular surgery, evidence suggests that patients on ACE inhibitors who are undergoing surgery have less of a drop in cardiac output and may have improved creatinine clearance.

On the other hand, patients who remain on ACE inhibitors during surgery can experience a "profound" drop in blood pressure requiring immediate intervention, he said.

Data to support the continue vs. hold debate are sparse, but include a trial of 51 patients randomized to continue ACE inhibitors on the day of surgery or to have the drugs held for 12-24 hours before surgery. In all, 33 of the patients were on captopril (Capoten), and 18 were on enalapril (Vasotec).

The investigators found that among patients randomized to continue ACE inhibitor therapy, 7 of 7 on captopril and 9 of 14 on enalapril developed hypotension, defined as a systolic blood pressure (SBP) less than 90 mm Hg. In contrast, among patients assigned to the ACE-inhibitor hold protocol, only 2 of 11 on captopril and 4 of 19 on enalapril developed hypotension during surgery.

In a second randomized trial, investigators looked at 37 patients on an ARB who were randomly assigned to either discontinue ARB on the day before surgery (18 patients), or to receive their ARB 1 hour before anesthesia induction (19 patients).

The authors defined hypotension for their study as an SBP less than 80 mm Hg for more than 1 minute. They found that all 19 patients who continued on ARB had hypotension during surgery, compared with 12 of 18 who discontinued their ARB the day before. Patients who received their ARB on the day of surgery used significantly more vasoactive drugs. Despite the discontinuation of the ARB, there were no differences in hypertension between the groups in the recovery period. Postoperative cardiac complications occurred in 1 patient in each group.

In the final randomized study that Dr. Grant cited, 40 patients on an ACE inhibitor with good left-ventricular function were scheduled to undergo coronary artery bypass graft (CABG). They were randomly assigned to hold or continue on ACE inhibitors on the day of surgery.

Patients in whom the ACE inhibitors were held before CABG had higher mean blood pressures than patients who continued on the drugs, and they used less vasopressor during the surgery. In contrast, patients who continued on ACE inhibitors needed more vasodilators after CABG and in the recovery period. The authors of this trial did not study other clinical endpoints, Dr. Grant noted.

Evidence from two observational studies was more equivocal, however.

In a retrospective observational study, investigators studied the relationship between the timing of discontinuing ACE inhibitors and angiotensin II receptor subtype 1 antagonists (ARA) and the onset of hypotension in 267 patients scheduled for general surgery.

They found that patients exposed to an ACE inhibitor or ARA within 10 hours of anesthesia had an adjusted odds ratio of 1.74 for moderate hypotension (SBP 85 mm Hg or less; P = .04), but there was no difference in severe hypotension between these patients and those who discontinued the drugs more than 10 hours before surgery. There were no differences in either vasopressor use or postoperative complications, including unplanned intensive care unit stay, myocardial infarction, stroke, renal impairment, or death.

A second, smaller study compared 12 vascular surgery patients on ARB the day of surgery with matched cohorts of patients taking beta-blockers and/or calcium channel blockers the day of surgery, or ACE inhibitors held on the day of surgery.

Hypotension (SBP less than 90 mm Hg in this study) occurred in all of the patients on ARB but in only 60% (27 of 45) patients on the beta-blocker/calcium channel blockers, and in 67% (18 of 27) in the ACE-inhibitor hold cohort. The ARB patients were also less responsive to ephedrine and phenylephrine than other patients, and in some cases responded only to a vasopressin system agonist, Dr. Grant noted.

Finally, the authors of a random-effects meta-analysis of five studies with a total of 434 patients reported that patients receiving an immediate preoperative ACE inhibitor or ARA dose had a relative risk of 1.50 for developing hypotension requiring vasopressors at or shortly after induction of anesthesia, compared with patients who did not receive the drugs.

Dr. Grant noted that the American College of Physicians’ Smart Medicine guidelines on perioperative management of hypertensive patients recommend continuing ACE inhibitors "with caution," and they advise clinicians to avoid hypovolemia in patients maintained on ACE inhibitors during surgery. He said that in certain cases, it may be appropriate to continue surgical patients on ACE inhibitors or ARB, as in patients with hypertension that is difficult to control with multiple medications, or in those with severe heart disease who have adequate blood pressure.

Dr. Grant reported having no financial disclosures.

SCOTTSDALE, ARIZ. – When it comes to holding or continuing with ACE inhibitors before surgery, all bets are off, a perioperative medicine consultant suggested.

Patients on angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) have about a 50% risk of developing hypotension during surgery, and a significant proportion of those episodes could be severe, said Dr. Paul Grant, of the University of Michigan Health System in Ann Arbor.

"I recommend having some sort of standard approach [to perioperative ACE inhibitor use] at your institution if that’s at all possible, either for a certain surgery type or across the board," he said at a meeting on perioperative medicine sponsored by the University of Miami.

Evidence from a small number of randomized trials and observational studies suggests that continuing ACE inhibitors during cardiac surgery may result in less cardiac enzyme release, less kidney injury, and a lower incidence of atrial fibrillation. In vascular surgery, evidence suggests that patients on ACE inhibitors who are undergoing surgery have less of a drop in cardiac output and may have improved creatinine clearance.

On the other hand, patients who remain on ACE inhibitors during surgery can experience a "profound" drop in blood pressure requiring immediate intervention, he said.

Data to support the continue vs. hold debate are sparse, but include a trial of 51 patients randomized to continue ACE inhibitors on the day of surgery or to have the drugs held for 12-24 hours before surgery. In all, 33 of the patients were on captopril (Capoten), and 18 were on enalapril (Vasotec).

The investigators found that among patients randomized to continue ACE inhibitor therapy, 7 of 7 on captopril and 9 of 14 on enalapril developed hypotension, defined as a systolic blood pressure (SBP) less than 90 mm Hg. In contrast, among patients assigned to the ACE-inhibitor hold protocol, only 2 of 11 on captopril and 4 of 19 on enalapril developed hypotension during surgery.

In a second randomized trial, investigators looked at 37 patients on an ARB who were randomly assigned to either discontinue ARB on the day before surgery (18 patients), or to receive their ARB 1 hour before anesthesia induction (19 patients).

The authors defined hypotension for their study as an SBP less than 80 mm Hg for more than 1 minute. They found that all 19 patients who continued on ARB had hypotension during surgery, compared with 12 of 18 who discontinued their ARB the day before. Patients who received their ARB on the day of surgery used significantly more vasoactive drugs. Despite the discontinuation of the ARB, there were no differences in hypertension between the groups in the recovery period. Postoperative cardiac complications occurred in 1 patient in each group.

In the final randomized study that Dr. Grant cited, 40 patients on an ACE inhibitor with good left-ventricular function were scheduled to undergo coronary artery bypass graft (CABG). They were randomly assigned to hold or continue on ACE inhibitors on the day of surgery.

Patients in whom the ACE inhibitors were held before CABG had higher mean blood pressures than patients who continued on the drugs, and they used less vasopressor during the surgery. In contrast, patients who continued on ACE inhibitors needed more vasodilators after CABG and in the recovery period. The authors of this trial did not study other clinical endpoints, Dr. Grant noted.

Evidence from two observational studies was more equivocal, however.

In a retrospective observational study, investigators studied the relationship between the timing of discontinuing ACE inhibitors and angiotensin II receptor subtype 1 antagonists (ARA) and the onset of hypotension in 267 patients scheduled for general surgery.

They found that patients exposed to an ACE inhibitor or ARA within 10 hours of anesthesia had an adjusted odds ratio of 1.74 for moderate hypotension (SBP 85 mm Hg or less; P = .04), but there was no difference in severe hypotension between these patients and those who discontinued the drugs more than 10 hours before surgery. There were no differences in either vasopressor use or postoperative complications, including unplanned intensive care unit stay, myocardial infarction, stroke, renal impairment, or death.

A second, smaller study compared 12 vascular surgery patients on ARB the day of surgery with matched cohorts of patients taking beta-blockers and/or calcium channel blockers the day of surgery, or ACE inhibitors held on the day of surgery.

Hypotension (SBP less than 90 mm Hg in this study) occurred in all of the patients on ARB but in only 60% (27 of 45) patients on the beta-blocker/calcium channel blockers, and in 67% (18 of 27) in the ACE-inhibitor hold cohort. The ARB patients were also less responsive to ephedrine and phenylephrine than other patients, and in some cases responded only to a vasopressin system agonist, Dr. Grant noted.

Finally, the authors of a random-effects meta-analysis of five studies with a total of 434 patients reported that patients receiving an immediate preoperative ACE inhibitor or ARA dose had a relative risk of 1.50 for developing hypotension requiring vasopressors at or shortly after induction of anesthesia, compared with patients who did not receive the drugs.

Dr. Grant noted that the American College of Physicians’ Smart Medicine guidelines on perioperative management of hypertensive patients recommend continuing ACE inhibitors "with caution," and they advise clinicians to avoid hypovolemia in patients maintained on ACE inhibitors during surgery. He said that in certain cases, it may be appropriate to continue surgical patients on ACE inhibitors or ARB, as in patients with hypertension that is difficult to control with multiple medications, or in those with severe heart disease who have adequate blood pressure.

Dr. Grant reported having no financial disclosures.

PHOENIX, ARIZ. – Cost and quality are not always synonymous, particularly when it comes to complex surgical procedures such as esophagectomy.

A review of records on more than 6,700 patients who underwent esophagectomy during a 4-year period showed that factors such as patient age, severity of illness, and hospital/surgeon volume can have a major effect on resource utilization and costs, said Dr. Daniel E. Abbott, assistant professor of surgery at the University of Cincinnati.

"There are certainly actionable risk factors for poor outcomes, such as mortality, and increased resource utilization, including dollar costs, the opportunity costs of increased length of stay, readmission, and rehabilitation and skilled nursing facilities," he reported at the annual Society of Surgical Oncology Cancer Symposium.

"I would argue that careful patient selection can have profound influences on cost-effectiveness. I think that as our health care is evolving and our outcomes are increasingly scrutinized, there will be increasing pressure to have better outcomes at lower costs," he added.

Neil Osterweil/Frontline Medical News

Dr. Abbott and his colleagues examined clinical variables in the cases of 6,737 esophagectomy patients treated from 2009 through 2012 in the University Healthsystems Consortium (UHC), an organization comprising 120 university hospitals and 299 affiliates.

They evaluated patient characteristics such as age and race, severity of illness index (1-4), esophagectomy type, and center and surgeon volume, and evaluated the effects of these variables on clinical outcomes that contribute to resource utilization, including deaths, readmissions, length of stay (LOS), and discharge disposition.

They found that the median LOS for all patients was 10 days (interquartile range, 8-17 days), but for patients over age 70, the median LOS was 11 days (P less than .01 vs. patients 70 and under).

Older patients did not have significantly higher readmission rates, but of the 4.2% of all patients who died in hospital, those over age 70 had more than twice the death rate of younger patients (7.0% vs. 3.2%, P less than .01).

Older patients were also significantly more likely to be discharged to a skilled nursing or rehabilitation facility than were younger patients (31.9% vs. 10.6%; P less than .01).

Total median cost per patient was $25,952, but again, older patients accounted for more of the expenses, at a median of $27,628 vs. $25,841 for those 70 and under (P less than .01).

In a multivariate analysis, patients over 70 had a more than twofold increase in risk of death (odds ratio, 2.12; P less than .01). Other factors significantly associated with greater risk for death were greater severity of illness (OR, 14.0; P less than .01) and black race vs. other races (OR, 1.88; P less than .01).

Factors associated with more frequent readmissions included greater severity of illness (OR, 1.33; P less than .01), and black race (OR, 1.34; P = .01), while patients of high-volume surgeons were less likely to need readmission (OR, 0.87; P = .04).

Lengths of stay were greater among patients over age 70, with every year over 70 translating into a 6% greater LOS (OR, 1.06; P =.03); older patients had a 16% increase in LOS for every year over 70 (OR, 1.16; P less than .01).

Similarly, each increase in severity of illness index score above 2 was associated with a 31% increase in LOS (OR, 1.31) and a 475% increase in intensive care unit (ICU) days (OR, 4.75; P less than .01 for both LOS and ICU days).

Black patients had a 22% increase in LOS vs. other races (OR, 1.22; P less than .01) and a 31% relative increase in ICU days (OR, 1.31; P = .01).

Because age and severity of illness were both strong predictors for mortality, readmission, and other perioperative outcomes, the authors conducted a further analysis combining the two variables, and found that for every 5 years of age, there were significant increases in the risk for death among patients with a greater severity of illness, compared with low severity.

Dr. Abbott noted that some of the odds ratios for older, sicker patients were "ridiculously high," probably because of the smaller sample sizes.

In a multivariate analysis of cost, factors associated with higher costs were age (OR, 1.14; P less than .01), greater severity of illness (OR, 2.14; P less than .01), and black race (OR, 1.15; P less than .01).

And in an analysis of cumulative resource use, the authors found what Dr. Abbott called a "snowball effect," in that hospitals with the lowest total costs discharged the majority of patients home, and that as costs increased, hospitals were less likely to discharge patients home and more likely to discharge them either to home health services or to extended care. In addition, as costs rose, the percentage of patients who died in hospital also rose.

He acknowledged that because the study used administrative data from university hospitals, it was skewed toward high-volume centers, and that the database did not include survival data, information about longitudinal resource use, or procedure-specific complications.

The authors did not disclose the funding source of the study. Dr. Abbott reported having no financial disclosures.

PHOENIX, ARIZ. – Cost and quality are not always synonymous, particularly when it comes to complex surgical procedures such as esophagectomy.

A review of records on more than 6,700 patients who underwent esophagectomy during a 4-year period showed that factors such as patient age, severity of illness, and hospital/surgeon volume can have a major effect on resource utilization and costs, said Dr. Daniel E. Abbott, assistant professor of surgery at the University of Cincinnati.

"There are certainly actionable risk factors for poor outcomes, such as mortality, and increased resource utilization, including dollar costs, the opportunity costs of increased length of stay, readmission, and rehabilitation and skilled nursing facilities," he reported at the annual Society of Surgical Oncology Cancer Symposium.

"I would argue that careful patient selection can have profound influences on cost-effectiveness. I think that as our health care is evolving and our outcomes are increasingly scrutinized, there will be increasing pressure to have better outcomes at lower costs," he added.

Neil Osterweil/Frontline Medical News

Dr. Abbott and his colleagues examined clinical variables in the cases of 6,737 esophagectomy patients treated from 2009 through 2012 in the University Healthsystems Consortium (UHC), an organization comprising 120 university hospitals and 299 affiliates.

They evaluated patient characteristics such as age and race, severity of illness index (1-4), esophagectomy type, and center and surgeon volume, and evaluated the effects of these variables on clinical outcomes that contribute to resource utilization, including deaths, readmissions, length of stay (LOS), and discharge disposition.

