Neil Osterweil

BOSTON – Relaxing eligibility criteria for cytoreductive surgery may improve overall survival among patients with carcinoid metastases to the liver, investigators report.

Lowering the debulking threshold from 90% to 70% and including patients with intermediate-grade disease and/or extrahepatic disease resulted in 5-year overall survival rates of 90%, compared with 61%-74% rates reported by other treatment centers, said Dr. Amanda N. Graff-Baker, a surgical oncology resident at the Oregon Health and Science University (OHSU), Portland.

Neil Osterweil/Frontline Medical News

"The use of expanded criteria would substantially increase the number of patients eligible for debulking without compromising survival," she reported at the annual meeting of the American Association of Endocrine Surgeons.

Carcinoid tumors, a subset of neuroendocrine tumors, originate in the enterochromaffin cells of the aerodigestive tract. Approximately 60% of these tumors occur in the gastrointestinal tract, most commonly in the small intestine.

Approximately 60%-80% of patients with small bowel carcinoid tumors will have metastases to the liver, with liver failure from hepatic replacement by tumor being the most common cause of death, she explained.

Although there are no standardized patient selection criteria for liver debulking surgery in these patients, many U.S. centers follow NANETS (North American Neuroendocrine Tumor Society) treatment guidelines, which recommend surgical excision of at least 90% of all visible tumor. In addition, many centers choose not to offer cytoreductive surgery to patients with extrahepatic disease, Dr. Graff-Baker said.

Using these criteria, centers have reported 5-year survival rates ranging from 61% to 74%, but only about 20% of patients with carcinoid metastases to the liver are eligible for resection.

The investigators hypothesized that expanded eligibility criteria used at OHSU for several years could improve both liver progression-free and disease-specific survival rates. The criteria include a lower liver debulking threshold (70% or greater) and allow inclusion of patients with extrahepatic disease and/or intermediate-grade tumors.

They tested this idea by reviewing records of patients with metastatic carcinoid tumors who underwent liver debulking procedures at their center from 2007 to 2011. A single pathologist rated the grade of primary and metastatic tumors, and investigators correlated clinical factors with outcomes.

They identified a total of 52 patients, ranging in age from 29 to 77 years. Of this group, 32 (62%) had carcinoid syndrome, and 34 (65%) had extrahepatic disease.

The patients underwent a total of 51 wedge resections and 16 anatomic resections.

The mean number of metastases resected was 22 (range, 1-131). The mean size of metastases was 3 cm (range, 0.3-16 cm).

On pathologic review, all primary tumors were found to be low grade, but one-third of patients had one or more intermediate-grade metastases, suggesting a significant degree of tumor heterogeneity, Dr. Graff-Baker said.

The median liver progression-free survival was 72 months. A comparison between patients with liver progression and those with stable liver disease showed that there were no significant differences between the groups in either the percentage of tumor resected, number of resections, tumor size, presence of one or more intermediate-grade metastases, or extrahepatic disease. The only factor associated with a significant difference between groups was age. The mean age of patients with stable disease was 60.1 years, compared with 52 years for patients with liver progression (P = .016).

A separate analysis by age confirmed the last finding, with patients 50 years and older having significantly better liver progression-free survival than patients under age 50 (P = .001).

The 5-year disease-specific survival rate among all patients was 90%. All deaths were due to liver failure caused by tumor progression.

An analysis of factors predicting disease-specific survival showed once again that older patients for a change fared better than their more youthful counterparts (P = .03).

"The number, size, grade, extent of resection, and presence of extrahepatic disease did not have an adverse impact on outcomes," Dr. Graff-Baker said.

The study was internally funded. Dr. Graff-Baker reported having no financial disclosures.

BOSTON – Relaxing eligibility criteria for cytoreductive surgery may improve overall survival among patients with carcinoid metastases to the liver, investigators report.

Lowering the debulking threshold from 90% to 70% and including patients with intermediate-grade disease and/or extrahepatic disease resulted in 5-year overall survival rates of 90%, compared with 61%-74% rates reported by other treatment centers, said Dr. Amanda N. Graff-Baker, a surgical oncology resident at the Oregon Health and Science University (OHSU), Portland.

Neil Osterweil/Frontline Medical News

"The use of expanded criteria would substantially increase the number of patients eligible for debulking without compromising survival," she reported at the annual meeting of the American Association of Endocrine Surgeons.

Carcinoid tumors, a subset of neuroendocrine tumors, originate in the enterochromaffin cells of the aerodigestive tract. Approximately 60% of these tumors occur in the gastrointestinal tract, most commonly in the small intestine.

Approximately 60%-80% of patients with small bowel carcinoid tumors will have metastases to the liver, with liver failure from hepatic replacement by tumor being the most common cause of death, she explained.

Although there are no standardized patient selection criteria for liver debulking surgery in these patients, many U.S. centers follow NANETS (North American Neuroendocrine Tumor Society) treatment guidelines, which recommend surgical excision of at least 90% of all visible tumor. In addition, many centers choose not to offer cytoreductive surgery to patients with extrahepatic disease, Dr. Graff-Baker said.

Using these criteria, centers have reported 5-year survival rates ranging from 61% to 74%, but only about 20% of patients with carcinoid metastases to the liver are eligible for resection.

The investigators hypothesized that expanded eligibility criteria used at OHSU for several years could improve both liver progression-free and disease-specific survival rates. The criteria include a lower liver debulking threshold (70% or greater) and allow inclusion of patients with extrahepatic disease and/or intermediate-grade tumors.

They tested this idea by reviewing records of patients with metastatic carcinoid tumors who underwent liver debulking procedures at their center from 2007 to 2011. A single pathologist rated the grade of primary and metastatic tumors, and investigators correlated clinical factors with outcomes.

They identified a total of 52 patients, ranging in age from 29 to 77 years. Of this group, 32 (62%) had carcinoid syndrome, and 34 (65%) had extrahepatic disease.

The patients underwent a total of 51 wedge resections and 16 anatomic resections.

The mean number of metastases resected was 22 (range, 1-131). The mean size of metastases was 3 cm (range, 0.3-16 cm).

On pathologic review, all primary tumors were found to be low grade, but one-third of patients had one or more intermediate-grade metastases, suggesting a significant degree of tumor heterogeneity, Dr. Graff-Baker said.

The median liver progression-free survival was 72 months. A comparison between patients with liver progression and those with stable liver disease showed that there were no significant differences between the groups in either the percentage of tumor resected, number of resections, tumor size, presence of one or more intermediate-grade metastases, or extrahepatic disease. The only factor associated with a significant difference between groups was age. The mean age of patients with stable disease was 60.1 years, compared with 52 years for patients with liver progression (P = .016).

A separate analysis by age confirmed the last finding, with patients 50 years and older having significantly better liver progression-free survival than patients under age 50 (P = .001).

The 5-year disease-specific survival rate among all patients was 90%. All deaths were due to liver failure caused by tumor progression.

An analysis of factors predicting disease-specific survival showed once again that older patients for a change fared better than their more youthful counterparts (P = .03).

"The number, size, grade, extent of resection, and presence of extrahepatic disease did not have an adverse impact on outcomes," Dr. Graff-Baker said.

The study was internally funded. Dr. Graff-Baker reported having no financial disclosures.

BOSTON – Relaxing eligibility criteria for cytoreductive surgery may improve overall survival among patients with carcinoid metastases to the liver, investigators report.

Lowering the debulking threshold from 90% to 70% and including patients with intermediate-grade disease and/or extrahepatic disease resulted in 5-year overall survival rates of 90%, compared with 61%-74% rates reported by other treatment centers, said Dr. Amanda N. Graff-Baker, a surgical oncology resident at the Oregon Health and Science University (OHSU), Portland.

Neil Osterweil/Frontline Medical News

"The use of expanded criteria would substantially increase the number of patients eligible for debulking without compromising survival," she reported at the annual meeting of the American Association of Endocrine Surgeons.

Carcinoid tumors, a subset of neuroendocrine tumors, originate in the enterochromaffin cells of the aerodigestive tract. Approximately 60% of these tumors occur in the gastrointestinal tract, most commonly in the small intestine.

Approximately 60%-80% of patients with small bowel carcinoid tumors will have metastases to the liver, with liver failure from hepatic replacement by tumor being the most common cause of death, she explained.

Although there are no standardized patient selection criteria for liver debulking surgery in these patients, many U.S. centers follow NANETS (North American Neuroendocrine Tumor Society) treatment guidelines, which recommend surgical excision of at least 90% of all visible tumor. In addition, many centers choose not to offer cytoreductive surgery to patients with extrahepatic disease, Dr. Graff-Baker said.

Using these criteria, centers have reported 5-year survival rates ranging from 61% to 74%, but only about 20% of patients with carcinoid metastases to the liver are eligible for resection.

The investigators hypothesized that expanded eligibility criteria used at OHSU for several years could improve both liver progression-free and disease-specific survival rates. The criteria include a lower liver debulking threshold (70% or greater) and allow inclusion of patients with extrahepatic disease and/or intermediate-grade tumors.

They tested this idea by reviewing records of patients with metastatic carcinoid tumors who underwent liver debulking procedures at their center from 2007 to 2011. A single pathologist rated the grade of primary and metastatic tumors, and investigators correlated clinical factors with outcomes.

They identified a total of 52 patients, ranging in age from 29 to 77 years. Of this group, 32 (62%) had carcinoid syndrome, and 34 (65%) had extrahepatic disease.

The patients underwent a total of 51 wedge resections and 16 anatomic resections.

The mean number of metastases resected was 22 (range, 1-131). The mean size of metastases was 3 cm (range, 0.3-16 cm).

On pathologic review, all primary tumors were found to be low grade, but one-third of patients had one or more intermediate-grade metastases, suggesting a significant degree of tumor heterogeneity, Dr. Graff-Baker said.

The median liver progression-free survival was 72 months. A comparison between patients with liver progression and those with stable liver disease showed that there were no significant differences between the groups in either the percentage of tumor resected, number of resections, tumor size, presence of one or more intermediate-grade metastases, or extrahepatic disease. The only factor associated with a significant difference between groups was age. The mean age of patients with stable disease was 60.1 years, compared with 52 years for patients with liver progression (P = .016).

A separate analysis by age confirmed the last finding, with patients 50 years and older having significantly better liver progression-free survival than patients under age 50 (P = .001).

The 5-year disease-specific survival rate among all patients was 90%. All deaths were due to liver failure caused by tumor progression.

An analysis of factors predicting disease-specific survival showed once again that older patients for a change fared better than their more youthful counterparts (P = .03).

"The number, size, grade, extent of resection, and presence of extrahepatic disease did not have an adverse impact on outcomes," Dr. Graff-Baker said.

The study was internally funded. Dr. Graff-Baker reported having no financial disclosures.

NEW YORK – Patients with panic disorder can be effectively treated with either a benzodiazepine or a selective serotonin reuptake inhibitor, or both, but even long-term therapy might not prevent relapse in the majority of patients.

That’s the conclusion of a team of Brazilian researchers who compared clonazepam, paroxetine, and a combination of the two in patients with panic disorder in a randomized, open-label trial.

By the third year of follow-up, about 77% of patients had experienced a relapse despite being treated for 3 years, and after 6 years, 94% of patients had experienced at least one new panic attack, reported Dr. Antonio E. Nardi of the Federal University of Rio de Janeiro.

However, resumption of therapy with either drug or with a different medication was successful in preventing or reducing the incidence of additional attacks in nearly all patients.

"We propose to discontinue drug treatment as soon as patients are asymptomatic for 1 year and to restart treatment at the first sign of relapse," he said at the annual meeting of the American Psychiatric Association.

The good and the bad

The benzodiazepine clonazepam and the SSRI paroxetine each have their advantages and drawbacks, Dr. Nardi said.