They found that the median LOS for all patients was 10 days (interquartile range, 8-17 days), but for patients over age 70, the median LOS was 11 days (P less than .01 vs. patients 70 and under).

Older patients did not have significantly higher readmission rates, but of the 4.2% of all patients who died in hospital, those over age 70 had more than twice the death rate of younger patients (7.0% vs. 3.2%, P less than .01).

Older patients were also significantly more likely to be discharged to a skilled nursing or rehabilitation facility than were younger patients (31.9% vs. 10.6%; P less than .01).

Total median cost per patient was $25,952, but again, older patients accounted for more of the expenses, at a median of $27,628 vs. $25,841 for those 70 and under (P less than .01).

In a multivariate analysis, patients over 70 had a more than twofold increase in risk of death (odds ratio, 2.12; P less than .01). Other factors significantly associated with greater risk for death were greater severity of illness (OR, 14.0; P less than .01) and black race vs. other races (OR, 1.88; P less than .01).

Factors associated with more frequent readmissions included greater severity of illness (OR, 1.33; P less than .01), and black race (OR, 1.34; P = .01), while patients of high-volume surgeons were less likely to need readmission (OR, 0.87; P = .04).

Lengths of stay were greater among patients over age 70, with every year over 70 translating into a 6% greater LOS (OR, 1.06; P =.03); older patients had a 16% increase in LOS for every year over 70 (OR, 1.16; P less than .01).

Similarly, each increase in severity of illness index score above 2 was associated with a 31% increase in LOS (OR, 1.31) and a 475% increase in intensive care unit (ICU) days (OR, 4.75; P less than .01 for both LOS and ICU days).

Black patients had a 22% increase in LOS vs. other races (OR, 1.22; P less than .01) and a 31% relative increase in ICU days (OR, 1.31; P = .01).

Because age and severity of illness were both strong predictors for mortality, readmission, and other perioperative outcomes, the authors conducted a further analysis combining the two variables, and found that for every 5 years of age, there were significant increases in the risk for death among patients with a greater severity of illness, compared with low severity.

Dr. Abbott noted that some of the odds ratios for older, sicker patients were "ridiculously high," probably because of the smaller sample sizes.

In a multivariate analysis of cost, factors associated with higher costs were age (OR, 1.14; P less than .01), greater severity of illness (OR, 2.14; P less than .01), and black race (OR, 1.15; P less than .01).

And in an analysis of cumulative resource use, the authors found what Dr. Abbott called a "snowball effect," in that hospitals with the lowest total costs discharged the majority of patients home, and that as costs increased, hospitals were less likely to discharge patients home and more likely to discharge them either to home health services or to extended care. In addition, as costs rose, the percentage of patients who died in hospital also rose.

He acknowledged that because the study used administrative data from university hospitals, it was skewed toward high-volume centers, and that the database did not include survival data, information about longitudinal resource use, or procedure-specific complications.

The authors did not disclose the funding source of the study. Dr. Abbott reported having no financial disclosures.

PHOENIX, ARIZ. – Cost and quality are not always synonymous, particularly when it comes to complex surgical procedures such as esophagectomy.

A review of records on more than 6,700 patients who underwent esophagectomy during a 4-year period showed that factors such as patient age, severity of illness, and hospital/surgeon volume can have a major effect on resource utilization and costs, said Dr. Daniel E. Abbott, assistant professor of surgery at the University of Cincinnati.

"There are certainly actionable risk factors for poor outcomes, such as mortality, and increased resource utilization, including dollar costs, the opportunity costs of increased length of stay, readmission, and rehabilitation and skilled nursing facilities," he reported at the annual Society of Surgical Oncology Cancer Symposium.

"I would argue that careful patient selection can have profound influences on cost-effectiveness. I think that as our health care is evolving and our outcomes are increasingly scrutinized, there will be increasing pressure to have better outcomes at lower costs," he added.

Neil Osterweil/Frontline Medical News

Dr. Abbott and his colleagues examined clinical variables in the cases of 6,737 esophagectomy patients treated from 2009 through 2012 in the University Healthsystems Consortium (UHC), an organization comprising 120 university hospitals and 299 affiliates.

They evaluated patient characteristics such as age and race, severity of illness index (1-4), esophagectomy type, and center and surgeon volume, and evaluated the effects of these variables on clinical outcomes that contribute to resource utilization, including deaths, readmissions, length of stay (LOS), and discharge disposition.

They found that the median LOS for all patients was 10 days (interquartile range, 8-17 days), but for patients over age 70, the median LOS was 11 days (P less than .01 vs. patients 70 and under).

Older patients did not have significantly higher readmission rates, but of the 4.2% of all patients who died in hospital, those over age 70 had more than twice the death rate of younger patients (7.0% vs. 3.2%, P less than .01).

Older patients were also significantly more likely to be discharged to a skilled nursing or rehabilitation facility than were younger patients (31.9% vs. 10.6%; P less than .01).

Total median cost per patient was $25,952, but again, older patients accounted for more of the expenses, at a median of $27,628 vs. $25,841 for those 70 and under (P less than .01).

In a multivariate analysis, patients over 70 had a more than twofold increase in risk of death (odds ratio, 2.12; P less than .01). Other factors significantly associated with greater risk for death were greater severity of illness (OR, 14.0; P less than .01) and black race vs. other races (OR, 1.88; P less than .01).

Factors associated with more frequent readmissions included greater severity of illness (OR, 1.33; P less than .01), and black race (OR, 1.34; P = .01), while patients of high-volume surgeons were less likely to need readmission (OR, 0.87; P = .04).

Lengths of stay were greater among patients over age 70, with every year over 70 translating into a 6% greater LOS (OR, 1.06; P =.03); older patients had a 16% increase in LOS for every year over 70 (OR, 1.16; P less than .01).

Similarly, each increase in severity of illness index score above 2 was associated with a 31% increase in LOS (OR, 1.31) and a 475% increase in intensive care unit (ICU) days (OR, 4.75; P less than .01 for both LOS and ICU days).

Black patients had a 22% increase in LOS vs. other races (OR, 1.22; P less than .01) and a 31% relative increase in ICU days (OR, 1.31; P = .01).

Because age and severity of illness were both strong predictors for mortality, readmission, and other perioperative outcomes, the authors conducted a further analysis combining the two variables, and found that for every 5 years of age, there were significant increases in the risk for death among patients with a greater severity of illness, compared with low severity.

Dr. Abbott noted that some of the odds ratios for older, sicker patients were "ridiculously high," probably because of the smaller sample sizes.

In a multivariate analysis of cost, factors associated with higher costs were age (OR, 1.14; P less than .01), greater severity of illness (OR, 2.14; P less than .01), and black race (OR, 1.15; P less than .01).

And in an analysis of cumulative resource use, the authors found what Dr. Abbott called a "snowball effect," in that hospitals with the lowest total costs discharged the majority of patients home, and that as costs increased, hospitals were less likely to discharge patients home and more likely to discharge them either to home health services or to extended care. In addition, as costs rose, the percentage of patients who died in hospital also rose.

He acknowledged that because the study used administrative data from university hospitals, it was skewed toward high-volume centers, and that the database did not include survival data, information about longitudinal resource use, or procedure-specific complications.

The authors did not disclose the funding source of the study. Dr. Abbott reported having no financial disclosures.

PHOENIX, ARIZ. – Neoadjuvant therapy appears to be safe in patients with rectal cancer and inflammatory bowel disease, investigators from the Netherlands reported at the annual Society of Surgical Oncology Cancer Symposium.

Among Dutch patients with a diagnosis of Crohn’s disease (CD), ulcerative colitis (UC), or unspecified colitis who underwent total mesorectal excision, neither neoadjuvant therapy nor immunosuppressive therapy significantly increased the rate of acute postsurgical complications, said Dr. Stefanus van Rooijen.

Patients with inflammatory bowel disease (IBD) have typically been excluded from studies of neoadjuvant chemotherapy and radiation because of fear of complications, but this study shows that "in IBD patients, rectal cancer can be treated the same way as in patients with sporadic rectal cancer, because there were no differences in complications after operations or after getting neoadjuvant therapy," Dr. van Rooijen said in an interview.

Neil Osterweil/Frontline Medical News

To determine whether neoadjuvant therapies might make life more difficult after surgery for patients with IBD and rectal cancer, the investigators reviewed records on all patients with IBD and rectal cancer treated in the Netherlands from 1990 through 2010, and compared their cases to those other patients with rectal cancer treated in the nation during the same period.

They identified a total of 173 patients with IBD: 89 with UC, 70 with CD, and 14 with indeterminate colitis. The majority of patients (112, 64.7%) were male. The mean age at rectal cancer diagnosis was 60.7 years, and the mean duration of IBD before diagnosis was 17.4 years, Dr. van Rooijen and his colleagues at Radboud University Medical Center, Nijmegen, the Netherlands, reported in a poster.

In all, 63 patients with IBD (36.4%) received neoadjuvant therapy, including short-course radiotherapy (29 patients), long-course radiotherapy (13) and chemoradiation (21).

Of the 154 patients who went on to tumor resection, 145 had a known diagnosis of rectal cancer, with significantly more patients with UC having a preoperative rectal cancer diagnosis (90.9% vs. 72.7% for patients with CD; P = .022).

Patients with CD were significantly younger at the time of rectal cancer diagnosis, at a mean of 53.7 years, compared with 63.5 years for patients with UC, and 76 years for those with indeterminate colitis (P = .022).

In all, 42% of patients developed one or more complications after surgery, as scored by the Clavien-Dindo Classification scale (Ann. Surg. 2004;240:205-13).

The most frequent complications reported were grade 2 complications in 27.4% of cases, including presacral or intra-abdominal abscesses, perineal or abdominal wounds, or urologic problems. A total of 48 grade 3 or greater complications were seen in 41 patients.

Rates of complications were similar between patients with IBD who were on chronic immunosuppressive therapy and those who were not, and between patients who received neoadjuvant therapy of any kind and those who did not, and were similar to those seen in the general rectal cancer population, Dr. van Rooijen said.

The authors also found that because rectal cancer may go unrecognized in patients with IBD until they undergo surgery for another reason, there are a relatively high number of incomplete (R1) resections compared with patients with sporadic rectal cancers.

The study was supported by Radboud Medical Center. Dr. van Rooijen reported having no financial disclosures.

PHOENIX, ARIZ. – Neoadjuvant therapy appears to be safe in patients with rectal cancer and inflammatory bowel disease, investigators from the Netherlands reported at the annual Society of Surgical Oncology Cancer Symposium.

Among Dutch patients with a diagnosis of Crohn’s disease (CD), ulcerative colitis (UC), or unspecified colitis who underwent total mesorectal excision, neither neoadjuvant therapy nor immunosuppressive therapy significantly increased the rate of acute postsurgical complications, said Dr. Stefanus van Rooijen.

Patients with inflammatory bowel disease (IBD) have typically been excluded from studies of neoadjuvant chemotherapy and radiation because of fear of complications, but this study shows that "in IBD patients, rectal cancer can be treated the same way as in patients with sporadic rectal cancer, because there were no differences in complications after operations or after getting neoadjuvant therapy," Dr. van Rooijen said in an interview.

Neil Osterweil/Frontline Medical News

To determine whether neoadjuvant therapies might make life more difficult after surgery for patients with IBD and rectal cancer, the investigators reviewed records on all patients with IBD and rectal cancer treated in the Netherlands from 1990 through 2010, and compared their cases to those other patients with rectal cancer treated in the nation during the same period.

They identified a total of 173 patients with IBD: 89 with UC, 70 with CD, and 14 with indeterminate colitis. The majority of patients (112, 64.7%) were male. The mean age at rectal cancer diagnosis was 60.7 years, and the mean duration of IBD before diagnosis was 17.4 years, Dr. van Rooijen and his colleagues at Radboud University Medical Center, Nijmegen, the Netherlands, reported in a poster.

In all, 63 patients with IBD (36.4%) received neoadjuvant therapy, including short-course radiotherapy (29 patients), long-course radiotherapy (13) and chemoradiation (21).

Of the 154 patients who went on to tumor resection, 145 had a known diagnosis of rectal cancer, with significantly more patients with UC having a preoperative rectal cancer diagnosis (90.9% vs. 72.7% for patients with CD; P = .022).

Patients with CD were significantly younger at the time of rectal cancer diagnosis, at a mean of 53.7 years, compared with 63.5 years for patients with UC, and 76 years for those with indeterminate colitis (P = .022).

In all, 42% of patients developed one or more complications after surgery, as scored by the Clavien-Dindo Classification scale (Ann. Surg. 2004;240:205-13).

The most frequent complications reported were grade 2 complications in 27.4% of cases, including presacral or intra-abdominal abscesses, perineal or abdominal wounds, or urologic problems. A total of 48 grade 3 or greater complications were seen in 41 patients.

Rates of complications were similar between patients with IBD who were on chronic immunosuppressive therapy and those who were not, and between patients who received neoadjuvant therapy of any kind and those who did not, and were similar to those seen in the general rectal cancer population, Dr. van Rooijen said.

The authors also found that because rectal cancer may go unrecognized in patients with IBD until they undergo surgery for another reason, there are a relatively high number of incomplete (R1) resections compared with patients with sporadic rectal cancers.

The study was supported by Radboud Medical Center. Dr. van Rooijen reported having no financial disclosures.

PHOENIX, ARIZ. – Neoadjuvant therapy appears to be safe in patients with rectal cancer and inflammatory bowel disease, investigators from the Netherlands reported at the annual Society of Surgical Oncology Cancer Symposium.

Among Dutch patients with a diagnosis of Crohn’s disease (CD), ulcerative colitis (UC), or unspecified colitis who underwent total mesorectal excision, neither neoadjuvant therapy nor immunosuppressive therapy significantly increased the rate of acute postsurgical complications, said Dr. Stefanus van Rooijen.

Patients with inflammatory bowel disease (IBD) have typically been excluded from studies of neoadjuvant chemotherapy and radiation because of fear of complications, but this study shows that "in IBD patients, rectal cancer can be treated the same way as in patients with sporadic rectal cancer, because there were no differences in complications after operations or after getting neoadjuvant therapy," Dr. van Rooijen said in an interview.

Neil Osterweil/Frontline Medical News

To determine whether neoadjuvant therapies might make life more difficult after surgery for patients with IBD and rectal cancer, the investigators reviewed records on all patients with IBD and rectal cancer treated in the Netherlands from 1990 through 2010, and compared their cases to those other patients with rectal cancer treated in the nation during the same period.

They identified a total of 173 patients with IBD: 89 with UC, 70 with CD, and 14 with indeterminate colitis. The majority of patients (112, 64.7%) were male. The mean age at rectal cancer diagnosis was 60.7 years, and the mean duration of IBD before diagnosis was 17.4 years, Dr. van Rooijen and his colleagues at Radboud University Medical Center, Nijmegen, the Netherlands, reported in a poster.