Clonazepam has a rapid onset of action, decreases anticipatory anxiety, and has a good safety profile in terms of interactions and overdose risk. On the other hand, patients might experience withdrawal symptoms, develop memory problems, and become dependent on the agent.

Paroxetine has well documented antidepressive effects and little if any potential for abuse but can cause sexual dysfunction, hyperstimulation, anticholinergic effects, and weight gain.

With either agent, from 20% to 40% of patients remain symptomatic after short- or intermediate-term treatment, and relapse is frequent, even after 1 year of treatment, Dr. Nardi said.

The investigators designed an open-label clinical trial in which patients would be randomized to either clonazepam 2 mg/day or paroxetine 40 mg/day. Those who did not respond well to either drug were switched after 8 weeks to a combination of the drugs at or near the dose levels assigned for the individual drugs.

After the 8-week efficacy phase, patients were followed for safety and efficacy of both agents and the combination during 3 years of continuous treatment. Patients were tapered off drugs at 3 years and followed up through 6 years for the number of panic attacks per month, clinical global impression severity score (CGI-S), and Hamilton Anxiety Scale score (HAM-A).

Of the 120 patients enrolled, 94 completed the 3 years of treatment (45 on clonazepam, 33 on paroxetine, and 16 on the combination). In all, 66 of these patients had annual assessments out to 6 years; the remaining 28 had assessments at 5 or 6 years of follow-up. Among the 66 patients who were seen annually, relapse rates were 41% 1 year after therapy taper was completed, 77% at 4 years, and 94% at 6 years.

For most patients, restarting the original drug resulted in either a partial remission (54%) or full remission (36%). With treatment resumption, 73% of patients remained free of panic attacks, 91% had a CGI-S score of 1 (very much improved), and 39% had a HAM-A score from 5 to 10, indicating low anxiety.

Both drugs were generally well tolerated, although clonazepam was associated with significantly fewer adverse events, including drowsiness/fatigue, sexual dysfunction, nausea/vomiting, appetite/weight change, dry mouth, hyperhydrosis, and diarrhea/constipation, compared with paroxetine, in all but one category. No significant differences were found between the two drugs in their effects on memory and concentration, however.

The study was supported by the Brazilian Council for Scientific and Technological Development, and Brazil\'s National Institute for Translational Medicine. Dr. Nardi disclosed serving on advisory boards for Aché, CNPq, GlaxoSmithKline, Grupo A, and Lundbeck, and serving on the speakers bureaus for Solvay, Cristalia, GSK, Roche, and Aché.

NEW YORK – Patients with panic disorder can be effectively treated with either a benzodiazepine or a selective serotonin reuptake inhibitor, or both, but even long-term therapy might not prevent relapse in the majority of patients.

That’s the conclusion of a team of Brazilian researchers who compared clonazepam, paroxetine, and a combination of the two in patients with panic disorder in a randomized, open-label trial.

By the third year of follow-up, about 77% of patients had experienced a relapse despite being treated for 3 years, and after 6 years, 94% of patients had experienced at least one new panic attack, reported Dr. Antonio E. Nardi of the Federal University of Rio de Janeiro.

However, resumption of therapy with either drug or with a different medication was successful in preventing or reducing the incidence of additional attacks in nearly all patients.

"We propose to discontinue drug treatment as soon as patients are asymptomatic for 1 year and to restart treatment at the first sign of relapse," he said at the annual meeting of the American Psychiatric Association.

The good and the bad

The benzodiazepine clonazepam and the SSRI paroxetine each have their advantages and drawbacks, Dr. Nardi said.

Clonazepam has a rapid onset of action, decreases anticipatory anxiety, and has a good safety profile in terms of interactions and overdose risk. On the other hand, patients might experience withdrawal symptoms, develop memory problems, and become dependent on the agent.

Paroxetine has well documented antidepressive effects and little if any potential for abuse but can cause sexual dysfunction, hyperstimulation, anticholinergic effects, and weight gain.

With either agent, from 20% to 40% of patients remain symptomatic after short- or intermediate-term treatment, and relapse is frequent, even after 1 year of treatment, Dr. Nardi said.

The investigators designed an open-label clinical trial in which patients would be randomized to either clonazepam 2 mg/day or paroxetine 40 mg/day. Those who did not respond well to either drug were switched after 8 weeks to a combination of the drugs at or near the dose levels assigned for the individual drugs.

After the 8-week efficacy phase, patients were followed for safety and efficacy of both agents and the combination during 3 years of continuous treatment. Patients were tapered off drugs at 3 years and followed up through 6 years for the number of panic attacks per month, clinical global impression severity score (CGI-S), and Hamilton Anxiety Scale score (HAM-A).

Of the 120 patients enrolled, 94 completed the 3 years of treatment (45 on clonazepam, 33 on paroxetine, and 16 on the combination). In all, 66 of these patients had annual assessments out to 6 years; the remaining 28 had assessments at 5 or 6 years of follow-up. Among the 66 patients who were seen annually, relapse rates were 41% 1 year after therapy taper was completed, 77% at 4 years, and 94% at 6 years.

For most patients, restarting the original drug resulted in either a partial remission (54%) or full remission (36%). With treatment resumption, 73% of patients remained free of panic attacks, 91% had a CGI-S score of 1 (very much improved), and 39% had a HAM-A score from 5 to 10, indicating low anxiety.

Both drugs were generally well tolerated, although clonazepam was associated with significantly fewer adverse events, including drowsiness/fatigue, sexual dysfunction, nausea/vomiting, appetite/weight change, dry mouth, hyperhydrosis, and diarrhea/constipation, compared with paroxetine, in all but one category. No significant differences were found between the two drugs in their effects on memory and concentration, however.

The study was supported by the Brazilian Council for Scientific and Technological Development, and Brazil\'s National Institute for Translational Medicine. Dr. Nardi disclosed serving on advisory boards for Aché, CNPq, GlaxoSmithKline, Grupo A, and Lundbeck, and serving on the speakers bureaus for Solvay, Cristalia, GSK, Roche, and Aché.

NEW YORK – Patients with panic disorder can be effectively treated with either a benzodiazepine or a selective serotonin reuptake inhibitor, or both, but even long-term therapy might not prevent relapse in the majority of patients.

That’s the conclusion of a team of Brazilian researchers who compared clonazepam, paroxetine, and a combination of the two in patients with panic disorder in a randomized, open-label trial.

By the third year of follow-up, about 77% of patients had experienced a relapse despite being treated for 3 years, and after 6 years, 94% of patients had experienced at least one new panic attack, reported Dr. Antonio E. Nardi of the Federal University of Rio de Janeiro.

However, resumption of therapy with either drug or with a different medication was successful in preventing or reducing the incidence of additional attacks in nearly all patients.

"We propose to discontinue drug treatment as soon as patients are asymptomatic for 1 year and to restart treatment at the first sign of relapse," he said at the annual meeting of the American Psychiatric Association.

The good and the bad

The benzodiazepine clonazepam and the SSRI paroxetine each have their advantages and drawbacks, Dr. Nardi said.

Clonazepam has a rapid onset of action, decreases anticipatory anxiety, and has a good safety profile in terms of interactions and overdose risk. On the other hand, patients might experience withdrawal symptoms, develop memory problems, and become dependent on the agent.

Paroxetine has well documented antidepressive effects and little if any potential for abuse but can cause sexual dysfunction, hyperstimulation, anticholinergic effects, and weight gain.

With either agent, from 20% to 40% of patients remain symptomatic after short- or intermediate-term treatment, and relapse is frequent, even after 1 year of treatment, Dr. Nardi said.

The investigators designed an open-label clinical trial in which patients would be randomized to either clonazepam 2 mg/day or paroxetine 40 mg/day. Those who did not respond well to either drug were switched after 8 weeks to a combination of the drugs at or near the dose levels assigned for the individual drugs.

After the 8-week efficacy phase, patients were followed for safety and efficacy of both agents and the combination during 3 years of continuous treatment. Patients were tapered off drugs at 3 years and followed up through 6 years for the number of panic attacks per month, clinical global impression severity score (CGI-S), and Hamilton Anxiety Scale score (HAM-A).

Of the 120 patients enrolled, 94 completed the 3 years of treatment (45 on clonazepam, 33 on paroxetine, and 16 on the combination). In all, 66 of these patients had annual assessments out to 6 years; the remaining 28 had assessments at 5 or 6 years of follow-up. Among the 66 patients who were seen annually, relapse rates were 41% 1 year after therapy taper was completed, 77% at 4 years, and 94% at 6 years.

For most patients, restarting the original drug resulted in either a partial remission (54%) or full remission (36%). With treatment resumption, 73% of patients remained free of panic attacks, 91% had a CGI-S score of 1 (very much improved), and 39% had a HAM-A score from 5 to 10, indicating low anxiety.

Both drugs were generally well tolerated, although clonazepam was associated with significantly fewer adverse events, including drowsiness/fatigue, sexual dysfunction, nausea/vomiting, appetite/weight change, dry mouth, hyperhydrosis, and diarrhea/constipation, compared with paroxetine, in all but one category. No significant differences were found between the two drugs in their effects on memory and concentration, however.

The study was supported by the Brazilian Council for Scientific and Technological Development, and Brazil\'s National Institute for Translational Medicine. Dr. Nardi disclosed serving on advisory boards for Aché, CNPq, GlaxoSmithKline, Grupo A, and Lundbeck, and serving on the speakers bureaus for Solvay, Cristalia, GSK, Roche, and Aché.

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.

SCOTTSDALE, ARIZ. – When patients on immunosuppressive therapies need surgery, the risks of disease flare and compromised postoperative recovery and rehabilitation must be weighed against the risk of increased infections and impaired wound healing.

"I’m not sure that there is necessarily a right answer, but I think most people would stop biologic [agents] beforehand," Dr. Paul Grant said at a meeting on perioperative medicine sponsored by the University of Miami.

The decision whether to suspend a disease-modifying antirheumatic drug before surgery may depend on the individual drug and on the patient, said Dr. Grant, director of perioperative and consultative medicine at the University of Michigan Health System in Ann Arbor.

For example, it appears to be safe for patients on methotrexate to continue on therapy during elective orthopedic surgery. Evidence for this comes from a randomized clinical trial in which patients with rheumatoid arthritis (RA) were assigned to either continue on methotrexate (MTX) or suspend taking it for 2 weeks before and 2 weeks after surgery. The study also contained a control of patients with RA who were not on MTX (Ann. Rheum. Dis. 2001;60:214-7).

The investigators found that there were no significant differences in early complication rates or in complications up to 1 year of follow-up between patients who suspended or remained on MTX. Patients who stayed on the drug had significantly lower rates of RA flare.

Additionally, two systematic reviews, one looking at eight studies echoes the findings of the aforementioned randomized trial, and the other looking at four studies, in which the reviewer concluded that "continued MTX therapy appears to be safe perioperatively and seems also to be associated with a reduced risk of flares (Clin. Exp. Rheumatol. 2009;27:856-62) (Clin. Rheumatol. 2008;27:1217-20).None of the examined papers addresses the issue of safety in connection with comorbidities, age, or high doses of methotrexate."

"The bottom line here is that methotrexate should be continued for most surgeries. I think it might be reasonable to hold it in certain situations, for example if the patient has pretty bad kidney or liver disease, or if it’s surgery to treat a major infection," Dr. Grant said.

TNF-alpha antagonists

In contrast, the data on tumor necrosis factor–alpha (TNF-alpha) antagonists are fuzzier, with limited and conflicting information on perioperative use of these agents (etanercept, infliximab, adalimumab, certolizumab, golimumab).

"The major concern with these drugs is infection," Dr. Grant said. He pointed to a meta-analysis published in JAMA in 2006, which showed that taking the drugs doubled the risk of serious infections in general. The study did not specifically look at perioperative use of TNF-alpha antagonists (JAMA 2006;295:2275-85).

A retrospective cohort studyof 127 patients with RA who were undergoing various orthopedic procedures found that there were no differences in surgical site infections but more cases of wound dehiscence in patients who continued on the drugs, compared with those who interrupted their use perioperatively (Clin. Exp. Rheumatol. 2007;25:430-6).

A second, prospective study in 31 patients with RA undergoing foot/ankle surgery found that there were no significant differences in infection or healing between patients who interrupted therapy and those who did not (Foot Ankle Clin. 2007;12:509-24).

Other studies and systematic reviews in patients with RA or Crohn’s disease generally found no significant differences in serious infection rates, but they did detect a higher incidence of skin and soft-tissue infections among patients on anti-TNF-alpha agents vs. other disease-modifying antirheumatic drugs.

The risk of infections tends to be highest at the start of therapy with a TNF-alpha antagonist and stopping therapy is more likely to result in RA flares among patients with established disease, compared with those in the early stages of RA. Therefore, TNF blocker therapy should be restarted as soon as possible after surgery to prevent flare, Dr. Grant said.

The American College of Rheumatology and British Society of Rheumatology recommend holding TNF-alpha antagonists for one dosing cycle before major surgery. For etanercept (Enbrel), that translates to a 1-week before surgery hold, for infliximab (Remicade) 6-8 weeks, and for adalimumab (Humira) 2 weeks. These agents should also be held for 10-14 days after surgery or until wound healing is satisfactory.

"It’s probably safe to continue these medications for minor surgeries," Dr. Grant said.

Other agents

The anti-CD20 agent rituximab (Rituxan) – currently used to treat RA, vasculitis, hematologic malignancies, and other conditions – has a lower risk for bacterial infections than does TNF-alpha antagonists and has been shown to be safe in patients with a history of recurrent bacterial infections.

"Hydroxychloroquine (or Plaquenil) is felt to be safe during the preoperative period. It is recommended to continue this medication without stopping," Dr. Grant said.

There is conflicting information on infection risk with the use leflunomide (Arava), but it may be wise to stop therapy 2-4 weeks before nonurgent surgery in higher-risk patients.

There is consensus that sulfasalazine (Azulfidine) and azathioprine (Imuran) can be safely continued perioperatively, he said, although some advise holding sulfasalazine on the day of surgery.

Regarding perioperative steroids, Dr. Grant recommended determining the patient’s steroid exposure over the past year.

"Stress dose steroids are not routinely needed as long as the patients continue their normal dose. That’s really the important piece: If someone’s taking prednisone every day, make sure they take at least that dose on the day of surgery," he said.

Dr. Grant reported having no financial disclosures.

SCOTTSDALE, ARIZ. – When patients on immunosuppressive therapies need surgery, the risks of disease flare and compromised postoperative recovery and rehabilitation must be weighed against the risk of increased infections and impaired wound healing.

"I’m not sure that there is necessarily a right answer, but I think most people would stop biologic [agents] beforehand," Dr. Paul Grant said at a meeting on perioperative medicine sponsored by the University of Miami.

The decision whether to suspend a disease-modifying antirheumatic drug before surgery may depend on the individual drug and on the patient, said Dr. Grant, director of perioperative and consultative medicine at the University of Michigan Health System in Ann Arbor.

For example, it appears to be safe for patients on methotrexate to continue on therapy during elective orthopedic surgery. Evidence for this comes from a randomized clinical trial in which patients with rheumatoid arthritis (RA) were assigned to either continue on methotrexate (MTX) or suspend taking it for 2 weeks before and 2 weeks after surgery. The study also contained a control of patients with RA who were not on MTX (Ann. Rheum. Dis. 2001;60:214-7).

The investigators found that there were no significant differences in early complication rates or in complications up to 1 year of follow-up between patients who suspended or remained on MTX. Patients who stayed on the drug had significantly lower rates of RA flare.

Additionally, two systematic reviews, one looking at eight studies echoes the findings of the aforementioned randomized trial, and the other looking at four studies, in which the reviewer concluded that "continued MTX therapy appears to be safe perioperatively and seems also to be associated with a reduced risk of flares (Clin. Exp. Rheumatol. 2009;27:856-62) (Clin. Rheumatol. 2008;27:1217-20).None of the examined papers addresses the issue of safety in connection with comorbidities, age, or high doses of methotrexate."

"The bottom line here is that methotrexate should be continued for most surgeries. I think it might be reasonable to hold it in certain situations, for example if the patient has pretty bad kidney or liver disease, or if it’s surgery to treat a major infection," Dr. Grant said.

TNF-alpha antagonists

In contrast, the data on tumor necrosis factor–alpha (TNF-alpha) antagonists are fuzzier, with limited and conflicting information on perioperative use of these agents (etanercept, infliximab, adalimumab, certolizumab, golimumab).

"The major concern with these drugs is infection," Dr. Grant said. He pointed to a meta-analysis published in JAMA in 2006, which showed that taking the drugs doubled the risk of serious infections in general. The study did not specifically look at perioperative use of TNF-alpha antagonists (JAMA 2006;295:2275-85).

A retrospective cohort studyof 127 patients with RA who were undergoing various orthopedic procedures found that there were no differences in surgical site infections but more cases of wound dehiscence in patients who continued on the drugs, compared with those who interrupted their use perioperatively (Clin. Exp. Rheumatol. 2007;25:430-6).

A second, prospective study in 31 patients with RA undergoing foot/ankle surgery found that there were no significant differences in infection or healing between patients who interrupted therapy and those who did not (Foot Ankle Clin. 2007;12:509-24).

Other studies and systematic reviews in patients with RA or Crohn’s disease generally found no significant differences in serious infection rates, but they did detect a higher incidence of skin and soft-tissue infections among patients on anti-TNF-alpha agents vs. other disease-modifying antirheumatic drugs.

The risk of infections tends to be highest at the start of therapy with a TNF-alpha antagonist and stopping therapy is more likely to result in RA flares among patients with established disease, compared with those in the early stages of RA. Therefore, TNF blocker therapy should be restarted as soon as possible after surgery to prevent flare, Dr. Grant said.

The American College of Rheumatology and British Society of Rheumatology recommend holding TNF-alpha antagonists for one dosing cycle before major surgery. For etanercept (Enbrel), that translates to a 1-week before surgery hold, for infliximab (Remicade) 6-8 weeks, and for adalimumab (Humira) 2 weeks. These agents should also be held for 10-14 days after surgery or until wound healing is satisfactory.

"It’s probably safe to continue these medications for minor surgeries," Dr. Grant said.

Other agents

The anti-CD20 agent rituximab (Rituxan) – currently used to treat RA, vasculitis, hematologic malignancies, and other conditions – has a lower risk for bacterial infections than does TNF-alpha antagonists and has been shown to be safe in patients with a history of recurrent bacterial infections.

"Hydroxychloroquine (or Plaquenil) is felt to be safe during the preoperative period. It is recommended to continue this medication without stopping," Dr. Grant said.

There is conflicting information on infection risk with the use leflunomide (Arava), but it may be wise to stop therapy 2-4 weeks before nonurgent surgery in higher-risk patients.

There is consensus that sulfasalazine (Azulfidine) and azathioprine (Imuran) can be safely continued perioperatively, he said, although some advise holding sulfasalazine on the day of surgery.

Regarding perioperative steroids, Dr. Grant recommended determining the patient’s steroid exposure over the past year.

"Stress dose steroids are not routinely needed as long as the patients continue their normal dose. That’s really the important piece: If someone’s taking prednisone every day, make sure they take at least that dose on the day of surgery," he said.

Dr. Grant reported having no financial disclosures.

SCOTTSDALE, ARIZ. – When patients on immunosuppressive therapies need surgery, the risks of disease flare and compromised postoperative recovery and rehabilitation must be weighed against the risk of increased infections and impaired wound healing.

"I’m not sure that there is necessarily a right answer, but I think most people would stop biologic [agents] beforehand," Dr. Paul Grant said at a meeting on perioperative medicine sponsored by the University of Miami.

The decision whether to suspend a disease-modifying antirheumatic drug before surgery may depend on the individual drug and on the patient, said Dr. Grant, director of perioperative and consultative medicine at the University of Michigan Health System in Ann Arbor.

For example, it appears to be safe for patients on methotrexate to continue on therapy during elective orthopedic surgery. Evidence for this comes from a randomized clinical trial in which patients with rheumatoid arthritis (RA) were assigned to either continue on methotrexate (MTX) or suspend taking it for 2 weeks before and 2 weeks after surgery. The study also contained a control of patients with RA who were not on MTX (Ann. Rheum. Dis. 2001;60:214-7).

The investigators found that there were no significant differences in early complication rates or in complications up to 1 year of follow-up between patients who suspended or remained on MTX. Patients who stayed on the drug had significantly lower rates of RA flare.

Additionally, two systematic reviews, one looking at eight studies echoes the findings of the aforementioned randomized trial, and the other looking at four studies, in which the reviewer concluded that "continued MTX therapy appears to be safe perioperatively and seems also to be associated with a reduced risk of flares (Clin. Exp. Rheumatol. 2009;27:856-62) (Clin. Rheumatol. 2008;27:1217-20).None of the examined papers addresses the issue of safety in connection with comorbidities, age, or high doses of methotrexate."

"The bottom line here is that methotrexate should be continued for most surgeries. I think it might be reasonable to hold it in certain situations, for example if the patient has pretty bad kidney or liver disease, or if it’s surgery to treat a major infection," Dr. Grant said.

TNF-alpha antagonists

In contrast, the data on tumor necrosis factor–alpha (TNF-alpha) antagonists are fuzzier, with limited and conflicting information on perioperative use of these agents (etanercept, infliximab, adalimumab, certolizumab, golimumab).

"The major concern with these drugs is infection," Dr. Grant said. He pointed to a meta-analysis published in JAMA in 2006, which showed that taking the drugs doubled the risk of serious infections in general. The study did not specifically look at perioperative use of TNF-alpha antagonists (JAMA 2006;295:2275-85).

A retrospective cohort studyof 127 patients with RA who were undergoing various orthopedic procedures found that there were no differences in surgical site infections but more cases of wound dehiscence in patients who continued on the drugs, compared with those who interrupted their use perioperatively (Clin. Exp. Rheumatol. 2007;25:430-6).

A second, prospective study in 31 patients with RA undergoing foot/ankle surgery found that there were no significant differences in infection or healing between patients who interrupted therapy and those who did not (Foot Ankle Clin. 2007;12:509-24).

Other studies and systematic reviews in patients with RA or Crohn’s disease generally found no significant differences in serious infection rates, but they did detect a higher incidence of skin and soft-tissue infections among patients on anti-TNF-alpha agents vs. other disease-modifying antirheumatic drugs.

The risk of infections tends to be highest at the start of therapy with a TNF-alpha antagonist and stopping therapy is more likely to result in RA flares among patients with established disease, compared with those in the early stages of RA. Therefore, TNF blocker therapy should be restarted as soon as possible after surgery to prevent flare, Dr. Grant said.

The American College of Rheumatology and British Society of Rheumatology recommend holding TNF-alpha antagonists for one dosing cycle before major surgery. For etanercept (Enbrel), that translates to a 1-week before surgery hold, for infliximab (Remicade) 6-8 weeks, and for adalimumab (Humira) 2 weeks. These agents should also be held for 10-14 days after surgery or until wound healing is satisfactory.

"It’s probably safe to continue these medications for minor surgeries," Dr. Grant said.

Other agents

The anti-CD20 agent rituximab (Rituxan) – currently used to treat RA, vasculitis, hematologic malignancies, and other conditions – has a lower risk for bacterial infections than does TNF-alpha antagonists and has been shown to be safe in patients with a history of recurrent bacterial infections.