In all, 63 patients with IBD (36.4%) received neoadjuvant therapy, including short-course radiotherapy (29 patients), long-course radiotherapy (13) and chemoradiation (21).

Of the 154 patients who went on to tumor resection, 145 had a known diagnosis of rectal cancer, with significantly more patients with UC having a preoperative rectal cancer diagnosis (90.9% vs. 72.7% for patients with CD; P = .022).

Patients with CD were significantly younger at the time of rectal cancer diagnosis, at a mean of 53.7 years, compared with 63.5 years for patients with UC, and 76 years for those with indeterminate colitis (P = .022).

In all, 42% of patients developed one or more complications after surgery, as scored by the Clavien-Dindo Classification scale (Ann. Surg. 2004;240:205-13).

The most frequent complications reported were grade 2 complications in 27.4% of cases, including presacral or intra-abdominal abscesses, perineal or abdominal wounds, or urologic problems. A total of 48 grade 3 or greater complications were seen in 41 patients.

Rates of complications were similar between patients with IBD who were on chronic immunosuppressive therapy and those who were not, and between patients who received neoadjuvant therapy of any kind and those who did not, and were similar to those seen in the general rectal cancer population, Dr. van Rooijen said.

The authors also found that because rectal cancer may go unrecognized in patients with IBD until they undergo surgery for another reason, there are a relatively high number of incomplete (R1) resections compared with patients with sporadic rectal cancers.

The study was supported by Radboud Medical Center. Dr. van Rooijen reported having no financial disclosures.

PHOENIX, ARIZ. – For patients with locally advanced esophageal cancer involving four or more lymph nodes, neoadjuvant chemoradiation and surgery may offer overall survival rates comparable with those of surgery alone in patients with less advanced disease, reported Dr. Hiroshi Okumura.

In a prospective study of 50 consecutive patients the 3-year survival rate for patients who received neoadjuvant chemoradiation because of extensive lymph node involvement was 71%, compared with 72% for patients with three or fewer involved nodes who were treated with surgery alone, a difference that was not significant, he reported at the annual Society for Surgical Oncology Cancer Symposium.

"The prognosis is poor for patients with esophageal squamous-cell cancer with multiple lymph-node metastases. In particular, the prognosis in patients with four or more lymph-node metastases is significantly poorer than in those with three or fewer. Chemoradiation therapy [CRT] is one of the most useful treatments. However, it remains controversial whether neoadjuvant CRT provides a significant advantage," he said.

To examine this question, Dr. Okumura of Kagoshima University, Japan, and his colleagues followed 50 patients with locally advanced esophageal squamous-cell carcinomas stages T3 or T4. Of this group, 20 patients had four or more metastatic lymph nodes and underwent CRT with 5-fluourouracil and cisplatin plus 40 Gy of radiation, and 30 patients had three or fewer metastatic lymph nodes and underwent surgery alone.

Two patients in the CRT group were subsequently found to have metastases, one to bone and one to the liver. These patients did not undergo surgery and were excluded from the final analysis.

The investigators found that of the CRT-treated patients, 8 had a grade 1 response, defined as tumor present in more than one-third of the whole lesion; 2 had a grade 2 response (tumor present in than one-third of the lesion); and 8 had a grade 3 response (no visible tumor cells).

Eight patients became node-negative (ypN0) after CRT, resulting in a decrease in mean overall metastatic lymph nodes from seven before treatment to three afterward.

Relapses occurred in four patients in the CRT group, three of whom died from cancer and one from pneumonia. In the surgery group, eight patients had relapses, and all died from their cancers.

Three-year survival by histologic response in the CRT cohort was 50% for grade 1, 100% for grade 2, and 80% for grade 3 (P = .05).

Following the presentation, Dr. Mitchell C. Posner, chief of surgical oncology at the University of Chicago, asked whether, given their results, Dr. Okumura and his colleagues would consider offering chemoradiation to patients with three or fewer metastatic lymph nodes.

Dr. Okumura replied that the number of involved lymph nodes was the key factor in the decision to offer chemoradiation in his practice.

The study was internally supported. Dr. Okumura reported having no financial disclosures.

PHOENIX, ARIZ. – For patients with locally advanced esophageal cancer involving four or more lymph nodes, neoadjuvant chemoradiation and surgery may offer overall survival rates comparable with those of surgery alone in patients with less advanced disease, reported Dr. Hiroshi Okumura.

In a prospective study of 50 consecutive patients the 3-year survival rate for patients who received neoadjuvant chemoradiation because of extensive lymph node involvement was 71%, compared with 72% for patients with three or fewer involved nodes who were treated with surgery alone, a difference that was not significant, he reported at the annual Society for Surgical Oncology Cancer Symposium.

"The prognosis is poor for patients with esophageal squamous-cell cancer with multiple lymph-node metastases. In particular, the prognosis in patients with four or more lymph-node metastases is significantly poorer than in those with three or fewer. Chemoradiation therapy [CRT] is one of the most useful treatments. However, it remains controversial whether neoadjuvant CRT provides a significant advantage," he said.

To examine this question, Dr. Okumura of Kagoshima University, Japan, and his colleagues followed 50 patients with locally advanced esophageal squamous-cell carcinomas stages T3 or T4. Of this group, 20 patients had four or more metastatic lymph nodes and underwent CRT with 5-fluourouracil and cisplatin plus 40 Gy of radiation, and 30 patients had three or fewer metastatic lymph nodes and underwent surgery alone.

Two patients in the CRT group were subsequently found to have metastases, one to bone and one to the liver. These patients did not undergo surgery and were excluded from the final analysis.

The investigators found that of the CRT-treated patients, 8 had a grade 1 response, defined as tumor present in more than one-third of the whole lesion; 2 had a grade 2 response (tumor present in than one-third of the lesion); and 8 had a grade 3 response (no visible tumor cells).

Eight patients became node-negative (ypN0) after CRT, resulting in a decrease in mean overall metastatic lymph nodes from seven before treatment to three afterward.

Relapses occurred in four patients in the CRT group, three of whom died from cancer and one from pneumonia. In the surgery group, eight patients had relapses, and all died from their cancers.

Three-year survival by histologic response in the CRT cohort was 50% for grade 1, 100% for grade 2, and 80% for grade 3 (P = .05).

Following the presentation, Dr. Mitchell C. Posner, chief of surgical oncology at the University of Chicago, asked whether, given their results, Dr. Okumura and his colleagues would consider offering chemoradiation to patients with three or fewer metastatic lymph nodes.

Dr. Okumura replied that the number of involved lymph nodes was the key factor in the decision to offer chemoradiation in his practice.

The study was internally supported. Dr. Okumura reported having no financial disclosures.

PHOENIX, ARIZ. – For patients with locally advanced esophageal cancer involving four or more lymph nodes, neoadjuvant chemoradiation and surgery may offer overall survival rates comparable with those of surgery alone in patients with less advanced disease, reported Dr. Hiroshi Okumura.

In a prospective study of 50 consecutive patients the 3-year survival rate for patients who received neoadjuvant chemoradiation because of extensive lymph node involvement was 71%, compared with 72% for patients with three or fewer involved nodes who were treated with surgery alone, a difference that was not significant, he reported at the annual Society for Surgical Oncology Cancer Symposium.

"The prognosis is poor for patients with esophageal squamous-cell cancer with multiple lymph-node metastases. In particular, the prognosis in patients with four or more lymph-node metastases is significantly poorer than in those with three or fewer. Chemoradiation therapy [CRT] is one of the most useful treatments. However, it remains controversial whether neoadjuvant CRT provides a significant advantage," he said.

To examine this question, Dr. Okumura of Kagoshima University, Japan, and his colleagues followed 50 patients with locally advanced esophageal squamous-cell carcinomas stages T3 or T4. Of this group, 20 patients had four or more metastatic lymph nodes and underwent CRT with 5-fluourouracil and cisplatin plus 40 Gy of radiation, and 30 patients had three or fewer metastatic lymph nodes and underwent surgery alone.

Two patients in the CRT group were subsequently found to have metastases, one to bone and one to the liver. These patients did not undergo surgery and were excluded from the final analysis.

The investigators found that of the CRT-treated patients, 8 had a grade 1 response, defined as tumor present in more than one-third of the whole lesion; 2 had a grade 2 response (tumor present in than one-third of the lesion); and 8 had a grade 3 response (no visible tumor cells).

Eight patients became node-negative (ypN0) after CRT, resulting in a decrease in mean overall metastatic lymph nodes from seven before treatment to three afterward.

Relapses occurred in four patients in the CRT group, three of whom died from cancer and one from pneumonia. In the surgery group, eight patients had relapses, and all died from their cancers.

Three-year survival by histologic response in the CRT cohort was 50% for grade 1, 100% for grade 2, and 80% for grade 3 (P = .05).

Following the presentation, Dr. Mitchell C. Posner, chief of surgical oncology at the University of Chicago, asked whether, given their results, Dr. Okumura and his colleagues would consider offering chemoradiation to patients with three or fewer metastatic lymph nodes.

Dr. Okumura replied that the number of involved lymph nodes was the key factor in the decision to offer chemoradiation in his practice.

The study was internally supported. Dr. Okumura reported having no financial disclosures.

SCOTTSDALE, ARIZ. – Optimal management of patients with chronic kidney disease involves knowing what can be modified, understanding that much is uncertain, and having the wisdom to know the difference, suggested an anesthesiologist at a meeting on perioperative medicine sponsored by the University of Miami.

"There is a lot to be done in terms of evaluation of chronic kidney disease and also defining interventions," said Dr. Claus U. Niemann, professor of anesthesia and surgery at the University of California, San Francisco.

Kidney disease is identified either by markers of function such as glomerular filtration rate (GFR), markers of damage such as proteinuria, and markers of volume sense, such as edema, ascites, and urinary sodium excretion.

None of these measures is particularly accurate at measuring disease, however. For example, GFR is not observed directly but estimated from creatinine clearance, which is produced by the body in varying amounts daily and which depends on muscle mass, so that values for a young, muscular man will be higher than those of a small, older woman, Dr. Niemann noted.

In addition, even in people without kidney disease, GFR declines gradually with age, from about 116 mL/min per 1.73 m² for people in their 20s, to about 75 mL/min per 1.73 m² in those aged 70 years and older.

In 2002, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) developed a five-stage classification for chronic kidney disease (CKD), based on GFR, with CKD defined as either a GFR of less than 60 mL/min per 1.73 m² for more than 3 months or evidence of kidney damage for more than 3 months, based on the presence of abnormalities such as proteinuria. The classification notes that a combination of GFR less than 60 mL/min per 1.73 m² and proteinuria is prognostic.

The classification includes moderately and severely reduced GFR, with respective rates of 30-59 and 15-29 mL/min per 1.73 m², respectively, and end-stage renal disease, with a GFR less than 15 mL/min per 1.73 m² or a need for dialysis,

The most common cause of CKD is diabetic nephropathy or hypertensive nephrosclerosis, which account for 67% of all cases. About 1 in 5 or 1 in 6 Americans has some form of CKD, and the problem can be lifelong, Dr. Niemann said.

Risk stratification

The goal of perioperative management of patients with CKD is to prevent further renal impairment from acute kidney injury, a rapid reduction in kidney function as measured by a significant rise in serum creatinine levels or reduction in urine output within 48 hours of exposure.

Approximately 5%-7% of all hospitalized patients experience some degree of acute kidney injury and changes in serum creatinine of only 0.3 mg/dL have been associated with greater length of stay and increased morbidity and mortality, Dr. Niemann said.

"What is really necessary is that we do perioperative risk stratification. We want to identify the subset of patients who are at risk, we can do tests potentially, and we want to understand what the procedure is, put it in the context of the patient and his renal disease, and then hopefully define a plan and get him to surgery," Dr. Niemann said.

Defining perioperative renal risk involves determining as best as possible the extent of renal insufficiency or CKD, the etiology of the kidney disease (including severity and complications), and the risk of loss of kidney function from the planned or urgent/emergent surgery. The preop clinical team should also know where the patient will be discharged after surgery (home, ICU, floor).

Risk factors for in-hospital acute renal failure include baseline risks, such as age, diabetes, heart or liver failure, and male sex; acute clinical conditions, such as sepsis, hypotension, shock, volume depletion, or rhabdomyolysis; and use of nephrotoxic agents, such as contrast media, aminoglycosides, chemotherapy drugs, or NSAIDs.

Mixed results

Dr. Niemann noted that in a systematic review of possible interventions for protecting renal function in the perioperative period found little in the way of solid evidence to support the use of various interventions, including dopamine agonists or analogs, loop diuretics, mannitol, calcium inhibitors, angiotensin-converting enzyme (ACE) inhibitors, N-acetylcysteine in contrast studies or surgery, or sodium bicarbonate (Cochrane Database of Syst. Rev. 2013;9:CD003590 [doi:10.1002/14651858.CD003590.pub]).

"The long and the short of it is that no interventions have definitely been shown to make a big difference in randomized trials," he said.

Nonetheless, to prevent further loss of renal function in at-risk patients, clinicians should optimize modifiable variables, such as blood pressure, and discontinue nephrotoxic medications, such as NSAIDs.

In addition, the perioperative team should strive to better control acidosis, anemia, and hyperphosphatemia.

"I think what is really important is that you counsel the patient in the preop clinic," Dr. Niemann said.

Preoperative clinic staff should review the procedure and risks based on the presence and severity of the patient’s CKD and outline possible outcomes based on the best available evidence.

"We do it for the heart, but we don’t do it for the kidney," he commented.

During surgery, the team should be aware of the risks of a potential "second hit" – that is, an acute injury on top of chronic disease, and after surgery, clinicians should monitor for the known risk factors, such as sepsis and infection, he said.

Dr. Niemann reported no relevant conflicts.

SCOTTSDALE, ARIZ. – Optimal management of patients with chronic kidney disease involves knowing what can be modified, understanding that much is uncertain, and having the wisdom to know the difference, suggested an anesthesiologist at a meeting on perioperative medicine sponsored by the University of Miami.

"There is a lot to be done in terms of evaluation of chronic kidney disease and also defining interventions," said Dr. Claus U. Niemann, professor of anesthesia and surgery at the University of California, San Francisco.

Kidney disease is identified either by markers of function such as glomerular filtration rate (GFR), markers of damage such as proteinuria, and markers of volume sense, such as edema, ascites, and urinary sodium excretion.

None of these measures is particularly accurate at measuring disease, however. For example, GFR is not observed directly but estimated from creatinine clearance, which is produced by the body in varying amounts daily and which depends on muscle mass, so that values for a young, muscular man will be higher than those of a small, older woman, Dr. Niemann noted.