"Hydroxychloroquine (or Plaquenil) is felt to be safe during the preoperative period. It is recommended to continue this medication without stopping," Dr. Grant said.

There is conflicting information on infection risk with the use leflunomide (Arava), but it may be wise to stop therapy 2-4 weeks before nonurgent surgery in higher-risk patients.

There is consensus that sulfasalazine (Azulfidine) and azathioprine (Imuran) can be safely continued perioperatively, he said, although some advise holding sulfasalazine on the day of surgery.

Regarding perioperative steroids, Dr. Grant recommended determining the patient’s steroid exposure over the past year.

"Stress dose steroids are not routinely needed as long as the patients continue their normal dose. That’s really the important piece: If someone’s taking prednisone every day, make sure they take at least that dose on the day of surgery," he said.

Dr. Grant reported having no financial disclosures.

SCOTTSDALE, ARIZ. – When patients on immunosuppressive therapies need surgery, the risks of disease flare and compromised postoperative recovery and rehabilitation must be weighed against the risk of increased infections and impaired wound healing.

"I’m not sure that there is necessarily a right answer, but I think most people would stop biologic [agents] beforehand," Dr. Paul Grant said at a meeting on perioperative medicine sponsored by the University of Miami.

The decision whether to suspend a disease-modifying antirheumatic drug before surgery may depend on the individual drug and on the patient, said Dr. Grant, director of perioperative and consultative medicine at the University of Michigan Health System in Ann Arbor.

'If someone's taking prednisone every day, make sure they take at least that dose on the day of surgery.'

For example, it appears to be safe for patients on methotrexate to continue on therapy during elective orthopedic surgery. Evidence for this comes from a randomized clinical trial in which patients with rheumatoid arthritis (RA) were assigned to either continue on methotrexate (MTX) or suspend taking it for 2 weeks before and 2 weeks after surgery. The study also contained a control of patients with RA who were not on MTX (Ann. Rheum. Dis. 2001;60:214-7).

The investigators found that there were no significant differences in early complication rates or in complications up to 1 year of follow-up between patients who suspended or remained on MTX. Patients who stayed on the drug had significantly lower rates of RA flare.

Two systematic reviews also looked at the question. One review of eight studies echoes the findings of the aforementioned randomized trial (Clin. Exp. Rheumatol. 2009; 27:856-62), while the other review of four studies concluded that "continued MTX therapy appears to be safe perioperatively and seems also to be associated with a reduced risk of flares" (Clin. Rheumatol. 2008; 27:1217-20). None of the examined papers addressed the issue of safety in connection with comorbidities, age, or high doses of methotrexate.

"The bottom line here is that methotrexate should be continued for most surgeries. I think it might be reasonable to hold it in certain situations, for example if the patient has pretty bad kidney or liver disease, or if it’s surgery to treat a major infection," Dr. Grant said.

TNF-alpha antagonists

In contrast, the data on tumor necrosis factor–alpha (TNF-alpha) antagonists are fuzzier, with limited and conflicting information on perioperative use of these agents (etanercept, infliximab, adalimumab, certolizumab, golimumab).

"The major concern with these drugs is infection," Dr. Grant said. He pointed to a meta-analysis published in JAMA in 2006, which showed that taking the drugs doubled the risk of serious infections in general. The study did not specifically look at perioperative use of TNF-alpha antagonists (JAMA 2006;295:2275-85).

A retrospective cohort study of 127 patients with RA who were undergoing various orthopedic procedures found that there were no differences in surgical site infections but more cases of wound dehiscence in patients who continued on the drugs, compared with those who interrupted their use perioperatively (Clin. Exp. Rheumatol. 2007;25:430-6).

A second, prospective study in 31 patients with RA undergoing foot/ankle surgery found that there were no significant differences in infection or healing between patients who interrupted therapy and those who did not (Foot Ankle Clin. 2007;12:509-24).

Other studies and systematic reviews in patients with RA or Crohn’s disease generally found no significant differences in serious infection rates, but they did detect a higher incidence of skin and soft-tissue infections among patients on anti-TNF-alpha agents vs. other disease-modifying antirheumatic drugs.

The risk of infections tends to be highest at the start of therapy with a TNF-alpha antagonist, and stopping therapy is more likely to result in RA flares among patients with established disease, compared with those in the early stages of RA. Therefore, TNF-blocker therapy should be restarted as soon as possible after surgery to prevent flare, Dr. Grant said.

The American College of Rheumatology and British Society of Rheumatology recommend holding TNF-alpha antagonists for one dosing cycle before major surgery. For etanercept (Enbrel), that translates to a 1-week before surgery hold, for infliximab (Remicade) 6-8 weeks, and for adalimumab (Humira) 2 weeks. These agents should also be held for 10-14 days after surgery or until wound healing is satisfactory.

"It’s probably safe to continue these medications for minor surgeries," Dr. Grant said.

Other agents

The anti-CD20 agent rituximab (Rituxan) – currently used to treat RA, vasculitis, hematologic malignancies, and other conditions – has a lower risk for bacterial infections than do TNF-alpha antagonists and has been shown to be safe in patients with a history of recurrent bacterial infections.

"Hydroxychloroquine (or Plaquenil) is felt to be safe during the preoperative period. It is recommended to continue this medication without stopping," Dr. Grant said.

There is conflicting information on infection risk with the use leflunomide (Arava), but it may be wise to stop therapy 2-4 weeks before nonurgent surgery in higher-risk patients.

There is consensus that sulfasalazine (Azulfidine) and azathioprine (Imuran) can be safely continued perioperatively, he said, although some advise holding sulfasalazine on the day of surgery.

Regarding perioperative steroids, Dr. Grant recommended determining the patient’s steroid exposure over the past year.

"Stress dose steroids are not routinely needed as long as the patients continue their normal dose.

"That’s really the important piece: If someone’s taking prednisone every day, make sure they take at least that dose on the day of surgery," he said.

Dr. Lary Robinson, FCCP, comments: Surgeons are rightfully concerned about the preoperative use of any medicines that might increase the risk of bleeding, infections or wound healing. The topic of immunomodulating drugs was explored by evaluating the published evidence about their safety in the perioperative period. These agents, used in patients with autoimmune/inflammatory diseases such as rheumatoid arthritis and Crohn's disease, are generally safe to continue although most authorities generally recommend holding the TNF-alpha antagonists prior to and after major surgery due to potential wound healing and infectious problems.

SCOTTSDALE, ARIZ. – When patients on immunosuppressive therapies need surgery, the risks of disease flare and compromised postoperative recovery and rehabilitation must be weighed against the risk of increased infections and impaired wound healing.

"I’m not sure that there is necessarily a right answer, but I think most people would stop biologic [agents] beforehand," Dr. Paul Grant said at a meeting on perioperative medicine sponsored by the University of Miami.

The decision whether to suspend a disease-modifying antirheumatic drug before surgery may depend on the individual drug and on the patient, said Dr. Grant, director of perioperative and consultative medicine at the University of Michigan Health System in Ann Arbor.

'If someone's taking prednisone every day, make sure they take at least that dose on the day of surgery.'

For example, it appears to be safe for patients on methotrexate to continue on therapy during elective orthopedic surgery. Evidence for this comes from a randomized clinical trial in which patients with rheumatoid arthritis (RA) were assigned to either continue on methotrexate (MTX) or suspend taking it for 2 weeks before and 2 weeks after surgery. The study also contained a control of patients with RA who were not on MTX (Ann. Rheum. Dis. 2001;60:214-7).

The investigators found that there were no significant differences in early complication rates or in complications up to 1 year of follow-up between patients who suspended or remained on MTX. Patients who stayed on the drug had significantly lower rates of RA flare.

Two systematic reviews also looked at the question. One review of eight studies echoes the findings of the aforementioned randomized trial (Clin. Exp. Rheumatol. 2009; 27:856-62), while the other review of four studies concluded that "continued MTX therapy appears to be safe perioperatively and seems also to be associated with a reduced risk of flares" (Clin. Rheumatol. 2008; 27:1217-20). None of the examined papers addressed the issue of safety in connection with comorbidities, age, or high doses of methotrexate.

"The bottom line here is that methotrexate should be continued for most surgeries. I think it might be reasonable to hold it in certain situations, for example if the patient has pretty bad kidney or liver disease, or if it’s surgery to treat a major infection," Dr. Grant said.

TNF-alpha antagonists

In contrast, the data on tumor necrosis factor–alpha (TNF-alpha) antagonists are fuzzier, with limited and conflicting information on perioperative use of these agents (etanercept, infliximab, adalimumab, certolizumab, golimumab).

"The major concern with these drugs is infection," Dr. Grant said. He pointed to a meta-analysis published in JAMA in 2006, which showed that taking the drugs doubled the risk of serious infections in general. The study did not specifically look at perioperative use of TNF-alpha antagonists (JAMA 2006;295:2275-85).

A retrospective cohort study of 127 patients with RA who were undergoing various orthopedic procedures found that there were no differences in surgical site infections but more cases of wound dehiscence in patients who continued on the drugs, compared with those who interrupted their use perioperatively (Clin. Exp. Rheumatol. 2007;25:430-6).

A second, prospective study in 31 patients with RA undergoing foot/ankle surgery found that there were no significant differences in infection or healing between patients who interrupted therapy and those who did not (Foot Ankle Clin. 2007;12:509-24).

Other studies and systematic reviews in patients with RA or Crohn’s disease generally found no significant differences in serious infection rates, but they did detect a higher incidence of skin and soft-tissue infections among patients on anti-TNF-alpha agents vs. other disease-modifying antirheumatic drugs.

The risk of infections tends to be highest at the start of therapy with a TNF-alpha antagonist, and stopping therapy is more likely to result in RA flares among patients with established disease, compared with those in the early stages of RA. Therefore, TNF-blocker therapy should be restarted as soon as possible after surgery to prevent flare, Dr. Grant said.

The American College of Rheumatology and British Society of Rheumatology recommend holding TNF-alpha antagonists for one dosing cycle before major surgery. For etanercept (Enbrel), that translates to a 1-week before surgery hold, for infliximab (Remicade) 6-8 weeks, and for adalimumab (Humira) 2 weeks. These agents should also be held for 10-14 days after surgery or until wound healing is satisfactory.

"It’s probably safe to continue these medications for minor surgeries," Dr. Grant said.

Other agents

The anti-CD20 agent rituximab (Rituxan) – currently used to treat RA, vasculitis, hematologic malignancies, and other conditions – has a lower risk for bacterial infections than do TNF-alpha antagonists and has been shown to be safe in patients with a history of recurrent bacterial infections.

"Hydroxychloroquine (or Plaquenil) is felt to be safe during the preoperative period. It is recommended to continue this medication without stopping," Dr. Grant said.

There is conflicting information on infection risk with the use leflunomide (Arava), but it may be wise to stop therapy 2-4 weeks before nonurgent surgery in higher-risk patients.

There is consensus that sulfasalazine (Azulfidine) and azathioprine (Imuran) can be safely continued perioperatively, he said, although some advise holding sulfasalazine on the day of surgery.

Regarding perioperative steroids, Dr. Grant recommended determining the patient’s steroid exposure over the past year.

"Stress dose steroids are not routinely needed as long as the patients continue their normal dose.

"That’s really the important piece: If someone’s taking prednisone every day, make sure they take at least that dose on the day of surgery," he said.

Dr. Lary Robinson, FCCP, comments: Surgeons are rightfully concerned about the preoperative use of any medicines that might increase the risk of bleeding, infections or wound healing. The topic of immunomodulating drugs was explored by evaluating the published evidence about their safety in the perioperative period. These agents, used in patients with autoimmune/inflammatory diseases such as rheumatoid arthritis and Crohn's disease, are generally safe to continue although most authorities generally recommend holding the TNF-alpha antagonists prior to and after major surgery due to potential wound healing and infectious problems.