In addition, even in people without kidney disease, GFR declines gradually with age, from about 116 mL/min per 1.73 m² for people in their 20s, to about 75 mL/min per 1.73 m² in those aged 70 years and older.

In 2002, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) developed a five-stage classification for chronic kidney disease (CKD), based on GFR, with CKD defined as either a GFR of less than 60 mL/min per 1.73 m² for more than 3 months or evidence of kidney damage for more than 3 months, based on the presence of abnormalities such as proteinuria. The classification notes that a combination of GFR less than 60 mL/min per 1.73 m² and proteinuria is prognostic.

The classification includes moderately and severely reduced GFR, with respective rates of 30-59 and 15-29 mL/min per 1.73 m², respectively, and end-stage renal disease, with a GFR less than 15 mL/min per 1.73 m² or a need for dialysis,

The most common cause of CKD is diabetic nephropathy or hypertensive nephrosclerosis, which account for 67% of all cases. About 1 in 5 or 1 in 6 Americans has some form of CKD, and the problem can be lifelong, Dr. Niemann said.

Risk stratification

The goal of perioperative management of patients with CKD is to prevent further renal impairment from acute kidney injury, a rapid reduction in kidney function as measured by a significant rise in serum creatinine levels or reduction in urine output within 48 hours of exposure.

Approximately 5%-7% of all hospitalized patients experience some degree of acute kidney injury and changes in serum creatinine of only 0.3 mg/dL have been associated with greater length of stay and increased morbidity and mortality, Dr. Niemann said.

"What is really necessary is that we do perioperative risk stratification. We want to identify the subset of patients who are at risk, we can do tests potentially, and we want to understand what the procedure is, put it in the context of the patient and his renal disease, and then hopefully define a plan and get him to surgery," Dr. Niemann said.

Defining perioperative renal risk involves determining as best as possible the extent of renal insufficiency or CKD, the etiology of the kidney disease (including severity and complications), and the risk of loss of kidney function from the planned or urgent/emergent surgery. The preop clinical team should also know where the patient will be discharged after surgery (home, ICU, floor).

Risk factors for in-hospital acute renal failure include baseline risks, such as age, diabetes, heart or liver failure, and male sex; acute clinical conditions, such as sepsis, hypotension, shock, volume depletion, or rhabdomyolysis; and use of nephrotoxic agents, such as contrast media, aminoglycosides, chemotherapy drugs, or NSAIDs.

Mixed results

Dr. Niemann noted that in a systematic review of possible interventions for protecting renal function in the perioperative period found little in the way of solid evidence to support the use of various interventions, including dopamine agonists or analogs, loop diuretics, mannitol, calcium inhibitors, angiotensin-converting enzyme (ACE) inhibitors, N-acetylcysteine in contrast studies or surgery, or sodium bicarbonate (Cochrane Database of Syst. Rev. 2013;9:CD003590 [doi:10.1002/14651858.CD003590.pub]).

"The long and the short of it is that no interventions have definitely been shown to make a big difference in randomized trials," he said.

Nonetheless, to prevent further loss of renal function in at-risk patients, clinicians should optimize modifiable variables, such as blood pressure, and discontinue nephrotoxic medications, such as NSAIDs.

In addition, the perioperative team should strive to better control acidosis, anemia, and hyperphosphatemia.

"I think what is really important is that you counsel the patient in the preop clinic," Dr. Niemann said.

Preoperative clinic staff should review the procedure and risks based on the presence and severity of the patient’s CKD and outline possible outcomes based on the best available evidence.

"We do it for the heart, but we don’t do it for the kidney," he commented.

During surgery, the team should be aware of the risks of a potential "second hit" – that is, an acute injury on top of chronic disease, and after surgery, clinicians should monitor for the known risk factors, such as sepsis and infection, he said.

Dr. Niemann reported no relevant conflicts.

SCOTTSDALE, ARIZ. – Optimal management of patients with chronic kidney disease involves knowing what can be modified, understanding that much is uncertain, and having the wisdom to know the difference, suggested an anesthesiologist at a meeting on perioperative medicine sponsored by the University of Miami.

"There is a lot to be done in terms of evaluation of chronic kidney disease and also defining interventions," said Dr. Claus U. Niemann, professor of anesthesia and surgery at the University of California, San Francisco.

Kidney disease is identified either by markers of function such as glomerular filtration rate (GFR), markers of damage such as proteinuria, and markers of volume sense, such as edema, ascites, and urinary sodium excretion.

None of these measures is particularly accurate at measuring disease, however. For example, GFR is not observed directly but estimated from creatinine clearance, which is produced by the body in varying amounts daily and which depends on muscle mass, so that values for a young, muscular man will be higher than those of a small, older woman, Dr. Niemann noted.

In addition, even in people without kidney disease, GFR declines gradually with age, from about 116 mL/min per 1.73 m² for people in their 20s, to about 75 mL/min per 1.73 m² in those aged 70 years and older.

In 2002, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) developed a five-stage classification for chronic kidney disease (CKD), based on GFR, with CKD defined as either a GFR of less than 60 mL/min per 1.73 m² for more than 3 months or evidence of kidney damage for more than 3 months, based on the presence of abnormalities such as proteinuria. The classification notes that a combination of GFR less than 60 mL/min per 1.73 m² and proteinuria is prognostic.

The classification includes moderately and severely reduced GFR, with respective rates of 30-59 and 15-29 mL/min per 1.73 m², respectively, and end-stage renal disease, with a GFR less than 15 mL/min per 1.73 m² or a need for dialysis,

The most common cause of CKD is diabetic nephropathy or hypertensive nephrosclerosis, which account for 67% of all cases. About 1 in 5 or 1 in 6 Americans has some form of CKD, and the problem can be lifelong, Dr. Niemann said.

Risk stratification

The goal of perioperative management of patients with CKD is to prevent further renal impairment from acute kidney injury, a rapid reduction in kidney function as measured by a significant rise in serum creatinine levels or reduction in urine output within 48 hours of exposure.

Approximately 5%-7% of all hospitalized patients experience some degree of acute kidney injury and changes in serum creatinine of only 0.3 mg/dL have been associated with greater length of stay and increased morbidity and mortality, Dr. Niemann said.

"What is really necessary is that we do perioperative risk stratification. We want to identify the subset of patients who are at risk, we can do tests potentially, and we want to understand what the procedure is, put it in the context of the patient and his renal disease, and then hopefully define a plan and get him to surgery," Dr. Niemann said.

Defining perioperative renal risk involves determining as best as possible the extent of renal insufficiency or CKD, the etiology of the kidney disease (including severity and complications), and the risk of loss of kidney function from the planned or urgent/emergent surgery. The preop clinical team should also know where the patient will be discharged after surgery (home, ICU, floor).

Risk factors for in-hospital acute renal failure include baseline risks, such as age, diabetes, heart or liver failure, and male sex; acute clinical conditions, such as sepsis, hypotension, shock, volume depletion, or rhabdomyolysis; and use of nephrotoxic agents, such as contrast media, aminoglycosides, chemotherapy drugs, or NSAIDs.

Mixed results

Dr. Niemann noted that in a systematic review of possible interventions for protecting renal function in the perioperative period found little in the way of solid evidence to support the use of various interventions, including dopamine agonists or analogs, loop diuretics, mannitol, calcium inhibitors, angiotensin-converting enzyme (ACE) inhibitors, N-acetylcysteine in contrast studies or surgery, or sodium bicarbonate (Cochrane Database of Syst. Rev. 2013;9:CD003590 [doi:10.1002/14651858.CD003590.pub]).

"The long and the short of it is that no interventions have definitely been shown to make a big difference in randomized trials," he said.

Nonetheless, to prevent further loss of renal function in at-risk patients, clinicians should optimize modifiable variables, such as blood pressure, and discontinue nephrotoxic medications, such as NSAIDs.

In addition, the perioperative team should strive to better control acidosis, anemia, and hyperphosphatemia.

"I think what is really important is that you counsel the patient in the preop clinic," Dr. Niemann said.

Preoperative clinic staff should review the procedure and risks based on the presence and severity of the patient’s CKD and outline possible outcomes based on the best available evidence.

"We do it for the heart, but we don’t do it for the kidney," he commented.

During surgery, the team should be aware of the risks of a potential "second hit" – that is, an acute injury on top of chronic disease, and after surgery, clinicians should monitor for the known risk factors, such as sepsis and infection, he said.

Dr. Niemann reported no relevant conflicts.

PHOENIX, ARIZ. – Even small pancreatic neuroendocrine tumors have the potential for malignancy and need excision or close monitoring, investigators caution.

A retrospective cohort study following outcomes for patients with nonfunctional pancreatic neuroendocrine tumors (PNETs) 2 cm in diameter or less found that in an unadjusted analysis stratified by surgery type, those who did not have surgery had significantly worse overall survival 5 years after diagnosis, although there were no significant survival differences among all surgery types, reported Dr. Lauren Gratian of Duke University, Durham, N.C.

PNETs 2 cm in size or smaller are increasing in incidence in the United States, Dr. Gratian said at the annual Society of Surgical Oncology Cancer Symposium. "This is important, because their malignant potential is uncertain, and optimal surgical management remains unclear."

Neil Osterweil/Frontline Medical News

She pointed to National Comprehensive Cancer Network (NCCN) guidelines, which say that nonfunctional PNETs 2 cm or smaller are candidates for either enucleation or partial pancreatic resection, and that in certain cases, observation may be considered. Specifically, tumors smaller than 1 cm that were discovered incidentally may be candidates for observation, with the decision based on estimated surgical risk, site of the tumor, and patient comorbidities.

To get a better handle on the incidence of nonfunctional PNETs over time, discern their malignant potential, and see what factors are associated with survival, the investigators drew from the American College of Surgeons’ National Cancer Data Base (NCDB) for records on patients diagnosed from 1998 through 2011 with nonfunctional PNETs that met the criteria. Patients with functional PNETs, carcinoids, and/or exocrine tumors were excluded.

Of the 1,854 patients identified, 487 with more than 1 malignant primary, unknown surgical status, or surgery/pancreatectomy not otherwise specified were excluded, leaving a survival cohort of 1,367. Of this group, 368 (27%) had no surgery, 586 (43%) had a partial pancreatic resection, 324 (24%) had a pancreatoduodenectomy (Whipple procedure) with or without a partial gastrectomy, and 89 (6%) underwent total pancreatectomy.

The researchers found that the incidence of small nonfunctional PNETs as a percentage of all PNETs increased significantly over time, from 7% in 1998 to 20% in 2010.

When they grouped tumors by size (5 mm or smaller, more than 5 mm up to 1 cm, and more than 1 cm up to 2 cm), they found that there were no differences in tumor propensity for either distant metastases (11%, 9%, and 13%, respectively) or regional lymph node involvement (34%, 21%, and 29%).

Patients with distant metastases were significantly more likely to have had no surgery (P less than .001), and patients with partial pancreatic sections were significantly more likely than those who had undergone Whipple or total procedures to have positive surgical margins (P = .009).

An unadjusted analysis of 5-year overall survival by surgery type showed no significant differences among patients treated with the various procedures, but significantly worse outcomes for patients who had no surgery vs. any surgery (P less than .01).

There were no significant differences in survival between patients who had some regional lymph nodes examined compared with those who had no nodal dissection.

In a proportional hazards analysis adjusted for demographic and clinical features, factors significantly associated with overall survival were older age at diagnosis, which was associated with a higher risk of death (hazard ratio, 1.04; 95% confidence interval, 1.02-1.06); later year of diagnosis, associated with a lower risk (HR, 0.85; 95% CI, 0.77-0.94); and Whipple procedure, which was associated with an increased risk for death vs. partial pancreatectomy (HR, 1.88; 95% CI, 1.13-3.11).

Dr. Gratian noted that the study was limited by the inclusion of only malignant tumors in the database; potential coding errors; missing data on grade and stage of diseases; and the lack of information on variables such as disease recurrence, mitotic rates, or the Ki67 proliferative index.

The funding source for the study was not disclosed. Dr. Gratian and her coauthors reported having no financial disclosures.

PHOENIX, ARIZ. – Even small pancreatic neuroendocrine tumors have the potential for malignancy and need excision or close monitoring, investigators caution.

A retrospective cohort study following outcomes for patients with nonfunctional pancreatic neuroendocrine tumors (PNETs) 2 cm in diameter or less found that in an unadjusted analysis stratified by surgery type, those who did not have surgery had significantly worse overall survival 5 years after diagnosis, although there were no significant survival differences among all surgery types, reported Dr. Lauren Gratian of Duke University, Durham, N.C.

PNETs 2 cm in size or smaller are increasing in incidence in the United States, Dr. Gratian said at the annual Society of Surgical Oncology Cancer Symposium. "This is important, because their malignant potential is uncertain, and optimal surgical management remains unclear."

Neil Osterweil/Frontline Medical News

She pointed to National Comprehensive Cancer Network (NCCN) guidelines, which say that nonfunctional PNETs 2 cm or smaller are candidates for either enucleation or partial pancreatic resection, and that in certain cases, observation may be considered. Specifically, tumors smaller than 1 cm that were discovered incidentally may be candidates for observation, with the decision based on estimated surgical risk, site of the tumor, and patient comorbidities.

To get a better handle on the incidence of nonfunctional PNETs over time, discern their malignant potential, and see what factors are associated with survival, the investigators drew from the American College of Surgeons’ National Cancer Data Base (NCDB) for records on patients diagnosed from 1998 through 2011 with nonfunctional PNETs that met the criteria. Patients with functional PNETs, carcinoids, and/or exocrine tumors were excluded.

Of the 1,854 patients identified, 487 with more than 1 malignant primary, unknown surgical status, or surgery/pancreatectomy not otherwise specified were excluded, leaving a survival cohort of 1,367. Of this group, 368 (27%) had no surgery, 586 (43%) had a partial pancreatic resection, 324 (24%) had a pancreatoduodenectomy (Whipple procedure) with or without a partial gastrectomy, and 89 (6%) underwent total pancreatectomy.

The researchers found that the incidence of small nonfunctional PNETs as a percentage of all PNETs increased significantly over time, from 7% in 1998 to 20% in 2010.

When they grouped tumors by size (5 mm or smaller, more than 5 mm up to 1 cm, and more than 1 cm up to 2 cm), they found that there were no differences in tumor propensity for either distant metastases (11%, 9%, and 13%, respectively) or regional lymph node involvement (34%, 21%, and 29%).

Patients with distant metastases were significantly more likely to have had no surgery (P less than .001), and patients with partial pancreatic sections were significantly more likely than those who had undergone Whipple or total procedures to have positive surgical margins (P = .009).

An unadjusted analysis of 5-year overall survival by surgery type showed no significant differences among patients treated with the various procedures, but significantly worse outcomes for patients who had no surgery vs. any surgery (P less than .01).