SCOTTSDALE, ARIZ. – When patients on immunosuppressive therapies need surgery, the risks of disease flare and compromised postoperative recovery and rehabilitation must be weighed against the risk of increased infections and impaired wound healing.

"I’m not sure that there is necessarily a right answer, but I think most people would stop biologic [agents] beforehand," Dr. Paul Grant said at a meeting on perioperative medicine sponsored by the University of Miami.

The decision whether to suspend a disease-modifying antirheumatic drug before surgery may depend on the individual drug and on the patient, said Dr. Grant, director of perioperative and consultative medicine at the University of Michigan Health System in Ann Arbor.

'If someone's taking prednisone every day, make sure they take at least that dose on the day of surgery.'

For example, it appears to be safe for patients on methotrexate to continue on therapy during elective orthopedic surgery. Evidence for this comes from a randomized clinical trial in which patients with rheumatoid arthritis (RA) were assigned to either continue on methotrexate (MTX) or suspend taking it for 2 weeks before and 2 weeks after surgery. The study also contained a control of patients with RA who were not on MTX (Ann. Rheum. Dis. 2001;60:214-7).

The investigators found that there were no significant differences in early complication rates or in complications up to 1 year of follow-up between patients who suspended or remained on MTX. Patients who stayed on the drug had significantly lower rates of RA flare.

Two systematic reviews also looked at the question. One review of eight studies echoes the findings of the aforementioned randomized trial (Clin. Exp. Rheumatol. 2009; 27:856-62), while the other review of four studies concluded that "continued MTX therapy appears to be safe perioperatively and seems also to be associated with a reduced risk of flares" (Clin. Rheumatol. 2008; 27:1217-20). None of the examined papers addressed the issue of safety in connection with comorbidities, age, or high doses of methotrexate.

"The bottom line here is that methotrexate should be continued for most surgeries. I think it might be reasonable to hold it in certain situations, for example if the patient has pretty bad kidney or liver disease, or if it’s surgery to treat a major infection," Dr. Grant said.

TNF-alpha antagonists

In contrast, the data on tumor necrosis factor–alpha (TNF-alpha) antagonists are fuzzier, with limited and conflicting information on perioperative use of these agents (etanercept, infliximab, adalimumab, certolizumab, golimumab).

"The major concern with these drugs is infection," Dr. Grant said. He pointed to a meta-analysis published in JAMA in 2006, which showed that taking the drugs doubled the risk of serious infections in general. The study did not specifically look at perioperative use of TNF-alpha antagonists (JAMA 2006;295:2275-85).

A retrospective cohort study of 127 patients with RA who were undergoing various orthopedic procedures found that there were no differences in surgical site infections but more cases of wound dehiscence in patients who continued on the drugs, compared with those who interrupted their use perioperatively (Clin. Exp. Rheumatol. 2007;25:430-6).

A second, prospective study in 31 patients with RA undergoing foot/ankle surgery found that there were no significant differences in infection or healing between patients who interrupted therapy and those who did not (Foot Ankle Clin. 2007;12:509-24).

Other studies and systematic reviews in patients with RA or Crohn’s disease generally found no significant differences in serious infection rates, but they did detect a higher incidence of skin and soft-tissue infections among patients on anti-TNF-alpha agents vs. other disease-modifying antirheumatic drugs.

The risk of infections tends to be highest at the start of therapy with a TNF-alpha antagonist, and stopping therapy is more likely to result in RA flares among patients with established disease, compared with those in the early stages of RA. Therefore, TNF-blocker therapy should be restarted as soon as possible after surgery to prevent flare, Dr. Grant said.

The American College of Rheumatology and British Society of Rheumatology recommend holding TNF-alpha antagonists for one dosing cycle before major surgery. For etanercept (Enbrel), that translates to a 1-week before surgery hold, for infliximab (Remicade) 6-8 weeks, and for adalimumab (Humira) 2 weeks. These agents should also be held for 10-14 days after surgery or until wound healing is satisfactory.

"It’s probably safe to continue these medications for minor surgeries," Dr. Grant said.

Other agents

The anti-CD20 agent rituximab (Rituxan) – currently used to treat RA, vasculitis, hematologic malignancies, and other conditions – has a lower risk for bacterial infections than do TNF-alpha antagonists and has been shown to be safe in patients with a history of recurrent bacterial infections.

"Hydroxychloroquine (or Plaquenil) is felt to be safe during the preoperative period. It is recommended to continue this medication without stopping," Dr. Grant said.

There is conflicting information on infection risk with the use leflunomide (Arava), but it may be wise to stop therapy 2-4 weeks before nonurgent surgery in higher-risk patients.

There is consensus that sulfasalazine (Azulfidine) and azathioprine (Imuran) can be safely continued perioperatively, he said, although some advise holding sulfasalazine on the day of surgery.

Regarding perioperative steroids, Dr. Grant recommended determining the patient’s steroid exposure over the past year.

"Stress dose steroids are not routinely needed as long as the patients continue their normal dose.

"That’s really the important piece: If someone’s taking prednisone every day, make sure they take at least that dose on the day of surgery," he said.

Dr. Lary Robinson, FCCP, comments: Surgeons are rightfully concerned about the preoperative use of any medicines that might increase the risk of bleeding, infections or wound healing. The topic of immunomodulating drugs was explored by evaluating the published evidence about their safety in the perioperative period. These agents, used in patients with autoimmune/inflammatory diseases such as rheumatoid arthritis and Crohn's disease, are generally safe to continue although most authorities generally recommend holding the TNF-alpha antagonists prior to and after major surgery due to potential wound healing and infectious problems.

PHOENIX – In patients with recurrent papillary thyroid cancer, fine-needle aspiration cytology and thyroglobulin washout was a highly sensitive and specific means of detecting metastatic disease, according to a retrospective analysis.

Surgeon-performed FNA-Tg washout appears to increase the diagnostic accuracy in detecting metastatic disease in this patient population. Routine performance of the combined modalities should be considered in patients with suspicious metastatic lymphadenopathies, said Dr. Hossam Mohamed of the division of endocrine and oncological surgery in the department of surgery at Tulane University, New Orleans.

In a retrospective study of 117 patients with recurrent papillary thyroid cancer, the combination of surgeon-performed fine-needle aspiration cytology (FNAC) with fine-needle aspiration thyroglobulin washout (FNA-Tg) had a 100% specificity, 94.9% sensitivity, and negative predictive value of 93.75%, with a diagnostic accuracy of 97.1%, he said.

"Cervical lymph node involvement has been reported to be up to 46% at initial diagnosis, hence ultrasonography and fine-needle aspiration have been standard diagnostic modalities used to detect and evaluate cervical lymph nodes in patients with thyroid malignancies," he said at the annual Society of Surgical Oncology Cancer Symposium.

His team hypothesized that by adding surgeon-performed ultrasonography with Tg washout to FNAC for the management of patients with suspicious lymphadenopathies, they might be able to increase the accuracy of the combined tests for detecting metastatic disease in patients with recurrent papillary thyroid cancers.

In a retrospective study, they looked at results for patients who underwent preoperative FNAC and FNA-Tg washout followed by selective neck dissection. All dissections were performed by senior author Dr. Emad Kandil, chief of the endocrine surgery section at Tulane University.

They correlated the test results with the final pathology results of the dissected lymph nodes, and compared the sensitivity and specificity of the combined modalities to those of standard FNAC alone.

Of the 117 patients, 76% were female, and mean age was 52 years. Nearly half of the patients (47.6%) had cervical lymph node dissections, 39.7% had modified radical lymph node dissections, 6.35% had combined modified-radical, and 12.7% had combined modified-radical and cervical resections. Half of the group required second resections.

When the researchers compared the individual modalities to the final pathology results, they found that the respective sensitivity of FNAC, FNA-Tg, and the two combined were 84.6%, 89.4%, and 94.9%. They found the respective specificities to be 100%, 96.8%, and 100%.

The negative predictive value of FNAC was 87.1%. and of FNA-Tg was 85.7%. When the two diagnostic methods were used together, they ruled out metastases with 93.75% accuracy.

"Only one patient had a negative lymph node pathology with a positive FNA-Tg washout, which we couldn’t find an explanation for," Dr. Mohamed said.

Two patients who had negative FNA-Tg washout levels had evidence of atypical cells on FNAC and elevated serum Tg levels. These patients were therefore taken to surgery, and were found to have metastatic disease on final pathology, he said.

The study was internally funded. Dr. Mohamed reported having no financial disclosures.

PHOENIX – In patients with recurrent papillary thyroid cancer, fine-needle aspiration cytology and thyroglobulin washout was a highly sensitive and specific means of detecting metastatic disease, according to a retrospective analysis.

Surgeon-performed FNA-Tg washout appears to increase the diagnostic accuracy in detecting metastatic disease in this patient population. Routine performance of the combined modalities should be considered in patients with suspicious metastatic lymphadenopathies, said Dr. Hossam Mohamed of the division of endocrine and oncological surgery in the department of surgery at Tulane University, New Orleans.

In a retrospective study of 117 patients with recurrent papillary thyroid cancer, the combination of surgeon-performed fine-needle aspiration cytology (FNAC) with fine-needle aspiration thyroglobulin washout (FNA-Tg) had a 100% specificity, 94.9% sensitivity, and negative predictive value of 93.75%, with a diagnostic accuracy of 97.1%, he said.

"Cervical lymph node involvement has been reported to be up to 46% at initial diagnosis, hence ultrasonography and fine-needle aspiration have been standard diagnostic modalities used to detect and evaluate cervical lymph nodes in patients with thyroid malignancies," he said at the annual Society of Surgical Oncology Cancer Symposium.

His team hypothesized that by adding surgeon-performed ultrasonography with Tg washout to FNAC for the management of patients with suspicious lymphadenopathies, they might be able to increase the accuracy of the combined tests for detecting metastatic disease in patients with recurrent papillary thyroid cancers.

In a retrospective study, they looked at results for patients who underwent preoperative FNAC and FNA-Tg washout followed by selective neck dissection. All dissections were performed by senior author Dr. Emad Kandil, chief of the endocrine surgery section at Tulane University.

They correlated the test results with the final pathology results of the dissected lymph nodes, and compared the sensitivity and specificity of the combined modalities to those of standard FNAC alone.

Of the 117 patients, 76% were female, and mean age was 52 years. Nearly half of the patients (47.6%) had cervical lymph node dissections, 39.7% had modified radical lymph node dissections, 6.35% had combined modified-radical, and 12.7% had combined modified-radical and cervical resections. Half of the group required second resections.

When the researchers compared the individual modalities to the final pathology results, they found that the respective sensitivity of FNAC, FNA-Tg, and the two combined were 84.6%, 89.4%, and 94.9%. They found the respective specificities to be 100%, 96.8%, and 100%.

The negative predictive value of FNAC was 87.1%. and of FNA-Tg was 85.7%. When the two diagnostic methods were used together, they ruled out metastases with 93.75% accuracy.

"Only one patient had a negative lymph node pathology with a positive FNA-Tg washout, which we couldn’t find an explanation for," Dr. Mohamed said.

Two patients who had negative FNA-Tg washout levels had evidence of atypical cells on FNAC and elevated serum Tg levels. These patients were therefore taken to surgery, and were found to have metastatic disease on final pathology, he said.

The study was internally funded. Dr. Mohamed reported having no financial disclosures.

PHOENIX – In patients with recurrent papillary thyroid cancer, fine-needle aspiration cytology and thyroglobulin washout was a highly sensitive and specific means of detecting metastatic disease, according to a retrospective analysis.

Surgeon-performed FNA-Tg washout appears to increase the diagnostic accuracy in detecting metastatic disease in this patient population. Routine performance of the combined modalities should be considered in patients with suspicious metastatic lymphadenopathies, said Dr. Hossam Mohamed of the division of endocrine and oncological surgery in the department of surgery at Tulane University, New Orleans.

In a retrospective study of 117 patients with recurrent papillary thyroid cancer, the combination of surgeon-performed fine-needle aspiration cytology (FNAC) with fine-needle aspiration thyroglobulin washout (FNA-Tg) had a 100% specificity, 94.9% sensitivity, and negative predictive value of 93.75%, with a diagnostic accuracy of 97.1%, he said.

"Cervical lymph node involvement has been reported to be up to 46% at initial diagnosis, hence ultrasonography and fine-needle aspiration have been standard diagnostic modalities used to detect and evaluate cervical lymph nodes in patients with thyroid malignancies," he said at the annual Society of Surgical Oncology Cancer Symposium.

His team hypothesized that by adding surgeon-performed ultrasonography with Tg washout to FNAC for the management of patients with suspicious lymphadenopathies, they might be able to increase the accuracy of the combined tests for detecting metastatic disease in patients with recurrent papillary thyroid cancers.

In a retrospective study, they looked at results for patients who underwent preoperative FNAC and FNA-Tg washout followed by selective neck dissection. All dissections were performed by senior author Dr. Emad Kandil, chief of the endocrine surgery section at Tulane University.

They correlated the test results with the final pathology results of the dissected lymph nodes, and compared the sensitivity and specificity of the combined modalities to those of standard FNAC alone.

Of the 117 patients, 76% were female, and mean age was 52 years. Nearly half of the patients (47.6%) had cervical lymph node dissections, 39.7% had modified radical lymph node dissections, 6.35% had combined modified-radical, and 12.7% had combined modified-radical and cervical resections. Half of the group required second resections.

When the researchers compared the individual modalities to the final pathology results, they found that the respective sensitivity of FNAC, FNA-Tg, and the two combined were 84.6%, 89.4%, and 94.9%. They found the respective specificities to be 100%, 96.8%, and 100%.

The negative predictive value of FNAC was 87.1%. and of FNA-Tg was 85.7%. When the two diagnostic methods were used together, they ruled out metastases with 93.75% accuracy.

"Only one patient had a negative lymph node pathology with a positive FNA-Tg washout, which we couldn’t find an explanation for," Dr. Mohamed said.

Two patients who had negative FNA-Tg washout levels had evidence of atypical cells on FNAC and elevated serum Tg levels. These patients were therefore taken to surgery, and were found to have metastatic disease on final pathology, he said.

The study was internally funded. Dr. Mohamed reported having no financial disclosures.

PHOENIX – There is more evidence that it’s best to go with the pros: Adrenalectomies performed by higher-volume surgeons are associated with fewer complications, lower costs, and shorter lengths of stay than are those done by surgeons who dabble in the procedure.

The findings, presented at the annual Society of Surgical Oncology Cancer Symposium, come from a cross-sectional study of outcomes on all patients who underwent unilateral, partial, or bilateral adrenalectomies in the United States over a 7-year span.

©Jana Blašková/ Thinkstockphotos.com

"The frequency of adrenalectomy has steadily increased in the United States within the last few years, and with improvement of diagnostic and imaging modalities it’s likely that the rate of adrenal surgery will continue to rise," said Dr. Adam Hauch, a research resident in the department of surgery at Tulane University, New Orleans.

The prospects for the growth in the procedure prompted Dr. Hauch and colleagues to look at clinical and economic outcomes following adrenalectomy, and to see how surgeon volume, diagnosis, and type of surgery might affect outcomes.

They drew on discharge data from the Healthcare Cost and Utilization Project – National Inpatient Sample (HCUP-NIS), an administrative database sponsored by the U.S. Agency for Healthcare Research and Quality.

The information included International Classification of Diseases, Ninth Revision (ICD-9) codes identifying all adult patients who underwent adrenalectomies in U.S. hospitals from 2003 through 2009. Patients were divided into benign and malignant lesion groups.

The investigators found 7,829 procedures. Mean patient age was 50 years, most of the patients (74.4%) were white, and the majority were female (58.2%) and were privately insured (58.9%). Nearly all of the patients (98.3%) had one or no comorbidities at the time of admission. Only 42 patients (0.5%) died during their hospital stays.

More than three-fourths of the procedures (79.2%) were for benign disease; the remaining 20.8% of surgeries were for malignancies.

Low-volume surgeons, defined as those who performed one or fewer adrenalectomies on average per year, performed 41.7% of all procedures, compared with 34.7% for intermediate-volume surgeons (two to five per year) and 23.6% for high-volume surgeons (more than five per year).

The vast majority (97.1%) of procedures were unilateral/partial, and approximately 95% of surgeons in each experience category performed such procedures. Procedures for malignant disease accounted for 10.6% of cases for low-volume surgeons, 6.3% for intermediate-volume docs, and 4.3% of the most prolific surgeons.

It’s complicated

Risks for any complication were significantly higher among low-volume surgeons (18.8% of their cases), compared with 14.6% for those in the middle, and 11.6% for the high-volume operators (P less than .0001). High-volume performers had significantly lower risk for cardiovascular complications (P = .0008), pulmonary complications (P = .0481), bleeding (P = .0106), and technical difficulties during surgery (P = .0024).

In an analysis adjusted for patient demographic factors, payer, primary diagnosis, obesity, comorbidities, inpatient death, admission type, hospital teaching status and volume, surgeon, and type of procedure, low-volume surgeons were nearly twice as likely as were high-volume surgeons to have complications (adjusted odds ratio [aOR] 1.822, P less than .0001), and intermediate-volume surgeons had a nearly 1.5-fold higher risk (aOR 1.479, P = .0044).

Other risk factors for complications were bilateral vs. unilateral procedures (aOR 2.165, P = .0018), and malignant vs. benign disease (aOR 1.685, P less than .0001).

Not surprisingly, complications more than doubled mean total case charges, which ranged from $33,659 for uncomplicated unilateral cases to $73,021 for complicated cases (P = .0013), and from $47,284 for bilateral cases with no complications, to $141,461 for two-sided procedures with complications (P = .0221). Charges were higher for malignant cases than for benign cases without complications (P less than .0001), but complications brought the charges for both benign and malignant cases closer together .

Charges for noncomplicated procedures performed by high-volume surgeons were a comparative bargain at $27,324, compared with $33,499 for low- and intermediate-volume surgeons combined (P = .001). However, there were no significant differences by surgeon volume when complications arose.

Similarly, lengths of stay were prolonged when complications ensued for both unilateral cases (mean 3.7 days vs. 9.3 for complicated cases, P = .0042) and for bilateral cases (9.3 vs. 19.8, P = .025).

Higher volume surgeons managed to get patients out faster, averaging 2.7 days for cases without complications, compared with 4.2 for low/intermediate-volume surgeons (P less than .0001). When complications arose, patients of higher-volume surgeons still had shorter lengths of stay (8.5 vs. 10.4 days), but this difference was not statistically significant.

Dr. Lawrence Kim, professor of surgery at the University of North Carolina, Chapel Hill, said after the presentation that the study showed the limitations of using administrative data.

He said that approximately "98% of the patients [in the study presented] had no comorbidities, which just does not mesh with the realities I have ever faced with adrenal patients."

The study was internally funded. Dr. Hauch reported having no financial disclosures.

PHOENIX – There is more evidence that it’s best to go with the pros: Adrenalectomies performed by higher-volume surgeons are associated with fewer complications, lower costs, and shorter lengths of stay than are those done by surgeons who dabble in the procedure.

The findings, presented at the annual Society of Surgical Oncology Cancer Symposium, come from a cross-sectional study of outcomes on all patients who underwent unilateral, partial, or bilateral adrenalectomies in the United States over a 7-year span.

©Jana Blašková/ Thinkstockphotos.com

"The frequency of adrenalectomy has steadily increased in the United States within the last few years, and with improvement of diagnostic and imaging modalities it’s likely that the rate of adrenal surgery will continue to rise," said Dr. Adam Hauch, a research resident in the department of surgery at Tulane University, New Orleans.

The prospects for the growth in the procedure prompted Dr. Hauch and colleagues to look at clinical and economic outcomes following adrenalectomy, and to see how surgeon volume, diagnosis, and type of surgery might affect outcomes.

They drew on discharge data from the Healthcare Cost and Utilization Project – National Inpatient Sample (HCUP-NIS), an administrative database sponsored by the U.S. Agency for Healthcare Research and Quality.

The information included International Classification of Diseases, Ninth Revision (ICD-9) codes identifying all adult patients who underwent adrenalectomies in U.S. hospitals from 2003 through 2009. Patients were divided into benign and malignant lesion groups.

The investigators found 7,829 procedures. Mean patient age was 50 years, most of the patients (74.4%) were white, and the majority were female (58.2%) and were privately insured (58.9%). Nearly all of the patients (98.3%) had one or no comorbidities at the time of admission. Only 42 patients (0.5%) died during their hospital stays.

More than three-fourths of the procedures (79.2%) were for benign disease; the remaining 20.8% of surgeries were for malignancies.

Low-volume surgeons, defined as those who performed one or fewer adrenalectomies on average per year, performed 41.7% of all procedures, compared with 34.7% for intermediate-volume surgeons (two to five per year) and 23.6% for high-volume surgeons (more than five per year).

The vast majority (97.1%) of procedures were unilateral/partial, and approximately 95% of surgeons in each experience category performed such procedures. Procedures for malignant disease accounted for 10.6% of cases for low-volume surgeons, 6.3% for intermediate-volume docs, and 4.3% of the most prolific surgeons.

It’s complicated

Risks for any complication were significantly higher among low-volume surgeons (18.8% of their cases), compared with 14.6% for those in the middle, and 11.6% for the high-volume operators (P less than .0001). High-volume performers had significantly lower risk for cardiovascular complications (P = .0008), pulmonary complications (P = .0481), bleeding (P = .0106), and technical difficulties during surgery (P = .0024).

In an analysis adjusted for patient demographic factors, payer, primary diagnosis, obesity, comorbidities, inpatient death, admission type, hospital teaching status and volume, surgeon, and type of procedure, low-volume surgeons were nearly twice as likely as were high-volume surgeons to have complications (adjusted odds ratio [aOR] 1.822, P less than .0001), and intermediate-volume surgeons had a nearly 1.5-fold higher risk (aOR 1.479, P = .0044).

Other risk factors for complications were bilateral vs. unilateral procedures (aOR 2.165, P = .0018), and malignant vs. benign disease (aOR 1.685, P less than .0001).

Not surprisingly, complications more than doubled mean total case charges, which ranged from $33,659 for uncomplicated unilateral cases to $73,021 for complicated cases (P = .0013), and from $47,284 for bilateral cases with no complications, to $141,461 for two-sided procedures with complications (P = .0221). Charges were higher for malignant cases than for benign cases without complications (P less than .0001), but complications brought the charges for both benign and malignant cases closer together .

Charges for noncomplicated procedures performed by high-volume surgeons were a comparative bargain at $27,324, compared with $33,499 for low- and intermediate-volume surgeons combined (P = .001). However, there were no significant differences by surgeon volume when complications arose.

Similarly, lengths of stay were prolonged when complications ensued for both unilateral cases (mean 3.7 days vs. 9.3 for complicated cases, P = .0042) and for bilateral cases (9.3 vs. 19.8, P = .025).

Higher volume surgeons managed to get patients out faster, averaging 2.7 days for cases without complications, compared with 4.2 for low/intermediate-volume surgeons (P less than .0001). When complications arose, patients of higher-volume surgeons still had shorter lengths of stay (8.5 vs. 10.4 days), but this difference was not statistically significant.