There were no significant differences in survival between patients who had some regional lymph nodes examined compared with those who had no nodal dissection.

In a proportional hazards analysis adjusted for demographic and clinical features, factors significantly associated with overall survival were older age at diagnosis, which was associated with a higher risk of death (hazard ratio, 1.04; 95% confidence interval, 1.02-1.06); later year of diagnosis, associated with a lower risk (HR, 0.85; 95% CI, 0.77-0.94); and Whipple procedure, which was associated with an increased risk for death vs. partial pancreatectomy (HR, 1.88; 95% CI, 1.13-3.11).

Dr. Gratian noted that the study was limited by the inclusion of only malignant tumors in the database; potential coding errors; missing data on grade and stage of diseases; and the lack of information on variables such as disease recurrence, mitotic rates, or the Ki67 proliferative index.

The funding source for the study was not disclosed. Dr. Gratian and her coauthors reported having no financial disclosures.

PHOENIX, ARIZ. – Even small pancreatic neuroendocrine tumors have the potential for malignancy and need excision or close monitoring, investigators caution.

A retrospective cohort study following outcomes for patients with nonfunctional pancreatic neuroendocrine tumors (PNETs) 2 cm in diameter or less found that in an unadjusted analysis stratified by surgery type, those who did not have surgery had significantly worse overall survival 5 years after diagnosis, although there were no significant survival differences among all surgery types, reported Dr. Lauren Gratian of Duke University, Durham, N.C.

PNETs 2 cm in size or smaller are increasing in incidence in the United States, Dr. Gratian said at the annual Society of Surgical Oncology Cancer Symposium. "This is important, because their malignant potential is uncertain, and optimal surgical management remains unclear."

Neil Osterweil/Frontline Medical News

She pointed to National Comprehensive Cancer Network (NCCN) guidelines, which say that nonfunctional PNETs 2 cm or smaller are candidates for either enucleation or partial pancreatic resection, and that in certain cases, observation may be considered. Specifically, tumors smaller than 1 cm that were discovered incidentally may be candidates for observation, with the decision based on estimated surgical risk, site of the tumor, and patient comorbidities.

To get a better handle on the incidence of nonfunctional PNETs over time, discern their malignant potential, and see what factors are associated with survival, the investigators drew from the American College of Surgeons’ National Cancer Data Base (NCDB) for records on patients diagnosed from 1998 through 2011 with nonfunctional PNETs that met the criteria. Patients with functional PNETs, carcinoids, and/or exocrine tumors were excluded.

Of the 1,854 patients identified, 487 with more than 1 malignant primary, unknown surgical status, or surgery/pancreatectomy not otherwise specified were excluded, leaving a survival cohort of 1,367. Of this group, 368 (27%) had no surgery, 586 (43%) had a partial pancreatic resection, 324 (24%) had a pancreatoduodenectomy (Whipple procedure) with or without a partial gastrectomy, and 89 (6%) underwent total pancreatectomy.

The researchers found that the incidence of small nonfunctional PNETs as a percentage of all PNETs increased significantly over time, from 7% in 1998 to 20% in 2010.

When they grouped tumors by size (5 mm or smaller, more than 5 mm up to 1 cm, and more than 1 cm up to 2 cm), they found that there were no differences in tumor propensity for either distant metastases (11%, 9%, and 13%, respectively) or regional lymph node involvement (34%, 21%, and 29%).

Patients with distant metastases were significantly more likely to have had no surgery (P less than .001), and patients with partial pancreatic sections were significantly more likely than those who had undergone Whipple or total procedures to have positive surgical margins (P = .009).

An unadjusted analysis of 5-year overall survival by surgery type showed no significant differences among patients treated with the various procedures, but significantly worse outcomes for patients who had no surgery vs. any surgery (P less than .01).

There were no significant differences in survival between patients who had some regional lymph nodes examined compared with those who had no nodal dissection.

In a proportional hazards analysis adjusted for demographic and clinical features, factors significantly associated with overall survival were older age at diagnosis, which was associated with a higher risk of death (hazard ratio, 1.04; 95% confidence interval, 1.02-1.06); later year of diagnosis, associated with a lower risk (HR, 0.85; 95% CI, 0.77-0.94); and Whipple procedure, which was associated with an increased risk for death vs. partial pancreatectomy (HR, 1.88; 95% CI, 1.13-3.11).

Dr. Gratian noted that the study was limited by the inclusion of only malignant tumors in the database; potential coding errors; missing data on grade and stage of diseases; and the lack of information on variables such as disease recurrence, mitotic rates, or the Ki67 proliferative index.

The funding source for the study was not disclosed. Dr. Gratian and her coauthors reported having no financial disclosures.

Controlling hyperglycemia before and after surgery in patients with diabetes is a balancing act, but when done properly, it can reduce infections and wound complications, according to Dr. David Baldwin.

The key to preoperative planning for patients with diabetes is a full list of medications and an understanding of how well (or how poorly) patients’ glycemia is controlled, said Dr. Baldwin, an endocrinologist at Rush University Medical Center in Chicago.

He discussed strategies for perioperative management of patients with diabetes and thyroid disorders at the Perioperative Medicine Summit 2014."You definitely want to write down exactly what they are and aren’t taking. We find that the medication list for people getting admitted for surgery is often fraught with a lack of little details," he said.

For patients with type 2 diabetes, it’s important to record an accurate description of antidiabetes medications, especially combination oral agents such as Actoplus MET (metformin and pioglitazone) or Janumet (sitagliptin and metformin). For patients with type 1 and 2 diabetes, it is important to record not just the type of insulin but the regimen the patient uses. Dr. Baldwin noted that many intake staff make the mistake of reporting that patients take "Novolin" or "Humulin," which are brand families of insulin and not specific insulin types.

"We often find, probably at least half of the time, that until we actually go and ask the patients what they take for insulin post-op, the correct information won’t have been in the medical record," he said.

The best way to determine whether a patient has good control of chronic hyperglycemia is with a hemoglobin A_1c (HbA_1c) level. A value above 6.5% is diagnostic for diabetes; well-controlled patients have HbA_1c levels from 6% to 8%. HbA1c values not more than 2 months old should be a routine part of preoperative evaluations for patients with diabetes or newly discovered hyperglycemia, Dr. Baldwin said.

Preoperative medications
The Rush University protocol for the preoperative management of antidiabetic therapies other than insulin notes that sulfonylureas, metformin, pioglitazone, exenatide, liraglutide, sitagliptin, linagliptin, saxagliptin, alogliptin, alpha-glucosidase inhibitors, and canagaflozin may all be taken with food on the eve of surgery, but none should be taken on the morning of surgery.

Specific rules also apply for patients who use insulin, depending on the insulin type, as follows:

• For long-acting insulins (glargine or detemir), the patient should take the full dose on the evening before surgery or the morning of surgery if the dose is prescribed for either morning or evening administration. Patients with prescriptions for a b.i.d. dose should take the full dose both the evening before and the morning of surgery.

• With intermediate-acting insulin (NPH), the patient should take the full dose on the evening before surgery and 80% of the morning dose on the morning of surgery.

• For rapid-acting insulins (aspart, lispro, glulisine, or regular) and premixed insulins (NPH or rapid acting), the patient should take the full dose with dinner the night before, and none on the morning of surgery.

Dr. Baldwin emphasized that except in rare circumstances, patients on subcutaneous insulin pumps should not use the pumps during surgery, and should get special instructions from their endocrinologists.

Ideally, the patient can convert to insulin glargine the night before surgery, with the dose equivalent to the total 24-hour basal insulin dose delivered by the pump. Two hours after the glargine dose is given, the patient should disconnect the pump and leave it at home.

Glycemic control in the hospital

As noted before, poor glycemic control can lead to poor wound healing from impaired leukocyte function, which can lead to decreased chemotaxis, phagocytosis, and bacteriocidal activity.

The risk of bacteremia is especially high among patients who are on total parenteral nutrition with poorly controlled glucose levels, he noted.

Forces conspiring against glucose control in the hospital can include elevated levels of hormones that counterregulate glucose; nausea/vomiting, anorexia, or nothing-by-mouth orders; erratic meal timing due to tests or interventions; intravenous glucose; glucocorticoid therapy; and "physician indifference and lack of attention to required adjustments in therapy," Dr. Baldwin noted.

Evidence from a randomized study showed that in patients with type 2 diabetes undergoing general surgery, basal-bolus treatment with insulin glargine once daily plus insulin glulisine before meals both improved glycemic control and reduced hospital complications compared with sliding-scale insulin therapy, he reported.

Hyper- and hypothyroid patients

Switching endocrinology hats, Dr. Baldwin said that patients who have significant weight loss or resting tachycardia before surgery should be evaluated for hyperthyroidism. A good rule of thumb is that in patients with hyperthyroidism, all but emergency procedures should be postponed until the condition can be controlled with methimazole.

Patients with undiagnosed or untreated hyperthyroidism who undergo anesthesia and surgery are at high risk for thyroid storm, a provoked crisis of multiorgan failure, he said.

If the surgery cannot be delayed until elevated levels of thyroxine are achieved, the team can initiate oral or intravenous beta-blockade, or if the patient is in critical condition, infusion with the beta-1 receptor blocker esmolol (Brevibloc) is preferred, he said.

Patients should also be started on methimazole 30-40 mg/day, and the patient should be given iodine if she has not already received iodinated radiologic contrast. Stress dose glucocorticoids and adequate volume resuscitation may also provide support in this situation.

In contrast, "hypothyroidism is usually not a big deal," Dr. Baldwin said.

Such patients usually tolerate major surgery without significant complications, he said, but patients with hypothyroidism may be more sensitive to sedatives, slower to wean from ventilation, and handle free-water excretion less well than euthyroid patients.

Patients who take levothyroxine (Synthroid and generics) should always have their free T₄ and thyroid-stimulating hormone (thyrotropin) levels checked during preoperative evaluation, he said.

Dr. Baldwin reported having no relevant financial conflicts of interest.

Controlling hyperglycemia before and after surgery in patients with diabetes is a balancing act, but when done properly, it can reduce infections and wound complications, according to Dr. David Baldwin.

The key to preoperative planning for patients with diabetes is a full list of medications and an understanding of how well (or how poorly) patients’ glycemia is controlled, said Dr. Baldwin, an endocrinologist at Rush University Medical Center in Chicago.

He discussed strategies for perioperative management of patients with diabetes and thyroid disorders at the Perioperative Medicine Summit 2014."You definitely want to write down exactly what they are and aren’t taking. We find that the medication list for people getting admitted for surgery is often fraught with a lack of little details," he said.

For patients with type 2 diabetes, it’s important to record an accurate description of antidiabetes medications, especially combination oral agents such as Actoplus MET (metformin and pioglitazone) or Janumet (sitagliptin and metformin). For patients with type 1 and 2 diabetes, it is important to record not just the type of insulin but the regimen the patient uses. Dr. Baldwin noted that many intake staff make the mistake of reporting that patients take "Novolin" or "Humulin," which are brand families of insulin and not specific insulin types.

"We often find, probably at least half of the time, that until we actually go and ask the patients what they take for insulin post-op, the correct information won’t have been in the medical record," he said.

The best way to determine whether a patient has good control of chronic hyperglycemia is with a hemoglobin A_1c (HbA_1c) level. A value above 6.5% is diagnostic for diabetes; well-controlled patients have HbA_1c levels from 6% to 8%. HbA1c values not more than 2 months old should be a routine part of preoperative evaluations for patients with diabetes or newly discovered hyperglycemia, Dr. Baldwin said.

Preoperative medications
The Rush University protocol for the preoperative management of antidiabetic therapies other than insulin notes that sulfonylureas, metformin, pioglitazone, exenatide, liraglutide, sitagliptin, linagliptin, saxagliptin, alogliptin, alpha-glucosidase inhibitors, and canagaflozin may all be taken with food on the eve of surgery, but none should be taken on the morning of surgery.

Specific rules also apply for patients who use insulin, depending on the insulin type, as follows:

• For long-acting insulins (glargine or detemir), the patient should take the full dose on the evening before surgery or the morning of surgery if the dose is prescribed for either morning or evening administration. Patients with prescriptions for a b.i.d. dose should take the full dose both the evening before and the morning of surgery.

• With intermediate-acting insulin (NPH), the patient should take the full dose on the evening before surgery and 80% of the morning dose on the morning of surgery.

• For rapid-acting insulins (aspart, lispro, glulisine, or regular) and premixed insulins (NPH or rapid acting), the patient should take the full dose with dinner the night before, and none on the morning of surgery.

Dr. Baldwin emphasized that except in rare circumstances, patients on subcutaneous insulin pumps should not use the pumps during surgery, and should get special instructions from their endocrinologists.

Ideally, the patient can convert to insulin glargine the night before surgery, with the dose equivalent to the total 24-hour basal insulin dose delivered by the pump. Two hours after the glargine dose is given, the patient should disconnect the pump and leave it at home.

Glycemic control in the hospital

As noted before, poor glycemic control can lead to poor wound healing from impaired leukocyte function, which can lead to decreased chemotaxis, phagocytosis, and bacteriocidal activity.

The risk of bacteremia is especially high among patients who are on total parenteral nutrition with poorly controlled glucose levels, he noted.

Forces conspiring against glucose control in the hospital can include elevated levels of hormones that counterregulate glucose; nausea/vomiting, anorexia, or nothing-by-mouth orders; erratic meal timing due to tests or interventions; intravenous glucose; glucocorticoid therapy; and "physician indifference and lack of attention to required adjustments in therapy," Dr. Baldwin noted.

Evidence from a randomized study showed that in patients with type 2 diabetes undergoing general surgery, basal-bolus treatment with insulin glargine once daily plus insulin glulisine before meals both improved glycemic control and reduced hospital complications compared with sliding-scale insulin therapy, he reported.

Hyper- and hypothyroid patients

Switching endocrinology hats, Dr. Baldwin said that patients who have significant weight loss or resting tachycardia before surgery should be evaluated for hyperthyroidism. A good rule of thumb is that in patients with hyperthyroidism, all but emergency procedures should be postponed until the condition can be controlled with methimazole.

Patients with undiagnosed or untreated hyperthyroidism who undergo anesthesia and surgery are at high risk for thyroid storm, a provoked crisis of multiorgan failure, he said.

If the surgery cannot be delayed until elevated levels of thyroxine are achieved, the team can initiate oral or intravenous beta-blockade, or if the patient is in critical condition, infusion with the beta-1 receptor blocker esmolol (Brevibloc) is preferred, he said.

Patients should also be started on methimazole 30-40 mg/day, and the patient should be given iodine if she has not already received iodinated radiologic contrast. Stress dose glucocorticoids and adequate volume resuscitation may also provide support in this situation.

In contrast, "hypothyroidism is usually not a big deal," Dr. Baldwin said.