Dr. Lawrence Kim, professor of surgery at the University of North Carolina, Chapel Hill, said after the presentation that the study showed the limitations of using administrative data.

He said that approximately "98% of the patients [in the study presented] had no comorbidities, which just does not mesh with the realities I have ever faced with adrenal patients."

The study was internally funded. Dr. Hauch reported having no financial disclosures.

PHOENIX – There is more evidence that it’s best to go with the pros: Adrenalectomies performed by higher-volume surgeons are associated with fewer complications, lower costs, and shorter lengths of stay than are those done by surgeons who dabble in the procedure.

The findings, presented at the annual Society of Surgical Oncology Cancer Symposium, come from a cross-sectional study of outcomes on all patients who underwent unilateral, partial, or bilateral adrenalectomies in the United States over a 7-year span.

©Jana Blašková/ Thinkstockphotos.com

"The frequency of adrenalectomy has steadily increased in the United States within the last few years, and with improvement of diagnostic and imaging modalities it’s likely that the rate of adrenal surgery will continue to rise," said Dr. Adam Hauch, a research resident in the department of surgery at Tulane University, New Orleans.

The prospects for the growth in the procedure prompted Dr. Hauch and colleagues to look at clinical and economic outcomes following adrenalectomy, and to see how surgeon volume, diagnosis, and type of surgery might affect outcomes.

They drew on discharge data from the Healthcare Cost and Utilization Project – National Inpatient Sample (HCUP-NIS), an administrative database sponsored by the U.S. Agency for Healthcare Research and Quality.

The information included International Classification of Diseases, Ninth Revision (ICD-9) codes identifying all adult patients who underwent adrenalectomies in U.S. hospitals from 2003 through 2009. Patients were divided into benign and malignant lesion groups.

The investigators found 7,829 procedures. Mean patient age was 50 years, most of the patients (74.4%) were white, and the majority were female (58.2%) and were privately insured (58.9%). Nearly all of the patients (98.3%) had one or no comorbidities at the time of admission. Only 42 patients (0.5%) died during their hospital stays.

More than three-fourths of the procedures (79.2%) were for benign disease; the remaining 20.8% of surgeries were for malignancies.

Low-volume surgeons, defined as those who performed one or fewer adrenalectomies on average per year, performed 41.7% of all procedures, compared with 34.7% for intermediate-volume surgeons (two to five per year) and 23.6% for high-volume surgeons (more than five per year).

The vast majority (97.1%) of procedures were unilateral/partial, and approximately 95% of surgeons in each experience category performed such procedures. Procedures for malignant disease accounted for 10.6% of cases for low-volume surgeons, 6.3% for intermediate-volume docs, and 4.3% of the most prolific surgeons.

It’s complicated

Risks for any complication were significantly higher among low-volume surgeons (18.8% of their cases), compared with 14.6% for those in the middle, and 11.6% for the high-volume operators (P less than .0001). High-volume performers had significantly lower risk for cardiovascular complications (P = .0008), pulmonary complications (P = .0481), bleeding (P = .0106), and technical difficulties during surgery (P = .0024).

In an analysis adjusted for patient demographic factors, payer, primary diagnosis, obesity, comorbidities, inpatient death, admission type, hospital teaching status and volume, surgeon, and type of procedure, low-volume surgeons were nearly twice as likely as were high-volume surgeons to have complications (adjusted odds ratio [aOR] 1.822, P less than .0001), and intermediate-volume surgeons had a nearly 1.5-fold higher risk (aOR 1.479, P = .0044).

Other risk factors for complications were bilateral vs. unilateral procedures (aOR 2.165, P = .0018), and malignant vs. benign disease (aOR 1.685, P less than .0001).

Not surprisingly, complications more than doubled mean total case charges, which ranged from $33,659 for uncomplicated unilateral cases to $73,021 for complicated cases (P = .0013), and from $47,284 for bilateral cases with no complications, to $141,461 for two-sided procedures with complications (P = .0221). Charges were higher for malignant cases than for benign cases without complications (P less than .0001), but complications brought the charges for both benign and malignant cases closer together .

Charges for noncomplicated procedures performed by high-volume surgeons were a comparative bargain at $27,324, compared with $33,499 for low- and intermediate-volume surgeons combined (P = .001). However, there were no significant differences by surgeon volume when complications arose.

Similarly, lengths of stay were prolonged when complications ensued for both unilateral cases (mean 3.7 days vs. 9.3 for complicated cases, P = .0042) and for bilateral cases (9.3 vs. 19.8, P = .025).

Higher volume surgeons managed to get patients out faster, averaging 2.7 days for cases without complications, compared with 4.2 for low/intermediate-volume surgeons (P less than .0001). When complications arose, patients of higher-volume surgeons still had shorter lengths of stay (8.5 vs. 10.4 days), but this difference was not statistically significant.

Dr. Lawrence Kim, professor of surgery at the University of North Carolina, Chapel Hill, said after the presentation that the study showed the limitations of using administrative data.

He said that approximately "98% of the patients [in the study presented] had no comorbidities, which just does not mesh with the realities I have ever faced with adrenal patients."

The study was internally funded. Dr. Hauch reported having no financial disclosures.

PHOENIX – More than one-fourth of men under age 50 undergoing surgery for benign goiter were found to have thyroid cancers, based on a chart review performed at the University of Pennsylvania.

The overall incidence of thyroid cancers in the patient series was 12%. Among men under age 45, the rate was "surprisingly" 28%, said Douglas R. Farquhar, a medical student at the University of Pennsylvania School of Medicine in Philadelphia.

Neil Osterweil/Frontline Medical News

Although thyroid goiters have traditionally been thought to be associated with a low risk for malignancy, recent studies have suggested otherwise. "In the literature we have seen published rates of up to 35%, which is much higher than we all had anticipated," Mr. Farquhar said at the annual Society of Surgical Oncology Cancer Symposium.

To get a better handle on the preoperative and patient characteristics associated with incident thyroid cancer and characterize the types of thyroid cancer discovered incidentally, Mr. Farquhar and his colleagues reviewed charts on all patients who underwent either total thyroidectomy or thyroid lobectomy for goiter at the center from 2004 through 2012.

Many cases of goiter can be medically managed, but surgery may be indicated in cases of pressure symptoms, cosmesis, or suspicion of malignancy, the investigators noted.

They excluded from their study patients with preoperative fine-needle aspiration pathology findings of Bethesda level III-VI (follicular lesion of undetermined significance, follicular neoplasm, suspicious or positive for malignancy).

Among 418 patients undergoing goiter surgery, 367 had goiter only, and 51 (12%) had an incident thyroid cancer. In all, 38 (75%) had papillary carcinomas, 10 (20%) had follicular carcinomas, 3 (6%) had Hürthle cell carcinomas, and 2 (4%) had thyroid lymphomas (two patients had multiple thyroid cancers, explaining the percentage greater than 100). An additional 67 patients (16%) were found to have micropapillary lesions.

Looking at the population as a whole, the investigators found that patients with thyroid cancer tended to be younger, with a mean age of 49.5 vs. 54.6 years (P = .012). There was a trend toward more cancers among men than women, but it was not significant.

There were no significant differences in any preoperative factors between patients with cancers and those with goiter only, including number of nodules, site of dominant nodule (right, left, or isthmus), thyroid function, thyroid weight, or fine-needle aspiration results (percentage deemed benign or nondiagnostic).

In a multivariate analysis, male sex was associated with a more than twofold risk for thyroid cancer (odds ratio, 2.39; 95% confidence interval, 1.152-4.978). There were also trends toward a lower risk of cancer with each additional decade of life, and a higher risk among patients who had undergone thyroid lobectomy, but these were nonsignificant associations.

"Knowledge of these associations may prove to be useful for both patient counseling and surgical decision making," Mr. Farquhar said.

The study was internally funded. The senior author was Dr. Douglas L. Fraker, chief of the division of endocrine and oncologic surgery at the University of Pennsylvania.

Mr. Farquhar and his coauthors reported having no relevant financial disclosures.

PHOENIX – More than one-fourth of men under age 50 undergoing surgery for benign goiter were found to have thyroid cancers, based on a chart review performed at the University of Pennsylvania.

The overall incidence of thyroid cancers in the patient series was 12%. Among men under age 45, the rate was "surprisingly" 28%, said Douglas R. Farquhar, a medical student at the University of Pennsylvania School of Medicine in Philadelphia.

Neil Osterweil/Frontline Medical News

Although thyroid goiters have traditionally been thought to be associated with a low risk for malignancy, recent studies have suggested otherwise. "In the literature we have seen published rates of up to 35%, which is much higher than we all had anticipated," Mr. Farquhar said at the annual Society of Surgical Oncology Cancer Symposium.

To get a better handle on the preoperative and patient characteristics associated with incident thyroid cancer and characterize the types of thyroid cancer discovered incidentally, Mr. Farquhar and his colleagues reviewed charts on all patients who underwent either total thyroidectomy or thyroid lobectomy for goiter at the center from 2004 through 2012.

Many cases of goiter can be medically managed, but surgery may be indicated in cases of pressure symptoms, cosmesis, or suspicion of malignancy, the investigators noted.

They excluded from their study patients with preoperative fine-needle aspiration pathology findings of Bethesda level III-VI (follicular lesion of undetermined significance, follicular neoplasm, suspicious or positive for malignancy).

Among 418 patients undergoing goiter surgery, 367 had goiter only, and 51 (12%) had an incident thyroid cancer. In all, 38 (75%) had papillary carcinomas, 10 (20%) had follicular carcinomas, 3 (6%) had Hürthle cell carcinomas, and 2 (4%) had thyroid lymphomas (two patients had multiple thyroid cancers, explaining the percentage greater than 100). An additional 67 patients (16%) were found to have micropapillary lesions.

Looking at the population as a whole, the investigators found that patients with thyroid cancer tended to be younger, with a mean age of 49.5 vs. 54.6 years (P = .012). There was a trend toward more cancers among men than women, but it was not significant.

There were no significant differences in any preoperative factors between patients with cancers and those with goiter only, including number of nodules, site of dominant nodule (right, left, or isthmus), thyroid function, thyroid weight, or fine-needle aspiration results (percentage deemed benign or nondiagnostic).

In a multivariate analysis, male sex was associated with a more than twofold risk for thyroid cancer (odds ratio, 2.39; 95% confidence interval, 1.152-4.978). There were also trends toward a lower risk of cancer with each additional decade of life, and a higher risk among patients who had undergone thyroid lobectomy, but these were nonsignificant associations.

"Knowledge of these associations may prove to be useful for both patient counseling and surgical decision making," Mr. Farquhar said.

The study was internally funded. The senior author was Dr. Douglas L. Fraker, chief of the division of endocrine and oncologic surgery at the University of Pennsylvania.

Mr. Farquhar and his coauthors reported having no relevant financial disclosures.

PHOENIX – More than one-fourth of men under age 50 undergoing surgery for benign goiter were found to have thyroid cancers, based on a chart review performed at the University of Pennsylvania.

The overall incidence of thyroid cancers in the patient series was 12%. Among men under age 45, the rate was "surprisingly" 28%, said Douglas R. Farquhar, a medical student at the University of Pennsylvania School of Medicine in Philadelphia.

Neil Osterweil/Frontline Medical News

Although thyroid goiters have traditionally been thought to be associated with a low risk for malignancy, recent studies have suggested otherwise. "In the literature we have seen published rates of up to 35%, which is much higher than we all had anticipated," Mr. Farquhar said at the annual Society of Surgical Oncology Cancer Symposium.

To get a better handle on the preoperative and patient characteristics associated with incident thyroid cancer and characterize the types of thyroid cancer discovered incidentally, Mr. Farquhar and his colleagues reviewed charts on all patients who underwent either total thyroidectomy or thyroid lobectomy for goiter at the center from 2004 through 2012.

Many cases of goiter can be medically managed, but surgery may be indicated in cases of pressure symptoms, cosmesis, or suspicion of malignancy, the investigators noted.

They excluded from their study patients with preoperative fine-needle aspiration pathology findings of Bethesda level III-VI (follicular lesion of undetermined significance, follicular neoplasm, suspicious or positive for malignancy).

Among 418 patients undergoing goiter surgery, 367 had goiter only, and 51 (12%) had an incident thyroid cancer. In all, 38 (75%) had papillary carcinomas, 10 (20%) had follicular carcinomas, 3 (6%) had Hürthle cell carcinomas, and 2 (4%) had thyroid lymphomas (two patients had multiple thyroid cancers, explaining the percentage greater than 100). An additional 67 patients (16%) were found to have micropapillary lesions.

Looking at the population as a whole, the investigators found that patients with thyroid cancer tended to be younger, with a mean age of 49.5 vs. 54.6 years (P = .012). There was a trend toward more cancers among men than women, but it was not significant.

There were no significant differences in any preoperative factors between patients with cancers and those with goiter only, including number of nodules, site of dominant nodule (right, left, or isthmus), thyroid function, thyroid weight, or fine-needle aspiration results (percentage deemed benign or nondiagnostic).

In a multivariate analysis, male sex was associated with a more than twofold risk for thyroid cancer (odds ratio, 2.39; 95% confidence interval, 1.152-4.978). There were also trends toward a lower risk of cancer with each additional decade of life, and a higher risk among patients who had undergone thyroid lobectomy, but these were nonsignificant associations.

"Knowledge of these associations may prove to be useful for both patient counseling and surgical decision making," Mr. Farquhar said.

The study was internally funded. The senior author was Dr. Douglas L. Fraker, chief of the division of endocrine and oncologic surgery at the University of Pennsylvania.

Mr. Farquhar and his coauthors reported having no relevant financial disclosures.

PHOENIX, ARIZ. – Induction therapy does not appear to significantly increase the risk of postoperative complications in patients who undergo minimally invasive esophagectomy for esophageal adenocarcinoma, according to results of a study reported at the annual Society of Surgical Oncology Cancer Symposium.

"After balancing pretreatment variables that can potentially influence treatment decisions, we found that induction therapy does not significantly impact on perioperative outcomes compared with patients who are treated with minimally invasive esophagectomy as primary therapy," said Dr. Katie Sue Nason, of the department of cardiothoracic surgery at the University of Pittsburgh.

That conclusion comes from a propensity-matched analysis in which patients with similar pretreatment predictor variables were paired in an attempt to reduce comparison biases.

The investigators found no significant differences in mortality, major adverse events, readmissions, reoperations, or length of stay between 197 patients who received induction therapy and minimally invasive esophagectomy and 178 who had esophagectomy alone.

Although induction chemoradiation therapy may reduce the incidence of local and distant treatment failures in patients with esophageal cancer, it has the potential to increase the risk of postoperative adverse outcomes.

"What’s often not considered is that these factors that influence postoperative outcomes may also be influencing treatment allocation," Dr. Nason said.

In observational studies, for example, there may be larger differences in observed covariates between treatment groups that could lead to biased estimates of treatment effects.

"This could be adjusted for using propensity score matching, where you generate the conditional probability of one individual being treated with a particular treatment approach given multiple pretreatment covariates. By doing propensity score matching, you can then balance these covariates such as age and various comorbid illnesses between the two groups, and perhaps eliminate this treatment allocation bias that impacts on the relationship between the treatment and the postoperative outcomes," Dr. Nason explained.

She and her colleagues applied the technique to an analysis of outcomes from 375 patients with clinical stage II or greater esophageal adenocarcinoma treated with minimally invasive esophagectomy. They assessed tumor variables, comorbidities, treatments, and outcomes, and created propensity matching scores to match surgery-only patients one-on-one with no repeats to a patient who also underwent induction therapy and had a propensity score within 0.05 of that for the surgery-only patient.

Patients without suitable matches were excluded from the data set.

The extensive list of variables included age, smoking status, alcohol use, history of Barrett’s esophagus, myriad comorbidities, cancer location, pretreatment clinical stage, and many others.

Among the 375 patients, the investigators were able to generate propensity-matching scores for 82 pairs for the comparison of treatments and outcome.

They found that there were no significant differences between induction and surgery-only patients in the primary outcome of adverse events within 30 days of surgery, including in-hospital and 30-day mortality, major adverse events or at least 1 postoperative adverse event, readmission within 30 days, reoperation in-hospital or within 30 days, or length of stay greater than 10 days.

Dr. Nason noted that although unmatched patients differed in age, presentation with alarm symptoms, daily alcohol use, clinical stage and comorbid illnesses, the pretreatment variables were all well balanced in the propensity-matched analysis.

Mortality after minimally invasive esophagectomy was 1.8% among all 375 patients, 1.5% among patients who underwent induction, and 2.3% among patients who underwent surgery alone; these differences were not significant.

Major adverse events occurred in 28% of patients overall, 27% of those who received induction, and 30% of those who had surgery alone, also not significant.

The study was internally funded. Dr. Nason reported having no financial disclosures.

PHOENIX, ARIZ. – Induction therapy does not appear to significantly increase the risk of postoperative complications in patients who undergo minimally invasive esophagectomy for esophageal adenocarcinoma, according to results of a study reported at the annual Society of Surgical Oncology Cancer Symposium.

"After balancing pretreatment variables that can potentially influence treatment decisions, we found that induction therapy does not significantly impact on perioperative outcomes compared with patients who are treated with minimally invasive esophagectomy as primary therapy," said Dr. Katie Sue Nason, of the department of cardiothoracic surgery at the University of Pittsburgh.

That conclusion comes from a propensity-matched analysis in which patients with similar pretreatment predictor variables were paired in an attempt to reduce comparison biases.

The investigators found no significant differences in mortality, major adverse events, readmissions, reoperations, or length of stay between 197 patients who received induction therapy and minimally invasive esophagectomy and 178 who had esophagectomy alone.

Although induction chemoradiation therapy may reduce the incidence of local and distant treatment failures in patients with esophageal cancer, it has the potential to increase the risk of postoperative adverse outcomes.

"What’s often not considered is that these factors that influence postoperative outcomes may also be influencing treatment allocation," Dr. Nason said.

In observational studies, for example, there may be larger differences in observed covariates between treatment groups that could lead to biased estimates of treatment effects.

"This could be adjusted for using propensity score matching, where you generate the conditional probability of one individual being treated with a particular treatment approach given multiple pretreatment covariates. By doing propensity score matching, you can then balance these covariates such as age and various comorbid illnesses between the two groups, and perhaps eliminate this treatment allocation bias that impacts on the relationship between the treatment and the postoperative outcomes," Dr. Nason explained.

She and her colleagues applied the technique to an analysis of outcomes from 375 patients with clinical stage II or greater esophageal adenocarcinoma treated with minimally invasive esophagectomy. They assessed tumor variables, comorbidities, treatments, and outcomes, and created propensity matching scores to match surgery-only patients one-on-one with no repeats to a patient who also underwent induction therapy and had a propensity score within 0.05 of that for the surgery-only patient.

Patients without suitable matches were excluded from the data set.

The extensive list of variables included age, smoking status, alcohol use, history of Barrett’s esophagus, myriad comorbidities, cancer location, pretreatment clinical stage, and many others.

Among the 375 patients, the investigators were able to generate propensity-matching scores for 82 pairs for the comparison of treatments and outcome.

They found that there were no significant differences between induction and surgery-only patients in the primary outcome of adverse events within 30 days of surgery, including in-hospital and 30-day mortality, major adverse events or at least 1 postoperative adverse event, readmission within 30 days, reoperation in-hospital or within 30 days, or length of stay greater than 10 days.

Dr. Nason noted that although unmatched patients differed in age, presentation with alarm symptoms, daily alcohol use, clinical stage and comorbid illnesses, the pretreatment variables were all well balanced in the propensity-matched analysis.

Mortality after minimally invasive esophagectomy was 1.8% among all 375 patients, 1.5% among patients who underwent induction, and 2.3% among patients who underwent surgery alone; these differences were not significant.

Major adverse events occurred in 28% of patients overall, 27% of those who received induction, and 30% of those who had surgery alone, also not significant.

The study was internally funded. Dr. Nason reported having no financial disclosures.

PHOENIX, ARIZ. – Induction therapy does not appear to significantly increase the risk of postoperative complications in patients who undergo minimally invasive esophagectomy for esophageal adenocarcinoma, according to results of a study reported at the annual Society of Surgical Oncology Cancer Symposium.

"After balancing pretreatment variables that can potentially influence treatment decisions, we found that induction therapy does not significantly impact on perioperative outcomes compared with patients who are treated with minimally invasive esophagectomy as primary therapy," said Dr. Katie Sue Nason, of the department of cardiothoracic surgery at the University of Pittsburgh.

That conclusion comes from a propensity-matched analysis in which patients with similar pretreatment predictor variables were paired in an attempt to reduce comparison biases.

The investigators found no significant differences in mortality, major adverse events, readmissions, reoperations, or length of stay between 197 patients who received induction therapy and minimally invasive esophagectomy and 178 who had esophagectomy alone.

Although induction chemoradiation therapy may reduce the incidence of local and distant treatment failures in patients with esophageal cancer, it has the potential to increase the risk of postoperative adverse outcomes.

"What’s often not considered is that these factors that influence postoperative outcomes may also be influencing treatment allocation," Dr. Nason said.

In observational studies, for example, there may be larger differences in observed covariates between treatment groups that could lead to biased estimates of treatment effects.

"This could be adjusted for using propensity score matching, where you generate the conditional probability of one individual being treated with a particular treatment approach given multiple pretreatment covariates. By doing propensity score matching, you can then balance these covariates such as age and various comorbid illnesses between the two groups, and perhaps eliminate this treatment allocation bias that impacts on the relationship between the treatment and the postoperative outcomes," Dr. Nason explained.

She and her colleagues applied the technique to an analysis of outcomes from 375 patients with clinical stage II or greater esophageal adenocarcinoma treated with minimally invasive esophagectomy. They assessed tumor variables, comorbidities, treatments, and outcomes, and created propensity matching scores to match surgery-only patients one-on-one with no repeats to a patient who also underwent induction therapy and had a propensity score within 0.05 of that for the surgery-only patient.

Patients without suitable matches were excluded from the data set.

The extensive list of variables included age, smoking status, alcohol use, history of Barrett’s esophagus, myriad comorbidities, cancer location, pretreatment clinical stage, and many others.

Among the 375 patients, the investigators were able to generate propensity-matching scores for 82 pairs for the comparison of treatments and outcome.

They found that there were no significant differences between induction and surgery-only patients in the primary outcome of adverse events within 30 days of surgery, including in-hospital and 30-day mortality, major adverse events or at least 1 postoperative adverse event, readmission within 30 days, reoperation in-hospital or within 30 days, or length of stay greater than 10 days.

Dr. Nason noted that although unmatched patients differed in age, presentation with alarm symptoms, daily alcohol use, clinical stage and comorbid illnesses, the pretreatment variables were all well balanced in the propensity-matched analysis.

Mortality after minimally invasive esophagectomy was 1.8% among all 375 patients, 1.5% among patients who underwent induction, and 2.3% among patients who underwent surgery alone; these differences were not significant.

Major adverse events occurred in 28% of patients overall, 27% of those who received induction, and 30% of those who had surgery alone, also not significant.

The study was internally funded. Dr. Nason reported having no financial disclosures.