Such patients usually tolerate major surgery without significant complications, he said, but patients with hypothyroidism may be more sensitive to sedatives, slower to wean from ventilation, and handle free-water excretion less well than euthyroid patients.

Patients who take levothyroxine (Synthroid and generics) should always have their free T₄ and thyroid-stimulating hormone (thyrotropin) levels checked during preoperative evaluation, he said.

Dr. Baldwin reported having no relevant financial conflicts of interest.

Controlling hyperglycemia before and after surgery in patients with diabetes is a balancing act, but when done properly, it can reduce infections and wound complications, according to Dr. David Baldwin.

The key to preoperative planning for patients with diabetes is a full list of medications and an understanding of how well (or how poorly) patients’ glycemia is controlled, said Dr. Baldwin, an endocrinologist at Rush University Medical Center in Chicago.

He discussed strategies for perioperative management of patients with diabetes and thyroid disorders at the Perioperative Medicine Summit 2014."You definitely want to write down exactly what they are and aren’t taking. We find that the medication list for people getting admitted for surgery is often fraught with a lack of little details," he said.

For patients with type 2 diabetes, it’s important to record an accurate description of antidiabetes medications, especially combination oral agents such as Actoplus MET (metformin and pioglitazone) or Janumet (sitagliptin and metformin). For patients with type 1 and 2 diabetes, it is important to record not just the type of insulin but the regimen the patient uses. Dr. Baldwin noted that many intake staff make the mistake of reporting that patients take "Novolin" or "Humulin," which are brand families of insulin and not specific insulin types.

"We often find, probably at least half of the time, that until we actually go and ask the patients what they take for insulin post-op, the correct information won’t have been in the medical record," he said.

The best way to determine whether a patient has good control of chronic hyperglycemia is with a hemoglobin A_1c (HbA_1c) level. A value above 6.5% is diagnostic for diabetes; well-controlled patients have HbA_1c levels from 6% to 8%. HbA1c values not more than 2 months old should be a routine part of preoperative evaluations for patients with diabetes or newly discovered hyperglycemia, Dr. Baldwin said.

Preoperative medications
The Rush University protocol for the preoperative management of antidiabetic therapies other than insulin notes that sulfonylureas, metformin, pioglitazone, exenatide, liraglutide, sitagliptin, linagliptin, saxagliptin, alogliptin, alpha-glucosidase inhibitors, and canagaflozin may all be taken with food on the eve of surgery, but none should be taken on the morning of surgery.

Specific rules also apply for patients who use insulin, depending on the insulin type, as follows:

• For long-acting insulins (glargine or detemir), the patient should take the full dose on the evening before surgery or the morning of surgery if the dose is prescribed for either morning or evening administration. Patients with prescriptions for a b.i.d. dose should take the full dose both the evening before and the morning of surgery.

• With intermediate-acting insulin (NPH), the patient should take the full dose on the evening before surgery and 80% of the morning dose on the morning of surgery.

• For rapid-acting insulins (aspart, lispro, glulisine, or regular) and premixed insulins (NPH or rapid acting), the patient should take the full dose with dinner the night before, and none on the morning of surgery.

Dr. Baldwin emphasized that except in rare circumstances, patients on subcutaneous insulin pumps should not use the pumps during surgery, and should get special instructions from their endocrinologists.

Ideally, the patient can convert to insulin glargine the night before surgery, with the dose equivalent to the total 24-hour basal insulin dose delivered by the pump. Two hours after the glargine dose is given, the patient should disconnect the pump and leave it at home.

Glycemic control in the hospital

As noted before, poor glycemic control can lead to poor wound healing from impaired leukocyte function, which can lead to decreased chemotaxis, phagocytosis, and bacteriocidal activity.

The risk of bacteremia is especially high among patients who are on total parenteral nutrition with poorly controlled glucose levels, he noted.

Forces conspiring against glucose control in the hospital can include elevated levels of hormones that counterregulate glucose; nausea/vomiting, anorexia, or nothing-by-mouth orders; erratic meal timing due to tests or interventions; intravenous glucose; glucocorticoid therapy; and "physician indifference and lack of attention to required adjustments in therapy," Dr. Baldwin noted.

Evidence from a randomized study showed that in patients with type 2 diabetes undergoing general surgery, basal-bolus treatment with insulin glargine once daily plus insulin glulisine before meals both improved glycemic control and reduced hospital complications compared with sliding-scale insulin therapy, he reported.

Hyper- and hypothyroid patients

Switching endocrinology hats, Dr. Baldwin said that patients who have significant weight loss or resting tachycardia before surgery should be evaluated for hyperthyroidism. A good rule of thumb is that in patients with hyperthyroidism, all but emergency procedures should be postponed until the condition can be controlled with methimazole.

Patients with undiagnosed or untreated hyperthyroidism who undergo anesthesia and surgery are at high risk for thyroid storm, a provoked crisis of multiorgan failure, he said.

If the surgery cannot be delayed until elevated levels of thyroxine are achieved, the team can initiate oral or intravenous beta-blockade, or if the patient is in critical condition, infusion with the beta-1 receptor blocker esmolol (Brevibloc) is preferred, he said.

Patients should also be started on methimazole 30-40 mg/day, and the patient should be given iodine if she has not already received iodinated radiologic contrast. Stress dose glucocorticoids and adequate volume resuscitation may also provide support in this situation.

In contrast, "hypothyroidism is usually not a big deal," Dr. Baldwin said.

Such patients usually tolerate major surgery without significant complications, he said, but patients with hypothyroidism may be more sensitive to sedatives, slower to wean from ventilation, and handle free-water excretion less well than euthyroid patients.

Patients who take levothyroxine (Synthroid and generics) should always have their free T₄ and thyroid-stimulating hormone (thyrotropin) levels checked during preoperative evaluation, he said.

Dr. Baldwin reported having no relevant financial conflicts of interest.

PHOENIX – Seeing is not always believing when it comes to determining whether pancreatic adenocarcinomas are resectable.

In patients with locally advanced or borderline resectable pancreatic adenocarcinoma who underwent neoadjuvant therapy with the FOLFIRINOX regimen (leucovorin, fluorouracil, irinotecan, and oxaliplatin), presurgical imaging was not a reliable determinant of resectability, said Dr. Cristina R. Ferrone from the department of general and gastrointestinal surgery at Massachusetts General Hospital in Boston.

Neil Osterweil/Frontline Medical News

"It really is a paradigm shift that we can’t rely on CT scans and MRIs the way we did before," she said at the annual Society of Surgical Oncology Cancer Symposium.

An important case

For her team, the paradigm shift was sparked by the case of a 41-year-old woman who presented with a 3.6-cm pancreatic adenocarcinoma involving the superior mesenteric artery (SMA), and a cancer antigen 19-9 (CA 19-9) level of 985 U/mL (normal values for the nonspecific biomarker range from 0 to 37 U/mL, according to National Comprehensive Cancer Network guidelines).

Following 4 months of FOLFIRINOX and 50.4 Gy of chemoradiation, her CA 19-9 level normalized to 37 U/mL. But her postchemotherapy imaging studies appeared identical to her prechemotherapy studies, with no apparent evidence of tumor regression and apparent continued involvement of the SMA following FOLFIRINOX.

"We had a big debate about this woman, because she had a normalized CA 19-9. Do we attempt to resect a patient like this?" Dr. Ferrone said.

After considerable discussion, the decision was made to take the patient into the operating room, approach the pancreas from the left side, and perform intraoperative biopsies on the SMA. If the biopsies were positive, the surgical team would either perform intraoperative radiation therapy (IORT) or use a soft-tissue ablation system (Nanoknife). If the biopsies were negative, the team would proceed to resection.

The patient went on to resection, and was found to have only minimal residual tumor on postoperative pathology samples, Dr. Ferrone reported.

Case comparisons

To see whether other patients could benefit from a similar approach, the investigators compared outcomes for 87 patients who underwent upfront resection for presumed organ-confined disease and 38 patients who received neoadjuvant FOLFIRINOX before surgery. Of the latter group, 5 received FOLFIRINOX chemotherapy only; 16 received FOLFIRINOX and 50.4 Gy of radiation; 10 received FOLFIRINOX, radiation, and IORT; 4 received FOLFIRINOX and proton-beam therapy; and 3 had FOLFIRINOX with other drug therapies.

The median CA 19-9 level fell from 169 U/mL before FOLFIRINOX to 16 U/mL after (P = .003), and more than twice as many patients had levels below 40 U/mL after therapy (31% vs. 72%; P = .03)

Median tumor diameter on CT also decreased after chemotherapy, from 3.6 cm to 2.2 cm (P = .001).

Pathology review of images from 20 cases with the observer blinded to treatment status showed 14 cases judged to be locally advanced disease and 6 borderline pre-FOLFIRINOX, and 12 locally advanced cases, 3 borderline, and 5 cases deemed resectable post-FOLFIRINOX.

When the investigators compared clinical and operative results in the surgery-only patients vs. results in those who had neoadjuvant FOLFIRINOX, they found that the latter group had higher mean operative times (300 minutes for surgery-only patients vs. 393 minutes for FOLFIRINOX-treated patients; P less than .001) and higher mean blood loss (400 mL vs. 600 mL, respectively; P = .01).

However, patients who received neoadjuvant therapy had significantly fewer postoperative complications (63% vs. 35% of patients; P = .004) and fewer pancreatic fistulas (29% vs. 0%; P less than .001).

Patients who received FOLFIRINOX also had a lower proportion of readmissions within 90 days (30% vs. 21%); shorter lengths of stay (7 days vs. 6 days); and no deaths, compared with 1 in the up-front surgery group, but these differences were not significant.

Pathology results showed that 79% of the surgery-only patients had positive lymph nodes, compared with only 37% of those in the neoadjuvant group (P less than .001). The neoadjuvant group also had lower proportions of both lymphatic invasion (70% vs. 37%, P less than .001) and perineural invasion (P less than .001).

There were proportionally more R0 (clean margin) resections in the FOLFIRINOX group, but the difference was not significant.

After a median follow-up of 10 months for the up-front surgery patients and 12 months for the FOLFIRINOX-treated patients, there have been no differences in local or distant progression or deaths from pancreatic cancer. Dr. Ferrone acknowledged that a larger patient sample and longer follow-up may be needed to detect significant differences.

However, Kaplan-Meier overall survival estimates from the time of diagnosis out to 34 months significantly favor the FOLFIRINOX-treated patients (P = .02).

"With this therapeutic modality and intensive surgical interventions, we hope that we are making an impact in these patients’ lives and improving their survival," she said.

The study was internally supported. Dr. Ferrone reported having no financial disclosures.

PHOENIX – Seeing is not always believing when it comes to determining whether pancreatic adenocarcinomas are resectable.

In patients with locally advanced or borderline resectable pancreatic adenocarcinoma who underwent neoadjuvant therapy with the FOLFIRINOX regimen (leucovorin, fluorouracil, irinotecan, and oxaliplatin), presurgical imaging was not a reliable determinant of resectability, said Dr. Cristina R. Ferrone from the department of general and gastrointestinal surgery at Massachusetts General Hospital in Boston.

Neil Osterweil/Frontline Medical News

"It really is a paradigm shift that we can’t rely on CT scans and MRIs the way we did before," she said at the annual Society of Surgical Oncology Cancer Symposium.

An important case

For her team, the paradigm shift was sparked by the case of a 41-year-old woman who presented with a 3.6-cm pancreatic adenocarcinoma involving the superior mesenteric artery (SMA), and a cancer antigen 19-9 (CA 19-9) level of 985 U/mL (normal values for the nonspecific biomarker range from 0 to 37 U/mL, according to National Comprehensive Cancer Network guidelines).

Following 4 months of FOLFIRINOX and 50.4 Gy of chemoradiation, her CA 19-9 level normalized to 37 U/mL. But her postchemotherapy imaging studies appeared identical to her prechemotherapy studies, with no apparent evidence of tumor regression and apparent continued involvement of the SMA following FOLFIRINOX.

"We had a big debate about this woman, because she had a normalized CA 19-9. Do we attempt to resect a patient like this?" Dr. Ferrone said.

After considerable discussion, the decision was made to take the patient into the operating room, approach the pancreas from the left side, and perform intraoperative biopsies on the SMA. If the biopsies were positive, the surgical team would either perform intraoperative radiation therapy (IORT) or use a soft-tissue ablation system (Nanoknife). If the biopsies were negative, the team would proceed to resection.

The patient went on to resection, and was found to have only minimal residual tumor on postoperative pathology samples, Dr. Ferrone reported.

Case comparisons

To see whether other patients could benefit from a similar approach, the investigators compared outcomes for 87 patients who underwent upfront resection for presumed organ-confined disease and 38 patients who received neoadjuvant FOLFIRINOX before surgery. Of the latter group, 5 received FOLFIRINOX chemotherapy only; 16 received FOLFIRINOX and 50.4 Gy of radiation; 10 received FOLFIRINOX, radiation, and IORT; 4 received FOLFIRINOX and proton-beam therapy; and 3 had FOLFIRINOX with other drug therapies.

The median CA 19-9 level fell from 169 U/mL before FOLFIRINOX to 16 U/mL after (P = .003), and more than twice as many patients had levels below 40 U/mL after therapy (31% vs. 72%; P = .03)

Median tumor diameter on CT also decreased after chemotherapy, from 3.6 cm to 2.2 cm (P = .001).

Pathology review of images from 20 cases with the observer blinded to treatment status showed 14 cases judged to be locally advanced disease and 6 borderline pre-FOLFIRINOX, and 12 locally advanced cases, 3 borderline, and 5 cases deemed resectable post-FOLFIRINOX.

When the investigators compared clinical and operative results in the surgery-only patients vs. results in those who had neoadjuvant FOLFIRINOX, they found that the latter group had higher mean operative times (300 minutes for surgery-only patients vs. 393 minutes for FOLFIRINOX-treated patients; P less than .001) and higher mean blood loss (400 mL vs. 600 mL, respectively; P = .01).

However, patients who received neoadjuvant therapy had significantly fewer postoperative complications (63% vs. 35% of patients; P = .004) and fewer pancreatic fistulas (29% vs. 0%; P less than .001).

Patients who received FOLFIRINOX also had a lower proportion of readmissions within 90 days (30% vs. 21%); shorter lengths of stay (7 days vs. 6 days); and no deaths, compared with 1 in the up-front surgery group, but these differences were not significant.

Pathology results showed that 79% of the surgery-only patients had positive lymph nodes, compared with only 37% of those in the neoadjuvant group (P less than .001). The neoadjuvant group also had lower proportions of both lymphatic invasion (70% vs. 37%, P less than .001) and perineural invasion (P less than .001).

There were proportionally more R0 (clean margin) resections in the FOLFIRINOX group, but the difference was not significant.

After a median follow-up of 10 months for the up-front surgery patients and 12 months for the FOLFIRINOX-treated patients, there have been no differences in local or distant progression or deaths from pancreatic cancer. Dr. Ferrone acknowledged that a larger patient sample and longer follow-up may be needed to detect significant differences.

However, Kaplan-Meier overall survival estimates from the time of diagnosis out to 34 months significantly favor the FOLFIRINOX-treated patients (P = .02).

"With this therapeutic modality and intensive surgical interventions, we hope that we are making an impact in these patients’ lives and improving their survival," she said.

The study was internally supported. Dr. Ferrone reported having no financial disclosures.

PHOENIX – Seeing is not always believing when it comes to determining whether pancreatic adenocarcinomas are resectable.

In patients with locally advanced or borderline resectable pancreatic adenocarcinoma who underwent neoadjuvant therapy with the FOLFIRINOX regimen (leucovorin, fluorouracil, irinotecan, and oxaliplatin), presurgical imaging was not a reliable determinant of resectability, said Dr. Cristina R. Ferrone from the department of general and gastrointestinal surgery at Massachusetts General Hospital in Boston.

Neil Osterweil/Frontline Medical News

"It really is a paradigm shift that we can’t rely on CT scans and MRIs the way we did before," she said at the annual Society of Surgical Oncology Cancer Symposium.

An important case

For her team, the paradigm shift was sparked by the case of a 41-year-old woman who presented with a 3.6-cm pancreatic adenocarcinoma involving the superior mesenteric artery (SMA), and a cancer antigen 19-9 (CA 19-9) level of 985 U/mL (normal values for the nonspecific biomarker range from 0 to 37 U/mL, according to National Comprehensive Cancer Network guidelines).

Following 4 months of FOLFIRINOX and 50.4 Gy of chemoradiation, her CA 19-9 level normalized to 37 U/mL. But her postchemotherapy imaging studies appeared identical to her prechemotherapy studies, with no apparent evidence of tumor regression and apparent continued involvement of the SMA following FOLFIRINOX.

"We had a big debate about this woman, because she had a normalized CA 19-9. Do we attempt to resect a patient like this?" Dr. Ferrone said.

After considerable discussion, the decision was made to take the patient into the operating room, approach the pancreas from the left side, and perform intraoperative biopsies on the SMA. If the biopsies were positive, the surgical team would either perform intraoperative radiation therapy (IORT) or use a soft-tissue ablation system (Nanoknife). If the biopsies were negative, the team would proceed to resection.

The patient went on to resection, and was found to have only minimal residual tumor on postoperative pathology samples, Dr. Ferrone reported.

Case comparisons

To see whether other patients could benefit from a similar approach, the investigators compared outcomes for 87 patients who underwent upfront resection for presumed organ-confined disease and 38 patients who received neoadjuvant FOLFIRINOX before surgery. Of the latter group, 5 received FOLFIRINOX chemotherapy only; 16 received FOLFIRINOX and 50.4 Gy of radiation; 10 received FOLFIRINOX, radiation, and IORT; 4 received FOLFIRINOX and proton-beam therapy; and 3 had FOLFIRINOX with other drug therapies.

The median CA 19-9 level fell from 169 U/mL before FOLFIRINOX to 16 U/mL after (P = .003), and more than twice as many patients had levels below 40 U/mL after therapy (31% vs. 72%; P = .03)

Median tumor diameter on CT also decreased after chemotherapy, from 3.6 cm to 2.2 cm (P = .001).

Pathology review of images from 20 cases with the observer blinded to treatment status showed 14 cases judged to be locally advanced disease and 6 borderline pre-FOLFIRINOX, and 12 locally advanced cases, 3 borderline, and 5 cases deemed resectable post-FOLFIRINOX.

When the investigators compared clinical and operative results in the surgery-only patients vs. results in those who had neoadjuvant FOLFIRINOX, they found that the latter group had higher mean operative times (300 minutes for surgery-only patients vs. 393 minutes for FOLFIRINOX-treated patients; P less than .001) and higher mean blood loss (400 mL vs. 600 mL, respectively; P = .01).

However, patients who received neoadjuvant therapy had significantly fewer postoperative complications (63% vs. 35% of patients; P = .004) and fewer pancreatic fistulas (29% vs. 0%; P less than .001).

Patients who received FOLFIRINOX also had a lower proportion of readmissions within 90 days (30% vs. 21%); shorter lengths of stay (7 days vs. 6 days); and no deaths, compared with 1 in the up-front surgery group, but these differences were not significant.

Pathology results showed that 79% of the surgery-only patients had positive lymph nodes, compared with only 37% of those in the neoadjuvant group (P less than .001). The neoadjuvant group also had lower proportions of both lymphatic invasion (70% vs. 37%, P less than .001) and perineural invasion (P less than .001).

There were proportionally more R0 (clean margin) resections in the FOLFIRINOX group, but the difference was not significant.

After a median follow-up of 10 months for the up-front surgery patients and 12 months for the FOLFIRINOX-treated patients, there have been no differences in local or distant progression or deaths from pancreatic cancer. Dr. Ferrone acknowledged that a larger patient sample and longer follow-up may be needed to detect significant differences.

However, Kaplan-Meier overall survival estimates from the time of diagnosis out to 34 months significantly favor the FOLFIRINOX-treated patients (P = .02).

"With this therapeutic modality and intensive surgical interventions, we hope that we are making an impact in these patients’ lives and improving their survival," she said.

The study was internally supported. Dr. Ferrone reported having no financial disclosures.

PHOENIX – Hope remains for patients with advanced cancers, even after curative-intent surgery fails them, investigators reported at the annual Society of Surgical Oncology Cancer Symposium.

A study of the effects of an online decision aid for advance care planning showed that patients whose cancers had advanced despite initial curative-intent surgery had degrees of hope and desires for the aggressiveness of additional therapy similar to those of patients who had undergone palliative therapy only, said Dr. Niraj J. Gusani, FACS, of Penn State College of Medicine, Hershey, Pa.

"As we do more advance care planning, stratify patients, and get them into these programs to help them figure out what their wishes really are, we should treat everybody the same , and they should all have a durable advance care planning process, maybe using a decision aid such as this," he said.

The results show that outcomes beyond whether a patient lives or dies also matter, commented Dr. Steven Chen, FACS, from City of Hope Medical Center, Duarte, Calif.

"The thing that patients care about at least as much as how long they’re going to live is how well they’re going to live until they die," he said in an interview. Dr. Chen was not involved in the study, but comoderated the poster discussion session where it was presented.

"Almost all of my patients have very advanced cancers with poor prognosis, and it’s all about their quality of life and how they’re going to feel," Dr. Gusani agreed. "They intuitively get that they have a poor prognosis, but if we can get them through with a better experience with their time and they are able to maintain their hope, then it makes a world of difference for the patient and the family as well."

Multimedia advance care planning

Dr. Gusani and his colleagues looked at data from a clinical trial evaluating the effects of an online multimedia decision aid tool for patients with advanced-stage disease. The program, called Making Your Wishes Known: Planning Your Medical Future, was developed by two of the authors.

The program "provides tailored education, values-clarification exercises, and a decision-making tool that translates an individual’s values and preferences into a specific medical plan than can be implemented by a health care team," they wrote.

The investigators hypothesized that patients who went into surgery hoping for or expecting a cure might opt for more aggressive treatment at the end of life and have more hope and/or less hopelessness than patients who underwent treatments that they knew would not be curative.

The researchers administered the advance care planning program to 159 patients from the parent clinical trial, in which 200 patients with stage IV cancers who were judged to have less than 12 months to live were randomly assigned to receive either standard advance care planning or the decision aid. All of the patients had non–central nervous system and nonhematologic malignancies and were classified as having had initial curative-intent surgery or treatment without curative intent (e.g., palliative therapy and tumor debulking).

Making patients’ wishes known

Both at baseline and after the intervention, the patients were rated for hope on the 12-item Herth Hope Index, with scores from 12 (low hope) to 48 (high hope), and for hopelessness on the 7-item Beck Hopelessness Scale, in which 0 is no hopelessness and 7 is the highest level of despair.

The patients were also asked to rate their desires for aggressiveness of additional therapy by choosing one of six general wishes statements. For this scale, questions 1-4 were deemed to be more aggressive, and 5-6 less aggressive.

Additionally, patients who used the decision aid were rated on a treatment aggressiveness scale scored from 0 (least aggressive) to 40 (most) based on their responses to questions within the decision aid that asked about their wishes for eight different treatments (such as mechanical ventilation or cardiopulmonary resuscitation) under five clinical scenarios (such as stroke or dementia).

In all, 46 of 95 patients (48%) who had originally had curative-intent surgery received the control intervention, and 49 (52%) received the decision aid. Of the 64 patients who had non–curative-intent therapy, 35 (52%) received standard advance care planning and 31 (48%) received the Making Your Wishes Known aid.

After either intervention, patients who had curative-intent surgery had a slight but not significant increase in hope, and patients in the non–curative-intent group had a slight but not significant decrease. There was no significant between-group difference.

Similarly, each group had a slight decrease in hopelessness scores, with no significant differences between the groups.

There were also no significant variations in the distribution of the general wishes statements between the curative and noncurative groups or between the decision-aid and control groups, nor were there differences in the median treatment aggressiveness score of patients who used the decision aid, regardless of whether they had initially had curative-intent surgery.

"Regardless of what they choose in terms of their level of aggressiveness, the patients are more satisfied with their decision, they feel more informed, and caregiver satisfaction has improved with the decision aid compared with traditional materials," Dr. Gusani said.

"This is really important work," commented Dr. Sandra L. Wong of the University of Michigan Medical Center, Ann Arbor, who comoderated the poster discussion session.

The study was supported by Penn State College of Medicine. Dr. Gusani, Dr. Chen, and Dr. Wong reported having no financial conflicts of interest.

PHOENIX – Hope remains for patients with advanced cancers, even after curative-intent surgery fails them, investigators reported at the annual Society of Surgical Oncology Cancer Symposium.

A study of the effects of an online decision aid for advance care planning showed that patients whose cancers had advanced despite initial curative-intent surgery had degrees of hope and desires for the aggressiveness of additional therapy similar to those of patients who had undergone palliative therapy only, said Dr. Niraj J. Gusani, FACS, of Penn State College of Medicine, Hershey, Pa.

"As we do more advance care planning, stratify patients, and get them into these programs to help them figure out what their wishes really are, we should treat everybody the same , and they should all have a durable advance care planning process, maybe using a decision aid such as this," he said.

The results show that outcomes beyond whether a patient lives or dies also matter, commented Dr. Steven Chen, FACS, from City of Hope Medical Center, Duarte, Calif.

"The thing that patients care about at least as much as how long they’re going to live is how well they’re going to live until they die," he said in an interview. Dr. Chen was not involved in the study, but comoderated the poster discussion session where it was presented.

"Almost all of my patients have very advanced cancers with poor prognosis, and it’s all about their quality of life and how they’re going to feel," Dr. Gusani agreed. "They intuitively get that they have a poor prognosis, but if we can get them through with a better experience with their time and they are able to maintain their hope, then it makes a world of difference for the patient and the family as well."

Multimedia advance care planning

Dr. Gusani and his colleagues looked at data from a clinical trial evaluating the effects of an online multimedia decision aid tool for patients with advanced-stage disease. The program, called Making Your Wishes Known: Planning Your Medical Future, was developed by two of the authors.

The program "provides tailored education, values-clarification exercises, and a decision-making tool that translates an individual’s values and preferences into a specific medical plan than can be implemented by a health care team," they wrote.

The investigators hypothesized that patients who went into surgery hoping for or expecting a cure might opt for more aggressive treatment at the end of life and have more hope and/or less hopelessness than patients who underwent treatments that they knew would not be curative.

The researchers administered the advance care planning program to 159 patients from the parent clinical trial, in which 200 patients with stage IV cancers who were judged to have less than 12 months to live were randomly assigned to receive either standard advance care planning or the decision aid. All of the patients had non–central nervous system and nonhematologic malignancies and were classified as having had initial curative-intent surgery or treatment without curative intent (e.g., palliative therapy and tumor debulking).

Making patients’ wishes known

Both at baseline and after the intervention, the patients were rated for hope on the 12-item Herth Hope Index, with scores from 12 (low hope) to 48 (high hope), and for hopelessness on the 7-item Beck Hopelessness Scale, in which 0 is no hopelessness and 7 is the highest level of despair.

The patients were also asked to rate their desires for aggressiveness of additional therapy by choosing one of six general wishes statements. For this scale, questions 1-4 were deemed to be more aggressive, and 5-6 less aggressive.

Additionally, patients who used the decision aid were rated on a treatment aggressiveness scale scored from 0 (least aggressive) to 40 (most) based on their responses to questions within the decision aid that asked about their wishes for eight different treatments (such as mechanical ventilation or cardiopulmonary resuscitation) under five clinical scenarios (such as stroke or dementia).

In all, 46 of 95 patients (48%) who had originally had curative-intent surgery received the control intervention, and 49 (52%) received the decision aid. Of the 64 patients who had non–curative-intent therapy, 35 (52%) received standard advance care planning and 31 (48%) received the Making Your Wishes Known aid.

After either intervention, patients who had curative-intent surgery had a slight but not significant increase in hope, and patients in the non–curative-intent group had a slight but not significant decrease. There was no significant between-group difference.

Similarly, each group had a slight decrease in hopelessness scores, with no significant differences between the groups.

There were also no significant variations in the distribution of the general wishes statements between the curative and noncurative groups or between the decision-aid and control groups, nor were there differences in the median treatment aggressiveness score of patients who used the decision aid, regardless of whether they had initially had curative-intent surgery.

"Regardless of what they choose in terms of their level of aggressiveness, the patients are more satisfied with their decision, they feel more informed, and caregiver satisfaction has improved with the decision aid compared with traditional materials," Dr. Gusani said.

"This is really important work," commented Dr. Sandra L. Wong of the University of Michigan Medical Center, Ann Arbor, who comoderated the poster discussion session.

The study was supported by Penn State College of Medicine. Dr. Gusani, Dr. Chen, and Dr. Wong reported having no financial conflicts of interest.

PHOENIX – Hope remains for patients with advanced cancers, even after curative-intent surgery fails them, investigators reported at the annual Society of Surgical Oncology Cancer Symposium.

A study of the effects of an online decision aid for advance care planning showed that patients whose cancers had advanced despite initial curative-intent surgery had degrees of hope and desires for the aggressiveness of additional therapy similar to those of patients who had undergone palliative therapy only, said Dr. Niraj J. Gusani, FACS, of Penn State College of Medicine, Hershey, Pa.

"As we do more advance care planning, stratify patients, and get them into these programs to help them figure out what their wishes really are, we should treat everybody the same , and they should all have a durable advance care planning process, maybe using a decision aid such as this," he said.

The results show that outcomes beyond whether a patient lives or dies also matter, commented Dr. Steven Chen, FACS, from City of Hope Medical Center, Duarte, Calif.

"The thing that patients care about at least as much as how long they’re going to live is how well they’re going to live until they die," he said in an interview. Dr. Chen was not involved in the study, but comoderated the poster discussion session where it was presented.

"Almost all of my patients have very advanced cancers with poor prognosis, and it’s all about their quality of life and how they’re going to feel," Dr. Gusani agreed. "They intuitively get that they have a poor prognosis, but if we can get them through with a better experience with their time and they are able to maintain their hope, then it makes a world of difference for the patient and the family as well."

Multimedia advance care planning

Dr. Gusani and his colleagues looked at data from a clinical trial evaluating the effects of an online multimedia decision aid tool for patients with advanced-stage disease. The program, called Making Your Wishes Known: Planning Your Medical Future, was developed by two of the authors.

The program "provides tailored education, values-clarification exercises, and a decision-making tool that translates an individual’s values and preferences into a specific medical plan than can be implemented by a health care team," they wrote.

The investigators hypothesized that patients who went into surgery hoping for or expecting a cure might opt for more aggressive treatment at the end of life and have more hope and/or less hopelessness than patients who underwent treatments that they knew would not be curative.

The researchers administered the advance care planning program to 159 patients from the parent clinical trial, in which 200 patients with stage IV cancers who were judged to have less than 12 months to live were randomly assigned to receive either standard advance care planning or the decision aid. All of the patients had non–central nervous system and nonhematologic malignancies and were classified as having had initial curative-intent surgery or treatment without curative intent (e.g., palliative therapy and tumor debulking).

Making patients’ wishes known

Both at baseline and after the intervention, the patients were rated for hope on the 12-item Herth Hope Index, with scores from 12 (low hope) to 48 (high hope), and for hopelessness on the 7-item Beck Hopelessness Scale, in which 0 is no hopelessness and 7 is the highest level of despair.

The patients were also asked to rate their desires for aggressiveness of additional therapy by choosing one of six general wishes statements. For this scale, questions 1-4 were deemed to be more aggressive, and 5-6 less aggressive.

Additionally, patients who used the decision aid were rated on a treatment aggressiveness scale scored from 0 (least aggressive) to 40 (most) based on their responses to questions within the decision aid that asked about their wishes for eight different treatments (such as mechanical ventilation or cardiopulmonary resuscitation) under five clinical scenarios (such as stroke or dementia).

In all, 46 of 95 patients (48%) who had originally had curative-intent surgery received the control intervention, and 49 (52%) received the decision aid. Of the 64 patients who had non–curative-intent therapy, 35 (52%) received standard advance care planning and 31 (48%) received the Making Your Wishes Known aid.

After either intervention, patients who had curative-intent surgery had a slight but not significant increase in hope, and patients in the non–curative-intent group had a slight but not significant decrease. There was no significant between-group difference.

Similarly, each group had a slight decrease in hopelessness scores, with no significant differences between the groups.

There were also no significant variations in the distribution of the general wishes statements between the curative and noncurative groups or between the decision-aid and control groups, nor were there differences in the median treatment aggressiveness score of patients who used the decision aid, regardless of whether they had initially had curative-intent surgery.

"Regardless of what they choose in terms of their level of aggressiveness, the patients are more satisfied with their decision, they feel more informed, and caregiver satisfaction has improved with the decision aid compared with traditional materials," Dr. Gusani said.

"This is really important work," commented Dr. Sandra L. Wong of the University of Michigan Medical Center, Ann Arbor, who comoderated the poster discussion session.

The study was supported by Penn State College of Medicine. Dr. Gusani, Dr. Chen, and Dr. Wong reported having no financial conflicts of interest.

SCOTTSDALE, ARIZ. – Concurrent chemoradiation offered better overall survival and disease-free survival than accelerated radiotherapy in patients with moderately advanced squamous cell carcinomas of the head and neck, investigators reported at the Multidisciplinary Head and Neck Symposium.

Actuarial rates of 2-year overall survival and disease-free survival in patients treated with concurrent chemoradiation (CCR) were significantly better than for patients treated with accelerated radiotherapy alone, reported Dr. Krzysztof Skladowski of the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Gliwice, Poland.

"CCR with conventional 7 weeks of fractionation and at least two courses of high-dose cisplatin is more effective than 6 weeks of accelerated radiotherapy alone," he said.

Even if patients can tolerate only a single course of cisplatin, CCR is still superior to accelerated radiation, he added.

The findings suggest that accelerated radiation protocols should be reserved for patients with more favorable prognosis, such as those with stage T2 disease with limited nodal involvement, and those who are positive for the human papillomavirus (HPV) p16 protein, Dr. Skladowski said at the symposium cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology.

The findings are "concordant with data that has been emerging now over approximately 10-14 years of the value of concurrent chemoradiation in head and neck cancer for a substantial cohort of patients over radiation alone," said Dr. Paul Harari of the University of Wisconsin, Madison, and the invited discussant.

Although a previous meta-analysis (Lancet 2006; 368:843-54) suggested that accelerated or hyperfractionated radiotherapy was associated with a 3.4% advantage in overall survival, compared with conventional radiotherapy over 5 years, there have been no randomized studies comparing accelerated radiotherapy protocols with concurrent chemoradiation in this population, Dr. Skladowski said.

He and colleagues compared the two modalities in 101 patients with moderately advanced cancers of the oropharynx (46 patients), hypopharynx (19), and larynx (36).

They defined moderately advanced cancers as stage T2N1-2, T3N0-2, or T4AN0-2 if the involved nodes are not larger than 3 cm in diameter. Patients with oropharyngeal cancers were tested for expression of the human papillomavirus (HPV) p16 protein.

Patients were randomly assigned to receive either concurrent chemoradiation with intensity-modulated radiation therapy–delivered doses of 66-70 Gy divided into 33-35 daily fractions over 45-49 days plus cisplatin 100 mg/m², delivered on days 1, 2 and 43, or to accelerated radiotherapy delivered via intensity-modulated radiation therapy in 1.8 Gy fractions 7 days/week to a total dose of 66.2-72 Gy.

Five patients in the CCR arm received only one dose of cisplatin, 30 received two doses, and 13 received the planned three doses.

At a median follow-up of 30 months, actuarial rates of 2-year overall survival of patients treated with CCR were 81%, compared with 62% for patients treated with accelerated radiation (P = .02). Disease-free survival rates were 75% and 60%, respectively (P = .05).

Acute adverse events were similar, with approximately 80% of patients in each treatment arm experiencing confluent mucositis, and about 10% having grade 3 dysphagia. There were no grade 4 toxicities.

The majority of treatment failures in each group were local, occurring in 21 of 52 patients treated with radiation alone, and in 11 of 49 patients treated with CCR (P = .03).

Significantly more deaths occurred in the radiation alone arm: 20 vs. 9 (P =.02).

The 2-year disease-free survival rate among patients in the CCR arm was dose dependent, at 60% of patients who received one course of cisplatin, 77% of those who received two courses, and 79% for those who received all three.

At the time of the analysis, all patients with oropharyngeal cancer who were positive for HPV p16 (five treated with accelerated radiation and six with CCR) were alive with no treatment failure. The overall survival rate for HPV-positive patients was 60% in the radiation only arm, and 80% in the CCR arm.

The study was supported by the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology. Dr. Skladowski reported having no financial disclosures. Dr. Harari has received research funding from Amgen.

SCOTTSDALE, ARIZ. – Concurrent chemoradiation offered better overall survival and disease-free survival than accelerated radiotherapy in patients with moderately advanced squamous cell carcinomas of the head and neck, investigators reported at the Multidisciplinary Head and Neck Symposium.

Actuarial rates of 2-year overall survival and disease-free survival in patients treated with concurrent chemoradiation (CCR) were significantly better than for patients treated with accelerated radiotherapy alone, reported Dr. Krzysztof Skladowski of the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Gliwice, Poland.

"CCR with conventional 7 weeks of fractionation and at least two courses of high-dose cisplatin is more effective than 6 weeks of accelerated radiotherapy alone," he said.

Even if patients can tolerate only a single course of cisplatin, CCR is still superior to accelerated radiation, he added.

The findings suggest that accelerated radiation protocols should be reserved for patients with more favorable prognosis, such as those with stage T2 disease with limited nodal involvement, and those who are positive for the human papillomavirus (HPV) p16 protein, Dr. Skladowski said at the symposium cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology.

The findings are "concordant with data that has been emerging now over approximately 10-14 years of the value of concurrent chemoradiation in head and neck cancer for a substantial cohort of patients over radiation alone," said Dr. Paul Harari of the University of Wisconsin, Madison, and the invited discussant.

Although a previous meta-analysis (Lancet 2006; 368:843-54) suggested that accelerated or hyperfractionated radiotherapy was associated with a 3.4% advantage in overall survival, compared with conventional radiotherapy over 5 years, there have been no randomized studies comparing accelerated radiotherapy protocols with concurrent chemoradiation in this population, Dr. Skladowski said.

He and colleagues compared the two modalities in 101 patients with moderately advanced cancers of the oropharynx (46 patients), hypopharynx (19), and larynx (36).

They defined moderately advanced cancers as stage T2N1-2, T3N0-2, or T4AN0-2 if the involved nodes are not larger than 3 cm in diameter. Patients with oropharyngeal cancers were tested for expression of the human papillomavirus (HPV) p16 protein.

Patients were randomly assigned to receive either concurrent chemoradiation with intensity-modulated radiation therapy–delivered doses of 66-70 Gy divided into 33-35 daily fractions over 45-49 days plus cisplatin 100 mg/m², delivered on days 1, 2 and 43, or to accelerated radiotherapy delivered via intensity-modulated radiation therapy in 1.8 Gy fractions 7 days/week to a total dose of 66.2-72 Gy.

Five patients in the CCR arm received only one dose of cisplatin, 30 received two doses, and 13 received the planned three doses.

At a median follow-up of 30 months, actuarial rates of 2-year overall survival of patients treated with CCR were 81%, compared with 62% for patients treated with accelerated radiation (P = .02). Disease-free survival rates were 75% and 60%, respectively (P = .05).

Acute adverse events were similar, with approximately 80% of patients in each treatment arm experiencing confluent mucositis, and about 10% having grade 3 dysphagia. There were no grade 4 toxicities.

The majority of treatment failures in each group were local, occurring in 21 of 52 patients treated with radiation alone, and in 11 of 49 patients treated with CCR (P = .03).

Significantly more deaths occurred in the radiation alone arm: 20 vs. 9 (P =.02).

The 2-year disease-free survival rate among patients in the CCR arm was dose dependent, at 60% of patients who received one course of cisplatin, 77% of those who received two courses, and 79% for those who received all three.

At the time of the analysis, all patients with oropharyngeal cancer who were positive for HPV p16 (five treated with accelerated radiation and six with CCR) were alive with no treatment failure. The overall survival rate for HPV-positive patients was 60% in the radiation only arm, and 80% in the CCR arm.

The study was supported by the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology. Dr. Skladowski reported having no financial disclosures. Dr. Harari has received research funding from Amgen.

SCOTTSDALE, ARIZ. – Concurrent chemoradiation offered better overall survival and disease-free survival than accelerated radiotherapy in patients with moderately advanced squamous cell carcinomas of the head and neck, investigators reported at the Multidisciplinary Head and Neck Symposium.

Actuarial rates of 2-year overall survival and disease-free survival in patients treated with concurrent chemoradiation (CCR) were significantly better than for patients treated with accelerated radiotherapy alone, reported Dr. Krzysztof Skladowski of the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Gliwice, Poland.

"CCR with conventional 7 weeks of fractionation and at least two courses of high-dose cisplatin is more effective than 6 weeks of accelerated radiotherapy alone," he said.

Even if patients can tolerate only a single course of cisplatin, CCR is still superior to accelerated radiation, he added.

The findings suggest that accelerated radiation protocols should be reserved for patients with more favorable prognosis, such as those with stage T2 disease with limited nodal involvement, and those who are positive for the human papillomavirus (HPV) p16 protein, Dr. Skladowski said at the symposium cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology.

The findings are "concordant with data that has been emerging now over approximately 10-14 years of the value of concurrent chemoradiation in head and neck cancer for a substantial cohort of patients over radiation alone," said Dr. Paul Harari of the University of Wisconsin, Madison, and the invited discussant.

Although a previous meta-analysis (Lancet 2006; 368:843-54) suggested that accelerated or hyperfractionated radiotherapy was associated with a 3.4% advantage in overall survival, compared with conventional radiotherapy over 5 years, there have been no randomized studies comparing accelerated radiotherapy protocols with concurrent chemoradiation in this population, Dr. Skladowski said.

He and colleagues compared the two modalities in 101 patients with moderately advanced cancers of the oropharynx (46 patients), hypopharynx (19), and larynx (36).

They defined moderately advanced cancers as stage T2N1-2, T3N0-2, or T4AN0-2 if the involved nodes are not larger than 3 cm in diameter. Patients with oropharyngeal cancers were tested for expression of the human papillomavirus (HPV) p16 protein.

Patients were randomly assigned to receive either concurrent chemoradiation with intensity-modulated radiation therapy–delivered doses of 66-70 Gy divided into 33-35 daily fractions over 45-49 days plus cisplatin 100 mg/m², delivered on days 1, 2 and 43, or to accelerated radiotherapy delivered via intensity-modulated radiation therapy in 1.8 Gy fractions 7 days/week to a total dose of 66.2-72 Gy.

Five patients in the CCR arm received only one dose of cisplatin, 30 received two doses, and 13 received the planned three doses.

At a median follow-up of 30 months, actuarial rates of 2-year overall survival of patients treated with CCR were 81%, compared with 62% for patients treated with accelerated radiation (P = .02). Disease-free survival rates were 75% and 60%, respectively (P = .05).

Acute adverse events were similar, with approximately 80% of patients in each treatment arm experiencing confluent mucositis, and about 10% having grade 3 dysphagia. There were no grade 4 toxicities.

The majority of treatment failures in each group were local, occurring in 21 of 52 patients treated with radiation alone, and in 11 of 49 patients treated with CCR (P = .03).

Significantly more deaths occurred in the radiation alone arm: 20 vs. 9 (P =.02).

The 2-year disease-free survival rate among patients in the CCR arm was dose dependent, at 60% of patients who received one course of cisplatin, 77% of those who received two courses, and 79% for those who received all three.

At the time of the analysis, all patients with oropharyngeal cancer who were positive for HPV p16 (five treated with accelerated radiation and six with CCR) were alive with no treatment failure. The overall survival rate for HPV-positive patients was 60% in the radiation only arm, and 80% in the CCR arm.

The study was supported by the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology. Dr. Skladowski reported having no financial disclosures. Dr. Harari has received research funding from Amgen.